The autosomal dominant polycystic kidney disease gene in a Jewish family from Uzbekistan is PKD1.

A large Jewish family from Tashkent (Uzbekistan) was studied for linkage of autosomal dominant polycystic kidney disease (ADPKD) to molecular markers on the short arm of chromosome 16. A restriction fragment length polymorphism (RFLP) analysis was performed on 28 family members, including 9 ADPKD diagnosed patients in 3 consecutive generations. A specific haplotype was found to segregate with the disease in eight of the nine affected individuals. The peak lod scores for linkage between the disease phenotype and the five informative flanking markers were: 3'HVR 1.70 at theta = 0.08; GGG1 1.18 at theta = 0.001; CMM65 1.50 at theta = 0.001; 26-6 0.86 at theta = 0.001 and 218EP6 1.39 at theta = 0.001. A particular haplotype of these markers segregated with the disease phenotype. The peak lod score of this haplotype was 3.046. Homogeneity test, comparing this family to 40 PKD European families, showed that the conditional probability that it belongs to the same group is 1.000. Taken together, these findings show that the defective gene in this Jewish family from Uzbekistan is PKD1. To our knowledge, this is the first ADPKD family in Israel in whom linkage studies were performed and one of the few originating from populations outside the Western world.

Reason for referrals among military primary care physicians.

In order to assess the reasons for high referral rates to secondary medical care services in the Israel Defence Force-Medical Corps, we conducted a study in which 28 physicians in five primary care clinics took part. Seven hundred thirty-seven patients were referred to specialists. The referral reasons were learned from questionnaires filled in for each of these patients. The study shows that factors related to the physicians are important in determining when referral is made: Israeli medical graduates showed less confidence than their peer graduates outside of Israel. A possible explanation is that the Israeli graduates are better prepared for working in a scientific, sophisticated medical environment rather than the ambulatory primary care environment.

Hereditary ovarian cancer: a dilemma in prognosis.

Five women in three generations developed ovarian cancer. We closely monitored 36 descendent women in this family who were at high risk for developing this disease. Prophylactic oophorectomy is considered the optimal way to prevent the development of ovarian cancer. In the light of the young age of the women at risk and their strong objection to oophorectomy, we closely monitored the examinees for early signs of cancer for more than 5 years. None of them developed cancer. The dilemma in treatment of women at risk is discussed.

Hypodipsic hypernatremia and hypertriglyceridemia associated with cleft lip and cleft palate: a new hypothalamic dysfunction syndrome?

We report on a 4-month-old girl with congenital hypodipsic hypernatremia resulting from decreased sensitivity of the hypothalamic osmoreceptors with increased tonicity in association with hyperlipemia and cleft lip and cleft palate. We postulate that the link among these various derangements is hypothalamic dysfunction.

Transport into brain of buthionine sulfoximine, an inhibitor of glutathione synthesis, is facilitated by esterification and administration of dimethylsulfoxide.

Buthionine sulfoximine (BSO), an inhibitor of glutathione synthesis, is poorly transported into the brain of adult mice, and only a slight decrease (approximately 10%) in the level of brain glutathione is found 30-60 min after intraperitoneal administration of BSO. When BSO is given as the ethyl ester, the brain level of BSO increases substantially after 5-15 min, and the glutathione level decreases by about 25% after 30-60 min. When BSO or its ester is given in 15% dimethylsulfoxide solution the brain levels of BSO are increased significantly and the brain glutathione levels are decreased by 20-35%. These observations suggest procedures that may be useful in decreasing the glutathione levels of the brains of adult animals. The finding that administration of BSO ethyl ester led to about a 25% decrease in the brain level of glutathione within 15 min suggests that a fraction of brain glutathione turns over very rapidly and may therefore be of special physiological significance.

Occult ocular damage as a leading sign in the battered child syndrome.

A three-month old, premature female infant is presented with severe bilateral occult ocular damage comprised of cataracts, lenses dislocation, retinal hemorrhages and total funnel-shaped retinal detachment without external signs such as bruises. This severe eye trauma is the result of child abuse. We would like to alert pediatricians as well as ophthalmologists that any ocular injury should raise the possible diagnosis of battered child syndrome even in the absence of other supportive evidence of external trauma.

Doxycycline prophylaxis for shigellosis.

The efficacy of oral doxycycline, 100 mg/d for 14 days, in reducing the incidence of shigellosis in newcomers to an area hyperendemic for the disease was examined in a double-blind, placebo-controlled trial. Of 107 entrants, 100 completed the study; 50 received the drug and 50 received a placebo. Diarrheal disease and associated symptoms were monitored for 8 weeks. Starting on the 3rd day of the trial, an outbreak was observed, and Shigella flexneri type 2a was isolated from 6 subjects. Eight of the subjects in the treatment group had diarrhea (16%) compared with 37 in the placebo group (74%), providing a 79% protection rate. There was no significant difference in the occurrence of accompanying symptoms between the subjects suffering from diarrhea in both groups, but the duration of disease was shorter in the treatment group. Serologic study of the outbreak showed no significant difference in antibody response to S flexneri between the treatment (14 of 43) and placebo (18 of 39) groups. Doxycycline prophylaxis apparently is effective and probably does not prevent subclinical infection.

Glutathione ester prevents buthionine sulfoximine-induced cataracts and lens epithelial cell damage.

Treatment of newborn rats and mice with buthionine sulfoximine, an inhibitor of glutathione synthesis, leads to development of cataracts, which are not prevented by treatment with glutathione, but they are prevented by treatment with glutathione monoester. Cataracts are associated with glutathione deficiency in the lens epithelium, which undergoes severe degeneration. The findings indicate that glutathione normally functions in the protection of the lens and lens epithelium against oxidative injury, suggesting that procedures that increase lens glutathione levels might be useful for prevention of other types of cataracts. Relatively low doses of buthionine sulfoximine produce cataracts in newborn animals, and treatment of pregnant mice with buthionine sulfoximine during the last part of gestation leads to cataract formation in the offspring. The high sensitivity of the developing lens to the effects of glutathione deficiency suggests that this tissue may be a useful model for studies on glutathione function.

Failure of etretinate therapy in twins with severe congenital lamellar ichthyosis.

We cared for twin females with severe lamellar exfoliation of the newborn (collodion babies) and a family history of death of two brothers at age 3 months. The twins were given a controlled trial of etretinate (Ro 10-9359, Tigason) after not responding to other therapeutic modalities. One of the infants received 1 mg/kg body weight of the drug for 24 hours, while her identical twin sister did not have the medication. Monthly skin biopsies taken from both patients during nine months of therapy did not demonstrate any histologic difference under light microscopy. The clinical course in both infants was basically the same. Etretinate plasma level measurements proved that the drug was absorbed from the gastrointestinal tract. We conclude that in the very severe forms of congenital lamellar ichthyosis, oral retinoids may fail to produce any beneficial effects.

Ultrastructural abnormalities in endoscopically and histologically normal and involved colon in ulcerative colitis.

Twenty colonoscopies (eight complete or almost complete; 12 short) were carried out on 15 patients with ulcerative colitis with the aim of comparing the endoscopic aspects with the light and electron microscopic features in biopsies taken from multiple sites. Patients with severe attacks were examined without prior preparation (two examinations). When the attack was mild to moderate (11 examinations), or the patient was in remission (seven examinations), two saline enemas were given up to 1 h before examination. There was a favorable correlation between the endoscopic and light microscopic features in 94.7% of the biopsies (total number of biopsies, 76). The electron microscope findings greatly exceeded those observed by light microscope and indicated that the major abnormality resides within the colonic epithelial cells. Distinctive ultrastructural changes were present both in apparently uninvolved (endoscopically and histologically) parts of colon and in inactive stages of ulcerative colitis. These findings suggest that colonic mucosal involvement may be universal, persist during clinical remission, and precede the light microscopic findings. They also support the importance of maintenance therapy.

Hydrocortisone resolves persistent neonatal jaundice in multiple hormone deficiencies.

Association of prolonged neonatal cholestasis with hypoglycemia, small penis and congenital hypothalamo-hypopituitary derangement is presented. The infant's jaundice was unresponsive to thyroxine replacement therapy but resolved rapidly with hydrocortisone therapy. The time relationships between persistent jaundice and thyroxine and cortisol deficiencies are discussed.

Hyperkalemia as a late side effect of prolonged adrenocorticotropic hormone therapy for infantile spasms.

Two infants developed hyperkalemia shortly after cessation of prolonged ACTH therapy for infantile spasms. We wish to call for cautious approach at time of cessation of prolonged ACTH therapy because of possible unexpected and only partially understood hazardous side effects such as hyperkalemia.

Noonan's syndrome and neurofibromatosis.

A child with Noonan syndrome and multiple cafe au lait spots, compatible in size and number with von Recklinghausen's neurofibromatosis, is presented. These features may represent a distinct genetic entity rather than the coincidence of two diseases.

Cystinosis phenotypes have identical defective cystine clearance pattern.

Exposure of cultured skin fibroblast of normal, infantile nephropathic, juvenile-late-onset and adult type cystinotic patients and their corresponding obligate heterozygotes to 0.5 mmol/l of 35S cystine dimethyl ester for 30 minutes, resulted in an accumulation of cystine within the cells, and was used to look for differences in cystine clearance between the different cell types. The results suggested that all cystinotic variants are defective in their capacity to eliminate cystine to the same extent. The presented data imply that, separate clinical phenotypic variants of cystinosis, cannot be differentiated biochemically by the assay of cystine egress.

Adenovirus type 3 infection with systemic manifestation in apparently normal children.

Between July 1983 and February 1984, eight children with adenovirus Type 3 infection, proven by virus isolation from sputum, stool or nasopharyngeal swabs and a fourfold increase in complement fixation antibody titers against the virus, were treated in our department. All eight patients had fever lasting at least 7 days, hepatomegaly, diffuse pulmonary infiltrates and abnormal liver function tests. Seven of the patients exhibited dyspnea and pulmonary wheezing. Six of the patients developed changes in state of consciousness, and three had repeated convulsions. EEG patterns in three of the patients were compatible with encephalopathy. Other clinical manifestations included: follicular tonsillitis in two patients, diarrhea in two, pneumothorax in one, and shock with disseminated intravascular coagulation in one. The spectrum of adenovirus Type 3 infection reported here has been described previously only in the viral hemorrhagic fevers. This adenovirus Type 3 infection shares the potential for disseminated disease that has been described previously for Type 7, simulating Reye's syndrome.