Skin tolerance is supported by the spleen.

The repeated application of antigens results in the induction of tolerance. Lymph nodes are responsible for this reaction by producing suppressor cells. Using an in vivo transplantation model, we showed recently that stromal cells from different lymph nodes induce different cell populations for suppression, which all produce a tolerogenic phenotype. In this study, we were interested in the role of the spleen in these tolerance reactions. Therefore, tolerance was induced via feeding or injecting ovalbumin several times in control and splenectomized mice. The delayed-type hypersensitivity (DTH) was measured as well as the cell subset composition of the spleen. The spleen of peripherally tolerized mice showed higher proliferation activity and a specific antibody production compared with orally tolerized mice, where regulatory T cells were predominantly found. Tolerance induction after removal of the spleen resulted in a reduced DTH response in antigen fed animals, whereas skin tolerance induction failed. In conclusion, the results illustrate that lymph nodes from different areas employ their individual pathways for similar immune reactions, and the spleen is part of this reaction initiated at the peripheral site.

Dose-related hemodynamic and electrocardiographic effects of the calcium promoter BAY y 5959 in the presence or absence of congestive heart failure.

OBJECTIVES: The aim of this study was to assess the cardiovascular effects of BAY y 5959, a calcium promoter modulating myocardial calcium channels, in the presence or absence of congestive heart failure. BACKGROUND: There is still a clinical need for short-term administration of intravenous positive inotropes. BAY y 5959 was developed as a new approach to increase myocardial performance by selectively enhancing calcium influx in the myocytes. METHODS: Forty-one patients (21 without and 20 with congestive heart failure) were studied in an open label, dose-ranging study. Hemodynamic variables (including left ventricular [LV] angiography) and plasma samples were obtained at baseline and after 20 min of intravenous infusion of BAY y 5959 at doses ranging from 0.25 to 4.5 microg/kg body weight per min. RESULTS: In both study groups, BAY y 5959 produced dose-dependent increases in the indexes of inotropic state, without affecting isovolumetric relaxation rate. The magnitude of the response was comparable in patients with or without heart failure (average 38% increase in maximal first derivative of LV pressure [dP/dt max] at plasma levels of 100 microg/liter). BAY y 5959 also induced mild but statistically significant bradycardia and significantly decreased end-systolic volume while producing a leftward shift of the pressure-volume loop. Mean aortic pressure was unaffected at doses up to 3.0 microg/kg per min, and cardiac index improved in patients with heart failure at doses of 2.0 microg/kg per min (+23%, p < 0.05). However, at a dose of 4.5 microg/kg per min, mean aortic pressure and LV systolic wall stress increased, suggesting systemic vasoconstriction. The QT interval was also prolonged significantly at most doses. CONCLUSIONS: BAY y 5959 exhibits positive inotropic effects in patients with and without heart failure. The optimal response--combining bradycardia, reduced preload and improved cardiac output--appeared to be achieved at a dose of approximately 2.0 microg/kg per min. The impact of QT prolongation with regard to potential antiarrhythmic or proarrhythmic effects is unclear at this time.

Osteoporosis unmasked by hyperthyroidism in a young man with osteogenesis imperfecta.

A young man presented with a vertebral fracture and generalized osteopenia that was initially attributed to coexisting hyperthyroidism. However, the rarity of fractures in young men with hyperthyroidism and the finding of blue sclerae led to the diagnosis of osteogenesis imperfecta. Since vertebral fractures are uncommon in young men with osteogenesis imperfecta, we postulate that the combined effects of the two disorders contributed to his clinical presentation.

Familial hyperinsulinism presenting in adults.

Two adult siblings presented with recurrent syncope due to severe hyperinsulinemic hypoglycemia. Exploratory laparotomy in the elder sibling showed a grossly normal pancreas, but histologic examination revealed islet cell hyperplasia. Neither sibling has any evidence of the multiple endocrine neoplasia type 1 syndrome, nor is there any other family history to suggest this diagnosis. To our knowledge, this is the first report of adult-onset familial hyperinsulinism without other manifestations of multiple endocrine neoplasia type 1 syndrome. A simple provocative test for hyperinsulinism was also suggested by these cases. Because the initial patient related his symptoms to exercise, we used treadmill exercise in both patients to diagnose hyperinsulinism and observe its response to therapy.

Stromal cells as trend-setters for cells migrating into the lymph node.

Lymph node stromal cells are known to be immunorelevant during inflammation and tolerance. Differences between peripheral lymph nodes and mesenteric lymph nodes are important for an efficient and effective immune defense. Stromal cells were considered to be perfectly adapted to their draining area and not changeable concerning their expression pattern. Here we show that stromal cells can change their profile after isolation and transplantation into a different draining area. Subsequently, these newly organized lymph nodes are able to induce not only a region-specific but also an antigen-specific immune response. Thus, stromal cells are trend-setters for immune cells in producing a microenvironment that allows an optimized immune defense.

The effects of theophylline and nifedipine on corticotropin-stimulated cortisol secretion.

The adrenal cortisol response to corticotropin appears to involve both calcium and cyclic adenosine 3',5'-monophosphate (cAMP) as intracellular mediators. In 10 healthy male volunteers, the short-term administration of theophylline, which affects both intracellular calcium and cAMP, lowered basal cortisol levels but augmented the in vivo cortisol response to short-term corticotropin stimulation. Short-term administration of nifedipine, a calcium channel antagonist, had no effect on basal or peak cortisol levels but reduced the incremental cortisol response to corticotropin. The effects of both theophylline and nifedipine, although statistically significant, were modest and of questionable clinical significance but should be considered in the interpretation of the clinical corticotropin stimulation test. They may also provide some insight into the post-receptor actions of corticotropin.

Sodium ipodate (oragrafin) in the preoperative preparation of Graves' hyperthyroidism.

Fourteen Graves' hyperthyroid patients who had been prepared for surgery with sodium ipodate (SI) 500 mg orally twice daily for 3 days were retrospectively studied. SI was administered in combination with propylthiouracil (10 cases) and beta blockers (all cases), which had been previously initiated. Free serum thyroxine (T4) and total triiodothyronine (T3) concentrations were measured before and after SI therapy on the morning of surgery. SI treatment significantly reduced total T3 concentration from 445.9 to 193.4 ng/dL (P < 0.0001) and free T4 concentration from 3.874 to 2.800 ng/dL (P = 0.0003). Preoperatively, only one patient had persistent tachycardia, and intraoperatively this same patient required beta blockers. Blood loss was unremarkable or reduced (average blood loss, 121 mL). On clinical examination glands were firm with normal or somewhat decreased vascularity. On histologic study all glands demonstrated changes consistent with treated Graves' disease. Preoperative treatment with SI appears to be a safe and efficacious method of preparing hyperthyroid patients for surgery.

Seat belt-related thyroiditis documented with thyroid Tc-99m pertechnetate scans.

A 64-year-old man presented with clinical unilateral thyroiditis after chronic left neck trauma from his car seat belt. Thyroid function tests were normal. The initial thyroid Tc-99m pertechnetate scan demonstrated decreased uptake in the entire left lobe of the thyroid. The follow-up scan 1 month later showed a more normal uptake in the left lobe. This patient's clinical course, laboratory values, and nuclear medicine scans are compatible with thyroiditis secondary to trauma sustained from his seat belt.

Current imaging and possible therapeutic management of glucagonoma tumors: a case report.

Glucagonomas, like other neuroendocrine tumors, express somatostatin receptors in more than 80% of cases. Unfortunately, because of the rarity of these tumors, the sensitivity and specificity of somatostatin analog (octreotide) imaging have not been established. Nonetheless, there have been limited reports in the literature supporting the use of indium In-111 DTPA N-terminal D-phenylalanine (D-PHE1) octreotide for glucagonoma imaging and may be most beneficial as an adjuvant to conventional imaging for tumor staging and therapeutic decision making. Current therapeutic applications of octreotide focus on stabilization of disease in tumors expressing somatostatin receptors, and tumor destruction, using beta-emitting isotopes. In this report, imaging of a glucagonoma with In-111 DTPA-D-PHE1 octreotide scintigraphy is described in a 51-year-old woman examined for a large palpable abdominal mass.

Long-term medical management of aldosterone-producing adenoma.

This case of Conn's syndrome demonstrates long-term (seven years) efficacy of triamterene-thiazide therapy in controlling both hypertension and hypokalemia. Studies done before the adrenal tumor was removed surgically showed that the tumor had increased in size and function since the first studies were done before triamterene-thiazide therapy. The resolution of hypertension after nine years of hyperaldosteronism suggests that surgery is effective even after chronic hyperaldosteronism has been present for some time.

Management of primary hyperparathyroidism in children.

Primary hyperparathyroidism is unusual in children. It is most commonly due to a solitary sporadic parathyroid adenoma, though parathyroid hyperplasia and related familial syndromes should be considered. In the case presented here, an 11-year-old boy with primary hyperparathyroidism had preoperative imaging studies that localized to the inferior aspect of the left side of the neck anteriorly, and a parathyroid adenoma was successfully resected. Screening for familial syndromes involving hyperparathyroidism should be individually considered in children with primary hyperparathyroidism. Preoperative localizing studies and the role of unilateral surgery are controversial issues in adults with primary hyperparathyroidism. Although such issues have not been addressed in children, localization and unilateral surgery proved successful in this case.

Viewpoint of a driver with epilepsy.

Persons with seizure disorders are a varied group, but the group is treated indiscriminately when U.S. state laws restrict driving privileges on the basis of a seizure incident without regard for individual driving record, level of personal responsibility, or the almost insignificant danger posed to ourselves and other motorists. From the viewpoint of a driver with epilepsy, seven characteristics encompass a model driver licensing law, which would (a) be a proportionate response to the problem addressed; (b) be reasonable enough to ensure compliance; (c) empower the individual (as opposed to a medical advisory board exclusively) to participate in decisions; (d) consider each individual's circumstances; (e) be consistent with U.S. Public Law 95-602, the Rehabilitation Act of 1973; (f) be based on performance rather than on medical incident; and (g) preserve for society the benefit of every driver's fullest participation.

Identification and characterization of the Myxococcus xanthus bsgA gene product.

The bsgA mutants of Myxococcus xanthus are blocked at a very early stage of the developmental program. They fail to produce fruiting bodies or to sporulate under normal conditions but can be rescued by extracellular complementation in mixtures with wild-type cells. A bsgA-lacZ gene fusion was constructed and expressed in Escherichia coli. The resulting fusion protein, which has beta-galactosidase enzyme activity, was partially purified by affinity chromatography and preparative polyacrylamide gel electrophoresis. The protein was used to immunize mice, which produced a hybridoma secreting monoclonal antibody that was specific for the bsgA gene product. The monoclonal antibody was used in Western blot (immunoblot) experiments to determine the apparent cellular location of the bsgA protein in M. xanthus and to compare the level of this protein at various times in the Myxococcus life cycle.

Lactic acidosis in pheochromocytoma.

Lactic acidosis is not generally recognized as a complication of pheochromocytoma. We review three prior case reports of lactic acidosis in patients with pheochromocytoma and one report of lactic acidosis following epinephrine poisoning and describe an additional case report of a patient with lactic acidosis in whom an unsuspected pheochromocytoma was discovered at autopsy. The pathophysiology of lactic acidosis in pheochromocytoma is related to the effect of catecholamines on intermediary metabolism and the peripheral circulation. Although the possible development of lactic acidosis in persons with pheochromocytoma is underappreciated, the differential diagnosis of lactic acidosis should include this tumor.

Thalidomide inhibits lipoarabinomannan-induced upregulation of human immunodeficiency virus expression.

Mycobacterium tuberculosis accelerates the progression of human immunodeficiency virus type 1 (HIV-1) infection. The results of this study, which show that thalidomide inhibits the upregulation of HIV-1 expression in U1 cells stimulated with mycobacterial lipoarabinomannans, support the rationale behind conducting controlled trials of this immunodeficiency agent with patients dually infected with HIV-1 and M. tuberculosis.

Effects of nisoldipine therapy on myocardial perfusion and neuro-hormonal status in patients with severe ischaemic left ventricular dysfunction.

The effects of nisoldipine on regional myocardial perfusion and neuro-hormonal status were assessed in a double-blind, placebo-controlled study of 32 patients. All patients had ischaemic left ventricular dysfunction, with a left ventricular ejection fraction between 25% and 35%; per protocol, they were stratified according to concomitant use of ACE inhibitors. After baseline measurements at rest, including single photon emission computed tomography (SPECT) with Tc-MIBI, plasma neuro-hormones (norepinephrine, renin, arginine vasopressin, atrial natriuretic peptide) and echocardiography, the patients were randomized to nisoldipine (core coat tablet, 20 mg once daily; n = 16) or placebo (n = 16). Measurements were repeated after 8 weeks. SPECT data were analysed qualitatively (visual comparison by blinded observer) and quantitatively to derive an index of hypoperfusion representing the percentage of the left ventricular mass with Tc-MIBI activity below normal. At baseline, all patients had left ventricular areas with reduced Tc-MIBI uptake and 29 patients also had increases in plasma neuro-hormones. With nisoldipine, the extent of hypoperfusion (quantitative analysis) was reduced in 8/14 patients vs only 2/14 patients with placebo (P = 0.046, 2-tailed test). The benefit of nisoldipine was similar in patients with or without ACE inhibitor therapy and was also confirmed by the visual analysis of the data. Further, none of the neuro-hormones examined was significantly modified by nisoldipine. Thus, chronically underperfused areas are present at rest in patients with ischaemic left ventricular dysfunction, and nisoldipine significantly improved Tc-MIBI uptake in these areas without evidence of detrimental changes in plasma neuro-hormones.(ABSTRACT TRUNCATED AT 250 WORDS)