How much insulin is enough? A quantitative assessment of the transdifferentiaton potential of liver.
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Animals↗
Biomedical subjects
B Hirshberg
Publications and source records attributed to B Hirshberg.
Is there a therapeutic role for octreotide in patients with ectopic Cushing's syndrome?
Cushing's syndrome (CS) due to ectopic ACTH secretion (EAS) has a high morbidity and mortality, because of the underlying tumor and the sequelae of severe hypercortisolemia. Therefore, rapid treatment of ectopic CS is mandatory. Scintigraphy shows that up to 80% of ectopic ACTH-producing tumors have somatostatin receptors. While this suggests that somatostatin analogs may reduce ACTH production and treat patients with EAS, the therapeutic role of these agents is still evolving. Here we demonstrate the spectrum of responses to octreotide therapy in 3 patients with EAS. Diagnostic imaging with the 111In-pentetreotide scan did not predict the therapeutic response to octreotide. Two patients with positive somatostatin receptor scintigraphy failed to respond to octreotide, while one with a negative scan reached eucortisolemia on a maintenance dose of 75 microg octreotide twice daily or octreotide LAR 30 mg per month. We conclude that octreotide is not a first line agent to control hypercortisolemia but may be a useful agent when other inhibitors of steroidogenesis fail or parenteral administration is required. Before therapy an octreotide challenge test may predict therapeutic response. Cortisol levels should be monitored regularly on somatostatin analog therapy, because of its unpredictable long-term pharmacodynamic profile.
Adrenocorticotropic Hormone↗
Preclinical evaluation of tolerance induction protocols and islet transplantation in non-human primates.
Non-human primate studies of tolerance induction strategies in solid organ transplantation represent a critical bridge between studies in rodents and humans. Our work demonstrates that strategies involving the blockade of co-stimulatory molecules, especially the CD40-CD154 pathway, have great potential for clinical adaptation. While the combination of anti-CD154 antibody with blockade of the CD28 pathway reduced donor antibody production, graft survival was not significantly improved over that achieved with anti-CD154 antibody alone. Moreover, although long courses of steroids seem to interfere with this approach, it may be possible to combine blockade of the CD40-CD154 pathway with other conventional immunosuppressants without sacrificing efficacy. This is a key issue for reducing the risk associated with eventual clinical trials. Work in the non-human primate islet transplant model demonstrates that viable islets can be recovered, isolated and infused in a reliable fashion. It also confirms the efficacy of a steroid sparing approach to immunosuppression for islet transplantation. These data have been expanded to the kidney allograft model, setting the stage for kidney islet transplantation studies. Overall, tolerance induction and islet transplant studies in non-human primates permit the preclinical screening of promising immunomodulatory approaches developed in rodents and reduce the inherent uncertainties associated with adapting new regimens to the clinic.
Animals↗
Repaglinide-induced factitious hypoglycemia.
We report the first case of repaglinide-induced factitious hypoglycemia in a young male. This case posed a challenging diagnostic dilemma because commercial assays for repaglinide are not available. Furthermore, the patient had a series of positive diagnostic tests such as high proinsulin and localizing intra-arterial calcium stimulation suggestive of insulinoma. This case, again, demonstrates the importance of pure clinical judgment in the face of often-conflicting laboratory data in making a correct diagnosis and the requirement of definitive data for an appropriate therapeutic resolution.
Adolescent↗
Natural course of insulin edema.
Generalized edema due to water retention is a very rare complication of insulin therapy. It affects mainly patients with newly diagnosed diabetes or patients with chronic hyperglycemia following initiation of insulin therapy. When it occurs, it is treated effectively with diuretics. This case report describes a female patient, who developed severe insulin edema following initiation of insulin. Diuretics were not given due to severe side effects, thus the natural outcome of insulin edema was observed. Edema was gradually replaced by fat tissue with persistent weight gain. Physicians treating diabetic patients should be aware of "insulin edema" in the differential diagnosis of weight gain in patients treated with insulin.
Body Weight↗
A sustained, non-insulin related, hypoglycaemic effect of electroacupuncture in diabetic Psammomys obesus.
AIM/HYPOTHESIS: Electroacupuncture has been shown to induce a short-term hypoglycaemic effect in streptozotocin diabetic rats. We designed an experiment to investigate the effect of electroacupuncture in Psammomys obesus, a model of insulin resistance and non-insulin-dependent diabetes mellitus. METHODS: We divided 29 diabetic Psammomys randomly into three groups: abdominal electroacupuncture (real, n = 11), back electroacupuncture (placebo, n = 9) and control (anaesthesia, n = 9). Electroacupuncture was carried out on days 1, 3 and 5 of the experiment. During the first week of the experiment, blood glucose was tested three times on treatment days and once on the following days. Over the next 2 weeks, blood glucose was tested every other day. Animals were weighed at the same time of blood sampling. After 3 weeks, at the end of the experiment, blood was drawn for measurement of insulin, fructosamine, cholesterol and triglycerides. RESULTS: At day 5 (end of intervention), blood glucose (as per cent of primary concentrations, means +/- SE) was 57 +/- 10, 93 +/- 13 and 89 +/- 11 for the real, placebo and control groups respectively (p = 0.02). At day 8, blood glucose 68 +/- 14, 86 +/- 16 and 97 +/- 9 for the real, placebo and control groups respectively (p = 0.04). At day 22, blood glucose was 79 +/- 11, 85 +/- 15 and 131 +/- 2 for the real, placebo and control groups (p = 0.04). Comparison of the decline in blood glucose, throughout the 3 weeks, between the real and placebo groups by ANOVA was highly significant (p < 0.0001), the difference between the placebo and control groups at the same time was not significant (p > 0.05). Animal weight gain, serum insulin, fructosamine, cholesterol and triglycerides were not significantly different between real and placebo groups. CONCLUSION/INTERPRETATION: Electroacupuncture at special abdominal acupoints induces a sustained hypoglycaemic effect in diabetic Psammomys compared with electroacupuncture at non-specific points, without weight loss. No hypoinsulinaemic effect was shown in the real and placebo groups.
Analysis of Variance↗
A dangerous complication of chronic sinusitis.
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Accidents, Home↗
Flow cytometric analysis of autonomous growth of erythroid precursors in liquid culture detects occult polycythemia vera in the Budd-Chiari syndrome.
BACKGROUND/AIMS: Hepatic vein thrombosis (Budd-Chiari syndrome) is associated with various hypercoagulable states, such as polycythemia vera (PV), presence of the lupus anticoagulant, paroxysmal nocturnal hemoglobinuria (PNH) and deficiencies of antithrombin III, protein C and protein S. In recent years, it has become evident that patients with the Budd-Chiari syndrome may have more than one risk factor that may cause a state of hypercoagulability. The aim of the current study was to assess the prevalence of occult PV in patients with Budd-Chiari syndrome using a novel method for the detection of spontaneous erythroid growth. METHODS: Twenty-two patients with Budd-Chiari syndrome were evaluated. As controls, we studied normal donors and four patients with liver cirrhosis and five patients with right-side heart failure, two conditions that in part mimic Budd-Chiari syndrome. The presence of PV was determined by flow cytometric analysis of autonomous growth of erythroid precursors. Patients were considered as having occult PV if they had spontaneous erythroid cell growth in the absence of erythropoietin and with no features of overt PV. RESULTS: Cells from ten patients with Budd-Chiari syndrome demonstrated spontaneous erythroid cell growth; eight patients (32%) were found to have occult PV and two patients had overt PV. None of the controls had spontaneous erythroid growth. Of the eight Budd-Chiari patients with occult PV, six had one or more additional recognized hypercoagulable states. Seven patients (32%) had protein C deficiency, six patients (27%) had activated protein C resistance, five (23%) had anti-cardiolipin antibodies, five (23%) had antithrombin III deficiency, and four patients (18%) had protein S deficiency. Three patients (14%) were homozygous to methyltetra hydrofolate reductase and ten (45.5%) were heterozygous. One patient had PNH. Overall, in 12 patients there were two or more combined risk factors. CONCLUSIONS: Using a flow cytometric analysis of autonomous growth of erythroid precursors we found a clear correlation between Budd-Chiari syndrome and occult PV.
Adult↗
Renal nitric oxide production during the early phase of experimental diabetes mellitus.
BACKGROUND: Diabetic nephropathy (DN) is characterized by hyperfiltration and hypertrophy in experimental models of diabetes mellitus (DM). Several studies have demonstrated that the pathophysiologic and morphologic changes in DN are mediated by either an increase or decrease in renal nitric oxide (NO) production and/or activity. The goal of the present study was to determine the effects that the early diabetic state has on NO production in the kidney of rats with streptozotocin-induced DM. METHODS: Experimental DM was induced in rats with streptozotocin. Urinary NO production was measured, and levels and activity of the different NOS isoforms were determined by a combination of techniques, including immunoblotting, immunohistochemistry, diaphorase staining, and reverse transcription-polymerase chain reaction. RESULTS: During the first week of DM, urinary NO metabolites (uNO2 + NO3) were reduced as compared with controls, which were unrelated to changes in serum levels of NO. Total NO synthase (NOS) activity was reduced in the renal cortex beginning at 30 hours after the induction of DM. NADPH diaphorase staining of renal cortical slices showed reduced NOS activity in the macula densa in diabetic animals. By immunohistochemical staining with antibodies to the different isoforms of NOS, it was found that protein levels of the neuroneal NOS (nNOS) isoform was diminished in the macula densa. No changes were found in the levels of endothelial NOS (eNOS) activity and protein in the renal cortex in the early diabetic state. CONCLUSIONS: This study provides strong evidence that renal production of NO is reduced in early DM and that this reduction is associated with decreased levels of nNOS activity and protein in the macula densa.
Animals↗
Diurnal thyrotropin secretion in short-term profound primary hypothyroidism: does it ever persist?
Circulating serum thyrotropin (TSH) levels in euthyroid humans show a definite circadian variation, which is maintained in both mild hyperthyroidism and mild hypothyroidism. Yet conflicting data exist with regard to whether this variation persists in at least some patients with severe primary hypothyroidism. We, therefore, studied the diurnal variation in serum TSH in 10 patients (age range 20 to 84 years) with a history of thyroid failure due to prior total thyroidectomy and radioiodine (RAI) ablative treatment performed for thyroid cancer after short-term discontinuation of thyroid hormone (TH) therapy. Serum TSH was measured hourly for a 24-hour period. All data were normalized by converting the TSH values to a percentage (%), designating the 11:00 hour value as 100% (baseline). The average serum TSH levels were markedly elevated in all patients. There was no statistically significant difference between the TSH % values at any time during the 24-hour period when compared with baseline. Further, cosine regression analysis showed absence of rhythmicity in TSH % values over time; notably, no patient showed a variation in TSH % values > or = 15% of baseline. In conclusion, diurnal rhythmicity in serum TSH levels was abolished in a uniform cohort of patients with short-term severe primary hypothyroidism. We speculate that the complete lack of peripheral negative feedback input to the hypothalamus or pituitary or both may override the central rhythm-sustaining influences on TSH secretion.
Adult↗
Safety of low dose methotrexate in elderly patients with rheumatoid arthritis.
Weekly low dose methotrexate is an established treatment for rheumatoid arthritis, but its use in elderly people has not been adequately examined. The aim of this study was to evaluate its safety in elderly patients with rheumatoid arthritis. A retrospective review of the clinical records of rheumatoid arthritis patients over the age of 65 attending a rheumatology unit was conducted. Eligible patients were followed for at least two years and treated with methotrexate in a dose of 7.5 mg/week while being maintained on concurrent treatment. Thirty three patients were studied. Their mean age was 78.8 years; 32 were female and one was male. Treatment was discontinued in four patients, two because of raised serum liver enzymes and two because of gastrointestinal irritation. No serious adverse events were reported. After two years, haemoglobin levels increased from a mean (SD) of 12.4 (1.3) g/dl to 13.0 (1.1) g/dl (r = 0.226, p < 0.005). The white blood count was significantly reduced from 7.9 (1.8) x 10(9)/l to 6.8 (1.7) x 10(9)/l (r = 0.184, p < 0.05). No episodes of neutropenia or agranulocytosis were observed. There was a non-significant decrease in platelet count. The erythrocyte sedimentation rate decreased from 56.8 (30.8) to 35.2 (24.6) mm/h (r = 0.246, p < 0.01). In conclusion, low methotrexate treatment in elderly patients appears to be safe. Routine determination of serum liver enzymes and renal function may reduce individual risk.
Aged↗
Forty-eight-hour fast: the diagnostic test for insulinoma.
Insulinoma causes fasting hypoglycemia due to inappropriate insulin secretion. Its diagnosis is based on demonstrating Whipple's triad during a supervised 72-h fast. For 75 yr, the 72-h fast has been the cornerstone for the diagnosis; however, it has never been critically assessed using newer assays for insulin, C peptide, and proinsulin. Thus, the aim of the current study is to assess the need for a full 72-h fast for the diagnosis of insulinoma. Patients with suspected hypoglycemia with documented glucose concentrations below 45 mg/dL were admitted to the NIH. Data obtained during the supervised fast of patients with pathologically proven insulinoma over a 30-yr period (1970-2000) were reviewed. We identified 127 patients with insulinoma. The average age of patients was 42.7 +/- 15.9 yr, with a predominance of females (62%). 107 patients had a benign tumor, 20 had malignant insulinoma, and 15 patients had multiple endocrine neoplasia type 1. The fast was terminated due to hypoglycemia in 44 patients (42.5%) by 12 h, 85 patients (66.9%) by 24 h, and 120 (94.5%) by 48 h. Seven patients fasted beyond 48 h despite subtle neuroglycopenic symptoms and glucose and insulin concentrations diagnostic of insulinoma. Immunoreactive proinsulin was elevated at the beginning of the fast in 90% of 42 patients. Proinsulin in noninsulinoma, in contrast to insulinoma, patients is usually suppressible; therefore, samples taken in the suppressed state have the greatest diagnostic value. We conclude that with the current available insulin and proinsulin assays, the diagnosis of insulinoma can be made within 48 h. Thus, the 48-h fast should replace the 72-h fast in textbooks and hospital protocols as the new diagnostic standard.
Adolescent↗
Zuclopenthixol-associated neutropenia and thrombocytopenia.
OBJECTIVE: To report a case of neutropenia and thrombocytopenia secondary to use of zuclopenthixol in a schizophrenic patient. CASE SUMMARY: A 66-year-old white man with chronic schizophrenia was referred to the hospital due to neutropenia and thrombocytopenia that developed shortly after initiation of zuclopenthixol therapy. Prior to zuclopenthixol administration, his white blood cell and platelet counts were 8.5 x 10(9) cells/L3 and 305 cells x 10(9)/L, respectively. Progressive reduction in leukocyte and platelet counts occurred, reaching a nadir of 2.9 x 10(9) cells/L3 (granulocytes 18.9%) and 109 cells x 10(9)/L, respectively. Zuclopenthixol was discontinued on admission, resulting in complete recovery within the next five days. DISCUSSION: Neutropenia and thrombocytopenia are well-known complications of antipsychotic drug therapy. Zuclopenthixol, a well-established antipsychotic agent, has relatively few adverse effects. The rapid decrease of white blood cell and platelet counts following the initiation of zuclopenthixol, as well as the rapid recovery, implicate zuclopenthixol as the predominant cause for neutropenia and thrombocytopenia in this patient. CONCLUSIONS: Although neutropenia and thrombocytopenia are rare complications of zuclopenthixol therapy, monitoring blood counts in patients receiving this agent seems to be justified.
Aged↗
Lack of mediastinal shift as a clue to delayed postpneumonectomy empyema.
Delayed postpneumonectomy empyema is uncommon. The condition is usually elusive and diagnosed late in the course of the disease, leading to increased morbidity. New air-fluid level on chest x-ray film or appearance of empyema necessitatis may enhance the index of suspicion and lead to early diagnosis, but in many cases no clinical or laboratory clues are apparent. We describe the case of a 60-year-old man with high fever and dyspnea 3(1/2) years after pneumonectomy. Diagnosis of postpneumonectomy empyema was delayed and finally suggested by the lack of expected mediastinal shift on chest film. Computed tomography (CT) of the chest showed a large quantity of fluid, which later proved to be empyema. The patient was treated successfully by continuous cavity irrigation with neomycin and systemic antibiotics. We conclude that in postpneumonectomy patients with septic fever, the only clue to diagnosis of delayed postpneumonectomy empyema may be hemithorax opacification without mediastinal shift, confirmed by CT-guided thoracocentesis. Therapy with cavity irrigation and systemic antibiotics seems appropriate.
Empyema, Pleural↗
6;9 translocation in myelodysplastic syndrome.
The 6;9 chromosomal translocation [t(6;9)] is usually associated with acute nonlymphocytic leukemia, and carries a poor prognosis. We present a case of refractory anemia with excess of blasts (RAEB) accompanied by t(6;9). Review of the literature revealed an additional ten patients in which myelodysplastic syndrome (MDS) was associated with the chromosomal translocation 6;9. The patients tend to be younger then the average MDS patient and, unlike leukemia, in which this translocation is associated with a poor prognosis, these patients tend to have the same overall RAEB and refractory anemia with excess of blasts in transformation (RAEBt) prognosis. It is therefore possible that this chromosomal aberration should not be considered as an unfavorable prognostic factor in MDS.
Adolescent↗
Chronic eosinophilic pneumonia associated with cutaneous T-cell lymphoma.
Cutaneous T-cell lymphomas (CTCL) are diseases characterized by cutaneous infiltrates of malignant clonally expanded T cells. CTCL cells exhibit a cytokine profile consistent with T helper-2 type (TH2) cells. Eosinophilic pneumonias are individual syndromes characterized by eosinophilic pulmonary infiltrates and commonly peripheral blood eosinophilia. CTCL and chronic eosinophilic pneumonia are rare clinical entities. We report a patient with the association of CTCL and chronic eosinophilic pneumonia. To understand the mechanism leading to the eosinophilia, we examined the patient's cytokine profile. This was consistent with a high TH2 activity. Her interleukin (IL) 5, 6, and 10 levels were extremely high, while her IL-2 and interferon-gamma (IFN-gamma) levels (TH1 profile) were low. We believe that eosinophilic pneumonia in this patient is probably secondary to high TH2 cytokine levels induced by tumor cells. We suggest that eosinophilic pneumonia should be considered as a possible diagnosis in patients with CTCL who have respiratory complaints.
Cytokines↗
Factors predicting mortality of patients with lung abscess.
BACKGROUND: The rates of morbidity and mortality associated with lung abscess are still significant despite the introduction of antibiotic treatments. The aim of this work was to identify the factors that predict a poor outcome for patients with lung abscess. METHODS: We retrospectively reviewed the records and the roentgenographic files of adult patients with lung abscess who were hospitalized from 1980 to 1996 at the Hadassah University Hospital, in Jerusalem, Israel. RESULTS: The study population comprised 75 patients, and the mean age was 52 years old (range, 12 to 89 years). The mean (+/- SD) hospitalization duration was 25.7+/-21.5 days (range, 5 to 94 days). Fifteen patients (20%) succumbed to the infection. The patients who died had more predisposing factors (+/-SD), such as pneumonia, neoplasm, and altered consciousness, than those who survived, respectively: 2.73+/-1.4 vs 1.9+/-1.3 (p < 0.03). The patients with anemia on admission (hemoglobin levels of < 10 g/dL) had a higher mortality rate than those with higher hemoglobin levels, respectively: 58.3 vs 12.9% (p = 0.0008). A higher mortality rate was also associated with infection by Pseudomonas aeruginosa (83%), Staphylococcus aureus (50%), and Klebsiella pneumoniae (44%). The patients who died had larger abscess volumes (+/-SD) than those who survived (233+/-99 vs 157+/-33 mL), although it did not reach statistical significance. The diameter of the abscess correlated with the hospitalization time (r = 0.5; p < 0.001). CONCLUSION: High rates of morbidity and mortality are associated with lung abscess despite appropriate antibiotic therapy and better supportive care. In patients with several predisposing factors, such as a large abscess size and a right-lower-lobe location, the prognosis was worse. The patients infected with S aureus, K pneumoniae, and particularly P aeruginosa had an ominous prognosis. As the prognosis for lung abscess has not improved sufficiently since the introduction of antibiotics, other modalities should be considered for patients with poor prognostic signs.
Adolescent↗
Recovery from blast lung injury: one-year follow-up.
BACKGROUND: Blast injury to the lung is one of the devastating threats facing victims of an explosion. Although the pathogenesis of blast injury has been studied, little is known about the long-term effects on lung function in survivors. OBJECTIVE: To examine the pulmonary function of survivors 1 year after sustaining a blast injury. DESIGN: Prospective study. SETTING: Pulmonary function test laboratory at Hadassah Medical Center, Jerusalem. PARTICIPANTS: Eleven surviving victims of a blast injury sustained during a bus terrorist explosion. MEASUREMENTS: Twelve months after the injury, physical examinations, lung function tests, and progressive cardiopulmonary exercise examinations were conducted, and chest radiographs were obtained. RESULTS: The average age was 28 +/- 9.8 years. Most of the victims had multiple injuries in addition to the lung injury. Ten patients received mechanical ventilation, and 6 patients required chest drainage. All patients were treated in the ICU, with an average stay of 11.8 +/- 9 days. The patients were discharged to their homes or to a rehabilitation center 32.4 +/- 27. 3 days after the explosion. One year later, none had any pulmonary-related complaints. Physical examination of the lungs was normal. Most of the patients demonstrated normal lung function tests and complete resolution of the chest radiograph findings. CONCLUSION: Most patients who survive lung blast injury will regain good lung function within a year.
Adult↗