Showing papers by "Rambam Health Care Campus published in 1999"

The hypothyroidism in an inbred kindred with congenital thyroid hormone and glucocorticoid deficiency is due to a mutation producing a truncated thyrotropin receptor

Abstract: Growth and function of the thyroid and adrenal glands are maintained and controlled by thyrotropin (TSH) and adrenocorticotrophic hormone (ACTH), respectively. The action of these trophic hormones requires the presence of functional TSH and ACTH receptors. We describe a large inbred Bedouin kindred in which profound congenital hypothyroidism and hypoadrenocortisolism occurred alone or together in eight family members belonging to four nuclear families. The high serum TSH and ACTH levels in the presence of normal or hypoplastic thyroid glands and low glucocorticoid, but not mineralocorticoid concentrations, are characteristic of resistance to TSH and ACTH. Linkage analysis, using specific polymorphic markers, excluded the involvement of the ACTH receptor but not thyrotropin receptor (TSHR). A novel point mutation was identified in exon 10 of the TSHR that replaces the normal cytosine in nucleotide 2024 with a thymidine. As a result the normal arginine in codon 609 (CGA) is replaced with a stop codon (TGA). This mutation produces a truncated TSHR lacking the third intracellular and extracellular loops, the sixth and seventh transmembrane segments, and the intracytoplasmic tail. The presence of hypothyroidism did not affect the timing, severity, and manner of clinical manifestation of hypoadrenocortisolism.

Cholesteatomas associated with ventilation tube insertion.

Abstract: Objectives To determine the incidence of cholesteatoma formation associated with ventilation tube (VT) placement and to identify and analyze the variables and risk factors that may predict or predispose to this complication. Design We reviewed the medical records of 2829 children following VT insertion between the years 1978 and 1997 to obtain 1- to 20-year follow-up data. Setting Departments of Otolaryngology–Head and Neck Surgery and outpatient clinics of 2 tertiary referral academic medical centers. Patients A study population of 2829 children, ranging in age from 1.2 to 14 years (5575 ears), underwent a total of 6701 VT placements. Main Outcome Measure Cholesteatomas were considered a complication of VT placement whenever they developed at or near the site of the tube insertion. Results Cholesteatomas directly attributed to VT placement occurred in 1.1% of the ears that were operated on. A higher incidence occurred (1) in children younger than 5 years, (2) when Goode T-tubes were used, (3) in cases with repeated insertions of tubes, (4) with intubation exceeding 12 months, and (5) in cases with frequent postoperative otorrhea. Conclusions Cholesteatoma formation associated with VT placement occurs in 1.1% of the ears that are operated on, and therefore it should be discussed with patients or parents prior to surgery. Periodic and long-term follow-up microscopic examinations of the eardrum should be performed in all patients following tubal extrusion or removal, especially in those at high risk for developing a secondary cholesteatoma, to detect this complication as early as possible.

Treatment of chronic myelogenous leukemia with autologous bone marrow transplantation followed by roquinimex.

Abstract: Unmanipulated autologous bone marrow transplant (ABMT) offers patients with chronic myelogenous leukemia (CML) a long-term survival of 10%, at best. Immunotherapy has a role in the myeloid leukemias, and there is increasing evidence that of all hematopoietic neoplasms, CML may be the most susceptible to immune regulation. Roquinimex is known to enhance T cell, NK cell and macrophage activity. A phase II study was initiated in March 1992 to evaluate the role of roquinimex in Ph chromosome-positive CML post ABMT. Patients were conditioned with busulfan/ cyclophosphamide followed by reinfusion of unmanipulated Ph-positive bone marrow stem cells (>1 x 108 NBC/kg). When engraftment of neutrophils (ANC) reached 100/microl, patients received oral roquinimex twice weekly, escalating to a maximal dose of 0.2 mg/kg in 2 weeks. Seventeen patients have entered the study; 11 in first chronic phase (CP1); two in second chronic phase (CP2) and four in accelerated phase (AP). All required significant myelosuppressive therapy prior to ABMT to maintain stable blood counts and most had also received prior interferon therapy. All patients survived the transplant. Subsequent toxicity consisted mainly of musculoskeletal aches and peripheral edema. Additionally, specific skin changes were observed including graft-versus-host-like disease and eccrine sweat gland necrosis. Eight out of 17 patients are alive 28-60 months post ABMT. Of the nine patients who died, two were in CP2 and three in AP. All patients in CP1 went into a complete hematological remission post ABMT and seven of the 11 patients had at least a major cytogenetic response (greater than 65% Ph-negative metaphases) at 1 year or beyond and four of the 11 patients had a complete cytogenetic response at 2 years or beyond. Cytogenetic response post transplant often developed over time and did not simply represent post ABMT engraftment with Ph-negative cells. The clinical and cytogenetic data in these patients are encouraging and suggest that roquinimex may have significant activity when given post ABMT to patients with Ph-positive CML.

Major salivary gland involvement in graft-versus-host disease: considerations related to pathogenesis, the role of cytokines and therapy.

Abstract: Chronic graft-versus-host-disease (GVHD) is an autoimmune-like complication often occurring in patients who have been treated with bone marrow and peripheral blood stem cell transplantation. Various tissues and organs are damaged via the cytotoxicity rendered by the infiltrating donor graft T cells. The mucosal insult is enhanced by the reduced quantity and the altered quality of the saliva, since the salivary glands are a known major target of GVHD. The salivary changes are also expressed by a reduction in related functions, such as anti-infection activity, protection against mechanical and chemical epithelial injuries, assistance in controlling periodontal disease and caries, etc. The purpose of this review is to summarize the data that have been published recently concerning salivary involvement in GVHD and to suggest an underlying mechanism for the disease and its related 'state-of-the-art' therapeutic policy.

One-year clinical follow-up with the serpentine balloon expandable stent: report of the first 100 patients.

Abstract: BACKGROUND We recently reported a high technical and 30-day clinical success rate among the first 100 patients treated with the tubular, serpentine design, stainless steel, balloon-expandable stent (beStent) in Israel. The present study examined the clinical results in these patients after the first year. METHODS Seventy-eight men and 22 women were included in the study. Previous myocardial infarction, bypass surgery and percutaneous transluminal coronary angioplasty had occurred in 52%, 12% and 26% of the patients, respectively. Diabetes mellitus was present in 30 patients and hypertension in 34 patients. One hundred and forty-eight stents of 15, 25, and 35 mm lengths were used. The indications for stenting were suboptimal results (n = 85), bailout conditions (n = 10) or for the prevention of restenosis (n = 8), and lesion types were A (n = 10), B1 (n = 29), B2 (n = 20), and C (n = 44). All patients were clinically monitored with regular visits at 1, 3, 6, 9 and 12 months. RESULTS Overall, the 12-month event-free survival rate was 82%. Subacute thrombosis occurred in two patients. There were two non-cardiac deaths, one O-wave myocardial infarction, six elective bypass surgeries and 12 target lesion revascularizations. Event-free survival was significantly higher for those with lesions shorter than 15 mm than for those with lesions longer than 15 mm (90% versus 67%, P = 0.003), and for women compared with men (96% versus 78%, P = 0.02). CONCLUSIONS The initial experience with the beStent shows favorable long-term results with an overall event rate of 18% for this subset of relatively complex lesions; higher event rates were observed for longer lesions.