The American Journal of the Medical Sciences

Published by Lippincott, Williams & Wilkins
Print ISSN: 0002-9629
Although anaerobic bacterial meningitis is uncommon, patients subjected to resection of head and neck malignancy appear at special risk. In this article, the authors report on a 72-year-old man in whom meningitis developed after extensive resection of the right sinuses for squamous cell carcinoma; initial treatment consisted of intravenous vancomycin and ceftazidime. Intravenous penicillin G was added after the fortuitous early finding of intracellular cocci in Wright-Giemsa stained cerebral spinal fluid submitted for cell count. Cerebral spinal fluid cultures then grew out a pure culture of Peptostreptococcus magnus. The patient had a complete recovery, without neurologic sequelae, recurrence of malignancy, or evidence of infection. Appropriate handling of cerebral spinal fluid specimens is crucial to ensure the correct diagnosis when anaerobic organisms are suspected.
Purpuric lesions have been described previously in 10 patients with disseminated strongyloidiasis. We identified three additional patients in whom purpura developed as a manifestation of disseminated strongyloidiasis. Nine (69%) of the 13 patients were men, and the median age of patients was 61 years (range, 32-75 years). Six patients were from the southeastern United States. Six patients had underlying malignancy and four patients had chronic lung disease. All patients had received prior corticosteroids. The parasite was identified in 11 (92%) of 12 patients where stool or sputum examination was performed. Skin biopsies of purpuric lesions were obtained in 12 patients, in 10 (83%) of which larvae were found. Despite recommended treatment with thiabendazole in 12 of 13 patients, 11 (85%) of the patients died, and at least 6 died within 16 days of onset of purpura. Physicians, particularly those in the southeastern United States, should strongly consider the diagnosis of disseminated strongyloidiasis in patients receiving corticosteroids and in whom purpura and systemic toxicity develops.
A case is described of an 88-year-old man with lung cancer, nephrotic syndrome, and renal dysfunction who died suddenly of an acute myocardial infarction and whose autopsy revealed many adenocarcinoma cells stacked within glomerular capillary lumina of his kidney, entering into basement membrane zones (ie, neoplastic cell interposition). In addition, glomeruli showed a lobular transformation, doubling of glomerular basement membrane, and electron dense deposits along the glomerular basement membrane. These changes were similar to those of membraneoproliferative glomerulonephritis. The association of intraglomerular metastasis and membranoproliferative glomerulonephritis-like lesions led the authors to speculate that the latter glomerular change might have provided an attractive opportunity for circulating tumor cells to be trapped and grow within the glomerular lumina. This mode of metastasis has not been well-recognized. The authors describe the experience, review the literature, and discuss its possible pathogenesis.
Surgically induced hypoparathyroidism often responds satisfactorily to intravenous Ca administration, oral CaCO3 and vitamin D2. A 17-year-old girl developed hypoparathyroidism following partial thyroidectomy for thyrotoxicosis. Hypocalcemia was refractory to treatment with massive doses of vitamin D2, up to 150,000 U, 3-6 gm of oral Ca as CaCO3 and 2 micrograms of 1,25-dihydroxycholecalciferol per day. Intravenous Ca gluconate (360 mg of elemental Ca/d, in divided doses) was needed to correct tetany. After 25 days of unsuccessful therapy, oral administration of 30 ml of a 10% solution of CaCl2 (1.09 gm of elemental Ca) was followed by normalization of serum Ca (8.9 mg/dl) within 7 hours. This dose was repeated every 8 hours for 6 days and oral CaCO3 and IV Ca gluconate were discontinued. Serum Ca remained within normal range but hyperchloremic acidosis developed. This was corrected by providing, in addition to vitamin D, 2 g/d of Ca supplementation, 1 gm in the form of 10% CaCl2 solution and 1 gm as CaCO3 in two doses given simultaneously. During 12 months of observation, serum Ca, P and Cl have been consistently within normal limits. This patient was found to have achlorhydria, unresponsive to normalization of thyroid function and serum Ca. These findings indicate that refractoriness to oral CaCO3 and vitamin D may be caused by achlorhydria. Oral administration of CaCl2 solution can promptly correct this defect. Monitoring of serum Cl and CO2 is needed to avoid hyperchloremic acidosis.
Toxic shock syndrome is a febrile, multiorgan illness related to toxins elaborated by staphylococcal or streptococcal infections. In the 1980s, most cases were associated with menstruation. More recently, many cases now are unrelated to menses. In this article, the authors describe a case of a nonmenstruating woman with toxic shock syndrome, associated with cellulitis of her arm. Cultures of the arm grew Staphylococcal aureus, which produced enterotoxin B.
A 26-year-old woman with features of bulimia nervosa presented with fever of unknown origin, hepatomegaly, marked leukocytosis, and increased erythrocyte sedimentation rate. Following prolonged observation, slight tenderness over the thyroid gland and signs of thyrotoxicosis occurred. A thyroid scan demonstrated no isotope uptake and the patient admitted abusing an organic iodine preparation in order to control her weight. The diagnosis of iodine-induced subacute thyroiditis with thyrotoxicosis was, therefore, considered. A brief course of low-dose steroids normalized both thyroid function and hematological parameters. On followup evaluation, urinary iodine excretion and thyroid function tests were normal.
Von Hippel-Lindau disease (VHLD) is a rare disorder known to occur with pheochromocytoma. We report a case with this association and also with pancreatic apudoma. We believe that this is the fifth reported case of this triad, which represents an overlap in the multiple endocrine neoplasia (MEN) classification. Many recent reports of overlap of MEN syndromes challenge the validity of this classification. New understanding of the embryologic origin of cells of endocrine organs has led to the elucidation of the APUD (amine precursor uptake and decarboxylation)-neuroendocrine system. Integration of the APUD system may be important to understanding the pathogenesis of the MEN-like syndromes as well as their relationship to the neurocutaneous syndromes. Any endocrine tumor or neurocutaneous syndrome should be evaluated to exclude a spectrum of possible associations.
A 24-year-old oil well tester was rendered semiconscious by hydrogen sulfide (H2S). He received oxygen and was hospitalized but released in 30 minutes. The next day, nausea, vomiting, diarrhea, and incontinence of urine and stool led to rehospitalization. These problems and leg shaking, dizziness, sweating, trouble sleeping, and nightmares prevented his return to work. A physical examination, chest x-ray, and pulmonary function tests were normal 39 months after the episode but vibration sense was diminished. Two choice visual reaction times were delayed. Balance was highly abnormal (5 to 6 cm/sec) with eyes closed. Blink reflex latency was slow (R-1 17.5 msec versus normal 14.3 msec). Numbers written on finger tips were not recognized. Verbal and visual recall were impaired but overlearned memory was intact. Cognitive functions measured by Culture Fair, block design, and digit symbol were impaired. Perceptual motor was slow. Scores for confusion, tension-anxiety, depression, and fatigue were elevated and vigor was reduced. Forty-nine months after exposure his reaction time, sway speed, and color vision had not improved. His recall and his cognitive, constructional, and psychomotor speeds had improved but remained abnormal. These deficits are most likely due to H2S. Similar testing of other survivors is recommended.
A previously healthy 32-year-old man presented with recurrent exercise induced painless gross hematuria and hematospermia. An extensive evaluation demonstrated classic von Willebrand's disease associated with vascular telangiectasia of the prostate gland as the locus of hemorrhage. The bleeding resolved spontaneously and without recurrence. The coexistence of von Willebrand's disease and vascular telangiectasia has been described previously, although it is a rare occurrence. However, a review of the English literature revealed no report of vascular telangiectasia involving the prostate gland, and therefore is the subject of this report. The prostate gland now should be added to the list of viscera associated with vascular telangiectasia and von Willebrand's disease.
Recurrence of surgically treated parathyroid cancer occurs in 30% to 65% of patients and has a poor prognosis; only 1 of 29 cases remained normocalcemic more than 2 years later. No medical attempts to prevent recurrence have been reported. A 24-year-old pregnant woman whose mother died of parathyroid cancer underwent apparently successful surgery for parathyroid cancer. Serum Ca and parathyroid hormone (PTH) returned to normal levels but 3 months after surgery, although normocalcemic, the serum PTH level was elevated. The administration of vitamin D 200,000 U/month or calcitriol 0.5 microgram daily and 1 g of Ca supplementation daily, resulted in the normalization of PTH during 81 months of follow-up. On three occasions, when vitamin D or calcitriol were omitted, serum intact, C-terminal, or mid-molecule PTH levels rose. Ionized and total serum Ca, creatinine, calcitriol and calcidiol levels were normal, and multiple ultrasounds of the neck remained negative after surgery. This observation suggests that serum PTH could be an early marker for the detection of recurrence in parathyroid cancer with normal serum Ca, and that suppression of PTH secretion by vitamin D or calcitriol could avert or delay the progression of recurrence. Additional trials with calcitriol in operated normocalcemic parathyroid cancer with an elevated serum PTH level is recommended.
Rheumatoid arthritis is a multi-system disease. Pulmonary manifestations and complications include pleural disease, pulmonary infections, pneumonitis and interstitial pulmonary fibrosis, bronchogenic carcinoma, arteritis with pulmonary hypertension, obliterative bronchiolitis, bronchiectasis, and amyloidosis. Pulmonary rheumatoid nodules, including rheumatoid pneumoconiosis (Caplan's Syndrome), can result in spontaneous pneumothorax. In this article, the authors present a patient with rheumatoid arthritis and recurrent spontaneous pneumothorax. Through investigation, a bronchopleural fistula caused by a rheumatoid nodule was revealed. The authors also discuss the potential pitfalls caused by a lung nodule in a patient with rheumatoid arthritis, including the overlap with bronchogenic carcinoma and confusion with tuberculosis.
Pneumocystis carinii infection is commonly seen in patients infected with HIV, and there is evidence of macrophage involvement in the disease process. Macrophage dysfunction can result in abnormal vitamin D metabolism as is often seen in a granulomatous disease such as sarcoidosis. This article describes a patient with AIDS who had P. carinii pneumonia and hypercalcemia and had elevated 1,25-dihydroxyvitamin D levels, the first such reported case in the literature. There was no other evidence of a granulomatous disease such as sarcoidosis or tuberculosis to account for this. It is suggested that the increase in 1,25-dihydroxyvitamin D level was secondary to P. carinii induced macrophage dysfunction. As the patient's P. carinii pneumonia resolved, his 1,25 dihydroxyvitamin D level normalized along with the resolution of hypercalcemia.
Renal phosphate wasting related to a tumor (oncogenous osteomalacia) is a rare disorder usually associated with benign mesenchymal tumors. In this article, the authors describe a man with renal phosphate wasting and the syndrome of inappropriate antidiuretic hormone associated with small cell carcinoma. Chemotherapy markedly reduced tumor burden and was associated with normalization of renal phosphate handling and serum sodium. With recurrence, renal phosphate wasting and the syndrome of inappropriate antidiuretic hormone developed again, with the additional complication of hypercortisolism secondary to ectopic corticotropin production. The authors report the rare occurrence of renal phosphate wasting with small cell carcinoma (5 previously reported cases) and the unique co-existence of this paraneoplastic syndrome with the syndrome of inappropriate antidiuretic hormone and ectopic corticotropin production.
In hyperandrogenic females, the ratio of dehydroepiandrosterone (DHEA) to testosterone may be an important determinant of insulin sensitivity. This study involved changes in insulin sensitivity and glucose metabolism with therapeutic manipulation of DHEA (S)/testosterone in a female patient with non-insulin-dependent diabetes and hyperandrogenism. Therapeutic intervention included 1-month treatment with 0.25 mg dexamethasone at bedtime and 1-month dexamethasone + DHEA. Insulin sensitivity and glucose tolerance were assessed before and after each treatment regimen by examining: 1) fasting and oral glucose tolerance test glucose and insulin levels, 2) hypoglycemic response to intravenous insulin, and 3) erythrocyte insulin receptor binding. With dexamethasone alone, DHEAS, testosterone, and their ratio were reduced with a concomitant increase (30%) in oral glucose tolerance test insulin levels and a decrease (33%) in erythrocyte insulin binding. With DHEA + dexamethasone, the ratio of DHEAS/testosterone increased 16-fold along with a marked improvement in insulin sensitivity, as determined by a more than 30% reduction in fasting and oral glucose tolerance test insulin levels, a threefold stimulation of the rate of glucose disappearance with intravenous insulin, and a 30% increase in insulin binding. DHEA improved insulin sensitivity and reduced fasting and oral glucose tolerance test glucose levels and ameliorated the diabetic state. The ratio of DHEAS/testosterone is an important regulator of insulin sensitivity and glucose tolerance and that DHEA therapy may be beneficial in the treatment of certain forms of insulin resistance.
Adolescence and pregnancy are periods with increased calcium requirement. Therefore, patients with underlying bone disease are at risk for further bone demineralization during these periods. In this article, the authors report on the treatment during pregnancy of an adolescent with idiopathic juvenile osteoporosis that resulted in a favorable outcome of maternal and fetal skeleton.
Urticaria has many known etiologies. An association with autoimmune thyroid disease is described. One individual had the triad of urticaria, Hashimoto's thyroiditis, and rheumatoid arthritis, whereas the other individual had urticaria preceding Graves' disease by over 1 year.
A 14-year-old girl with chronic idiopathic thrombocytopenic purpura (ITP) presented in relapse with a platelet count of 1,000/microL and a high-level serum antiplatelet IgG antibody. She previously had been unresponsive to courses of therapy with steroids, vincristine, and splenectomy. When treatment with danazol and purified immunoglobulins was unsuccessful in controlling her rapidly progressive course, an 8-day plasma exchange procedure was initiated in combination with platelet transfusion therapy and immunosuppression with cyclophosphamide and vincristine. Within 2 days, her clinical state improved markedly, correlating with a drop in her serum antiplatelet antibody level. She continued to improve and was discharged on a regimen of cyclophosphamide and danazol. Her antiplatelet antibody level had fallen to within the normal range, despite a typical platelet count of 5,000/microL during the 8-day period. Two weeks later her platelet count rose to 65,000/microL. This case suggests that a course of therapeutic plasma exchange may have a temporizing role in the acute management of life-threatening chronic ITP relapse, generating time for the more definitive therapy of immunosuppression to take effect.
This article reports the case of a boy aged 2 years 6 months, who had fever, arthritis, and necrotizing cutaneous vasculitis. Evaluation revealed no evidence of direct infectious causes. However, high anti-streptolysin and streptozyme titers during the acute phase support the possibility that streptococcal infection played an important role in the pathogenesis of this disease. The patient's condition improved significantly with the administration of prednisone. However, several attempts to diminish the prednisone dose resulted in relapses. Subsequently, the prednisone was successfully tapered and discontinued after intravenous gamma globulin administration. It is recommended that intravenous gamma globulin should be considered before immunosuppressive therapy in the treatment of necrotizing vasculitis.
Progressive shortness of breath developed in an elderly woman with a 25-year history of recurrent superficial phlebitis and hemoptysis. Extensive mural thrombosis and ectasia of the large and medium-sized pulmonary arteries and aorta were revealed on echocardiography and computerized tomography. The patient died 2 months later. On autopsy, the gross morphologic findings were similar with those observed by imaging. Histologically, there was mild inflammation in the intima and media of the aorta and the large pulmonary arteries, consistent with nonspecific arteritis. The extensive thrombosis and ectasia of the pulmonary arteries and aorta differ from previously published cases and cannot be assigned to a known nosologic entity. Two alternative explanations are proposed. First, an endothelial disorder was responsible for a diffuse vasculopathy that involved veins, pulmonary arteries, and aorta. Second, a vasculopathy of the Hugh-Stovin type, characterized by phlebitis and pulmonary thromboembolism, caused pulmonary hypertension and low cardiac output. The low flow state favorized aortic thrombosis and, at the site of interaction between the clot and the arterial wall, arteritis developed as an epiphenomenon, which induced arterial dilatation. Combined idiopathic pulmonary artery and aortic thrombosis and ectasia is rare and calls for corroboration of sporadic observations such as the current one.
Recent advances in molecular genetics have made possible the use of retroviral "vectors" to transfer cloned human genes into somatic cells. With this new technology, the genetic defect underlying many recessive inherited disorders can probably be corrected by inserting a normal gene into the patient's hematopoietic stem cells. This article reviews the design and safety of the viral vectors and the results of in vivo studies in mice and large animals that have led to the first human trials. Other target cells for gene transfer, such as endothelial cells, fibroblasts, keratinocytes, and hepatocytes, are also discussed. The use of recombinant retroviruses for gene transfer in vivo is still a new area of research, but the feasibility of "gene therapy" for genetic disorders is rapidly gaining medical and scientific acceptance.
Chronic spinal cord injury, when complicated by chronic suppurative infections, has replaced chronic tuberculosis as a leading cause of secondary amyloidosis. Renal involvement with secondary amyloidosis is characterized by the presence of nephrotic range proteinuria and an increased incidence of renal vein thrombosis. Two cases of acute renal vein thrombosis associated with secondary amyloidosis in patients with spinal cord injury are presented. In both cases, a past history of extensive decubitus ulcerations and urinary tract infections preceded the development of nephrotic range proteinuria. In case 1, nonoliguric acute renal failure occurred after the development of acute bilateral renal vein thrombosis. The patient declined dialytic therapy and expired with uremia. In case 2, worsening renal function and increased proteinuria resulted after the development of acute unilateral renal vein thrombosis. These cases include the clinical and anatomic findings of acute renal vein thrombosis that occur as a complication of secondary amyloidosis. Acute renal vein thrombosis should be considered whenever an acute change in renal function or increase in proteinuria is noted in this setting.
The authors present two cases of systemic blastomycosis successfully treated with fluconazole. In one case, the disease involved the respiratory tract, and the central nervous system was presumed to be involved. The second case consisted only of pulmonary blastomycosis. Both patients were treated with oral fluconazole 200 mg twice per day for 9 and 6 months, respectively. Treatment with this new triazole antifungal agent resulted in the complete resolution of the disease in both patients. They have remained asymptomatic for more than 6 months after the completion of therapy.
Under the assumption that in some patients with refractory anemia with excess of blasts (RAEB), the abnormal clones might be less responsive to granulocyte colony-stimulating factor than normal clones, the authors tried alternation therapy with a recombinant form of this factor (rhG-CSF) and antileukemic agents in the treatment of two patients with RAEB in transformation. After repetition of the short-cycled alternation therapy, the hematologic findings of both patients were completely normalized and have remained so without any adverse side effects under the continuation of this therapy for more than 5 months. Judging from our clinical experience, the alternation therapy may be a new efficient therapeutic strategy for RAEB and some types of slowly progressive leukemia.
The authors describe a young man with hemophilia complicated by chronic hepatic dysfunction, hypodysfibrinogenemia, and immune thrombocytopenia that resulted in a complex coagulopathy. The patient had a ruptured occipital arteriovenous malformation. The malformation was managed by temporary correction of the coagulopathy using cryoprecipitate, platelet transfusions, and plasmapheresis with fresh frozen plasma replacement. The patient underwent staged preoperative embolization followed by surgical excision of the lesion. Hemostasis was acceptable during the neurointerventional and subsequent surgical management, and no complications of coagulopathy occurred. Plasmapheresis may provide effective preparation for patients with hemophilia and complex coagulation abnormalities who require neurosurgical intervention.
Endometriosis is a common disorder affecting women of all ages. Although urinary tract involvement is not uncommon, ureteral obstruction is an infrequent complication of endometriosis. A case is reported of acute renal failure caused by bilateral ureteral obstruction resulting from extensive pelvic endometriosis. All reported cases of ureteral endometriosis are reviewed with special emphasis on bilateral ureteral involvement. Physicians need to be aware of this reversible complication of endometriosis.
Corticosteroids are the mainstay for treatment of oral lichen planus (OLP) and have their own side effects. The aim of this study was to compare the therapeutic effects of aloe vera (AV) mouthwash with triamcinolone acetonide 0.1% (TA) on OLP. A total of 46 patients with OLP were enrolled in this study. The patients were randomly divided into 2 groups. Each group was treated with received AV mouthwash or TA. The treatment period for both groups was 4 weeks. The basement data were recorded for each patient. Patients were evaluated on days 8, 16 and after completing the course of treatment (visit 1-3). The last follow-up was 2 months after the start of treatment (visit 4). Visual analogue scale was used for evaluating pain and burning sensation and Thongprasom index for clinical improvement and healing. In addition, lesion sizes were measured and recorded at each visit using a grid. Baseline characteristics, including pain and burning sensation score, size and clinical characteristics of the lesions according to Thongprasom index, were not different between the 2 treatment groups. Both AV and TA significantly reduced visual analogue scale score, Thongprasom score and size of the lesions after treatment (P < 0.001) and after 2 months of discontinuation of the treatment (P < 0.001). In the AV group, 74% of patients and in the TA group 78% of patients showed some degrees of healing in the last follow-up. AV mouthwash is an effective substitute for TA in the treatment of OLP.
Although associations between the expression of particular HLA genes and susceptibility to specific autoimmune diseases has been known for some time, the role HLA molecules play in the autoimmune response is unclear. Through the establishment of chimeric HLA-DR/I-E transgenes, the authors examined the function of the rheumatoid arthritis (RA) susceptibility alleles HLA-DR1 (DRB1*0101) and DR4 (DRB1*0401) in presenting antigenic peptides derived from the model antigen, type II collagen (CII), and in mediating an autoimmune response. As a transgene, these chimeric DR molecules confer susceptibility to an autoimmune arthritis induced by immunization with human CII. Both the DR1 and DR4-restricted T cell responses to CII are focused on an immunodominant determinant CII(263-270). Peptide binding studies revealed that the majority of the CII-peptide binding affinity for DR1 and DR4 is controlled by the Phe at 263 and, unexpectedly, the adjacent Lys. Only these 2 CII amino acids were found to provide binding anchors. Amino acid substitutions at the remaining positions had either no effect or significantly increased the affinity of the hCII peptide. These data indicate that DR1 and DR4 bind this CII peptide in a nearly identical manner and that the primary structure of CII may dictate a different binding motif for DR1 and DR4 than has been described for other peptides. In all, these studies demonstrate that DR1 and DR4 are capable of binding peptides derived from human type II collagen (hCII) and support the hypothesis that autoimmune responses to hCII play a role in the pathogenesis of RA.
Direct hemoperfusion with the polymyxin B-immobilized fiber (PMX-20R) column has a positive effect on outcome in patients with sepsis or septic shock. The PMX-05R column has a low priming volume and has been used in pediatric patients with septic shock. The aim of the present study was to determine whether PMX-F treatment with the PMX-05R column is effective in elderly patients with septic shock. We performed direct hemoperfusion twice with the PMX-05R column in 8 septic shock patients who were over 80 years of age. Five of the 8 patients survived. The 3 patients who died were undergoing hemodialysis for chronic renal failure, and methicillin-resistant Staphylococcus aureus was detected in all 3. PMX-F treatment significantly increased systolic and diastolic blood pressures (P = 0.0004 for both) and significantly reduced heart rate (P < 0.0001), the blood endotoxin level (P = 0.0011), blood IL-6 level (P = 0.039), C-reactive protein level (P < 0.0001), and white blood cell count (P < 0.0001). Direct hemoperfusion with the PMX-05R column is effective in ameliorating clinical and laboratory abnormalities in elderly septic shock patients.
The authors previously demonstrated that pretreatment with 1,25(OH)2D3 protects from Cytoxan-induced alopecia in the rat model. The current study was designed to investigate whether 1,25(OH)2D3 protects the transplantable rat chloroleukemia (C51) cells from the cytotoxic effects of Cytoxan. In vitro, 4-hydroperoxycyclophosphamide had a dose-dependent cytotoxic effect on C51 cells. In separate experiments, preincubation with 1,25(OH)2D3 did not protect the C51 cells from the cytotoxic effects of 4-hydroperoxycyclophosphamide. In vivo, 4 groups of 10 5-day-old rats were treated as follows: Groups 1 and 2 received 0.2 micrograms of 1,25(OH)2D3 topically in ethanol daily starting on day 5 through day 10. Groups 3 and 4 received ethanol topically similarly. On day 7, all rats received 1 x 10(5) C51 cells intraperitoneally. On day 11, groups 1 and 3 received 35 mg/kg Cytoxan intraperitoneally. All rats in groups 2 and 4 were dead of leukemia by day 34. In groups 1 and 3, only 1 of 10 and 2 of 10 rats died of leukemia, respectively. Alopecia developed in all rats in group 3. In contrast, all rats in group 1 were protected from Cytoxan-induced alopecia. These results indicate that, in vivo, pretreatment with 1,25(OH)2D3 does not protect the rat chloroleukemia cells from the cytotoxic effect of Cytoxan, while protecting from Cytoxan-induced alopecia.
Recent studies showed that 1,25(OH)2 vitamin D3 stimulates calcium uptake in vascular smooth muscle cells resulting in increased vascular reactivity. Despite reliable effects on vascular tissue, daily injections of 1,25(OH)2 vitamin D3 have not consistently altered basal blood pressure. In the current study, 1,25(OH)2 vitamin D3 was examined for vascular reactivity in vitro as well as blood pressure reactivity in vivo. 1,25(OH)2 vitamin D3 was either injected as a daily subcutaneous dose of 48 ng/kg or placed in an osmotic minipump that was implanted subcutaneously and delivered at a rate of 2/ng/kg/hr (48 ng/kg/d). Blood pressure reactivity to bolus injections of norepinephrine (NE) and angiotensin II (AII) was tested after 1, 6, and 7 days of 1,25(OH)2 vitamin D3 treatment. On the seventh day, the animals were killed and rings from the aorta and mesenteric artery were placed in a muscle bath for measurement of vascular reactivity to NE and potassium chloride. Vessels from animals injected with 1,25(OH)2 vitamin D3 had significantly greater responses to NE (p < 0.001) and potassium chloride (p < 0.001) than those from minipump or control animals. There was no significant difference in baseline BP across treatment conditions or any reliable difference in blood pressure reactivity to NE or AII. The data showed that 1,25(OH)2 vitamin D3 can enhance vascular reactivity without altering baseline blood pressure or blood pressure reactivity. Moreover, intermittent administration of calcitriol may enhance vascular reactivity to norepinephrine and potassium chloride to a greater extent than the same dose of calcitriol given as a continuous infusion.
1,25-Dihydroxyvitamin D (1,25-(OH)2D) plays a crucial role in the maintenance of blood calcium and phosphorus levels and in normal skeletal mineralization. The concentration of this metabolite in the blood is, by necessity, tightly regulated. The most important stimuli for renal 1,25-(OH)2D synthesis include parathyroid hormone (PTH), its second messenger cyclic adenosine monophosphate (cAMP) and phosphate deprivation. Hypocalcemia and calcitonin, initially thought to act via stimulation of PTH release, have now been shown to directly stimulate 1-hydroxylation. Estrogens also increase 1,25-(OH)2D production, probably by upregulating renal PTH receptors. Inhibitors of the renal 25-(OH)D 1 alpha-hydroxylase include 1,25-(OH)2D itself, hypercalcemia, and phosphate loading. The PTH-vitamin D axis as modulated by the serum ionized calcium level controls adaptation to alterations in dietary calcium and sodium intake and to changes in skeletal turnover based on the level of physical activity. Although normally the renal production of 1,25-(OH)2D is tightly regulated and changes little in response to vitamin D challenge, there are certain conditions in which 1,25-(OH)2D appears to be substrate-dependent. These include hypoparathyroidism, hyperparathyroidism, vitamin D deficiency, sarcoidosis and the anephric state, conditions in which PTH is not well-modulated by alterations in serum ionized calcium or in which extrarenal synthesis of 1,25-(OH)2D occurs. In several disorders, including absorptive hypercalciuria, pseudohypoparathyroidism, hypophosphatemic rickets, and tumoral calcinosis, the regulation of the renal 1 alpha-hydroxylase appears to be altered.
Hypercalcemia associated with the extrarenal production of 1,25-dihydroxyvitamin D (1,25(OH)2D) has been reported in several disorders, most notably granulomatous diseases such as sarcoidosis. The authors describe a woman with hypercalcemia, renal insufficiency, microscopic hematuria, and anemia. The circulating 1,25(OH)2D level was higher than appropriate for the ambient conditions (renal insufficiency, suppressed intact parathyroid hormone, and hypercalcemia). A kidney biopsy was consistent with Wegener's granulomatosis, and treatment with prednisone and cyclophosphamide was associated with normalization of serum calcium levels, improved renal function, a marked decrease in serum 1,25(OH)2D levels, and increased serum intact parathyroid hormone levels. These findings are consistent with the unregulated production of 1,25(OH)2D by inflammatory cells associated with Wegener's granulomatosis.
Complement 5a receptor (C5aR) mediates both acute and chronic participation of monocytes in the immune response. In the human U937 monoblast, C5aR is maximally expressed 4 days after treatment with 1,25(OH)2D3 (or cycloheximide) and prostaglandin E2 combined. The authors asked whether these agents altered expression of C5aR messenger RNA (mRNA). Unstimulated U937 cells expressed neither C5aR mRNA nor C5a binding. Complement 5aR mRNA rose 3 hours after prostaglandin E2 application and fell to basal levels by 12 hours. This early rise in C5aR mRNA did not cause an acute rise in C5a binding, which gradually increased between 1 and 4 days. Neither 1,25(OH)2D3 nor cycloheximide induced expression of C5aR mRNA in the absence of prostaglandin E2 but did enhance prostaglandin E2-stimulated C5aR mRNA expression and C5a binding. The authors observed a late increase in C5aR mRNA at day 3 in treated cells. Inhibition of this late rise in mRNA with 5,6-dichlorobenzimidazole riboside attenuated C5a binding by 65%, indicating its importance in the generation of C5a binding sites. The expression of functional C5aR is, therefore, a complex process involving regulation at transcriptional and posttranscriptional levels.
The phagocytic behavior of the reticuloendothelial system in the rat was assessed by a quantitative technique following fructose-1,6-diphosphate (FDP) administration. In addition, the effect of FDP on the carbohydrate metabolism of human leukocytes was investigated. The rate of colloidal carbon clearance from the blood was increased significantly in the FDP-treated rats as compared to dextrose and saline controls (p less than 0.001). FDP also attenuated the hepatic decrease of ATP (p less than 0.005) and creatine phosphate (p less than 0.005) that has been observed after intravenous administration of colloidal carbon. Carbohydrate metabolism in human leukocytes was enhanced by FDP, with a concomitant increase in ATP content (p less than 0.001). Experimental evidence suggests that FDP intervenes in the Embden-Meyerhof pathway both as a metabolic regulator and as a high energy substrate. These properties of FDP in stimulating the carbohydrate metabolism have recently been described in man.
The effects of physical activity and site of intramuscular administration of 1,200,000 units of benzathine penicillin G on the duration of detectable serum penicillin levels were studied. An active naval recruit population was compared with a less active hospitalized population. The two areas of injection evaluated were the traditional posterior-buttocks site and the anterior gluteal region. The duration of penicillin in the serum specimens was one-third to one half as long as those reported in other nonrecruit populations. The more active group had a longer penicillinemia than the less active, hospitalized group, but only with the posterior site of injection. Various reasons for this phenomenon are discussed. The anterior intramuscular approach resulted in higher initial penicillin levels, but the duration of penicillin in the serum was less than that obtained with the conventional "posterior site." There was more pain on sitting with the posterior injection site. Le Effectos de Activitate Physic e del Sito del Injection Super le Penicillemia Resultante del Administration de 1,2 Milliones Unitates de Penicillina G Benzathina Esseva studiate le effectos de activitate physic e del sito de injection super le duration de detegibile nivellos serai de penicillina resultante del administration per via intramuscular de 1.200.000 unitates de penicillina G benzathina. Un population active de recrutas de marina esseva comparate con un population minus active de patientes de hospital. Le areas de injection comparate esseva le sito conventional in le aspecto posterior del clunes e un sito in le region gluteal anterior. Le duration del presentia de penicillina in le specimens de sero esseva inter un tertio e un medietate de illo reportate pro altere populationes. Le gruppo plus active habeva un plus prolongate penicillemia que le gruppo minus active, sed isto valeva solmente pro le sito posterior de injection. Varie possibile rationes pro iste phenomeno es discutite. Le injection anterior resultava in un plus alte nivello initial de penicillina in le sero que le injection in le sito conventional posterior, sed le resultante duration del presentia de penicillina in le sero esseva minus prolongate post le injection anterior. Le sito de injection posterior causava plus disconforto in seder.
The HEIRS Study will evaluate the prevalence, genetic and environmental determinants, and potential clinical, personal, and societal impact of hemochromatosis and iron overload in a multiethnic, primary care-based sample of 100,000 adults over a 5-year period. Participants are recruited from 5 Field Centers. Laboratory testing and data management and analysis are performed in a Central Laboratory and Coordinating Center, respectively. Participants undergo testing for serum iron measures and common mutations of the hemochromatosis gene ( ) on chromosome 6p and answer questions on demographics, health, and genetic testing attitudes. Participants with elevated values of transferrin saturation and serum ferritin and/or C282Y homozygosity are invited to undergo a comprehensive clinical examination (CCE), as are frequency-matched control subjects. These examinations provide data on personal and family medical history, lifestyle characteristics, physical examination, genetic counseling, and assessment of ethical, legal, and social implications. Primary and secondary causes of iron overload will be distinguished by clinical criteria. Iron overload will be confirmed by quantification of iron stores. Recruiting family members of cases will permit DNA analysis for additional genetic factors that affect iron overload. Of the first 50,520 screened, 51% are white, 24% are African American, 11% are Asian, 11% are Hispanic, and 3% are of other, mixed, or unidentified race; 63% are female and 37% are male. Information from the HEIRS Study will inform policy regarding the feasibility, optimal approach, and potential individual and public health benefits and risks of primary care-based screening for iron overload and hemochromatosis.
One hundred and four patients affected by hereditary angioedema belonging to 31 families have been studied. Twenty-two percent had the variant form related to the deficiency of the functional activity of serum C1 esterase inhibitor. The remaining 78% of patients had the predominant form, characterized by low antigenic levels and low functional activity of serum C1 esterase inhibitor. Attacks of swelling affected the subcutaneous tissue in 86% of patients; the upper airways in 76% of patients, and the bowel mucose in 75% of patients. Before treatment was available the mortality rate was 56%. One or more attacks a month were present in 46% of cases. The infusion of C1 inhibitor concentrate promptly reversed 14 severe attacks without any side effect. Twenty-nine patients were given long term prophylactic treatment with androgen derivatives with full success. Tranexamic acid reduced the frequency of swelling of 70% of the patients.
The course and outcome of 104 patients with acute renal failure were studied. Nephrotoxic drugs emerged as the second commonest cause of this disease. Overall mortality was 57 per cent; surgery, age, and sex had no significant effect on it. The mortality in the group caused by nephrotoxic drugs (36 per cent) was significantly lower than that in the groups caused by hypovolemic shock (64 per cent), cardiogenic shock (77 per cent) or arrhythmia (80 per cent). Oliguria was not observed in 25 per cent of patients; in this group mortality was lower (38 per cent) than in the oliguric group (62 per cent). The development of congestive heart failure and ascites adversely affected the outcome. Furosemide administration resulted in a sustained diuresis in 22 per cent, and transient diuresis in 14 per cent of patients. Except for a significant reduction in the need for dialysis, furosemide had no other salutary effect.
: A 7'3″ basketball player was noted to have 2 to 3 times thicker tissue in his hands than 6'10″ players by an endocrinologist sitting 10 rows above the player in a basketball arena. This led to the diagnosis of pituitary gigantism where the history revealed that he was 7'3″ at 15 years of age. At age 19 when the acryl enlargement was noted, a diagnostic workup revealed elevated growth hormones and insulin-like growth factor 1 (IGF-1) with a 2 × 1.3 cm pituitary tumor. His history suggested that his epiphyseal plates had closed at age 15, and because he continued to produce IGF-1, he now has acromegaly. His elevated adrenocorticotropic hormone (ACTH) before surgery suggests that he also had preclinical Cushing's disease. After pituitary transsphenoidal surgery, all acryl enlargement in hands and ligaments disappeared. His growth hormone, IGF-1 and ACTH returned to normal 2 weeks after surgery.
Aldosterone, the most important mineralocorticoid, regulates electrolyte excretion and intravascular volume mainly through its effects on renal cortical collecting ducts, where it acts to increase sodium resorption from and potassium excretion into the urine. Excess secretion of aldosterone or other mineralocorticoids, or abnormal sensitivity to mineralocorticoids, may result in hypokalemia, suppressed plasma renin activity, and hypertension. The syndrome of apparent mineralocorticoid excess (AME) is an inherited form of hypertension in which 11beta-hydroxysteroid dehydrogenase (11-HSD) is defective. This enzyme converts cortisol to its inactive metabolite, cortisone. Because mineralocorticoid receptors themselves have similar affinities for cortisol and aldosterone, it is hypothesized that the deficiency allows these receptors to be occupied by cortisol, which normally circulates at levels far higher than those of aldosterone. We cloned cDNA and genes encoding two isozymes of 11-HSD. The liver or 11-HSD1 isozyme has relatively low affinity for steroids, is expressed at high levels in the liver but poorly in the kidney, and is not defective in AME. The kidney or 11-HSD2 isozyme has high steroid affinity and is expressed at high levels in the kidney and placenta. Mutations in the gene for the latter isozyme have been detected in all kindreds with AME. Moreover, the in vitro enzymatic activity conferred by each mutation is strongly correlated with the ratio of cortisone to cortisol metabolites in the urine, with age of diagnosis, and with birth weight. This suggests that the biochemical and clinical phenotype of AME is largely determined by genotype.
Top-cited authors
Martin Alpert
  • University of Missouri
Neil Kurtzman
  • Texas Tech University Health Sciences Center
Kessarin Panichpisal
  • Aurora Health Care
Errol D Crook
  • University of South Alabama
Gerald S Berenson
  • Louisiana State University Health Sciences Center New Orleans