pital day 2), her blood pressure had decreased to 164/113 mm Hg and her heart rate had increased to 92 bpm. She then received 1 dose each of oral nifedipine XL (60 mg), clonidine (0.1 mg), hydralazine (10 mg), metoprolol (200 mg), and diltiazem 180 mg. Following these medications, the patient became confused and semi-comatose, and her blood pressure dropped to 90/62 mm Hg. An ECG taken at that time showed P waves occurring after the QRS complex (Figure 2, upper panel). Intravenous glucagon (7.5 mg) was administered to counteract the effects of both the betablockers and calcium channel blockers, 1 and the patient’s blood pressure improved to 120/72 mm Hg. A rhythm strip recorded 6 min after the administration of glucagon (Figure 2, middle panel) showed a small increase in the time interval between the QRS and the subsequent P waves. Normal sinus rhythm was obtained 4 min later (Figure 2, lower panel). Later that day, the patient’s blood pressure decreased again to 96/64 mm Hg. ECG rhythm strips showed a narrow QRS complex rhythm at 70 bpm with P waves of sinus morphology preceding the QRS complex, short and variable PR intervals, and periodically disappearing P waves (Figure 3). The administration of a second dose of intravenous glucagon (7.5 mg) resulted in the return of normal sinus rhythm and improved blood pressure (112/70 mm Hg).
Numerous studies have shown that effective control of elevated blood pressure has greatly reduced the risk of stroke and, to a lesser extent, the risk of coronary artery disease. Although the relationship between diastolic blood pressure and both stroke and coronary disease is significant, systolic blood pressure correlates more strongly with stroke, congestive heart failure, coronary artery disease, declining renal function, and left ventricular hypertrophy. Studies have also shown that the presence of a wide pulse pressure (>/=60-70 mm Hg) also has an independent and major impact on coronary disease mortality and is strongly correlated with increased risk for cardiovascular disease. Because many hypertensives have end-organ damage (cardiac, central nervous system, renal), and the majority also have a comorbid condition such as diabetes and hyperlipidemia, which also increases cardiovascular risk, it is necessary to view the risks and comorbidity of hypertension and antihypertensive therapy in light of these problems. Despite evidence that antihypertensive therapy reduces the risk of stroke and coronary events, and despite the availability of effective agents, roughly half of the hypertensives in the United States remain untreated and only 24% have blood pressure <140 mm Hg systolic and 90 mm Hg diastolic. To ensure that hypertensive patients receive adequate therapy, physicians should treat patients aggressively and appropriately, avoiding antihypertensive drugs that adversely affect comorbid conditions and selecting those that also exert favorable therapeutic effects on these conditions.
For the patient-administered treatment of anogenital warts, 0.5% podofilox (podophyllotoxin), one of the active compounds of podophyllin, has been shown to be more effective than the vehicle alone. This study was designed to evaluate the safety and efficacy of 0.5% podofilox treatment followed by prophylaxis.
Patients and methods:
A total of 103 patients were entered in stage 1 of the study. Stage 1 was an open label study, and patients self-administered 0.5% podofilox twice daily for 3 consecutive days per week for 4 weeks. A total of 100 patients remained available for efficacy and safety analyses. At the end of stage 1, patients who had a complete response proceeded to stage 2 of the study. Patients who had a 50% to 99% reduction in measured total wart area were offered cryotherapy every 10 days, up to 5 times. If cleared of warts, they were also entered into stage 2. A total of 57 patients were enrolled into stage 2, a double-blind, randomized, placebo-controlled prophylactic study of 0.5% podofilox self-administered once daily for 3 days per week for 8 weeks, on the sites of healed warts. A total of 45 patients in stage 2 were available for efficacy analysis.
By the end of stage 1, 68% of the warts had disappeared, and 29 of 100 patients (29%) had a complete response. A total of 49 patients had a 50% or greater improvement in wart area and underwent cryotherapy. Rates of local side effects after 1 week of treatment were 57% for inflammation, 39% for erosion, 47% for pain, 48% for burning, and 44% for itching. However, these symptoms and signs were mostly mild to moderate in intensity and diminished over time. Therefore, overall treatment was well tolerated. In stage 2, only 4 of 21 patients (19%) in the podofilox group experienced a recurrence as opposed to 12 of 24 (50%) in the placebo group (P = 0.031). As in stage 1, the side effects were modest, and the drug was well tolerated.
This study confirms the efficacy and good tolerance of 0.5% podofilox in the treatment of anogenital warts. It also establishes the safety and superior efficacy of patient-administered podofilox over the vehicle alone as prophylaxis against recurrence of lesions. Although long-term efficacy and tolerance remain to be established, podofilox appears to be a useful agent in the control of this disease.
The contribution of M-mode echocardiography to cardiac diagnosis was evaluated in a series of 1,000 successive patients. Among subjects in whom a presumptive clinical diagnosis had been made, echocardiography demonstrated totally unexpected findings in 10 per cent, supported the clinical diagnosis in 50 per cent and was entirely within normal limits in 19 per cent. Among patients with evidence of heart disease but no firm clinical diagnosis, echocardiography established the diagnosis in 23 per cent, including 20 per cent of all patients referred for evaluation of chest pain or arrhythmia of unclear etiology. "Missed" clinical diagnosis frequently involved patients with mitral valve prolapse, congestive cardiomyopathy, pericardial disease or asymmetrical septal hypertrophy of the heart. This study quantifies the amount of independent information contributed by echocardiography to cardiac diagnosis and demonstrates that this technic provides data of important clinical relevance in a surprisingly large number of cardiac patients.
One thousand unselected patients admitted to large urban medical centers were examined for the presence of a diagonal ear lobe crease and evaluated for the presence of coronary artery disease. A high degree of correlation between the two was seen, using both clinical and angiographic criteria for the diagnosis of coronary artery disease. The association between the ear lobe crease and coronary artery disease was independent of patient age. Prospective analysis of single risk factors in 112 consecutive patients subjected to coronary cineangiography revealed that demonstrable coronary artery disease was correlated only with the ear lobe crease and with previous acute myocardial infarction (although less strongly with the latter). These conclusions are consistent with those of the world's literature, which also finds a strong correlation between coronary artery disease and the ear lobe crease, with the exception of Oriental patients, native American Indian patients, and children with Beckwith's syndrome.
Two-hundred-sixty-nine otherwise healthy persons experiencing periodic, moderately severe headache of a type that had previously responded to nonprescription medications completed this randomized, parallel, double-blind study. The three demographically similar subgroups took either 1,000 mg acetaminophen, 650 mg aspirin, or an identical placebo, for headache. Headache intensity and relief scores over the following six hours were obtained and assessed by sums of pain intensity difference and values of pain relief scores analyses. Responses for the group, and for the subgroup with tension headaches (107 persons) showed no differences between the effects of the active medications. The effects of each medication were strongly superior to placebo. There were no differences in side effects among the three treatment modalities. In persons experiencing tension-vascular headaches (162), only aspirin, at two hours, was superior to placebo, but direct comparison with acetaminophen suggested no real difference. Acetaminophen (1,000 mg) and aspirin (650 mg) are clinically similar in treating the headaches for which they are commonly taken. Recommendations for their use in treating headache should be based on individual patient suitability and on cost factors.
We have used a low-calcium diet providing only 2 mg/kg (body weight) per 24 hours of calcium to distinguish between "renal" and "absorptive" idiopathic hypercalciuria. Sixteen of 27 hypercalciuric subjects excreted calcium in excess of intake during days seven, eight and nine of he diet, suggesting some element of renal hypercalciuria; however, all patients had low or normal serum PTH and urine cAMP levels. In general, fasting urine calcium was elevated in these 16 subjects and normal in the remaining 11, who conserved calcium more normally. SErum 1,25(OH)2D3 levels were the same in patients and normal subjects, even though PTH levels of the patients were below those of he normal subjects. Urine magnesium excretion and phosphorus excretion were both increased in the patients who excreted calcium in excess of intake. Our findings suggest that renal and absorptive hypercalciuria may not be distinct entities but rather the two extremes of a continuum of behavior. A uniform elevation of intestinal calcium absorption and a variable defect of renal calcium reabsorption could explain our results far better than the hypothesis of distinct absorptive and renal forms of hypercalciuria.
Two patients with lepromatous leprosy and hypercalcemia are presented. Serum immunoreactive parathyroid hormone and urinary cyclic adenosine monophosphate concentrations were suppressed. Serum 1,25-dihydroxyvitamin D [1,25-(OH)2D] concentrations were elevated in one patient and normal in the other. Urinary hydroxyproline excretion was slightly high in both patients. Hypercalcemia resolved excretion was slightly high in both patients. Hypercalcemia resolved with prednisone therapy. Abnormal 1,25-(OH)2D production and/or metabolism may play a role in the pathogenesis of hypercalcemia in some patients with leprosy.
Three patients are described in whom there was no simple correlation between plasma 1,25(OH)2D3 concentration and the occurrence of osteomalacia. One patient had severe osteomalacia with high plasma 1,25(OH)2D3 and normal mineral ion product; the second had a normal mineral ion product and no evidence of osteomalacia even though plasma 1,25(OH)2D3 was undetectable; and the third had osteomalacia, low plasma 1,25(OH)2D3 and a reduced mineral ion product. In considering these data in the light of presently available information, it is concluded that osteomalacia can occur as a consequence of a lack of a vitamin D metabolite other than 1,25(OH)2D3, or a consequence of a reduced mineral ion product, but not as a consequence of 1,25(OH)2D3 lack if the mineral ion product is normally maintained and other D metabolites are present. However, a deficiency of 1,25(OH)2D3 normally leads to a reduction in the mineral ion product hence 1,25(OH)2D3 deficiency may play a role in the development of certain forms of osteomalacia.
Two boys aged six and four with the syndrome of hereditary resistance to 1,25-dihydroxyvitamin D3 with rickets alopecia and growth retardation are presented. After unsuccessful therapeutic trials with pharmacologic doses of vitamin D or its active metabolites, the patients were treated by long-term intracaval infusions of calcium through an implantable catheter. A total of 0.5 to 0.9 g of elemental calcium was infused daily for 18 months and the serum calcium concentration was maintained at 9 to 10 mg/dl. Bone pain subsided within one week of treatment. Serum phosphorus, immunoreactive parathyroid hormone, and 1,25-dihydroxyvitamin D concentrations and alkaline phosphatase activity were normalized within four to nine months. Radiographs of the knees and hands revealed progressive healing of rickets with complete resolution after one year of treatment. The patients gained 12 cm and 8 cm per year in height as compared with 3 cm and 2 cm, respectively, in the previous year. A transilial bone biopsy obtained from one patient prior to treatment revealed severe osteomalacia associated with osteitis fibrosa. A follow-up biopsy examined after 12 months of therapy showed almost complete healing of osteomalacia and normal mineralization. These observations indicate the following: (1) Long-term intracaval calcium infusions are an effective mode of therapy for these patients, and (2) When adequate serum calcium and phosphorus concentrations are maintained, healing of rickets and normal growth rate could be achieved even in the absence of a normal 1,25-dihydroxyvitamin D3 receptor-effector system.
The short-term effects of 1,25-dihydroxycholecalciferol (1,25-(OH)2D3) on disordered calcium metabolism were studied in 15 trials in patients with advanced renal failure and, for comparison, in 20 trials in normal persons. The steroid was given orally in doses of 0.027, 0.14, 0.68 and 2.7 μg/day for 7 to 15 days. Calcium absorption and urinary calcium increased after the administration of 0.14 to 2.7 μg/day in normal subjects, but 0.68 to 2.7 μg/day was needed to augment calcium absorption in the patients with uremia. Fecal calcium decreased significantly during metabolic balance studies. Serum calcium increased markedly only in the patients with uremia, and hypercalcemia occurred at a dosage level of 2.7 μg/day. With the increase in serum calcium, the blood levels of immunoreactive parathyroid hormone (iPTH) decreased. Urinary calcium increased substantially only in normal subjects. The steroid corrected the "vitamin D resistance" of uremia, suggesting that the renal production of 1,25-(OH)2D3 in uremia is defective.
Principal among the many relationships involving the metabolism and function of vitamin D is the central role of the kidney in the production of the biologically active steroid, 1,25-dihydroxychole-calciferol. Three important topics under intensive investigation in many laboratories are (1) the role of the kidney as an endocrine organ producing the biologically active form of vitamin D, (2) the regulation of the endocrine organ and its integration in the process of calcium homeostasis, and (3) reevaluation of the wide variety of vitamin D-related disease states as they relate to the central role of the kidney in vitamin D action.
In calcium deficiency states such as chronic renal failure, 1,25-dihydroxyvitamin D3 increases calcium and magnesium absorption toward normal levels. In the present study, the ability of exogenous 1,25-dihydroxyvitamin D3 to increase calcium and magnesium absorption above normal rates in healthy subjects was investigated. Steady-state perfusion studies were performed in 30 cm segments of jejunum and ileum before and after one week of 1,25-dihydroxyvitamin D3 administration (2 micrograms per day, 10 subjects). Serum 1,25-dihydroxyvitamin D concentration increased from 25.8 +/- 2.5 pg/ml to 56.4 +/- 6.6 (mean +/- SEM, p less than 0.05). In the basal state, calcium absorption was significantly higher in the jejunum than in the ileum. Vitamin D administration resulted in a significant increase in calcium absorption which was quantitatively similar in both the jejunum and ileum. The changes in net movement were due to an increase in lumen-to-plasma flux of calcium; the plasma-to-lumen flux remained unchanged. Jejunal magnesium absorption also was enhanced by 1,25-dihydroxyvitamin D3. These studies demonstrate that in healthy persons, exogenous 1,25-dihydroxyvitamin D3 increases calcium absorption in both the jejunum and the ileum, and increases magnesium absorption in the jejunum.
Two unrelated kindreds with four affected children having 1,25-dihydroxyvitamin D resistance, rickets, and alopecia are described. The children exhibited early onset of severe rickets with hypocalcemia, hypophosphatemia, elevated serum alkaline phosphatase levels, and secondary hyperparathyroidism. Radiography showed diffuse demineralization and classic changes of rickets. All affected children had total-body alopecia. Serum levels of 1,25-dihydroxyvitamin D3 were elevated and rose to extremely high values during treatment, with no apparent change in the mineral disorder. However, secondary hyperparathyroidism and hypophosphatemia did remit during treatment despite persistently low calcium levels. Skin biopsy was performed in the parents and affected children in one kindred. Analysis of 1,25-dihydroxyvitamin D3 receptors in cultured fibroblasts indicated apparent normal receptors in the parents and undetectable receptors in both affected children. After long periods of treatment with vitamin D metabolites and mineral replacement, healing took place in the older child in each kindred. These data suggest that the healing occurred spontaneously as the children reached seven to nine years of age rather than as a result of the treatment. The biochemical lesion in these children appeared to be a genetically transmitted defect in the 1,25-dihydroxyvitamin D3 receptor. The mechanisms by which healing was initiated and maintained remain to be elucidated.
Hypercalcemia has been infrequently associated with Hodgkin's disease. When seen, most cases have been attributable to skeletal invasion by disease. Herein is described a 40-year-old man with a 15-year history of Hodgkin's disease. Each of four disease recurrences was heralded by hypercalcemia occurring in the absence of bone disease or elevation of parathyroid hormone levels. Marked elevations of 1,25-dihydroxyvitamin D levels were observed that paralleled his disease course and response to therapy. The repetitive association of hypercalcemia with an elevation of 1,25-dihydroxyvitamin D in this case provides further evidence of lymphoma-associated production of this vitamin.
Six long-term hemodialysis patients with progressive skeletal deterioration during long-term pharmacologic vitamin D2 therapy were treated for six to 12 months with oral 1,25-dihydroxycholecalciferol (1,25-(OH)2D3) to determine its therapeutic effectiveness in vitamin D2-unresponsive osteodystrophy. On bone biopsy, three of the patients had severe osteomalacia and three showed predominant osteitis fibrosa. Previous therapies, including phosphate binders and dialysis schedules, were maintained. The three patients with osteomalacia and the two with osteitis fibrosa showed clinical deterioration. There was no significant change in serum calcium, phosphate, alkaline phosphatase, bone densitometry, immunoreactive parathyroid hormone levels or bone histology. Roentgenograms showed multiple new fractures of ribs and femoral necks in the patients with osteomalacia and increased bone resorption in two of three patients with osteitis fibrosa. 1,25-(OH)2D3 dosage had to be decreased in all patients because of hypercalcemia with a mean tolerated dose of 0.22 microgram/day. In these patients, 1,25-(OH)2D3 was not effective therapy for progressive osteodystrophy unresponsive to pharmacologic vitamin D2.
Hypoparathyroidism was diagnosed in nine members of a kindred of three generations. This study investigated why these persons were asymptomatic and without developmental abnormalities, in contrast to the common presentation of idiopathic hypoparathyroidism. In the hypocalcemic subjects, serum calcium level was 7.4 +/- 0.8 mg/dl (mean +/- SD) and ionized serum calcium level was 3.48 +/- 0.21 mg/dl. Immunoreactive parathyroid hormone values were inappropriately low. Injection of EDTA in one patient lowered ionized calcium levels, but immunoreactive parathyroid hormone values did not rise. Serum levels of 1,25-dihydroxyvitamin D and other vitamin D metabolites were normal or elevated and substantially higher than in other hypoparathyroid states. The normally observed positive correlation between the fasting urinary calcium/creatinine ratio and serum 1,25-dihydroxyvitamin D that reflects the dependence of net bone resorption on 1,25-dihydroxyvitamin D was upheld in hypoparathyroid patients. It is proposed that the subjects with familial hypoparathyroidism in this kindred had moderate asymptomatic hypocalcemia without developmental abnormalities because normal or elevated serum 1,25-dihydroxyvitamin D levels enhanced intestinal calcium absorption. This may represent one point in the spectrum of idiopathic hypoparathyroidism. Alternately, both the moderate degree of hypocalcemia and the normal serum calcitriol values could have been related to mild, partial hypoparathyroidism, which could have been inherited in this kindred.
The impact of strenuous exercise and environmental hypoxia on sickle cell trait (SCT) remains controversial. To determine if these factors induce cardiopulmonary and gas exchange abnormalities in SCT, healthy, young black male volunteers, 25 with SCT (HbAS) and 16 control subjects (HbAA), were evaluated during incremental and steady-state exercise tests using a cycle ergometer at 1,270 meters and 24 degrees C. Peak incremental exercise values for power (242 +/- 7 versus 253 +/- 10 watts), oxygen consumption (3.08 +/- 0.1 versus 3.26 +/- 0.14 liters/minute), heart rate (188 +/- 2 versus 189 +/- 3 beats/minute), minute ventilation (129 +/- 4.6 versus 144 +/- 7.7 liters/minute), oxygen pulse (16.4 +/- 0.5 versus 17.3 +/- 0.8 ml/beat), and respiratory exchange ratio (1.31 +/- 0.01 versus 1.33 +/- 0.02) revealed no significant differences (p less than 0.05) between the SCT and control groups, respectively. Peak incremental exercise values for arterial oxygen tension (82 +/- 1.7 versus 82 +/- 2.2 mm Hg), arterial carbon dioxide tension (32 +/- 0.7 versus 31 +/- 0.9 mm Hg), and alveolar-arterial oxygen pressure differences (19 +/- 1.4 versus 21 +/- 1.9 mm Hg) were similar for the SCT and control groups, respectively. Steady-state exercise results corroborate incremental exercise findings. It is concluded that cardiopulmonary and gas exchange responses to a brief period of strenuous exercise performed at low altitude at 24 degrees C in a well-characterized SCT sample of recruits were within normal limits and comparable to those of a carefully selected control sample.
Misoprostol at a dose of 200 micrograms inhibits gastric acid secretion and protects the gastric mucosa against the injurious effects of a single 1,300-mg dose of aspirin. The purpose of this study was to determine whether lower subantisecretory doses of misoprostol protect the gastric mucosa in this single-dose aspirin model. Protection was defined as no more than 10 hemorrhagic spots and no more than two hemorrhagic streaks. A total of 140 men participated in the two phases of the study. In the first phase, groups of 10 subjects each received placebo or misoprostol in doses of 200 micrograms, 100 micrograms, 50 micrograms, or 25 micrograms in a double-blind design. All misoprostol doses protected 50 to 70 percent of subjects as compared with 20 percent of subjects in the placebo group. To expand the number of observations, 90 additional subjects in groups of 30 each were evaluated after receiving misoprostol 50 micrograms or 25 micrograms or placebo. Misoprostol 50 micrograms protected 14 of 30 subjects (47 percent), 25 micrograms protected 11 of 30 (37 percent), and placebo protected six of 30 (20 percent). The dose-response trend was statistically significant (p less than 0.05). It is concluded that misoprostol protects the gastric mucosa against a single 1,300-mg dose of aspirin and that there is a significant dose-response relationship.
This report from the Canadian survey of thyroid cancer describes 1,074 patients with papillary thyroid cancer and 504 with follicular thyroid cancer followed for four to 24 years. The study groups included more patients with "advanced" disease and fewer with "early" disease than in the general population because these patients were referred to radiotherapy cancer centers, sometimes routinely, but often because referring physicians believed that certain clinical features indicated the need for additional treatment. Although this report is subject to all the problems of retrospective studies, a careful assessment of the pretreatment extent of disease combined with a long follow-up period has allowed an analysis of prognostic factors with considerable confidence. Univariate analysis of 12 possible prognostic factors (excluding treatment) demonstrated that nine of them were of statistical significance: postoperative status, age at diagnosis, extrathyroidal invasion, distant metastases, nodal involvement, differentiation, sex, tumor size, and pathologic type (in descending order of importance). Multivariate analysis was carried out using cause-specific survival rates. Independently important prognostic factors at initial treatment were age at diagnosis, extrathyroidal invasion, and degree of differentiation histologically for papillary cancers; and extrathyroidal invasion, distant metastases, primary tumor size, nodal involvement, age at diagnosis, and postoperative status for follicular cancers. The prognostic factors for tumor recurrence were quite different for the papillary and follicular cancers and ranked differently for the two groups.
A review of 1,997 patients to whom carinamide was administered has demonstrated that the drug possesses a low order of toxicity. Exclusive of nausea (12.1 per cent) and vomiting (5.5 per cent) the incidence of toxic manifestations was less than 2 per cent. True drug sensitivity was confirmed in fourteen patients and may be assumed in twenty-three additional cases although the concurrent administration of penicillin raises some questions as to the etiologic role of carinamide in all of the latter cases. Nausea may preclude therapy with the drug but this symptom may in large measure be ascribed to the mechanical factor of swallowing a large and oft-repeated dose of drug rather than to toxicity of the drug itself. From the observations recorded there is no indication that carinamide interfered with the elimination of normal nitrogenous metabolites or permanently impaired renal functions. Carinamide should be withheld in the presence of renal disease not because it is damaging to the kidneys but because its administration is unnecessary. Since carinamide is excreted almost entirely by glomerular filtration and sub-clinical grades of renal impairment cause accumulation of the drug in the circulation, dosage should be individualized and controlled by plasma carinamide estimations. It is possible that carinamide, by exerting its pharmacologic action upon the renal tubules, may inhibit the tubular excretion of some commonly employed medications. Few drugs in common use, even those that are granted to have little or no toxicity, can be given in the large doses, 18 to 32 Gm. per day, over periods of time up to sixty days, that are recorded here for carinamide.
In 1963, 10,000 men aged 40 years and over were examined; those without myocardial infarction or angina pectoris were followed for the next 5 years (1963–1968) to see what factors (variables) found in 1963 were associated with the development of angina pectoris by 1968.The average annual adjusted incidence for angina pectoris was 7.2/1,000; the incidence was highest (11.2) in those bom in Southeastern Europe and lowest (3.8) in those born in the Middle East. The incidence rose with age until age 59 and then plateaued off.The variables found significantly associated (p <0.01) with the development of angina pectoris were as follows: Clinical—blood pressure (systolic and diastolic), intermittent claudication, diabetes mellitus, nonspecific T waves in the electrocardiogram, serum cholesterol (total and in beta-lipoprotein). Psychosocial—anxiety and severe problems as seen by the subject in whatever area of his life situation, as well as, or because of, moving from one country to another. Blood group—A1BJka−. In addition, overweight, peptic ulcer and lack of physical activity are probably of importance.A knowledge of the factors associated with the development of angina pectoris is a “sine qua non” for the clinician who is interested in preventing the condition or aiding the patient who already has it.
The major independent role played by anxiety and severe psychosocial problems (especially family ones) is demonstrated by this multivariate analysis of a five year prospective study of the development of new angina pectoris among almost 10,000 adult men (average annual incidence = 5.7/1,000). The independent effect of these two variables is considerably augmented by the other significant risk factors of age, total serum cholesterol, systolic or diastolic blood pressure, certain electrocardiographic abnormalities and diabetes mellitus. The presence of all seven risk factors (at a high level) increases the probability of angina pectoris developing within five years to 289/1,000 from 14/1,000, when these factors are low or absent. The wife's love and support is an important balancing factor, which apparently reduces the risk of angina pectoris even in the presence of high risk factors. The implications of these findings to the pathophysiology and prevention of angina are stressed.
Recently there has been increased interest in the special mental health needs of women. We used data from the PRIME-MD 1000 study to assess gender differences in the frequency of mental disorders in primary care settings, and to explore the potential impact of these differences on health-related quality of life (HRQL).
One thousand primary care patients (559 women) were interviewed during the PRIME-MD study, which was conducted at four primary care clinics affiliated with university hospitals throughout the eastern United States. Patients completed a one-page questionnaire in the waiting room prior to being seen by the physician; patients and physicians then completed together a clinician evaluation guide that used DSM-III-R algorithms to diagnose mood, anxiety, somatoform, eating, and alcohol related disorders. Health-related quality of life was assessed with the Medical Outcomes Study SF-20 General Health Survey.
Women were more likely than men to have at least one mental disorder (43% versus 33%, P < 0.05). Higher rates were particularly prominent for mood disorders (31% of women versus 19% of men, odds ratio [OR] = 1.9, 95% confidence interval [CI] 1.4 to 2.6), anxiety disorders (22% versus 13%, OR = 1.9, CI = 1.3 to 2.8), and somatoform disorders (18% versus 9%, OR = 2.2, CI = 1.5 to 3.4). Psychiatric comorbidity was also more common in women (26% of women had two or more mental disorders versus 15% of men, P < 0.05). Unadjusted HRQL scores, ranging from 0 to 100, with 100 = best health, were all significantly lower in women than in men (eg, physical function = 67 in women versus 76 in men, P < 0.0001; mental health = 69 in women versus 76 in men, P < 0.0001). Many HRQL differences persisted after controlling for age, education, ethnicity, marital status, and number of physical disorders; however, differences in HRQL were eliminated in 5 of 6 domains after controlling for number of mental disorders. When compared with female patients of male physicians, female patients of female physicians demonstrated similar satisfaction with care, health care utilization, HRQL, and recognition rate of mental disorders.
In the 1,000 patients of the PRIME-MD study, mood, anxiety, and somatoform disorders and psychiatric comorbidity were all significantly more common in women than men. The HRQL scores were poorer in women than men, although most of this difference was accounted for by the difference in prevalence of mental disorders. These data suggest that one of the most important aspects of a primary care physician's care of female patients is to screen for and treat common mental disorders.
The ACTH secreting potential of the pituitary gland was tested, using the steroidal 11β-hydroxylase inhibitor, Metopirone®, in eighty patients (1 gm. Metopirone orally each six hours for forty-eight hours) on 101 occasions, and the increase in 17-oxogenicsteroid (OGS) excretion was followed. Twenty-one patients had a maximum OGS response of less than 50 mg. Of these, fifteen had a history of hypopituitarism, pituitary damage or steroid suppression, and the remainder were either suffering from metastatic breast cancer or had been treated with tranquilizer drugs. All patients judged clinically to have a normal adrenal-pituitary axis had a response of between 50 and 100 mg. per day. Of the twenty-three patients who had an OGS response greater than 100 mg. per day, nine were suffering from Cushing's syndrome, four from acromegaly and five were obese.The effect of Metopirone on OGS excretion provides a clinically useful test of pituitary ACTH “reserve”. Metopirone caused increases in the excretion of 11-desoxy-OGS which were about half the OGS increases and which gave no better correlation with clinical status.
The electrocardiographic findings in 102 consecutive patients with scleroderma were reviewed to determine the frequency and nature of the electrocardiographic abnormalities associated with this disease. Septal infarction pattern unassociated with QRS prolongation was present in 10 percent, compared with none of 96 control subjects (p less than 0.001). Ventricular conduction abnormalities were present in 17 percent. A normal electrocardiogram was obtained in 49 percent. A subset of 48 patients underwent detailed cardiopulmonary evaluation including exercise thallium scintigraphy, rest and exercise radionuclide ventriculography, pulmonary function tests, and chest roentgenography. Functional correlations of the electrocardiographic findings were examined in this subset. Septal infarction pattern (five of 48) and ventricular conduction abnormalities (10 of 48) were both associated with septal or anteroseptal thallium perfusion abnormalities (10 of 15 versus six of 33 of the remainder, p less than 0.005), which were present despite normal coronary angiographic results. Thallium defect scores were greater in patients with septal infarction pattern or ventricular conduction abnormalities compared with the remainder (defect scores 3.0 +/- 2.6 versus 1.4 +/- 2.2, respectively, p less than 0.025). In patients with ventricular conduction abnormalities, both left bundle branch block and right bundle branch block with left anterior fascicular block were associated with abnormal left ventricular function, whereas isolated right bundle branch block or left anterior fascicular block was associated with normal left ventricular function. A normal electrocardiographic finding (19 of 48) was associated with normal left ventricular function at rest (19 of 19). However, 11 of 19 (58 percent) had thallium perfusion defects and four of 19 (21 percent) had an abnormal response to exercise, although in none was the peak ejection fraction less than 50 percent. It is concluded that both septal infarction pattern and ventricular conduction abnormalities are electrocardiographic abnormalities associated with scleroderma heart disease; they appear to be a result of myocardial fibrosis. Some degree of myocardial fibrosis may be present with a normal electrocardiographic result, but significant left ventricular dysfunction is unlikely. Septal infarction pattern and ventricular conduction abnormalities, when present, are indicators of more advanced fibrosis.
Although it is difficult to estimate the overall prevalence of genital human papillomavirus (HPV) infection, current figures suggest that visible genital warts are present in approximately 1% of sexually active adults in the United States and that at least 15% have subclinical infection, as detected by HPV DNA assays. Genital HPV infection is thus extremely common. The highest rates of genital HPV infection are found in adults 18-28 years of age. Although risk factors for infection are difficult to assess because of the high frequency of subclinical infection, it is clear that major risk factors for acquiring genital HPV infection involve sexual behavior, particularly multiple sex partners. Other possible risk factors for acquisition of genital HPV infection include oral contraceptive use, pregnancy, and impairment of cell-mediated immunity. Strong epidemiologic and molecular data link HPV infection to cervical and other anogenital cancers. The types of HPV most commonly detected in cancers are HPV-16 and HPV-18. In summary, genital HPV infection is common among sexually active populations and causes both benign and malignant neoplasms of the genital tract.
Gaucher disease is the first lysosomal storage disorder to be treated with macrophage-targeted enzyme replacement therapy. Previous studies in relatively small numbers of patients demonstrated short-term efficacy of this treatment. This study describes the effects of 2 to 5 years of treatment on specific manifestations of type 1 Gaucher disease.
Physicians reported data from 1028 patients to the Gaucher Registry. Assessment of response included serial measurements of hemoglobin concentration, platelet count, liver and spleen volumes, and the occurrence of bone pain and bone crises.
Among anemic patients, hemoglobin concentration increased to normal or near normal within 6 to 12 months, with a sustained response through 5 years. In thrombocytopenic patients with intact spleens, the most rapid response occurred during the first 2 years, with slower improvement thereafter. The likelihood of achieving a normal platelet count decreased with increasing severity of baseline thrombocytopenia. In patients who had undergone splenectomy, platelet counts returned to normal within 6 to 12 months. Hepatomegaly decreased by 30% to 40% during follow-up; splenomegaly decreased 50% to 60%, but rarely to volumes below five times normal size. In patients with pretreatment bone pain or bone crises, 52% (67/128) were pain free after 2 years and 94% (48/51) reported no additional crises.
Enzyme replacement therapy prevents progressive manifestations of Gaucher disease, and ameliorates Gaucher disease-associated anemia, thrombocytopenia, organomegaly, bone pain, and bone crises.
Acute abdomen (AA) in systemic lupus erythematosus (SLE) is a challenging diagnostic and therapeutic problem. Most patients are on steroid and/or immunosuppressive treatment and mortality is high.
We assessed the relationship between the causes of AA in SLE and the SLE disease activity index (SLEDAI).
Of 51 patients with SLE and AA, 36 had active disease (Group 1) and 15 inactive disease (Group 2). Group 1 included 19 patients with vasculitis (mean SLEDAI 15.4, range 13 to 24). Three patients with intraabdominal thrombosis and high titers of anticardiolipin antibodies (mean SLEDAI 18.3) and 14 patients with non-SLE-related AA (SLEDAI 8.2, range 5 to 11). Group 2 consisted of 15 inactive SLE patients (mean SLEDAI 1.7, range 0 to 4). Mortality was high in the active group (14 patients) compared with inactive SLE (2 cases). A delay in surgical exploration (39.3 vs 178.6 hours) had a negative influence on the prognosis.
In SLE patients with AA, a SLEDAI score below 5 is indicative of non-SLE-related AA. Elevated aCL were found in patients with intraabdominal thrombosis. AA in inactive SLE is non-SLE-related and has low mortality, provided an appropriate surgical treatment is given. Early laparotomy influences positively the prognosis of SLE patients with AA.
The epidemiologic evidence for an association between estrogen and cognitive function among healthy postmenopausal women remains controversial. Equivocal findings may be explained, in part, by differences in the methodologic approaches of these studies. Overall, the evidence for a positive relationship comes primarily from randomized clinical trials. These trials suggest an acute effect on specific tests of recent verbal memory and tasks incorporating concept formation and reasoning. The potential long-term effects of estrogen in slowing or delaying the age-related decline in cognitive function require further study. More data are needed to determine the effects of estrogen replacement therapy on cognitive function, independent of changes in mood and depressive symptoms. In addition, evidence suggests that progesterone may mitigate the beneficial effects of estrogen on mood. Research should be undertaken to determine the interactive effects of estrogen and progesterone on cognitive function. Lastly, there should be continued investigation by both epidemiologic and basic neuroscientific studies to further elucidate the specific cognitive domains that may respond to estrogen.
An extensive outbreak of waterborne typhoid fever occurred in 1973 at a migrant labor camp in Dade County, Florida. Blood cultures from 105 of the 188 patients with proved or presumptive cases of typhoid fever grew Salmonella typhi. The clinical and laboratory findings in these patients were reviewed. Fever, usually with temperatures above 38.8 degrees C and of the sustained type, was a primary manifestation of disease, although a majority of the patients also complained of headache and gastroenteric symptoms. Hepatic or splenic enlargement was present in 52 per cent and 42 per cent, respectively, whereas rose spots were detected in only 13 per cent. The total leukocyte count was normal in 74 per cent, but serum levels of liver and muscle enzymes were frequently elevated. Gastrointestinal, pulmonary and neurologic complications were infrequent; circulatory failure was not observed. Defervescence in response to antibiotic therapy was variable; however, the median response among 68 patients who received chloramphenicol was two days less than that in 34 patients treated with ampicillin. There was one possible treatment failure with ampicillin. The relapse rate of 10 per cent in chloramphenicol-treated patients was not significantly greater than the 3 per cent rate among those treated with ampicillin. Serologic studies for typhoid fever were of limited diagnostic value since the titer of agglutinins was 1:160 or higher in 49 per cent of the serums obtained before treatment, and a fourfold rise in titer occurred in only 24 per cent of 57 patients studied. The serologic response to chloramphenicol treatment did not differ from that to ampicillin.
Colorectal cancer is the fourth most common cancer and the second leading cause of cancer death in the United States. Accumulating evidence indicates that postmenopausal hormone therapy may reduce the risk of colorectal cancer in women.
Through MEDLINE computer searches (January 1966 to September 1998) and a review of references, we identified English-language articles with quantitative data on the relation of postmenopausal hormone therapy to colorectal cancer. We reviewed the studies and made summary estimates of relative risks (RR) by weighting the results of each study in proportion to its precision, using a general variance-based, fixed-effects model.
In our meta-analysis of 18 epidemiologic studies of postmenopausal hormone therapy and colorectal cancer, we found a 20% reduction [RR = 0.80, 95% confidence interval (CI), 0.74 to 0.86] in risk of colon cancer and a 19% decrease (RR = 0.81, 95% CI, 0.72 to 0.92) in the risk of rectal cancer for postmenopausal women who had ever taken hormone therapy compared with women who never used hormones. Much of the apparent reduction in colorectal cancer was limited to current hormone users (RR = 0.66, 95% CI, 0.59 to 0.74).
Observational studies suggest a reduced risk of colorectal cancer among women taking postmenopausal hormones. There is biologic evidence to support this association.
Measles occurred in 3,220 Air Force recruits between January 1976 and July 1979 and was complicated by pneumonia in 106 cases (3.3 percent). Although no deaths occurred, the illness was characterized as clinically severe with high fever and prolonged hospitalization (mean, 14.5 days). Bacterial superinfection as documented by transtracheal aspiration occurred in 35 cases (30.3 percent) and was caused by Hemophilus influenzae (18), Hemophilus parainfluenzae (two), Neisseria meningitidis (nine), Streptococcus pneumoniae (three), Streptococcus pyogenes (two) and Moraxella kingae (one). Clinical evidence of bronchospasm was present in 18 patients (17 percent) and required bronchodilators in six. Other complications included liver function abnormalities (31 percent), otitis media (29 percent) and sinusitis (25 percent). Measles pneumonia in adolescents is clinically severe with a generally benign outcome.
Ingestion of toxin, traumatic events, adverse drug reactions, and motion can all result in nausea and emesis. In addition, cyclic vomiting syndrome is quite prevalent in the pediatric population. Coordination of the various autonomic changes associated with emesis occurs at the level of the medulla oblongata of the hindbrain. Chemosensitive receptors detect emetic agents in the blood and relay this information by means of neurons in the area postrema to the adjacent nucleus tractus solitarius (NTS). Abdominal vagal afferents that detect intestinal luminal contents and gastric tone also terminate in the NTS (gelatinosus, commissural, and medial subnuclei). The NTS is viscerotopically organized into subnuclei that subserve diverse functions related to swallowing (subnucleus centralis), gastric sensation (subnucleus gelatinosus), laryngeal and pharyngeal sensation (intermediate and interstitial NTS), baroreceptor function (medial NTS), and respiration (ventrolateral NTS). Neurons from the NTS project to a central pattern generator (CPG), which coordinates the sequence of behaviors during emesis, as well as directly to diverse populations of neurons in the ventral medulla and hypothalamus. Thus, it is critical to realize that there is not an isolated "vomiting center," but rather groups of loosely organized neurons throughout the medulla that may be activated in sequence by a CPG. The newer antiemetic agents appear to block receptors in the peripheral endings of vagal afferents to reduce "perception" of emetic stimuli and/or act in the dorsal vagal complex. A primary site of action of 5-HT(3)-receptor antagonists is by means of the vagal afferents. Neurokinin-1 receptor (NK(1)R) antagonists are antiemetics, because they act at a site in the dorsal vagal complex. Part of their effectiveness may be the result of inhibition of the NK(1)R on vagal motor neurons to prevent fundic relaxation, which is a prodromal event essential for emesis. Delta(9)-tetrahydrocannabinol (Delta(9)-THC), the major psychoactive component of marijuana, can be therapeutically useful as an antiemetic. The site of action of Delta(9)-THC is on cannabinoid CB1 receptors in the dorsal vagal complex. However, it decreases fundic tone and antral motility. It is not easy to predict the potential antiemetic effects of drugs that alter motility. Although antiemetic drugs are available for management of acute chemotherapeutic-induced emesis, few treatments are effective for delayed emesis or cyclic vomiting syndrome.
To describe clinical features and outcomes of enterococcal left-sided native valve endocarditis and to compare it to endocarditis caused by other pathogens.
Patients in the International Collaboration on Endocarditis-Merged Database were included if they had left-sided native valve endocarditis. Demographic characteristics, clinical features, and outcomes were analyzed. Multivariable analysis evaluated enterococcus as a predictor of mortality.
Of 1285 patients with left-sided native valve endocarditis, 107 had enterococcal endocarditis. Enterococcal endocarditis was most frequently seen in elderly men, frequently involved the aortic valve, tended to produce heart failure rather than embolic events, and had relatively low short-term mortality. Compared to patients with non-enterococcal endocarditis, patients with enterococcal endocarditis had similar rates of nosocomial acquisition, heart failure, embolization, surgery, and mortality. Compared to patients with streptococcal endocarditis, patients with enterococcal endocarditis were more likely to be nosocomially acquired (9 of 59 [15%] vs 2 of 400 [1%]; P <.0001) and have heart failure (49 of 107 [46%] vs 234 of 666 [35%]; P = 0.03). Compared to patients with S. aureus endocarditis, patients with enterococcal endocarditis were less likely to embolize (28 of 107 [26%] vs 155 of 314 [49%]; P <.0001) and less likely to die (12 of 107 [11%] vs 83 of 313 [27%]; P = 0.001). Multivariable analysis of all patients with left-sided native valve endocarditis showed that enterococcal endocarditis was associated with lower mortality (odds ratio [OR] 0.49; 95% confidence interval [CI] 0.24 to 0.97).
Enterococcal native valve endocarditis has a distinctive clinical picture with a good prognosis.
Observations made from histologie study of the entire extramural coronary arterial tree are described in 107 patients who died of acute ischemie heart disease: seventy-four had transmural left ventricular myocardial infarction, nine had necrosis limited to the inner one half of the left ventricular myocardium (acute subendocardial infarcts) and twenty-four died suddenly (less than six hours from onset of symptoms of myocardial ischemia) without histologically detectable myocardial necrosis. Old atherosclerotic plaquing was diffuse and extensive in the extramural coronary arteries in 104 of the 107 patients. The lumens of at least two of the three major extramural coronary arteries (right, left anterior descending and left circumflex) were narrowed more than 75 per cent by old atherosclerotic plaques in 101 of the 107 patients.Coronary arterial thrombi were found in forty (54 per cent) of the seventy-four patients with transmural necrosis, in none of the nine with only subendocardial necrosis and in two (8 per cent) of the twenty-four who died suddenly. In thirty-seven of the forty-two patients with antemortem coronary arterial clots the lumen of the vessel containing the thrombus was already narrowed more than 75 per cent by old atherosclerotic plaques at or distal to the thrombus. The infrequency of coronary thrombi in patients who died of acute cardiovascular collapse without myocardial necrosis, in those in whom necrosis was limited to the subendocardium, in those who died without cardiogenic shock or congestive cardiac failure, and their occurrence at, or proximal to, sites already severely narrowed by old atherosclerotic plaques suggest that coronary thrombi are consequences rather than causes of acute myocardial infarction. The occurrence of components of thrombi, i.e., fibrin and platelets, in old atherosclerotic plaques and the finding of components of old atherosclerotic plaques, i.e., foam cells, cholesterol clefts, pultaceous debris and calcific deposits, in known thrombi (for example, those located in the left atrium of patients with mitral stenosis) strongly suggest, however, that old atherosclerotic plaques are derived, at least in part, from organization of thrombi.
The current circumstances associated with Pseudomonas aeruginosa bacteremia are reviewed in 108 episodes to assess the impact of new antimicrobial drugs on this infection. Since 1961, Pseudomonas bacteremia has apparently become more frequent with proportional increases in middle-aged patients. The respiratory tract has become the major source of infection. Clinical features are not characteristic, but infected patients are almost uniformly severely ill before blood stream invasion occurs. The use of gentamicin, carbenicillin and colistin has not changed the outcome of Pseudomonas bacteremia. Although better than no antimicrobial treatment, these drugs cannot be shown to be superior to any other available antibiotics. A reassessment is needed to evaluate the relationship between the in vitro action and the effectiveness of antibiotics in the treatment of Pseudomonas infection and the use of gentamicin, carbenicillin and colistin in these bacteremias. In view of the poor results with antibiotics, investigation into immunologic prophylaxis and therapy is needed. At the present time, control of the patients' underlying disease contributes most towards assuring survival with Pseudomonas bacteremia.
The purpose of this study was to determine the clinical and laboratory characteristics, diagnostic methods, and prognostic variables in adults treated for miliary tuberculosis in the rifampicin era.
Computerized records of our community-based university teaching hospital over a 10-year period (1978 to 1987) were analyzed. A total of 109 patients were identified, including 12 who did not have miliary nodules on the chest radiograph (all of whom were shown to have hematogenous dissemination). Predisposing conditions were present in 46 patients.
Clinical features were similar to those of previously reported series. Hematologic abnormalities were common: leukopenia (less than 4 x 10(9)/L) was present in 16 of 107 patients (15%), thrombocytopenia (less than 150 x 10(9)/L) in 24 of 104 (23%), and lymphopenia (less than 1.5 x 10(9)/L) in 82 of 94 (87%). Pancytopenia was found in six patients, three of whom recovered. Disseminated intravascular coagulation occurred in four patients, all of whom died. Adenosine deaminase levels were elevated in only seven of 11 serosal exudates and in seven of 12 samples of abnormal cerebrospinal fluid. Fiberoptic bronchoscopy was diagnostic in 44 of 51 patients (86%), bone marrow examination in 19 of 22 (86%), and liver biopsy in all 10 patients. Twenty-six patients (24%) died of miliary tuberculosis a median of 6 days after starting treatment. Survivors were followed up for a median of 51 weeks. Stepwise logistic regression identified aged (greater than 60 years), lymphopenia, thrombocytopenia, hypoalbuminemia, elevated transaminase levels, and treatment delay as independent predictors of mortality.
Miliary tuberculosis commonly causes hematologic derangements, some of which are helpful prognostically. Fiberoptic bronchoscopy compares favorably to liver and bone marrow biopsy in sputum smear-negative cases. Mortality remains high and treatment should be begun as soon as the diagnosis is suspected.
Blood for culture was obtained over a six week period from 17 patients undergoing long-term hemodialysis. Bacteremia was detected during 18 of 201 dialyses. Blood drawn during fifteen of these dialyses contained pseudomonas aeruginosa. Ten of the 17 patients (59 per cent) had a Pseudomonas bacteremia some time during the study. Only one patient was symptomatic. The frequency of positive cultures was related to reuse of coils. No cultures were positive until after the fifth use, but by the tenth use, 41 per cent of the dialyses were associated with bacteremia. All coils that were used repeatedly and 32 of 48 of those used only once, grew Ps. aeruginosa when filled with media and incubated. This suggests that the coils were inoculated during dialysis and that benzalkonium chloride, the sterilizing agent, was unable to eradicate this organism. With repeated uses, the number of residual bacteria in the coil became large enough to cause detectable bacteremia during dialysis.
Seventy-two members of 11 kindred with the nail-patella syndrome were studied. Twelve patients who had electron microscopic examinations of renal tissue had abnormalities of the glomerular basement membrane. An unaffected family member did not. This lesion consisted of irregular basement membrane thickening, epithelial foot process fusion and the presence of fibrillar collagen-like material within the substance of the membrane. Many patients also showed areas of increased lucency giving the membrane a “moth-eaten” appearance. The presence of the ultrastructural lesion bore no relation to the presence or absence of abnormalities by light or immunofluorescent microscopy and also no relation to demonstrable alterations of renal function. The determinants of clinically significant nephropathy are unknown but in most patients the prognosis is favorable.