Therapy for disseminated coccidioidomycosis with transfer factor from a related donor

A 17 year old Caucasian woman in whom disseminated coccidioidomycosis developed with culture positive meningitis during her third trimester of pregnancy was treated with amphotericin B and subsequently with transfer factor prepared from her father's peripheral lymphocytes. Clinical response and in vivo and in vitro immunologic data indicated that this transfer factor afforded a significant contribution to her survival whereas previous therapy with transfer factor from an unrelated donor provided only transient immunologic reactivity. This experience suggests that transfer factor prepared from a related donor with positive responses to C. immitis may be more efficacious than that prepared from an unrelated donor.     

Echocardiographic recognition of atrioventricular valve stenosis associated with endocardial cushion defect: Pathologic and surgical correlates

The association of either mitral or tricuspid stenosis with endocardial cushion defects has been well recognized pathologically but is infrequently diagnosed clinically. M mode echocardiographic features such as markedly disproportionate ventricular size, abnormal mitral or tricuspid diastolic echoes or failure to define adequately an atrioventricular (A-V) valve are strongly suggestive of associated stenosis of that valve. In this study mitral stenosis in association with endocardial cushion defect was correctly diagnosed in four of five patients. In the fifth patient (the first seen) the condition was easily diagnosed retrospectively. Tricuspid stenosis was similarly diagnosed prospectively in three of four patients. Significant stenosis was not overlooked or misdiagnosed in any patient with an endocardial cushion defect.

Significant stenosis of an A-V valve in association with endocardial cushion defect carries a high mortality. It is important to recognize the combined lesion clinically because infants with it are not suitable for total surgical correction. Palliative surgical procedures with aggressive medical therapy probably offer the infant the best chance of surviving until ventricular growth may render corrective surgery feasible.     

Diabetic neuropathy and plasma glucose control

Diabetic neuropathy is defined, and theories of its pathogenesis are reviewed. Recent studies designed to investigate the influence of plasma glucose on nerve function in noninsulin-dependent diabetic patients are summarized. Motor nerve conduction velocities in the median and peroneal nerves were measured using a double-stimulus technique, and sensory conduction velocity was measured by conventional methods before and after therapy with oral agents or insulin. The degree of hyperglycemia was assessed by measurement of fasting plasma glucose and glycosylated hemoglobin concentrations. The degree of slowing in motor nerve conduction velocity in untreated patients was found to correlate with the fasting plasma glucose and glycosylated hemoglobin concentrations, but sensory nerve function, although abnormal, did not show such correlation. Reduction of hyperglycemia was associated with improvement in motor nerve conduction velocity in the peroneal and median motor nerves of these patients, but sensory nerve conduction velocity showed no such improvement. Improvement in median motor nerve conduction velocity was directly related to the degree of reduction in fasting plasma glucose concentration. These findings suggest that metabolic factors related to hyperglycemia are important in the impaired motor nerve function seen in noninsulin-dependent patients with maturity-onset diabetes.     

Pooled analyses of randomized trials of streptokinase and heparin in phlebographically documented acute deep venous thrombosis

Although thrombolysis with streptokinase has been compared with heparin anticoagulation for treating acute proximal deep venous thrombosis in several randomized trials, no individual study has had a sample of sufficient size to determine with adequate power both efficacy and safety. Therefore, results were pooled from six randomized studies in which phlebography was used to confirm the diagnosis and to assess therapy. Thrombolysis was achieved 3.7 times more often among patients treated with streptokinase than among patients treated with heparin (95 percent confidence limits 2.5, 5.7; p less than 0.0001). Only three studies allowed comparison of these drugs for major bleeding complications, which were 2.9 times greater with streptokinase than with heparin (95 percent confidence limits 1.1, 8.1; p = 0.04). Thus, in aggregate, streptokinase-treated patients achieved thrombolysis but also seemed to experience major bleeding complications more frequently than those assigned at random to receive heparin. Future trials of sufficient sample size should be undertaken to evaluate efficacy and safety. Such trials, which should include newer fibrinolytic agents, are necessary to determine optimal therapy for acute proximal deep venous thrombosis.     

Pseudo-Gaucher cells in multiple myeloma.

A bone biopsy specimen from a patient with multiple myeloma showed numerous Gaucher-like cells scattered throughout a homogeneous background of plasma cells. Further studies using histochemical stains, immunofluorescence, and light and electron microscopy were carried out to further define these cells. Light microscopy of Wright-stained and hematoxylin and eosin-stained marrow preparations showed large, round cells with fibrillar appearing cytoplasm and eccentric, pyknotic nuclei. These cells were periodic acid-Schiff positive, resistant to diastase digestion. Electron microscopy demonstrated plasma cells containing crystals in membrane-bound vesicles. Also, large macrophages among these plasma cells contained similar crystals surrounded by a single limiting membrane. Immunofluorescence staining of thin sections of marrow with fluorescein-labelled specific antiserums showed fluorescence of these large cells. Strong immunofluorescence was seen with polyvalent kappa and gamma antiserums but not with anti-albumin or serums with anti-lambda, mu or alpha specificity. It appears that these large cells have the light microscopic and histochemical characteristics of true Gaucher cells but, when studied with immunofluorescence and electron microscopy, it appears that the pseudo-Gaucher cells of multiple myeloma are bone marrow macrophages engorged with immunoglobulin.     

The genetics of the glucose intolerance disorders

Genetic heterogeneity, the concept that diabetes can have many different causes, was first suggested by the existence of rare genetic syndromes with diabetes, ethnic differences in clinical features and genetic heterogeneity of animal models. Genetic heterogeneity is now considered to be firmly established by family, twin, metabolic, immunologic and HLA disease association studies that separate idiopathic diabetes into insulin-dependent types (juvenile-onset type) and noninsulin-dependent types (maturity-onset type). Further heterogeneity is being demonstrated within each of these broad groups of disorders—within insulin-dependent diabetes using the HLA antigens and immunologic studies, and within noninsulindependent diabetes using such criteria as obesity, insulin response, age of onset and chlorpropamide-primed alcohol-induced flushing. This heterogeneity has major implications for the research and care of our diabetic patients since the precise etiology, risk of complications and genetic counseling are likely to vary among these different disorders that result in diabetes.     

Familial recurrent rhabdomyolysis due to carnitine palmityl transferase deficiency.

Muscle carnitine palmityltransferase (CPT) activity was very low (0 to 14 per cent of controls) in two brothers with a syndrome of recurrent rhabdomyolysis and myoglobulinuria. In isolated muscle mitochondria the majority (87.5 per cent) of total measurable CPT enzyme activity could be attributed to external membrane CPT with severe deficiency of inner membrane CPT. By contrast, control mitochondria demonstrated a 1:1 distribution of external membrane CPT to inner membrane CPT. Thus, myoglobinuria may be due to a genetic defect of lipid metabolism in skeletal muscle, with inner membrane CPT deficiency presenting the same clinical features as external membrane CPT deficiency.     

Protected environment-prophylactic antibiotic program for malignant lymphoma. Randomized trial during chemotherapy to induce remission.

Fifty-eight patients with malignant lymphoma were randomly allocated to receive three courses of chemotherapy to induce remission with CHOP-Bleo on the protected environment-prophylactic antibiotic (PEPA) program (30 patients) or as controls (28 patients). The complete remission rate for all patients was 74 per cent, for patients with diffuse histiocytic lymphoma 78 per cent and for patients with nodular poorly differentiated lymphocytic lymphoma 65 per cent. There were no significant differences in response rates and duration of responses between those on the PEPA program and control patients. The frequency of infection was significantly lower among the patients on the PEPA program, and dosage escalation of the chemotherapeutic agents was accomplished more often among these patients. Dosage escalation did not increase the complete remission rate, but it did reduce the relapse rate and signficantly reduced the fatality rate. The duration of remission and survival was significantly longer for those patients who received dosage escalation.     

Epidemic viral gastroenteritis.

Epidemic viral gastroenteritis is a significant world wide problem. In developed countries, gastroenteritis accounts for significant morbidity and loss of time from work; in the Third World it is the leading cause of mortality among infants and children. Recent technologic advances have been associated with an explosion of research activity. Two virus groups, the Norwalk-like agents and the rotaviruses, are currently accepted as causative agents of viral gastroenteritis in man. The problem of viral gastroenteritis is reviewed both from a current and a historic perspective.     

Multiple adenocarcinomas and premalignant changes in "backwash" ileitis.

In a patient with long-staning ulcerative colitis and "backwash" ileitis, multiple carcinomas developed in the colon and ileum. In both locations premalignant mucosal changes of the basal cell proliferation type were seen adjacent to and remote from sites of carcinoma. Although the frequency of such premalignant and malignant changes in "backwash" ileitis is unknown, their concurrence in this case suggests that ulcerative colitis involving the terminal ileum increases the risk of small bowel carcinoma.     

Idiopathic thrombocytopenic purpura

Idiopathic thrombocytopenic purpura occurs at all ages, in acute and chronic forms. Children mainly have the acute form, which usually follows a recent viral illness, occurs equally in both sexes, and generally resolves within six months. Chronic idiopathic thrombocytopenic purpura occurs more often in adults, often has an insidious onset, and shows a three:one female preponderance. Both forms are now thought to be due to an antiplatelet antibody, usually of the IgG class (platelet-associated IgG), which coats autologous platelets and leads to their phagocytosis and destruction by the reticuloendothelial system. In most patients, the spleen is the major site of the production of this platelet antibody and the destruction of the platelets. Many methods have been developed to detect this antiplatelet factor in the serum and on the platelets of patients with idiopathic thrombocytopenic purpura. Recent methods are becoming highly sensitive and may soon be simple and fast enough for routine clinical use and should significantly aid the diagnosis and management of these patients. Platelet-associated IgG levels appear significantly higher in patients with idiopathic thrombocytopenic purpura than in normal subjects, and in patients with nonimmune thrombocytopenia. Higher levels are also seen in children than in adults, and in acute cases than in chronic ones. Platelet-associated IgG levels also vary inversely with platelet count and platelet life span, can predict the disease course and response to therapy, and may predict neonatal consequences of maternal idiopathic thrombocytopenic purpura. Evidence of other alterations in immune status, as well as alterations in platelet function and HLA associations, remains controversial. Classic treatment with corticosteroids and splenectomy remains highly successful in most cases. More recent therapies include the use of immunosuppressants and alkaloid-coated platelets, plasma-exchange transfusion, and high-dose immunoglobulin. Overall, fewer than 5 percent of patients have severe hemorrhage or refractory or fatal disease.     

Radioiodine-induced thyroid storm. Case report and literature review

Thyroid storm developed following radioiodine therapy in a 43-year-old man with Graves' disease, weight loss, myopathy, severe thyrotoxic hypercalcemia, and a pituitary adenoma. The hypercalcemia may have been a significant, and previously unreported, predisposing factor for the radioiodine-associated thyroid storm. This case and 15 other well-documented cases of radioiodine-associated storm found in the literature are reviewed, as are several other cases of less severe exacerbations of thyrotoxicosis associated with radioiodine therapy. Although not often seen, these complications are often fatal. High-risk patients, such as the elderly, those with severe thyrotoxicosis, and those with significant underlying diseases, may benefit from preventive measures such as the judicious use of thyrostatic medications during the periods before and after isotope administration.     

Skeletal responsiveness in pseudohypoparathyroidism. A spectrum of clinical disease

Three cases of pseudohypoparathyroidism with roentgenographic evidence of hyperparathyroid bone disease are described. Renal resistance to exogenous parathyroid hormone (PTH), the hallmark of pseudohypoparathyroidism, was documented by markedly blunted or absent urinary phosphate and cyclic AMP responses to parathyroid extract. At the time of diagnosis all patients were hypocalcemic and hyperphosphatemic with elevated serum alkaline phosphatase levels and subperiosteal resorption noted on skeletal films. Bone biopsy in one patient revealed a histologic appearance consistent with hyperparathyroidism. Serum PTH levels, measured in two patients while they were hypocalcemic, were elevated. None of the patients had short stature, brachydactyly, subcutaneous calcification or mental deficiency. These cases are compared to the 15 well-documented cases previously reported. The presently available information on pseudohypoparathyroidism indicates a variable skeletal response to PTH mediated by several factors extrinsic to bone and suggests that pseudohypoparathyroidism with hyperparathyroid bone disease is one extreme of a clinical spectrum of skeletal responsiveness to PTH. This disorder is part of an expanding clinical picture which makes pseudohypoparathyroidism a diagnostic consideration in any patient with unexplained hypocalcemia, hyperphosphatemia, elevated alkaline phosphatase levels or metabolic bone disease.     

Plasmapheresis and immunosuppressive agents in antibasement membrane antibody-induced Goodpasture's syndrome

Four patients with rapidly progressive glomerulonephritis and pulmonary hemorrhage (Goodpasture's syndrome) induced by circulating anti-glomerular basement membrane (GBM) antibodies were treated with immunosuppressive agents and varying amounts of plasma exchange. All four patients showed progressive decreases in circulating anti-GBM antibody during therapy. Two patients with established renal failure before therapy showed no improvement in renal function but had a remission from pulmonary disease. In two other patients, renal failure developed early in the course of therapy and required maintenance hemodialysis. Later, their renal function improved coincident with a decrease in circulating anti-GBM antibody. Aggressive measures to reduce the levels of circulating anti-GBM antibody may have a salutory effect on the clinical course of the disease, particularly when undertaken early.     

Focal segmental glomerulosclerosis

Renal and hepatic function were studied in 20 patients with cirrhosis and ascites, before and during infusion of prostaglandin A₁ (PG-A₁), and in 7 patients during infusion of furosemide, with and without PG-A₁. Liver function was evaluated by using 10 clinically related criteria to determine a liver function profile. A significant negative correlation was found between the liver function profile and both glomerular filtration rate (GFR) (r = ?0.74, p < 0.01) and effective renal plasma flow (ERPF) (r = ?0.71, p < 0.01). Patients were then grouped according to their ERPF: Group I (450 ml/min), group II (150 to 450 ml/min) and group III (< 150 ml/min). During PG-A₁ infusion, ERPF increased significantly only in groups I and II, by (±SE) 138 ± 67 ml/min and 131 ± 40 ml/ min, respectively. The GFR and sodium excretion also increased only in groups I and II. During furosemide infusion, there were highly significant increases in urine volume and sodium excretion but no consistent change in either GFR or ERPF. The effects of PG-A₁ and furosemide were not additive.The results show that in cirrhotic patients with ascites, PG-A₁ infusion can significantly increase both GFR and ERPF in all patients but those with the most severe liver impairment. Furosemide consistently increased urine volume and sodium excretion but did not affect GFR or ERPF. Both GFR and ERPF could be related to the extent of hepatic impairment by means of a liver function profile.     

Pure primary hyperaldosteronism due to adrenal cortical carcinoma

A 47-year-old woman is described who had pure primary hyperaldosteronism due to an adrenal cortical carcinoma. This may represent the first such case in which modern laboratory tests allowed specific diagnosis and exclusion of hypersecretion of other adrenal steroids, and also the first reported case in which modern localizing procedures have been utilized. Other interesting facets of the case include calcification of the tumor, visualization with 131l iodomethylnorcholesterol , metaplastic histologic changes, and coexistent bilateral renal artery fibromuscular disease.