B cells play a key role in regulating the immune system by producing antibodies, acting as antigen-presenting cells, providing support to other mononuclear cells, and contributing directly to Inflammatory pathways. Accumulating evidence points to disruption of these tightly regulated processes in the pathogenesis of autoimmune disorders. Although the exact mechanisms involved remain to be elucidated, a fundamental feature of many autoimmune disorders is a loss of B-cell tolerance and the inappropriate production of autoantibodies. Dysfunctional immune responses resulting from genetic mutations that cause intrinsic B-cell abnormalities and induction of autoimmunity in the T-cell compartment by B cells that have broken tolerance may also contribute to these disorders. These findings provide the rationale for B-cell depletion as a potential therapeutic strategy in autoimmune disorders and other disease states characterized by inappropriate immune responses. Preliminary results with the CD20-targeted monoclonal antibody rituximab indicate that rituximab can improve symptoms in a number of autoimmune and neurologic disorders (including rheumatoid arthritis, systemic lupus erythematosus, and paraneoplastic neurologic syndromes). Additional studies are warranted to further characterize the role of B cells in autoimmune diseases and the therapeutic utility of B-cell depletion.
Letters of inquiry, with invitations to return for an examination, regarding the long term results of the varicose vein operation were sent to 1,000 consecutive patients operated on for varicose veins 10 or more years ago. Of the 656 patients who answered the letter, 86% considered the present condition of their legs to be good to excellent. Also, 278 of these 656 returned for an objective examination of their legs and, on the basis of the presence or absence of 'recurrent' varicose veins, 85% were considered to have a good to excellent result.
Since 1972 we have used the Self-Administered Alcoholism Screening Test (SAAST) in impatient alcoholics and their spouses and in patients from a general medical population. The SAAST, a 35-item test with a yes/no format, was administered to 1,002 consecutive Mayo Clinic patients who generally were not acutely ill and were requesting an annual examination or a general reexamination for chornic but stable problems. Of the 1,002 patients, 5.4% gave responses to the SAAST that would indicate the presence of possible or probable alcoholism. The medical record review on a random selection of patients revealed a false-negative rate of 6.7%. We believe that the SAAST is an effective tool for the detection of alcoholism and that it can be used in the general medical setting.
Hypercalcemia occurs in 10 to 30% of renal transplant recipients and is most often due to persistent hyperparathyroidism. Herein we describe a patient with a history of hyperparathyroidism who sought medical assessment because of recurrence of hypercalcemia 7 years after a successful renal transplantation. The hypercalcemia was associated with a normal serum phosphate level, a low to normal parathyroid hormone level, virtually undetectable levels of parathyroid hormone-related protein, and increased 1,25-dihydroxyvitamin D levels. Further assessment led to the diagnosis of an underlying lymphoma. To our knowledge, this is the first report of 1,25-dihydroxyvitamin D-mediated hypercalcemia in a renal transplant recipient with lymphoma. The possibility of an underlying lymphoproliferative disorder should be considered in the differential diagnosis of hypercalcemia in a renal transplant recipient.
Although most patients with postmenopausal osteoporosis have normal or low values for serum immunoreactive parathyroid hormone (iPTH), we have reported previously that a small subset (about 10% of the total group) have increased values. We studied three patients representative of this latter group. Serum iPTH was two to three times higher than the age-adjusted normal mean, serum ionized calcium and total calcium were in the lower half of the normal range, and serum 1,25-dihydroxyvitamin D [1,25(OH)2D] was in the low-normal range. Six months of treatment of one patient with 0.5 microgram/day of synthetic 1,25(OH)2D improved calcium absorption and balance; however, serum iPTH remained high. After surgical removal of 1,010 mg of hyperplastic parathyroid tissue, serum iPTH decreased to normal. These and other data suggest that increased serum iPTH in these patients was caused by secondary hyperparathyroidism, possibly because of inadequate conversion of 25-OH-D to 1,25(OH)2D.
Because of evidence in experimental animals that prolactin stimulates production of 1,25-dihydroxyvitamin D, we evaluated several indices of calcium metabolism in patients who had hyperprolactinemia due to functioning pituitary adenomas and in normal age-matched controls. Plasma levels of 1,25-dihydroxyvitamin D in hyperprolactinemic patients were in the normal range (15 to 24 pg/ml versus 15 5o 75 pg/ml in controls). Intestinal absorption of calcium, plasma levels of immunoreactive parathyroid hormone, and serum values for calcium, phosphorus, and alkaline phosphatase were similar in patients and controls. We conclude that prolactin probably has no effect on plasma 1,25-dihydroxyvitamin D levels or calcium metabolism in man.
To describe a method of laparoscopy without use of the Veress needle and to analyze the associated complications.
We retrospectively reviewed all 1,600 laparoscopic procedures performed in the Department of Obstetrics and Gynecology at Nitra Hospital from Aug. 23, 1989, to Jan. 31, 1994.
Our laparoscopic techniques were outlined, and our complication rate was assessed and compared with that from the literature.
In the 1,600 procedures, 6 complications occurred (0.375%)--4 technical failures in extremely obese patients, 1 case of umbilical granuloma 2 months after the procedure, and 1 case of omental prolapse on the sixth postlaparoscopic day.
Results from this series of procedures suggest that laparoscopy without use of the Veress needle is simple, safe, efficient, and easy to learn.
On 247 of the 1,711 scintiscans (15%), the appearance of renal or urinary tract areas differed sufficiently from normal to merit mention in interpretation. For 162 patients (195 surveys), the abnormalities noted were classified as "minor." For 39 patients (52 surveys), the abnormalities noted were classified as "major"--that is, confirmed by other means or considered of major importance to diagnosis and management. Of these, 9 were filling defects (2 each were renal cell carcinoma, simple cyst, and polycystic disease; 3 were a mass of undetermined nature) and 30 were unilateral or bilateral urinary tract obstruction indicated by hydroureter and massive retention in renal area(s). These obstructive manifestations were associated with primary pelvic or prostatic malignancy or extension of malignant disease; in nine patients, progression or remission of obstruction was noted on sequential imaging. These changes were compatible with changes in clinical status and may afford an added means of following response to therapy in appropriate patients.
To determine the efficacy of alendronate treatment on risk of vertebral fracture in a subgroup of women from the Fracture Intervention Trial who had bone mineral density T scores between -1.6 and -2.5 at the femoral neck and to describe how soon after initiation of therapy alendronate becomes effective and whether it is consistent in women with and without existing radiographic vertebral fracture.
From May 1992 to March 1997, postmenopausal women aged 55 to 80 years were randomized to receive alendronate at 5 mg/d for 2 years and 10 mg/d thereafter or placebo for up to 4.5 years (mean, 3.8 years) in a controlled, double-blind, multicenter study.
A total of 3737 postmenopausal women were included in the study, 1878 in the alendronate group and 1859 in the placebo group. Risk of vertebral fracture was significantly reduced by alendronate compared with placebo for clinical (relative risk [RR], 0.40; 95% confidence interval [CI], 0.19-0.76; P=.005) and radiographic (RR, 0.57; 95% CI, 0.41-0.81; P=-.002) fracture. The reductions in vertebral fracture risk were consistent in women with and without an existing radiographic vertebral fracture for clinical (RR, 0.34; 95% CI, 0.12-0.84; and RR, 0.46; 95% CI, 0.16-1.17; respectively) and radiographic (RR, 0.53; 95% CI, 0.34-0.82; and RR, 0.64; 95% CI, 0.38-1.10; respectively) fractures. In both groups, the effect of alendronate on clinical vertebral fracture was noted soon after therapy was initiated. The absolute risk of vertebral fracture was low in women without a baseline radiographic fracture.
In women with low bone mass who do not meet the bone mineral density criterion for osteoporosis, alendronate is effective in reducing the risk of vertebral fractures. The absolute benefit of this therapy in women with a T score between -1.6 and -2.5 is greater in women with an existing vertebral fracture and/or with other risk factors. The effect of alendronate occurs early.
To determine factors that influence clinicians' decisions to treat subclinical hypothyroidism.
We studied patients living within 120 miles of our institution in Rochester, Minn, whose serum thyrotropin value was between 5.1 and 10.0 mIU/L from January 1, 1995, through December 31,1996. Exclusion criteria were history of thyroid disease or prior abnormal thyrotropin level and fewer than 5 follow-up visits or fewer than 2 follow-up thyrotropin measurements. Of the 2655 patients in this cohort, only 55% (1466) had measurement of thyroid microsomal antibodies (TMAb). From this group, records of 539 patients were selected randomly according to antibody status (238 with positive, 199 with negative, and 102 with no TMAb measurement). After exclusion of patients receiving thyroxine replacement and other medications affecting thyroid function, patients with postpartum thyroiditis, and patients in the intensive care unit, data from 450 patients were analyzed.
Thyroxine therapy was prescribed for 39% of the patients with thyrotropin levels between 5.1 and 10.0 mIU/L. In multivariate analysis, TMAb status (P < .001), index thyrotropin (P < .002), and free thyroxine (FT4) (P = .03) were the strongest predictors for the decision to treat. Fifty-nine percent of the patients with positive TMAb were treated compared with 24% of those with negative TMAb and 30% of those who did not have a TMAb test. The mean thyrotropin level in the treated group was 7.1 mIU/L compared with 63 mIU/L in the untreated group. The mean FT4 level was 1.08 ng/dL in the treated group who had this measured compared with 1.16 ng/dL in the untreated group. Treated patients were younger than untreated patients (56.5 years vs 60.6 years), and the proportion of female patients was higher in the treated group compared with the untreated group (75.8% vs 65.2%); however, neither of these differences was significant after correction for the multiple comparisons. In multivariate analysis neither age nor sex was a significant predictor of treatment, but in the subgroup comparison, patients aged 31 to 50 years were twice as likely to be treated compared with those aged 61 to 80 years.
Among patients with serum thyrotropin levels of 5.1 to 10.0 mIU/L, those with positive TMAb values, those with higher thyrotropin values, and those with lower FT4 values were more likely to receive thyroxine therapy. Younger patients were more likely to be treated than older patients.
To study the safety of a protocol that allows ambulation 1 hour after diagnostic cardiac catheterization with a transfemoral approach using a 5F catheter system.
A total of 1005 consecutive patients (1009 procedures) undergoing outpatient diagnostic cardiac catheterization with a transfemoral approach using a 5F catheter system at the Mayo Clinic in Rochester, Minn, were included in this study from January 1, 2004, to August 31, 2005. All patients underwent standard manual compression to achieve hemostasis and were ambulated after 1 hour of bed rest.
The mean age of the patients was 64.5 years, and 62% were male. Minor vascular complications occurred in 33 procedures (3.3%), Including 14 hematomas (1.4%) less than 4 cm and 19 cases of rebleeding (1.9%) that required repeated manual compression. Only 1 patient (0.1%) had a hematoma greater than 4 cm. No patient had a major complication, such as surgical repair, red blood cell transfusion, retroperitoneal bleeding, formation of an arteriovenous fistula or pseudoaneurysm, arterial occlusion, or an infection.
Ambulation 1 hour after diagnostic cardiac catheterization with a transfemoral approach using a 5F catheter system is safe and associated with low rates of vascular complications. This strategy may improve patient comfort, reduce resource utilization, and be preferable to use of vascular closure devices.
To determine the clinical and laboratory features of newly diagnosed multiple myeloma.
Records of all patients in whom multiple myeloma was initially diagnosed at the Mayo Clinic in Rochester, Minn, from January 1, 1985, to December 31, 1998, were reviewed.
Of the 1027 study patients, 2% were younger than 40 years, and 38% were 70 years or older. The median age was 66 years. Anemia was present initially in 73% of patients, hypercalcemia (calcium level > or = 11 mg/dL) in 13%, and a serum creatinine level of 2 mg/dL or more in 19%. The beta2-microglobulin level was increased in 75%. Serum protein electrophoresis revealed a localized band in 82% of patients, and immunoelectrophoresis or immunofixation showed a monoclonal protein in 93%. A monoclonal light chain was found in the urine in 78%. Nonsecretory myeloma was recognized in 3% of patients, whereas light-chain myeloma was present in 20%. Conventional radiographs showed an abnormality in 79%. The plasma cell labeling index was 1% or more in 34% of patients. Multivariate analysis revealed that age, plasma cell labeling index, low platelet count, serum albumin value, and the log of the creatinine value were the most important prognostic factors.
The median duration of survival was 33 months and did not improve from 1985 through 1998.
To determine the relative efficacy and safety of cerivastatin and pravastatin in patients with type II hypercholesterolemia.
In this prospective, double-blind, parallel-group study, hypercholesterolemic patients were randomized to treatment with cerivastatin, 0.3 mg (n=250) or 0.4 mg (n=258), or pravastatin, 20 mg (n=266) or 40 mg (n=256), for 8 weeks.
Cerivastatin, 0.3 mg, was significantly more effective than pravastatin, 20 mg, in reducing low-density lipoprotein (LDL) cholesterol from baseline (-29.6% vs -26.8%; P=.008). Cerivastatin, 0.4 mg, was significantly more effective than pravastatin, 40 mg, in reducing LDL cholesterol (-34.2% vs -30.3%; P<.001). A larger proportion of cerivastatin-treated patients had greater than 40% reductions in LDL cholesterol than those receiving pravastatin (11.1% vs 6.0%). The percentage of patients who achieved the National Cholesterol Education Program (NCEP) target was 71.3% with cerivastatin, 0.3 mg, compared with 67.5% with pravastatin, 20 mg, and 74.0% with cerivastatin, 0.4 mg, compared with 71.1% with pravastatin, 40 mg (no significant difference). Cerivastatin, 0.3 mg, reduced total cholesterol to a greater extent than did pravastatin, 20 mg (P<.03). Both agents reduced triglycerides and increased high-density lipoprotein cholesterol to a similar degree (no significant differences). Cerivastatin and pravastatin were well tolerated.
Cerivastatin, 0.3 mg and 0.4 mg, showed greater efficacy than pravastatin, 20 mg and 40 mg, respectively, in lowering LDL cholesterol. Cerivastatin is safe and effective for patients with hypercholesterolemia who require aggressive LDL cholesterol lowering to achieve NCEP-recommended targets.
To further characterize the clinical features, etiologic associations, laboratory findings, and treatment of pernio.
This is a retrospective review of patients with pernio seen at our institution between January 1, 2000, and December 31, 2011.
Of 104 patients with pernio (mean age at diagnosis, 38.3 years), 82 (79%) were women. Pernio affected the toes in 85 patients (82%) and the fingers in 31 (30%). Thirty-eight patients (37%) had at least 1 abnormal laboratory test result, and test results were positive for cold agglutinins in 11 (55%) of 20 tested patients. Results were negative for cryoglobulins in all tested patients (n=53). Four patients (4%) had connective tissue disease (nonlupus) associated with pernio; 3 patients (3%) had an associated hematologic malignant disease. Conservative treatments (eg, warming, drying, and smoking cessation) provided complete response in 23 (82%) of 28 patients with follow-up data.
To our knowledge, this study represents one of the largest single-center case series of pernio to date. Most of the patients did not have an underlying systemic association with pernio, although a few patients had pernio in association with connective tissue disease or hematologic malignant disease.
Chromosome studies were done in 104 patients with various stages of polycythemia vera (PV): 10 had leukemia-myelodysplastic syndrome, 28 had post-PV with myeloid metaplasia (PPVMM), 12 had PV with myelofibrosis, and 54 had PV. Chromosome studies were successful in 86 patients, 37 (43%) of whom had a chromosome abnormality. At diagnosis, 4 of 28 patients (14%) had an abnormal clone; the incidence was 78% in PPVMM and 100% in leukemia-myelodysplastic syndrome. Among the 63 patients with successful chromosome studies during the first 10 years of disease, 27% had an abnormal clone. In contrast, of the 23 patients who had the disease for more than 10 years, 87% had an abnormal clone. Chromosome abnormalities were found in 11 of the 60 patients who either were untreated or underwent only phlebotomy and in 26 of the 44 patients who were treated with myelosuppressive agents. Trisomy 8, +9, and 20q- were found in some patients early during the course of their disease and also among untreated patients. These chromosome abnormalities seem to be related to the natural course of PV rather than to therapy. Patients with a chromosomally abnormal clone at the time of diagnosis of PV had a poorer survival than did those with only normal metaphases. Cytogenetic results did not predict evolution of the disease, but they did provide clues to hematologic phenotype, duration of the disease, and consequences of myelosuppressive therapy.
Persons older than 85 years of age will constitute the fastest growing segment of the US population in the next decade, and despite the recent decline in mortality from heart disease, cardiovascular disease remains the single greatest cause of death in these elderly persons. We studied the pathologic changes in the hearts of 237 patients (93 men and 144 women) who had lived to the age of 90 years or older. The degree and extent of coronary atherosclerosis in these senescent hearts were similar to findings reported in younger patients who died of coronary heart disease, but calcification of the coronary arteries, mitral annulus, and aortic valve was more prevalent, as was cardiac amyloidosis. Multiple cardiac disorders were common in these very elderly hearts, but they seemed to play a lesser role in precipitating heart failure or shortening the life-span of the patients. Important factors in attaining longevity seem to be protection from the development of severe coronary artery disease by an unexplained mechanism and an innate resistance to cardiac dysfunction from a multitude of structural changes that occur with advancing age.
This study portrays the manifestations of diabetic polyradiculopathy. We emphasize the age of patients at inception, mode of symptomatic onset, manner of evolution and resolution of the syndrome, character and territorial extent of clinical and electromyographic findings, tendency to relapse and remit, frequent association with diabetic polyneuropathy, and prognostic implications of the disease.
To report the incidence of reading disability among school-aged children.
In this population-based, retrospective birth cohort study, subjects included all 5718 children born between 1976 and 1982 who remained in Rochester, Minn, after the age of 5 years. Based on records from all public and nonpublic schools, medical facilities, and private tutorial services and on results of all individually administered IQ and achievement tests, extensive medical, educational, and socioeconomic information were abstracted. Reading disability was established with use of research criteria based on 4 formulas (2 regression-based discrepancy, 1 non-regression-based discrepancy, and 1 low achievement).
Cumulative incidence rates of reading disability varied from 5.3% to 11.8% depending on the formula used. Boys were 2 to 3 times more likely to be affected than girls, regardless of the identification methods applied.
In this population-based birth cohort, reading disability was common among school-aged children and significantly more frequent among boys than girls, regardless of definition.
Hip arthroplasty using the Thompson femoral prosthesis with methyl methacrylate fixation was performed on 109 hips in 106 patients. During an average follow-up period of 36 months, 26 patients died. Fifty-one procedures were performed for fresh fractures of the femoral neck and results were satisfactory in this group provided the patient was minimally active. Results were unsatisfactory in patients who had idiopathic avascular necrosis (18), painful, failed noncemented prostheses (6), and osteoarthritis (3). In these last three groups, one-half required conversion to total hip arthroplasty and an additional one-third had pain. Reoperation was required in 22 cases. Intraoperative death occurred in one elderly patient after insertion of cement. Results suggest that the primary indication for this procedure is in the minimally ambulatory or nonambulatory elderly osteoporotic patient who has a fresh fracture of the femoral neck.
Small cell carcinoma of the lung has reportedly been associated with structural abnormalities of the short arm of chromosome 3, but most of the previous studies were done on long-term cultures that involved cell lines. In the current study, we investigated the chromosome abnormalities in specimens from primary lung tumors grown in short-term cultures. Cytogenetic studies were done in 11 patients with small cell carcinoma of the lung, and a chromosomally abnormal clone was observed in each tumor. An abnormality of chromosome 3 was observed in six of these tumors.
Five percent of all tumors occur in the head and neck, and approximately half of those occur specifically in the oral cavity. Of the 615,000 new cases of head and neck [corrected] tumors reported worldwide in 2000, 300,000 were primary oral cavity squamous cell carcinomas. Recent data from the Surveillance, Epidemiology, and End Results Program suggest that 28,900 new cases of oral cancer will be identified and 7400 deaths attributed to oral cancer each year in the United States. The sixth leading cause of cancer-related mortality, oral cancer accounts for 1 death every hour in the United States. However, despite advances in screening tools, imaging technology, and access to primary care physicians, a considerable percentage of patients present with advanced-stage disease. Clinical signs and symptoms of head and neck tumors are often nonspecific and may be mistaken for other common ailments. Primary care physicians must be aware of the possibility of oral cancer, particularly the increasing incidence in young patients without traditional risk factors of alcohol and tobacco abuse. To improve survival, all patients should be routinely and vigilantly screened for oral mucosal lesions.
To report a series of cases of surgically resected granular cell tumors in an attempt to better characterize their clinical presentation, imaging features, and treatment outcomes with attention to previously published literature.
This is a retrospective study of 11 patients with granular cell tumors. Information obtained from patients' medical records was supplemented by direct physician and patient telephone contact.
The study group consisted of 9 women and 2 men, with a mean +/- SD age of 50 +/- 15 years (range, 26-73 years). Seven patients were symptomatic, 3 of whom presented with visual complaints. Four patients presented primarily with endocrine dysfunction (2) or headaches (2). The duration of symptoms varied from 1 to 12 months (mean +/- SD, 6.0 +/- 4.5 months). Formal visual field testing revealed bitemporal hemianopsia in 6 and a right-sided visual field deficit in 2. The tumor appeared as a well-defined, relatively homogeneously (6) or heterogeneously (1) enhancing suprasellar mass on contrast infusion. Tumor size varied from 1.5 to 6.0 cm (mean +/- SD, 3.1 +/- 1.6 cm). At surgery, the mass was noted to be firm and vascular, and in at least 3 patients these features prevented gross total resection. Only 1 patient who had undergone biopsy of his lesion received adjuvant radiation therapy. Follow-up was obtained in all but 1 patient. Nine of these 10 patients are alive and are either free of disease or have had no disease progression. Follow-up in these 9 patients varied from 1 to 16 years (mean +/- SD, 6.5 +/- 53 years).
A granular cell tumor is generally a surprise finding in that it is seldom considered in the differential diagnosis of contrast-enhancing, demarcated sellar region masses. Granular cell tumors are benign and slow growing with no pronounced tendency for invasion or recurrence. Because of the indolent growth of granular cell tumors, the surgical goal of tumor decompression is a reasonable therapeutic approach.
The toxic shock syndrome has only recently been described. Eleven female patients aged 13 to 43 years (median 17) with toxic shock syndrome have been seen at the Mayo Clinic since August 1975. One patient died. Seven patients had one or more recurrences. As previously described, the syndrome was often life-threatening, afflicted mostly menstruating females, and was characterized by a very brief prodromal illness consisting of high fever, vomiting, diarrhea, conjunctivitis, headache, irritability, sore throat, myalgias, abdominal tenderness, and erythematous rash. The disorder can progress to hypotension or prolonged refractory shock, adult respiratory distress syndrome, diffuse intravascular coagulation with severe thrombocytopenia, and renal failure. Pancreatitis was observed in two cases. During convalescence, pronounced desquamation and peeling of the skin occurred. Numerous laboratory abnormalities are observed. In 5 of the 11 patients, Staphylococcus aureus was isolated from conjunctiva, oral cavity or nares, vagina, or stool. A recently described pyrogenic exotoxin was identified in the isolates of three patients; its etiologic role remains speculative. Therapy is mainly supportive. Antistaphylococcal therapy for the acute illness and for prevention of recurrences has not yet proved to be of any benefit. The role of vaginal tampons, if any, in the pathogenesis of this disorder remains unclear.
Plasma cell granuloma occurs in children, typically as an intrapulmonary mass. Surgical excision is the treatment of choice and is usually curative. We report an atypical and unresectable plasma cell granuloma that occurred asymptomatically in the heart of a child and spontaneously decreased in size by 40% during an 11-month period. Thus, plasma cell granuloma should be considered in the differential diagnosis of any child who has a cardiac mass. Observation should be considered a treatment option because this case demonstrated that the cardiac mass can spontaneously recede without therapy.
Excess secretion of 18-hydroxy-11-deoxycorticosterone (18-OH-DOC) occurs in more than 10% of hypertensive patients with suppressed plasma renin activity, but it also is reported to occur in essential hypertension without impairment of the renin system. Preliminary studies measuring plasma 18-OH-DOC by radioimmunoassay support the idea that 18-OH-DOC secretion is elevated in some patients with essential hypertension. Interpretation of these data must take into account endogenous ultradien and circadian variations in plasma 18-OH-DOC, however. 18-OH-DOC serves as a precursor of another steroid secretory product. Conversion of labeled 18-OH-DOC to a new structure, 16alpha, 18-dihydroxy-11-deoxycorticosterone (16alpha, 18-diOH-DOC), was demonstrated to be greatly accelerated by the adrenal tissue in low-renin patients as compared with those with normal adrenal tissue (70 to 80% versus 15% conversion). Hypersecretion of 16alpha, 18-diOH-DOC occurred in each. This steroid exerted no effect on sodium metabolism in adrenalectomized rats or in the toad bladder assay, but it markedly enhanced activity of subthreshold doses of aldosterone in reducing sodium excretion in urine of adrenal-ectomized rats. Because of the unique activity of this steroid, we have concluded that excessive 16alpha, 18-diOH-DOC secretion may be important in the genesis of suppressed renin in some patients with hypertension.
Vitamin B12 is essential for life. Lack of it results in pernicious anemia and death. Conversely, the demand for vitamin B12 increases in rapidly dividing tumors. This is secondary to the direct involvement of vitamin B12 in mitochondrial metabolism as well as its indirect role in the production of thymidylate and S-adenosylmethionine. The latter 2 substances are needed for DNA synthesis and cellular methylation reactions, respectively. Novel radiolabeling of adenosylcobalamin has proven to be useful in the imaging of transplanted and spontaneous tumors in animals. Herein, we describe what we believe to be the first human to have imaging with conventional gamma cameras of vitamin B12 metabolism in a breast tumor.
To evaluate changes in the institution's red blood cell (RBC) transfusion practice during the past 15 years and the influence of these changes on neurologic or cardiac morbidity after carotid endarterectomy.
Based on a retrospective analysis of the Mayo Clinic database, 1,114 patients who underwent carotid endarterectomy were stratified into 1 of 2 groups: (1) 1980 to 1985 (ie, pre-human immunodeficiency virus screening, early-practice group [n=552]) and (2) 1990 to 1995 (ie, recent-practice group [n=562]). Data were compared between time periods using the chi2 test for categorical variables and the rank sum test for continuous variables. Logistic regression was used to assess the association between perioperative transfusion practice and the occurrence of stroke or myocardial infarction. Two-tailed P values < or = 05 were considered statistically significant.
Patients in the recent-practice group were significantly older (mean +/- SD age, 69.6 +/- 8.7 years) vs 65.9 +/- 8.3 years in the early-practice group (P<.001). The proportion of patients receiving perioperative RBC transfusion decreased dramatically from 72.9% in 1980-1985 to 8.7% in 1990-1995 (P<.001). Additionally, the mean +/- SD number of RBC units transfused decreased from 1.10 +/- 1.30 U in 1980-1985 to 0.27 +/- 1.22 U in 1990-1995 (P<.001). Mean +/- SD discharge hemoglobin concentration decreased from 13.7 +/- 1.4 g/dL in 1980-1985 to 11.8 +/- 1.5 g/dL in 1990-1995 (P<.001). Rates of perioperative stroke and myocardial infarction did not differ between the 2 time periods (early-practice group vs recent-practice group: stroke, 5.1% vs 3.6% [P=.22]; myocardial infarction, 1.5% vs 2.3% [P=.29]).
Our results suggest that elderly patients undergoing carotid endarterectomy (ie, individuals known to be at high risk for cerebral and cardiac ischemia) can tolerate modest perioperative anemia despite a considerable change in the institution's transfusion practice (lower "transfusion trigger," the hemoglobin concentration or hematocrit value below which RBC transfusion is indicated).
A new radioisotopic technique has been developed for quantification of deposition of neutrophilic granulocytes on vascular grafts. Nine healthy mongrel dogs underwent bilateral femoral artery resection and reconstruction with grafts of femoral vein and Gore-Tex. Pure granulocytes that had been separated from whole blood by centrifugal elutriation were labeled with 111In-tropolone in plasma. The granulocyte harvesting efficiency was 25 +/- 12%, and the labeling efficiency was 87 +/- 7%. Three hours after injection of labeled granulocytes and 2 hours after reperfusion, the grafts were harvested and cut into several segments for study of areas of anastomoses and midsections. On the basis of the radioactivity in the blood and in anastomotic and graft sections, the area of graft sections, and the neutrophilic granulocyte and differential leukocyte counts, the number of neutrophilic granulocytes adherent to a unit area and the total number of neutrophilic granulocytes on graft sections were calculated. These quantifications of the deposition of neutrophilic granulocytes indicated that the midsections of Gore-Tex grafts retained more neutrophilic granulocytes than did the midsections of vein grafts. Although the anastomotic areas retained more neutrophilic granulocytes than did the midsections of vein grafts, the opposite finding prevailed for the Gore-Tex grafts. A major fraction of neutrophilic granulocytes on Gore-Tex grafts was incorporated into thrombus. Semiquantitative information obtained by scintigraphy of the deposition of neutrophilic granulocytes on vascular grafts also confirmed this observation.
At 8 and 32 hours after saphenous vein aortocoronary artery bypass graft surgery in four dogs, images of the grafts were obtained with a gamma camera after intravenous injection, 2 hours postoperatively, of autologous platelets labeled with indium-111. The location of platelet deposition could be accurately estimated from the scintiphotos. In vitro radioactivity counting of the segments of the isolated grafts showed 4 to 15 times greater activity in the grafts than in blood and 25 to 100 times greater activity than in normal myocardium. This was sufficient for delineating accurately the area of platelet deposition. This noninvasive technique may be a promising tool for a better understanding of the role played by platelets in the process of occlusion of saphenous vein bypass grafts in man.
This study clearly indicates that In-labeled mixed granulocyte preparations used for graft-infection studies are questionable because the total 111In uptake in infected synthetic vascular grafts reflects depostion both of granulocytes due to infection and of platelets due to the thrombogenicity of the graft. Ficoll-Hypaque double-density separation can be used to determine the distribution of 111In among platelets, granulocytes, and erythrocytes. A preparation of labeled platelets can easily be obtained with few 111In-labeled granulocytes and erythrocytes, and such a preparation is adequate for platelet thrombus imaging and platelet kinetics. For diagnosing an abscess with use of 111In-labeled granulocytes, some labeled platelets localize together with labeled granulocytes. Furthermore, the imaging of abscesses with labeled granulocytes is complicated by the inevitable presence of labeled platelets and erythrocytes. Despite this, the radioactivity ratio of abscess to muscle is almost 50 to 500. Thus, the quality of images obtained from 111In granulocyte scintiscans is satisfactory.
To evaluate consecutive therapeutic echocardiographically (echo)-guided pericardiocenteses performed at Mayo Clinic, Rochester, Minn, from 1979 to 2000 and to determine whether patient profiles, practice patterns, and outcomes have changed over time.
Consecutive echo-guided pericardiocenteses performed between February 1, 1979, and January 31, 2000, for treatment of clinically significant pericardial effusions were identified in the Mayo Clinic Echocardiographic-guided Pericardiocentesis Registry. The medical records of these patients were examined, and a follow-up survey was conducted. Clinical profiles, echocardiographic findings, procedural details, and outcomes were determined for 3 periods: February 1, 1979, through January 31, 1986; February 1, 1986, through January 31, 1993; and February 1, 1993, through January 31, 2000.
During the 21-year study period, 1127 therapeutic echo-guided pericardiocenteses were performed in 977 patients. The mean +/- SD age at pericardiocentesis increased from 49+/-14 years in period 1 to 57+/-14 years in period 3. In recent years, cardiothoracic surgery replaced malignancy as the leading cause of an effusion requiring pericardiocentesis and together with malignancy and perforation from catheter-based procedures accounted for nearly 70% of all pericardiocenteses performed. The procedural success rate was 97% overall, with a total complication rate of 4.7% (major, 1.2%; minor, 3.5%). These rates did not change significantly over time. The use of a pericardial catheter for extended drainage increased from 23% in period 1 to 75% in period 3 (P<.001), whereas rates of effusion recurrence and pericardial surgery decreased significantly (P<.001).
The profile of patients presenting with clinically significant pericardial effusion has changed over time. Increasing numbers of older patients and those who have undergone cardiothoracic surgery or catheter-based procedures develop effusions that can be rapidly, safely, and effectively managed with echo-guided pericardiocentesis. Extended drainage with use of a pericardial catheter has become standard practice, and concomitantly, recurrence rates and need for surgical management have decreased considerably.
The gross surgical pathologic features of the pulmonary valve were reviewed in 116 patients (63 male and 53 female) who had undergone a cardiac operation with pulmonary valve excision at our institution during the period 1973 through 1987. Although the mean age was 12 years, subjects ranged in age from 3 months to 73 years, and 25 patients, including 19 with congenital heart disease, were older than 20 years of age. Among 105 patients who had pure pulmonary stenosis, 61 (58%) had tetralogy of Fallot, 18 had isolated pulmonary stenosis, 23 had other congenital cardiac anomalies, and 3 had carcinoid heart disease. Five patients had pure pulmonary regurgitation (four with tetralogy and one with infective endocarditis), and four had combined pulmonary stenosis and regurgitation (two with congenital cardiac anomalies and two with carcinoid heart disease). In two patients, the valve was neither stenotic nor regurgitant. Thus, congenital heart disease accounted for 110 of the 116 cases (95%), and tetralogy of Fallot was the most commonly observed form (65 cases). Bicuspid pulmonary valve was the most common anomaly and was present in 58% of patients with tetralogy but in only 17% of those with isolated pulmonary stenosis.
To determine standard left ventricular Doppler measurements in a large reference group of various ages to reflect the senescence process.
We prospectively studied the influence of aging on left ventricular diastolic filling by performing Doppler echocardiography in 117 normal healthy volunteers.
Transthoracic pulsed-wave Doppler echocardiographic studies of pulmonary venous flow and left ventricular inflow were done in the 53 male and 64 female study subjects. For analysis, the study subjects were arbitrarily classified into two groups: those younger than 50 years of age (group 1; N = 61) and those 50 years old or older (group 2; N = 56).
A striking difference was found in pulmonary venous flow and left ventricular inflow between group 1 and group 2 subjects. Group 2 had increased pulmonary venous peak systolic flow velocity (71 +/- 9 versus 48 +/- 9 cm/s), decreased peak diastolic flow velocity (38 +/- 9 versus 50 +/- 10 cm/s), increased peak atrial reversal flow velocity (23 +/- 4 versus 19 +/- 4 cm/s), and increased percentage of forward flow in systole (65 +/- 7 versus 55 +/- 8%) in comparison with group 1. In group 2, peak early filling velocity (62 +/- 14 versus 72 +/- 14 cm/s) and ratio of early filling to atrial filling (1.1 +/- 0.3 versus 1.9 +/- 0.6) were lower and peak atrial filling velocity (59 +/- 14 versus 40 +/- 10 cm/s) was higher than in group 1. Deceleration time (210 +/- 36 versus 179 +/- 20 ms) and isovolumic relaxation time (90 +/- 17 versus 76 +/- 11 ms) were prolonged in group 2 in comparison with group 1.
This study confirms the major influence of the aging process on left ventricular diastolic function in a large series of normal subjects. This physiologic factor should be considered in Doppler assessment of left ventricular diastolic filling in future studies.
To evaluate the influence of cardiorespiratory fitness (fitness) on the obesity paradox in middle-aged men with known or suspected coronary artery disease.
This study consists of 12,417 men aged 40 to 70 years (44% African American) who were referred for exercise testing at the Veterans Affairs Medical Centers in Washington, DC, or Palo Alto, CA (between January 1, 1983, and June 30, 2007). Fitness was quantified as metabolic equivalents achieved during a maximal exercise test and was categorized for analysis as low, moderate, and high (defined as <5, 5-10, and >10 metabolic equivalents, respectively). Adiposity was defined by body mass index (BMI) according to standard clinical guidelines. Separate and combined associations of fitness and adiposity with all-cause mortality were assessed by Cox proportional hazards analyses.
We recorded 2801 deaths during a mean+/-SD follow-up of 7.7+/-5.3 years. Multivariate hazard ratios (95% confidence interval) for all-cause mortality, with normal weight (BMI, 18.5-24.9 kg/m2) used as the reference group, were 1.9 (1.5-2.3), 0.7 (0.7-0.8), 0.7 (0.6-0.7), and 1.0 (0.8-1.1) for BMIs of less than 18.5, 25.0 to 29.9, 30.0 to 34.9, and 35.0 or more kg/m2, respectively. Compared with highly fit normal-weight men, underweight men with low fitness had the highest (4.5 [3.1-6.6]) and highly fit overweight men the lowest (0.4 [0.3-0.6]) mortality risk of any subgroup. Overweight and obese men with moderate fitness had mortality rates similar to those of the highly fit normal-weight reference group.
Fitness altered the obesity paradox. Overweight and obese men had increased longevity only if they registered high fitness.
Survival indices are presented for 122 consecutive patients who had presumed solitary cerebral metastasis treated in a consistent fashion during a short period. The site of intracranial metastasis, extent of tumor removal, tissue of origin, and age and sex of the patient were found to have a considerable bearing on prognosis.
To explore whether the radioligand 2 beta-carboxymethoxy-3 beta-(4-[123I] iodophenyl) tropane ([123I]beta-CIT) and single-photon emission computed tomography (SPECT) can detect decreased striatal uptake in at-risk relatives of patients with Parkinson disease (PD).
Ten PD patients, 10 at-risk first-degree relatives of PD patients, and 10 controls underwent [123I]beta-CIT and SPECT brain imaging. Their striatal uptake ratios were compared.
Age-adjusted specific to nonspecific striatal uptake ratios were lower in patients compared with controls and with relatives; however, ratios were similar in relatives and controls. Among relatives, ratios were consistently lower in subgroups postulated to be at higher risk for preclinical PD.
Our findings provide preliminary support that [123I]beta-CIT and SPECT may detect decreased striatal uptake in relatives of PD patients postulated to be at higher risk for PD.
To determine the association between elevated levels of serum cancer antigen (CA) 125 and liver disease and to explore the possibility that CA 125 is produced by the peritoneum as a nonspecific response to the presence of fluid in the peritoneal cavity.
Between June and October 1992, CA 125 levels were measured in serum stored from 50 consecutive patients with cirrhotic ascites, 20 patients with cirrhosis but without ascites, and 12 patients with acute viral hepatitis without ascites. Serum CA 125 was also measured in 4 patients with chronic renal failure before and after initiation of continuous ambulatory peritoneal dialysis.
Levels of CA 125 were elevated in patients with all forms of liver disease, especially in those with cirrhotic ascites irrespective of the etiology of cirrhosis or the presence of spontaneous bacterial peritonitis or hepatocellular carcinoma. Levels of CA 125 did not change significantly 1 month after initiation of continuous ambulatory peritoneal dialysis.
Cancer antigen 125 is elevated in patients with acute and chronic liver disease, especially in those with cirrhotic ascites. This elevation in CA 125 is not because of a nonspecific response of the peritoneum to fluid in the peritoneal cavity. Awareness of the association of elevated CA 125 in patients with cirrhotic ascites can prevent unnecessary surgical intervention.
Pituitary glands obtained at autopsy of 125 women with disseminated breast carcinoma were studied to determine whether pituitary prolactin cell abnormalities (hyperplasia or adenoma) might be involved in the pathogenesis of breast carcinoma. In addition, we studied 85 pituitary glands obtained from unselected, consecutive autopsies in women without breast carcinoma but who died of other diseases (control group). The frequency of lactotroph hyperplasia was slightly higher in patients with breast carcinoma than in the control group, but the difference was not statistically significant, nor were differences in the frequency and size of pituitary adenomas, prolactin-producing or otherwise. No correlation was found between the presence of lactotroph hyperplasia or prolactin-producing adenomas (or both) and such factors as the patient's age, bilaterality of the carcinoma, previous treatment with tamoxifen citrate or oophorectomy, stage of disease, or survival. The frequency of breast carcinoma metastatic to the pituitary gland was higher in the study group than in the control group; however, the difference was not statistically significant. No preferential site of metastatic involvement in the pituitary gland was noted. Relative proportions of other lesions such as infarcts, cysts, lymphocytic infiltrates, and basophilic invasion were similar in the study and control groups. This study indicates that accumulation of prolactin cells, whether hyperplastic or adenomatous, cannot be considered a major risk factor for the genesis or progression of breast carcinoma.