Showing papers by "Mayo Clinic published in 1984"
TL;DR: The incidence and size of the patent foramen ovale were studied in 965 autopsy specimens of human hearts, which were from subjects who were evenly distributed by sex and age.
2,262 citations
TL;DR: Among 161 necropsy cases of aortic dissection, 87 (54%) were type I, 34 (21%) type II, and 40 (25%) type III, and an intimal tear was identified in each, and the major risk factors were systemic hypertension, the Marfan syndrome, and, for type I and II dissections, congenitally bicuspid or unicommissural aorti valves.
Abstract: Among 161 necropsy cases of aortic dissection, 87 (54%) were type I, 34 (21%) type II, and 40 (25%) type III, and an intimal tear was identified in each. Systemic hypertension had been present in 63 of 121 cases (52%) with type I or II dissection and in 30 of 40 (75%) with type III dissection. Aortic dissection involved 7 of 16 cases (44%) with the Marfan syndrome. In the 154 cases without the Marfan syndrome, grade 3 or 4 medial degeneration (cystic medial necrosis) was observed in the ascending aorta in only 27 (18%). The risk of aortic dissection in persons with congenitally bicuspid and unicommissural aortic valves, respectively, was 9 and 18 times that in subjects with tricuspid aortic valves. The mean age of those with aortic dissection and tricuspid, bicuspid and unicommissural aortic valves was 63, 55 and 40 years, respectively, and aortic dissection was more common in men than in women. Grade 3 or 4 atherosclerosis involved the intimal tear in only 11 of 121 type I or II dissections (9%) but 32 of 40 type III dissections (80%). Accordingly, the major risk factors for aortic dissection were systemic hypertension, the Marfan syndrome, and, for type I and II dissections, congenitally bicuspid or unicommissural aortic valves. Aortic medial degeneration was a less important risk factor. Rupture of ulcerocalcific aortic atheromas may have initiated the intimal tear in some type III dissections.
867 citations
TL;DR: T‐B, T‐T, and T‐macrophage cooperativities are likely to exist in muscle in different myopathies and T cell‐mediated fiber injury plays a role in polymyositis and inclusion body myositis.
Abstract: In 76 muscle specimens (normal controls, 9; Duchenne dystrophy, 11; scleroderma, 11; dermatomyositis, 13; polymyositis, 15; inclusion body myositis, 17), mononuclear cells were analyzed at perivascular, perimysial, and endomysial sites of accumulation. Monoclonal antibodies reactive for B cells, T cells, T cell subsets, killer (K) or natural killer (NK) cells, and the Ia antigen were used for cell typing. Macrophages were identified by the acid phosphatase reaction. Few extravascular mononuclear cells occurred in normal muscle. In all inflammatory myopathies, a mixed exudate of T cells, B cells, and macrophages was present. Mature K/NK cells were rare in all diseases. In dermatomyositis, polymyositis, and inclusion body myositis, there was a positive gradient for T cells, T8+ cells, and activated T cells and a negative gradient for B cells and T4+ cells between perivascular and endomysial sites. In scleroderma the predominant perimysial exudate consisted mostly of T cells and macrophages. The percentage of B cells at all sites, and the T4+/T cell ratio in the endomysium, were significantly higher in dermatomyositis than in the other diseases. In polymyositis and inclusion body myositis, the endomysial exudate contained a large number of T cells, T8+ cells, and activated T cells but only sparse B cells. T cells accompanied by macrophages focally surrounded and invaded nonnecrotic fibers in polymyositis and inclusion body myositis. Rare fibers in Duchenne dystrophy and a very few fibers in dermatomyositis and scleroderma were similarly affected. We infer that (1) T-B, T-T, and T-macrophage cooperativities are likely to exist in muscle in different myopathies; (2) T cell-mediated fiber injury plays a role in polymyositis and inclusion body myositis; (3) T cell-mediated fiber injury can also occur in inherited diseases, such as Duchenne dystrophy; and (4) a local humoral response may occur in muscle in dermatomyositis and possibly in polymyositis and inclusion body myositis.
602 citations
TL;DR: It is demonstrated that synthetic ANF results in a marked natriuretic response that is in part mediated by an increase in glomerular filtration rate, and the increase in fractional lithium and phosphate excretion suggests that this factor may also have an action on proximal tubule reabsorption.
Abstract: Studies were performed in anesthetized dogs (n = 5) to determine the effects of synthetic atrial natriuretic factor on renal function and renin release. Intrarenal infusion of synthetic atrial natriuretic factor (ANF) (0.3 microgram X kg-1 X min-1) resulted in a transient increase in renal blood flow (126 +/- 8 to 148 +/- 11 ml/min). The duration of this transient vasodilation was 3.1 +/- 0.4 min. Continued infusion was followed by a slight decrease in renal blood flow (126 +/- 8 to 117 +/- 8 ml/min) and an increase in glomerular filtration rate (23.1 +/- 3.5 to 30.7 +/- 1.9 ml/min), with filtration fraction thus being increased (0.19 +/- 0.04 to 0.27 +/- 0.03). These hemodynamic alterations were associated with increases in fractional sodium excretion (0.6 +/- 0.2 to 5.8 +/- 0.8%), fractional potassium excretion (30.8 +/- 9.4 to 56.3 +/- 7.4%), fractional lithium excretion (32.2 +/- 7.1 to 60.3 +/- 5.7%), and fractional phosphate excretion (8.7 +/- 3.5 to 41.6 +/- 11.7%). Intrarenal infusion of synthetic ANF markedly suppressed renin secretion rate (295.5 +/- 84.6 to 17.2 +/- 10.6 ng/min) despite a slight reduction in arterial pressure (123 +/- 9 to 118 +/- 9 mmHg). Our studies demonstrate that synthetic ANF results in a marked natriuretic response that is in part mediated by an increase in glomerular filtration rate. The increase in fractional lithium and phosphate excretion suggests that this factor may also have an action on proximal tubule reabsorption. Further, these studies demonstrate that synthetic ANF markedly inhibits renin secretion.
553 citations
TL;DR: It is believed that until the long-term effects in humans are known, polytef paste should not be used in children or young adults with normal life expectancy.
Abstract: Although patients with urinary incontinence have been treated successfully by periurethral injection of polytef paste, this study in continent animals demonstrates migration of polytef particles from the injection site. We injected polytef paste periurethrally into female dogs and male monkeys. Particles were found at 50 to 70 days in pelvic nodes in six of seven animals and lungs in four of seven (the kidneys and brain were not studied); and at 10 1/2 months in pelvic nodes, lungs, and brain in seven of seven; kidneys in four of seven; and spleen in two of seven. X-ray microanalysis confirmed that the particles were polytef. At 10% months, polytef granulomas were found at all injection sites and some sites of distant migration. Since these granulomas signify chronic foreign-body reaction, we believe that until the long-term effects in humans are known, polytef paste should not be used in children or young adults with normal life expectancy. (JAMA1984;251:3277-3281)
550 citations
TL;DR: Ki's for blocking uptake of norepinephrine, serotonin, and dopamine into synaptosomal preparations of rat brain were determined for 25 antidepressants and putative antidepressants, some neuroleptics, stimulants, antihistamines and other monoamines to compare the relative potencies of a drug at the three processes.
548 citations
TL;DR: The results show that dipyridamole and aspirin continue to be effective in preventing vein-graft occlusion late after operation, and it is believed that such treatment should be continued for at least one year.
Abstract: To study the prevention of occlusion of aortocoronary-artery bypass grafts, we concluded a prospective, randomized, double-blind trial comparing long-term administration of dipyridamole (begun two days before operation) plus aspirin (begun seven hours after operation) with placebo in 407 patients. Results at one month showed a reduction in the rate of graft occlusion in patients receiving dipyridamole and aspirin. At vein-graft angiography performed in 343 patients (84 per cent) 11 to 18 months (median, 12 months) after operation, 11 per cent of 478 vein-graft distal anastomoses were occluded in the treated group, and 25 per cent of 486 were occluded in the placebo group. The proportion of patients with one or more distal anastomoses occluded was 22 per cent of 171 patients in the treated group and 47 per cent of 172 in the placebo group. All grafts were patent within a month of operation in 94 patients in the placebo group and 116 patients in the treated group; late development of occlusions was reduced from 27 per cent in the placebo group to 16 per cent in the treatment group. The results show that dipyridamole and aspirin continue to be effective in preventing vein-graft occlusion late after operation, and we believe that such treatment should be continued for at least one year.
504 citations
TL;DR: It is suggested that estrogen deficiency, and not aging, may be the predominant cause of bone loss occurring during the first two decades after natural menopause.
Abstract: Debate continues on whether aging or estrogen deficiency is the more important determinant of postmenopausal bone loss. We compared 14 women who had undergone oophorectomy during young adulthood, 14 normal perimenopausal women, and 14 normal postmenopausal women (mean ages, 54, 52, and 73 years, respectively; mean duration of estrogen deficiency, 22, 0.3, and 22 years, respectively). Bone mineral density was assessed by single-photon and dual-photon absorptiometry. As compared with the perimenopausal group, the other two groups had significantly lower bone mineral density at the midradius, femoral neck, femoral intertrochanteric area, and lumbar spine (-15 per cent, -25 per cent, -16 per cent, and -23 per cent, respectively, in the oophorectomized group and -18 per cent, -28 per cent, -26 per cent, and -23 per cent, respectively, in the postmenopausal group). Because bone loss in the oophorectomized group (differing from the perimenopausal group in menopausal status but not in age) was almost as ...
503 citations
TL;DR: The records of all patients with abdominal aortic aneurysms in a Midwest city with a stable population over a 30-year period were reviewed, revealing an absolute increase in the incidence of AAAs in the population under study and the frequency of rupture was greatest in the last decade.
426 citations
TL;DR: The data show that proliferative keratinocytes can be growth arrested in medium that does not induce differentiation and that such a procedure significantly limits the cell's subsequent proliferative potential, suggesting that proliferation and differentiation are regulated in an integrated manner.
Abstract: The effects of growth factors, hormones, and calcium on the growth and differentiation of secondary cultures of normal human prokeratinocytes, i.e., proliferative keratinocytes, derived from adult or neonatal skin were determined by culture in serum-free basal medium, MCDB 153. Clonal growth was achieved when MCDB 153 was supplemented with either epidermal growth factor (EGF) or bovine pituitary extract (BPE), provided insulin was present. In the absence of insulin, however, both EGF and BPE were required for clonal growth. Using this assay, it was established that colony-forming efficiency is independent of calcium concentrations above 0.03 mM and averages 56%; colony size, however, was influenced by calcium and EGF concentrations. Optimal clonal growth occurred in medium containing 10 ng/ml EGF and 0.3 mM calcium. By contrast, differentiation was enhanced by the combination of low EGF (0.1 ng/ml) and high calcium (2 mM). This suggests that an inverse relationship exists between the growth response (extent of clonal growth) and the differentiation response (extent of differentiation). These results suggest that proliferation and differentiation are regulated in an integrated manner. Detailed kinetic studies and cytofluorimetric and autoradiographic analyses also showed that exponentially growing secondary cultures of adult and neonatal prokeratinocytes have a 24-hour cell generation time with G1, S, G2, and M phases of 12, 8, 3, and 1 hours, respectively. In addition, the data show that such cells can be growth arrested in medium that does not induce differentiation and that such a procedure significantly limits the cell's subsequent proliferative potential. Furthermore, prolonged culture of adult (greater than 30 population doublings) and neonatal prokeratinocytes (greater than 50 population doublings) is associated with senescence and the G1 arrest of noncycling cells.
420 citations
TL;DR: The results obtained in this neuropathy suggest that the reduction in nerve blood flow which occurs in experimental diabetic neuropathy is due largely to factors other than sugar-alcohol accumulation in nerve.
Abstract: Endoneurial hypoxia has been postulated to be important in the pathogenesis of diabetic peripheral neuropathy and may be due to reduced nerve blood flow. Neither blood flow nor oxygen tension have previously been measured in peripheral nerve in diabetic neuropathy. We have therefore measured both nerve blood flow and endoneurial oxygen tension in the sciatic nerves of 8 rats with streptozotocin-induced diabetes for four months, and in 8 age-matched controls. In 7 of the diabetic animals mean nerve blood flow was 8.7 +/- 1.3 ml X min-1 X 100 g-1 which is significantly less than mean nerve blood flow in the controls (13.08 +/- 0.8 ml X min-1 X 100 g-1; P less than 0.01). In one diabetic animal, nerve blood flow was too low to be accurately measured. The reduction in nerve blood flow in diabetic neuropathy is due to an increase in resistance to flow which may be due to microangiopathy and to blood hyperviscosity. Endoneurial oxygen tension was also significantly reduced in experimental diabetic neuropathy in which 60 per cent of the oxygen measurements were less than 25 mmHg, compared with 19 per cent in the controls. Nerve blood flow was also measured in rats with experimental galactose neuropathy in which there is more marked sugar-alcohol accumulation, endoneurial oedema and elevation of endoneurial fluid pressure than in experimental diabetic neuropathy. The results obtained in this neuropathy suggest that the reduction in nerve blood flow which occurs in experimental diabetic neuropathy is due largely to factors other than sugar-alcohol accumulation in nerve. We postulate that endoneurial hypoxia may produce many of the observed morphological and biochemical changes in experimental diabetic neuropathy.
TL;DR: The prevalence of EBV and CMV infections in AIDS and the chronic lymphadenopathy syndrome may be the result of an important interaction between these viruses and the cause of AIDS.
Abstract: Herpesvirus infections were studied in persons with or at risk for the acquired immune deficiency syndrome (AIDS). The infections diagnosed were as follows: patients with AIDS, cytomegalovirus (CMV) in 34 of 34, Epstein-Barr virus (EBV) in 33 of 34, herpes simplex viruses (HSV) in eight of 34, and varicella zoster virus in four of 34; patients with chronic lymphadenopathy syndrome, CMV in eight of nine and EBV in nine of nine; in healthy homosexual men, CMV in five of 13 and EBV in seven of eight. Cytomegalovirus infections were frequently related to disease and death. Herpesvirus infections are frequent causes of serious diseases in AIDS. The prevalence of EBV and CMV infections in AIDS and the chronic lymphadenopathy syndrome may be the result of an important interaction between these viruses and the cause of AIDS. ( JAMA 1984;252:72-77)
TL;DR: Tumor size was inversely related to prognosis and was strongly associated with stage, and pathologic staging based on depth of tumor invasion and regional nodal involvement was strongly predictive of survival.
Abstract: Among 188 patients presenting with carcinoma of the anal canal the predominant cell types were squamous cell (56%) and nonkeratinizing basaloid (35%). Thirteen patients who had predominantly small (less than or equal to 2 cm) and only superficially invasive squamous cell lesions were treated with local excision, and although one required later abdominal perineal (AP) resection for local recurrence, all were apparently cured. Local excision should be preferred as initial treatment for such lesions. One hundred eighteen patients with squamous cell and nonkeratinizing basaloid carcinomas were primarily treated with AP resection. The operative mortality rate was 2.5%. Among 114 patients who survived surgery and had adequate follow-up, 40% developed recurrent disease, and 71% have survived 5 or more years. Pathologic staging based on depth of tumor invasion and regional nodal involvement was strongly predictive of survival as was tumor histology with progressively poorer survival rates from low-grade squamous cell to high-grade squamous cell to nonkeratinizing basaloid types. Tumor size was inversely related to prognosis and was strongly associated with stage. Squamous cell anal carcinoma was dominantly a local disease with approximately 70% of patients presenting with tumor apparently limited to the bowel wall, only 20% with regional node involvement and only 2% with distant metastasis. Even among those patients who recurred after AP resection approximately 80% had all known disease still limited to the pelvic area. Corresponding figures for nonkeratinizing basaloid tumors were 50 percent presenting limited to the bowel wall, 30% with regional nodes, 20% with distant metastasis, and 60% with initial recurrence limited to the pelvis. Among the 13 patients studied with small cell anal carcinoma, the authors found the disease to be very virulent either initially presenting with or rapidly evolving into diffuse dissemination. Only one of the seven patients who could be treated surgically survived 5 years. As is true for small cell carcinomas primary to other sites, this neoplasm should be regarded as a systemic disease. With these findings as a foundation, possible future strategies for management of anal carcinoma are discussed.
TL;DR: There was no significant difference in overall rate of recurrence among the various cell types, and lung cancer survival (Kaplan-Meier) was 69.1% at 5 years and 61.9% at 9 years.
TL;DR: Early hyperreactivity was related to future hypertension in enough subjects to suggest that an abnormal response to an external cold stimulus may be useful as an indicator of future hypertension.
Abstract: To determine the usefulness of the cold pressor test as a predictor of hypertension, we compared the blood pressure recordings available from 142 patients in 1979 with readings obtained during performance of two cold pressor tests, the first in 1934 when these subjects were children, and the second in 1961. Forty-eight subjects were hyperreactors to the tests in either 1934 or 1961, and 94 were normoreactors. At last follow-up, blood pressures in 14 of the hyperreactors were between 140 and 160 mm Hg systolic or 90 and 100 mm Hg diastolic (Stratum 1) and in 20 exceeded 160 mm Hg systolic or 100 mm Hg diastolic (Stratum 2). Ten normoreactors had casual blood pressures in Stratum 1 and eight in Stratum 2. Hypertension had thus occurred in 71% of the hyperreactors and 19% of the normoreactors. Fifteen hyperreactors were receiving antihypertensive therapy, and this reduced the severity of the casual blood pressure elevation in most patients to Stratum 1. Antihypertensive therapy had been started in three normoreactors. The duration of follow-up, 45 years, and the mean age at follow-up, almost 57 years, were greater in this study than in any previously reported study. Early hyperreactivity was related to future hypertension in enough subjects to suggest that an abnormal response to an external cold stimulus may be useful as an indicator of future hypertension.
TL;DR: Several experimental techniques, including geometric measurement, tendon-joint displacement measurement and direct load measurement, are available for the determination of orientation and moment arms of the muscles about a joint.
Abstract: In muscle force analysis, orientations and moment arms of the muscles about a joint provide essential coefficients in the equilibrium equations. For the determination of these parameters, several experimental techniques, including geometric measurement, tendon-joint displacement measurement and direct load measurement, are available. Advantages and disadvantages associated with each of the techniques are reviewed and compared based on our extensive experience.
TL;DR: It is concluded that an impaired ability of the aging kidney to synthesize 1,25(OH)2D could contribute to the pathogenesis of senile osteoporosis.
Abstract: Calcium absorption decreases with aging, particularly after age 70 yr. We investigated the possibility that this was due to abnormal vitamin D metabolism by studying 10 normal premenopausal women (group A), 8 normal postmenopausal women within 20 yr of menopause (group B), 10 normal elderly women (group C), and 8 elderly women with hip fracture (group D) whose ages (mean +/- SD) were 37 +/- 4, 61 +/- 6, 78 +/- 4, and 78 +/- 4 yr, respectively. For all subjects, serum 25-hydroxyvitamin D [25(OH)D] did not decrease with age, but serum 1,25-dihydroxyvitamin D [1,25(OH)2D], the physiologically active vitamin D metabolite, was lower (P = 0.01) in the elderly (groups C and D; 20 +/- 3 pg/ml) than in the nonelderly (groups A and B; 35 +/- 4 pg/ml). The increase of serum 1,25(OH)D after a 24-h infusion of bovine parathyroid hormone fragment 1-34, a tropic agent for the enzyme 25(OH)D 1 alpha-hydroxylase, correlated inversely with age (r = -0.58; P less than 0.001) and directly with glomerular filtration rate (r = 0.64; P less than 0.001). The response was more blunted (P = 0.01) in elderly patients with hip fracture (13 +/- 3 pg/ml) than in elderly controls (25 +/- 3 pg/ml). We conclude that an impaired ability of the aging kidney to synthesize 1,25(OH)2D could contribute to the pathogenesis of senile osteoporosis.
TL;DR: An epidemiological study of parkinsonism over a 13-year period is presented, updating previous reports on incidence and trend in the population of Rochester, Minnesota, which revealed no remarkable change following the 1976 swine flu vaccination program.
Abstract: An epidemiological study of parkinsonism over a 13-year period (1967 through 1979) is presented, updating previous reports on incidence and trend in the population of Rochester, Minnesota. The overall average annual incidence of parkinsonism per 100,000 population was 20.5, adjusted to the 1970 total United States population, which is virtually unchanged from previous observations. Incidences calculated for each calendar year (1967 through 1979) revealed no remarkable change following the 1976 swine flu vaccination program. There was no sex difference and the peak incidence occurred between ages 75 and 84 years. Idiopathic Parkinson's disease was the most common variant (86%), followed by drug-induced parkinsonism (7%). There were no new cases of postencephalitic parkinsonism diagnosed during the study period. Relative frequency of other types of Parkinson's disease as identified by practicing neurologists is presented. For each case two age- and sex-matched controls were selected from the Rochester population. The survival rates in the controls were comparable to the general population of the west north central region of the United States. The mortalities in the patients were significantly higher (p = 0.001) than the controls and were unchanged from previous rates reported from the same community. In the 69 (50%) patients treated with levodopa, the mortality was comparable to that in controls. The favorable outcome in these cases is attributed to bias resulting from selection of healthier patients for treatment.
TL;DR: An alternative procedure is proposed that offers a good opportunity for early termination when initial results are extreme, while essentially maintaining the power provided by the procedure that applies when the corresponding test statistic is computed only at the predetermined time of final analysis.
TL;DR: Young patients treated for a first-time anterior glenohumeral dislocation in Olmsted County, Minnesota, from 1970 through 1979 were identified and advised immobilization for from 3 to 6 weeks, followed by extensive rehabilitation before return to athletic activity.
Abstract: All patients treated for a first-time anterior glenohumeral dislocation in Olmsted County, Minnesota, from 1970 through 1979 were identified. Of these 124 patients, 116 were available for study at a mean followup of 4.63 years (range 2 to 11). Of the 116 patients, 38 (33%) had recurrence of dislocation: 21 of the 32 (66%) patients less than 20 years old, 17 of the 43 (40%) patients 20 through 40 years old, and none of the 41 patients older than 40 years. Symptomatic instability remained a problem in 24 patients. Twenty-seven of 33 (82%) young athletes had recurrence of dislocation as compared with only 8 of 27 (30%) nonathletes of similar ages. Patients restricted from resuming sports participation for 6 weeks or more had significantly better results than those restricted for less than 6 weeks. The recurrence rate of dislocation is not as high as previously reported. However, the rate in athletes is much higher than that in nonathletes. Many patients continue to complain of symptomatic instability without actual redislocation. In our younger patients, we now advise immobilization for from 3 to 6 weeks, followed by extensive rehabilitation before return to athletic activity.
TL;DR: Recurrent attacks of angioedema, urticaria, and fever with eosinophils localized and degranulated in the dermis, and they appeared to induce edema are believed to be a separate entity.
Abstract: We studied four patients with recurrent attacks of angioedema, urticaria, and fever. During attacks, body weights increased up to 18 per cent, and leukocyte counts reached 108,000 per microliter (88 per cent eosinophils). The disease did not appear to threaten the function of vital organs. The two children received prednisone intermittently; the adults did not require treatment or were given alternate-day prednisone. Glucocorticoid therapy caused defervescence and diuresis and decreased total leukocyte and eosinophil counts. No patient had evidence of cardiac involvement (follow-up, 2 to 17 years). One patient remained in spontaneous remission for 20 years before symptoms recurred. Histologic studies showed that eosinophils localized and degranulated in the dermis, and they appeared to induce edema. Although this syndrome might be classified as a variant of the hypereosinophilic syndrome, we believe it is a separate entity because of its distinctive characteristics and its benign course.
TL;DR: In polymyositis and inclusion body myositis, nonnecrotic muscle fibers are injured by autoinvasive T8+ cells that act in concert with macrophages, which strongly imply previous sensitization of clones of T cells to muscle fiber—associated surface antigen(s).
Abstract: In 6 cases of polymyositis and 6 of inclusion body myositis, phenotypes of mononuclear cells focally surrounding and invading muscle fibers were analyzed. By localizing the T8, T4, and Ia markers with direct immunofluorescence and acid phosphatase enzyme cytochemically in the same sections, five different phenotypes were simultaneously identified in a given section: T8+ and T4+ cells that were either activated (Ia+) or not activated (Ia-), and acid phosphatase--reactive and Ia+ macrophages. This approach permitted the separate and quantitative assessment of the distributions of the different phenotypes among the invading versus the surrounding cells. In both polymyositis and inclusion body myositis, the invading cells were selectively enriched in the T8+ phenotype. One-third of all invading cells and one-half of the invading T8+ cells were activated. T4+ cells were more abundant among the surrounding than the invading cells, and only a small proportion of the T4+ cells were activated. These findings are especially significant in view of the cytotoxic capability of the T8+ cells and because histocompatibility factors permit T8+ but not T4+ cells to recognize an antigen on muscle fibers. Macrophages accounted for 21 to 31% of the cells invading or surrounding nonnecrotic fibers. For purposes of comparison, we also analyzed mononuclear cells in necrotic fibers: 80% of these cells were macrophages, and only 20% were T cells. The findings indicate that in polymyositis and inclusion body myositis, nonnecrotic muscle fibers are injured by autoinvasive T8+ cells that act in concert with macrophages. Further, the findings strongly imply previous sensitization of clones of T cells to muscle fiber-associated surface antigen(s).
Journal Article•
TL;DR: At the human brain histamines H1 receptor, antidepressants remained among the most potent histamine H1 antagonists known, although their affinities for human receptors were lower than those for animal receptors.
Abstract: Using radioligand binding techniques, we determined the equilibrium dissociation constants (KDS) for a series of antidepressants at the histamine H1, muscarinic acetylcholine, alpha-1 and alpha-2 adrenergic and dopamine (D-2) receptors of normal human brain tissue obtained at autopsy. Twenty-five different antidepressants were studied at all but the D-2 receptor at which the number was 13 (including a metabolite of an antidepressant). Of all the receptor interactions studied, that at the histamine H1 receptor was in general the most potent interaction of this class of compounds, corresponding to results from studies using animal tissue as the source of receptors. At the human brain histamine H1 receptor, antidepressants remained among the most potent histamine H1 antagonists known, although their affinities for human receptors were lower than those for animal receptors. The most potent and the least potent compounds at the receptors were doxepin (KD = 0.24 nM) and fluvoxamine (KD = 109 microM) at the histamine H1 receptor, amitriptyline (KD = 18 nM) and trazodone (KD = 324 microM) at the muscarinic receptor, doxepin (KD = 24 nM) and viloxazine (KD = 14 microM) at the alpha-1 receptor, mianserin (KD = 73 nM) and bupropion (KD = 81 microM) at the alpha-2 receptor and amoxapine (KD = 160 nM) and trazodone (KD = 3800 nM) at the D-2 receptor, respectively. In general, compared to older drugs, the newer compounds tended to have lower affinities for these receptors.
TL;DR: A fine structural analysis ofLewy body-like hyaline inclusions in the soma and swollen, cord-like cell processes are characteristic alterations of the anterior horn cells in familial amyotrophic lateral sclerosis with posterior column and spinocerebellar tract involvement.
Abstract: Lewy body-like hyaline inclusions in the soma and swollen, cord-like cell processes are characteristic alterations of the anterior horn cells in familial amyotrophic lateral sclerosis (ALS) with posterior column and spinocerebellar tract involvement. A fine structural analysis of these two structures has been performed in two brothers from a family ("C" family) previously described by Kurland and Mulder in 1955. The perikaryal hyaline inclusions consisted of accumulations of randomly oriented neurofilaments interspersed with thick linear densities associated with granular material. Some of the accumulations showed a central condensation. Cord-like, swollen neuronal processes were composed, for the most part, of numerous neurofilaments arranged parallel to the long axes. Dense structures were sometimes observed within the large bundles of filaments. They were composed of ill-defined dense, granular and fibrillar material associated with scattered vesicles and mitochondria. These dense areas were sometimes surrounded by various amounts of fine filaments, approximately 5 nm in diameter.
TL;DR: The passive transfer of high levels of anti-type II collagen antibody from mice with type II collagen-induced arthritis may transfer arthritis to syngeneic recipient animals, but the transfer of either arthritogenic or sub-arthritogenic doses of polyclonal anti-types II collagen antibodies may protect mice against the subsequent induction of arthritis by type II gelatin.
Abstract: The passive transfer of high levels of anti-type II collagen antibody from mice with type II collagen-induced arthritis may transfer arthritis to syngeneic recipient animals. However, the transfer of either arthritogenic or sub-arthritogenic doses of polyclonal anti-type II collagen antibody, or non-arthritogenic monoclonal anti-type II collagen antibody may protect mice against the subsequent induction of arthritis by type II collagen. A protective effect was also observed in mice given free native type II collagen intravenously before the administration of collagen in an arthritogenic protocol.
TL;DR: While the majority of patients exhibited the expected reduction in antral pressure activity and gastric phase III, a small subgroup of three patients exhibited a peculiar continuous 3 min‐1 antral contractile activity.
Abstract: . Gastroparesis syndrome is a recognized complication of longstanding diabetes mellitus and is attributed to reduced gastric contractility due to ‘autovagotomy’. However, motor abnormalities associated with this syndrome may not be limited to the stomach. To test this hypothesis we have studied the fasting and fed manometric profiles of the proximal small intestine of fourteen patients with the clinical diagnosis of gastroparesis. Abnormal intestinal manometric patterns were observed in twelve out of the fourteen patients. In four patients there was reduced duodenojejunal phasic pressure activity, whereas in nine there were non-propagated long bursts of powerful contractions. Furthermore, while the majority of patients (eleven out of fourteen) exhibited the expected reduction in antral pressure activity and gastric phase III, a small subgroup of three patients exhibited a peculiar continuous 3 min-1 antral contractile activity.
Our findings show that the small intestine is frequently affected in patients with diabetic gastroparesis, and that the motility disorder both in the stomach and the small bowel is not invariably of a ‘paretic’ type. The occurrence of incoordinated intestinal long bursts and continuous antral activity suggests that disturbed sympathetic innervation participates in the aetiopathogenesis of their upper-gut dysfunction.
TL;DR: The incidence of osteoporotic fractures in patients who have been diagnosed as having rheumatoid arthritis was found to be increased, though not dramatically so: the relative risk for hip fracture, for example, was 1.5.
Abstract: In a population-based study, the incidence of osteoporotic fractures in patients who have been diagnosed as having rheumatoid arthritis was investigated. This incidence was found to be increased, though not dramatically so: the relative risk for hip fracture, for example, was 1.5. Univariate analyses generally indicated increased risk associated with increasing age, earlier age at diagnosis of rheumatoid arthritis, disability, impaired ambulation, steroid use, and thinness, and decreased risk associated with obesity and estrogen use. In multivariate analyses, only aging, impaired ambulation, and thinness were identified as independent risk factors.
TL;DR: An increase in Plasma cortisol within the physiologic range increases proteolysis and the de novo synthesis of alanine, a potential gluconeogenic substrate, and physiologic changes in plasma cortisol play a role in the regulation of whole body protein and amino acid metabolism in man.
Abstract: Prolonged exposure to glucocorticoids in pharmacologic amounts results in muscle wasting, but whether changes in plasma cortisol within the physiologic range affect amino acid and protein metabolism in man has not been determined. To determine whether a physiologic increase in plasma cortisol increases proteolysis and the de novo synthesis of alanine, seven normal subjects were studied on two occasions during an 8-h infusion of either hydrocortisone sodium succinate (2 micrograms/kg X min) or saline. The rate of appearance (Ra) of leucine and alanine were estimated using [2H3]leucine and [2H3]alanine. In addition, the Ra of leucine nitrogen and the rate of transfer of leucine nitrogen to alanine were estimated using [15N]leucine. Plasma cortisol increased (10 +/- 1 to 42 +/- 4 micrograms/dl) during cortisol infusion and decreased (14 +/- 2 to 10 +/- 2 micrograms/dl) during saline infusion. No change was observed in plasma insulin, C-peptide, or glucagon during either saline or cortisol infusion. Plasma leucine concentration increased more (P less than 0.05) during cortisol infusion (120 +/- 1 to 203 +/- 21 microM) than saline (118 +/- 8 to 154 +/- 4 microM) as a result of a greater (P less than 0.01) increase in its Ra during cortisol infusion (1.47 +/- 0.08 to 1.81 +/- 0.08 mumol/kg X min for cortisol vs. 1.50 +/- 0.08 to 1.57 +/- 0.09 mumol/kg X min). Leucine nitrogen Ra increased (P less than 0.01) from 2.35 +/- 0.12 to 3.46 +/- 0.24 mumol/kg X min, but less so (P less than 0.05) during saline infusion (2.43 +/- 0.17 to 2.84 +/- 0.15 mumol/kg X min, P less than 0.01). Alanine Ra increased (P less than 0.05) during cortisol infusion but remained constant during saline infusion. During cortisol, but not during saline infusion, the rate and percentage of leucine nitrogen going to alanine increased (P less than 0.05). Thus, an increase in plasma cortisol within the physiologic range increases proteolysis and the de novo synthesis of alanine, a potential gluconeogenic substrate. Therefore, physiologic changes in plasma cortisol play a role in the regulation of whole body protein and amino acid metabolism in man.
TL;DR: It is demonstrated that the endothelial cells mediate relaxation induced by vasopressin via specific Vi-vasopressedinergic receptors.
Abstract: The effect of synthetic 8-arginine vasopressin (vasopressin) was studied in isolated canine basilar, left circumflex coronary, and femoral arteries of the dog. Vascular rings with and without endothelium were suspended for isometric tension recording in physiological salt solution. The removal of the endothelium was confirmed by the absence of relaxations induced by either thrombin (basilar arteries) or acetylcholine (coronary and femoral arteries). In the basilar artery, vasopressin induced concentration-dependent inhibition of myogenic tone. In basilar and coronary arteries, the hormone caused concentration-dependent relaxations during contractions evoked by prostaglandin F2 alpha. In femoral arteries, vasopressin caused contraction. After removal of the endothelium, the inhibitory responses to vasopressin were abolished in basilar arteries and significantly reduced in left circumflex coronary arteries. The contractions of femoral arteries were not affected by endothelium removal. The V1-vasopressinergic antagonist d(CH2)5Tyr(Me)AVP prevented the inhibitory response to vasopressin, but did not alter endothelium-dependent relaxations of basilar arteries caused by adenosine diphosphate. These results demonstrate that the endothelial cells mediate relaxation induced by vasopressin via specific V1-vasopressinergic receptors.