Pendred syndrome is caused by mutations in a putative sulphate transporter gene (PDS).

Pendred syndrome is a recessively inherited disorder with the hallmark features of congenital deafness and thyroid goitre. By some estimates, the disorder may account for upwards of 10% of hereditary deafness. Previous genetic linkage studies localized the gene to a broad interval on human chromosome 7q22-31.1. Using a positional cloning strategy, we have identified the gene (PDS) mutated in Pendred syndrome and found three apparently deleterious mutations, each segregating with the disease in the respective families in which they occur. PDS produces a transcript of approximately 5 kb that was found to be expressed at significant levels only in the thyroid. The predicted protein, pendrin, is closely related to a number of known sulphate transporters. These studies provide compelling evidence that defects in pendrin cause Pendred syndrome thereby launching a new area of investigation into thyroid physiology, the pathogenesis of congenital deafness and the role of altered sulphate transport in human disease.

Thyroid-stimulating hormone (TSH) binding to extrathyroidal human tissues: TSH binding to extrathyroidal human tissues: TSH and thyroid-stimulating immunoglobulin effects on adenosine 3',5'-monophosphate in testicular and adrenal tissues.

Binding of [125I]bovine TSH to human thyroid, testicular, fat, adrenal, liver, kidney, pancreas, and lung cell membranes has been studied. The first four tissues were found to have comparable high affinity constant values; the rest of the tissues lacked high affinity sites. With the exception of fat tissue, the capacities of the high affinity sites of the first four tissues were similar. Bovine TSH concentrations of 100-20,000 microIU/ml stimulated increased cAMP production in human cryopreserved testicular slices. Forty percent of the specimens of thyroid-stimulating immunoglobulin (TSI) from Graves' disease sera also increased human testicular cAMP production. In addition, bovine TSH caused a significant rise in cAMP in the whole decapsulated rat testis. Twenty-five percent of the TSI specimens tested also induced such responses. The rat adrenal gland responded with increased cAMP production to concentrations of 1,000 microU/ml bovine TSH. The physiological significance of high affinity bovine TSH and TSI binding and subsequent cAMP production in nonthyroidal tissues in not known. However, since these stimulators are present in hypothyroidism and hyperthyroidism, respectively, it is possible that the pathophysiological effects of this binding could be of some importance.

Sulfate transport is not impaired in pendred syndrome thyrocytes.

Pendred syndrome is the most common form of syndromic deafness, characterized by dyshormonogenic goiter associated with sensory-neural deafness. The gene responsible for the disease (PDS) has been cloned, but its function is as yet unknown and the connection between thyroid goiter and sensory-neural deafness remains an enigma. PDS codes for a novel protein, pendrin, which is closely related to a number of sufate transporters. Mechanisms by which abnormal sulfate transport could deleteriously affect iodide organification have been proposed. We tested sulfate transport in thyrocytes obtained from Pendred syndrome patients and found that it was not defective. This suggests that pendrin in fact may not be a sulfate transporter, and emphasizes the importance of functional studies on this novel protein.

Laparoscopic cholecystectomy for acute cholecystitis performed by residents in surgery: a risk factor for conversion to open laparotomy?

Recent observations point to a seemingly high conversion rate to laparotomy in cases of laparoscopic operations for acute cholecystitis that are performed by surgical residents. The purpose of the study is to evaluate those observations. In a retrospective nonrandomized study, conducted between February 1992 and December 1997, 285 laparoscopic operations for acute cholecystitis were analyzed. Those performed by attending surgeons were compared with those performed by residents assisted by attending surgeons. Of 123 laparoscopic operations performed by laparoscopic surgeons between February 1992 and September 1995, 20.3% were converted to laparotomy, compared with 41.3% of the 29 operations performed by the residents (p < 0.017), with no increase in complication rate. Factors like male sex, duration of upper abdominal pain, and severity of the inflammatory process were not significantly different in both groups. The residents' seniority did not influence the conversion rate. A constant and significant decrease in conversion rate to laparotomy was observed over the course of time, as the study proceeded to December 31, 1997 (p < 0.01). We conclude that the performance of difficult laparoscopic cholecystectomy by residents with the assistance of attending surgeons is feasible, but carries a higher conversion rate to laparotomy for reasons that are not entirely clear. The possibility of a learning curve of the residents is suggested.

[Brucella orchitis].

Brucellosis is a multi-organ infectious disease which affects the genito-urinary system in 2-10% of cases, mainly as orchitis. There have been very few reports in Israel of genito-urinary system involvement in patients with brucellosis, possible due to a low index of suspicion. Identification of brucella orchitis would result in proper medical treatment, thus preventing unnecessary surgery. We present a case of brucella orchitis, highlighting the place of brucellosis in the differential diagnosis of orchitis.

[Malignant mesothelioma in families of asbestos workers].

Malignant mesothelioma is primarily an occupational disease of asbestos workers. While there is usually a latent period of 20-40 years between exposure and appearance of the tumor, the duration of exposure may be as short as a single month. Rarely, it may appear in family members and others living with asbestos workers who might be exposed to asbestos from work clothes during laundering, or from fibers on the skin or hair of the asbestos worker. Attention should therefore be paid to those with nonoccupational contact with asbestos. We report 2 cases of pleural mesothelioma in families of asbestos workers. In both cases the laundering of work clothes was done at home. The first was a 33-year-old man; during his childhood his father worked with asbestos boards for 5 years. The second was a 76-year-old woman whose husband worked in an asbestos factory for 32 years, up to 18 years before diagnosis.

[Ring-valve abscess--a diagnostic challenge].

Infective endocarditis is a life-threatening disease which may be complicated by ring-valve abscess. Since this complication increases morbidity and mortality early diagnosis is important. Pericardial effusion complicating infective endocarditis is uncommon and should raise suspicion of the presence of an abscess. We describe 2 patients admitted for infective endocarditis and pericarditis. In both, ring-valve abscess was suspected on clinical grounds. At surgery there was pathological confirmation of the diagnosis. Both patients underwent successful aortic valve replacement with complete recovery. Controlled trials are providing increasing evidence for the superiority of transesophageal echocardiography in detecting valvular vegetations. Moreover, it is the most accurate means of detecting ring-valve abscess in cases of infective endocarditis. In view of these advantages, we propose the use of transesophageal echocardiography in every case of infective endocarditis.

Amanita verna poisoning in Israel--report of a rare case out of time and place.

A rare case of A. verna poisoning in Israel is presented; this occurred in mid-winter at a place hitherto free of the fungus. The unsuspecting victim sought help only after anuria had developed. Charcoal hemoperfusion and large dosages of penicillin with hemodialysis were followed by prompt recovery, despite the late start of treatment. It is suggested that such treatment is essential in A. verna poisoning, and is indicated at all stages of intoxication.

Influence of Judaism and Jewish physicians on Greek and Byzantine medicine and their contribution to nephrology.

Both the Old Testament and the Talmud contain a great deal of information on medicine, nephrology, health and disease. The basic premise of early Jewish medicine is based on the notion that disease is due to structural changes in internal organs. This is in contrast to the mythical dogma of humoralism as the basis of health and disease espoused by Hippocrates and Galen. The Old Testament and the Mosaic Codes provided the basis for modern public health and for the hygienic rules practised in our times. The Talmudists laid the foundations for the science of pathology as we know it today. These issues are discussed in detail and the contributions of three prominent medieval physicians (Asaph Judaeus, Isaac Judaeus and Maimonides) are presented.

Combined ultrasound and needle aspiration cytology in the assessment and management of hypofunctioning thyroid nodule.

We evaluated the efficacy of combining B-scan bistable and gray-scale ultrasound with needle aspiration cytology in assessing and managing solitary hypofunctioning solid and cystic nodules. Of the 150 cases surveyed, 90 had surgical follow-up histology for comparison to preoperative aspiration cytology results. Overall neoplasm rate in these 90 cases was 66%, increasing to 93% if colloid nodules were included. Adequate material for cytology preoperatively was obtained in 83 (92%). In cases with adequate preoperative needle aspiration cytology, there were 66 solid and 17 cystic or mixed lesions. Overall accuracy for differentiating benign from malignant nodules for solid lesions was 63 of 66 (95%), compared to 15 of 17 (88%) for predominantly cystic or mixed lesions. Of the 17 cases of proven carcinoma, correct preoperative cytology diagnosis for malignancy was obtained in 12 (71%). Malignancy was most often correctly diagnosed for solid papillary and metastatic cancer lesions. No false-positives were noted and atypical adenomas and Hürthle-cell adenomas have been correctly diagnosed. The simplicity and safety of these diagnostic procedures justify their use for "selective" surgery and particularly for those cases that have been initially assigned to conservative, nonsurgical therapy.

Jewish medicine and the University of Padua: contribution of the Padua graduate Toviah Cohen to nephrology.

During the period of the 11th to 17th century, the access of Jews to European universities was restricted and even those who were fortunate enough to be admitted to a university were not awarded a degree at the end of their studies. An exception to this situation was the University of Padua that allowed Jewish students to study and awarded them degrees; indeed 229 physicians graduated from this university between 1409 and 1721. Among these physicians there were many luminaries such as Joseph Del Medigo, Salmon Congeliano and Toviah Cohen. The latter made many contributions to the field of nephrology. In this treatise Maaseh Toviah he discussed uroscopy, kidney function, body fluid homeostasis and obstructive uropathy.