Cystinuria is an autosomal recessive disease characterized by the development of kidney stones. Guided by the identification of the SLC3A1 amino acid-transport gene on chromosome 2, we recently established genetic linkage of cystinuria to chromosome 2p in 17 families, without evidence for locus heterogeneity. Other authors have independently identified missense mutations in SLC3A1 in cystinuria patients. In this report we describe four additional cystinuria-associated mutations in this gene: a frameshift, a deletion, a transversion inducing a critical amino acid change, and a nonsense mutation. The latter stop codon was found in all of eight Ashkenazi Jewish carrier chromosomes examined. This report brings the number of disease-associated mutations in this gene to 10. We also assess the frequency of these mutations in our 17 cystinuria families.

Stress has a significant influence on the function of the human organism. A simple, rapid, inexpensive, and reliable marker for stress would therefore be of great value. We have recently noted that stress increases the state of leukocyte adhesiveness and aggregation in the peripheral blood. We evaluated 64 patients who had various degrees of congestive heart failure, a condition known to induce a state of physiologic stress, to verify whether a relation exists between the intensity of the stress response and the magnitude of leukocyte adhesiveness. Included in the 64 were 53 patients without congestive heart failure, 23 with compensated failure, 22 with significant congestive heart failure, and 19 with florid pulmonary edema. The percentage of aggregated leukocytes in these four group was 6% +/- 4%, 6% +/- 4%, 10.5% +/- 5%, and 15% +/- 14%. Values for the third and fourth group differed in a statistically significant way. Thus, with further investigation into additional stress-inducing conditions, the state of leukocyte adhesion and aggregation may prove to be a reliable marker for the detection of stress and an inexpensive tool for quantifying its severity.

The objective of this study was to prospectively determine the efficacy of the results of routine testing of thyroid functions in patients admitted to a general medical ward. Blood for thyroid function tests was drawn on admission as part of the laboratory screening panel from 270 consecutive patients. Fifty-one were excluded due to recognition of thyroid-related problems by the clinical staff. 138 patients (63%) had normal free thyroxin (FT4) levels, one patient had hyperthyroidism, 15 patients (6.8%) had laboratory primary hypothyroidism and 65 patients (29.6%) had equivocal results (FT4 < 0.9 ng/dL and TSH < 5.0 mmu/L). In eight out of 31 patients in the latter group, the thyroid releasing hormone (TRH) test revealed primary or secondary hypothyroidism. A total of 55 patients (25.1%) expired within one year. The mortality rate was significantly higher among the low FT4 patients (p < 0.01), and was independent of age and sex. We conclude that inclusion of FT4 in a laboratory screening panel will reveal a large patient population with abnormal results. However, establishing the diagnosis requires additional tests. Therefore, screening for occult hypothyroidism among a select population, not the acutely sick, populations may be more efficient.

Background: Data concerning group C streptococcal bacteremia come mainly from case reports; thus, population-based studies from different geographic areas are needed to validate these findings.Methods: Eight years of data on group C streptococcal infection in Israel and cases of bacteremia in five hospitals were reviewed. We compared data from our survey as well as from other population-based studies with multiple cases published as case reports.Results: The organisms were isolated in 78 cases (excluding pharyngitis); 16 had bacteremia. Ten cases of bacteremia were reviewed in five hospitals; none of the patients reported exposure to animals, and nine had severe underlying diseases. The clinical syndromes included four cases of primary bacteremia, four cutaneous infections, and one case each of meningitis and pneumonia. There were two deaths, one patient underwent amputation of a toe, one had a stroke, and one had a relapse. We compared 80 cases published as case reports with 59 cases reported in five population-based studies from different countries. We found higher rates of underlying diseases, alcohol abuse, liver diseases, and cutaneous infections, and lower rates of exposure to animals or raw products, endovascular infections, and central nervous system infections in population-based studies. Morbidity and mortality were 20% to 30% each in both types of studies.Conclusions: Group C streptococcal bacteremia affects patients with underlying diseases; exposure to animals is variable and less frequent than previously reported. Morbidity and mortality are high and probably reflect the patients' underlying state as well as the severity of the infection.

The epidemiology of typhoid fever in Western countries may be affected by immigration from developing countries. We studied the immigration of Ethiopian Jews to Israel to find the effects of an influx of many individuals infected with typhoid into an area with a low incidence of the disease. Typhoid fever affected 204 Israelis and 121 (1.1%) of 10,654 Ethiopian immigrants during the period of 1984-1985. Of those Ethiopian cases, 107 occurred during a 3-month period. During the 5 months following that 3-month period, there was no increase in the number of cases of typhoid among Israelis. Although after that time there was a local waterborne outbreak of typhoid that affected 83 Israelis, no Ethiopians resided in the area where the outbreak occurred; therefore, we concluded that these 83 cases of typhoid fever were not related to the immigration of Ethiopians into Israel. In fact, if those 83 cases were excluded from the statistical analysis, there was no increase in the occurrence of typhoid during the 2-year period studied. Therefore, the immigration of many people with typhoid into an area of low incidence does not necessarily confer a risk of infection to the local population.

Cystinuria is an autosomal recessive disorder of amino acid transport. It is a common hereditary cause of kidney stones worldwide, and is associated with significant morbidity. in 17 affected families, we found linkage between cystinuria and three chromosome 2p markers. Maximal two-point rod scores between cystinuria and D2S119, D2S391 and D2S288 were 8.23 (theta=0.07), 3.73 (theta=0.15) and 3.03 (theta=0.12), respectively. Analysis of recombinants and multipoint linkage data indicated that the most likely order is cen-D2S391-D2S119-cystinuria-D2S177-tel. We also observed high rates of homozygosity for markers in this chromosomal region among 11 affected offspring of consanguineous marriages. Based on its map position and function, the recently cloned SLC3A1 amino acid transporter gene is a primary candidate gene for this disease.

OBJECTIVE:To determine the state of leukocyte adhesiveness/aggregation (LAA), in the peripheral blood of patients with ischaemic heart disease.METHODS:All the patients were examined during their hospitalization in the Chaim Sheba Medical Center Intensive Coronary Care Unit. The patients were divided into four diagnostic categories according to the clinical picture, electrocardiographic and echocardiographic findings, as well as enzyme levels. The white blood cell count (WBCC), the erythrocyte sedimentation (ESR) and the state of LAA were measured daily for a maximum of six days.RESULTS:The LAA in ten patients with acute anterolateral myocardial infarction, increased from 5 +/- 5% day one to 13 +/- 6% at day five; the respective values for ten patients with a diaphragmatic MI were 2 +/- 2% and 5 +/- 3% respectively. Normal LAA values were noted in ten patients with myocardial ischaemia, and no evidence for infarction, as well as in ten controls. The increases LAA correlated significantly with the erythrocyte sedimentation rate (r = 0.53, p < 0.0001), raising the possibility that fibrinogen is involved in induction and/or maintenance of an increased LAA.CONCLUSIONS:Our findings suggest that the state of LAA increases during the evolution of the infarction/inflammation process. Considering that sticky leukocytes may contribute to capillary flow retardation, the results of the present study would be relevant if optimal timing for anti-adhesive therapy is considered.

The aim of the present study was to determine if normal liver cell kinetics can be evaluated using bromodeoxyuridene (BrdU) as the label. BrdU was injected intraperitoneally into 10 male adult rats, 5 were sacrified after 1 hr, and the remainder after 30 days. The livers were fixed in 70% ethanol, embedded in paraffin and histological slides were prepared. The labelled nuclei were revealed using indirect immunoperoxidase staining and easily counted by light microscopy. One hr after labelling, labelled hepatocytes and littoral cells were detected within 164 +/- 12.3 Crm and 161 +/- 13 mu m respectively from the portal tract rim. After 30 days, both cell types reached the respective distances of 290 +/- 4.6 mu m and 294 +/- 17.7 mu m. Their respective displacement velocities were 4.2 mu m/d and 4.3 mu m/d. These results were identical to those we obtained using tritiated thymidine. This laboratory method provides a useful and simpler alternative method to tritiated thymidine.

82 patients were retrospectively evaluated for the effects of maximal and minimal temperatures, barometric pressure, wet and dry temperatures and heat stress on the five consecutive days preceding an acute gouty attack. Maximal temperature on day four preceding the attack was higher than the monthly mean [p < 0.01], the fifth day's lower than the monthly mean minimal temperature [p < 0.05], and the mean barometric pressure of the fifth day before the attack higher then the monthly mean [p < 0.02]. On day four before the acute gouty arthritic attack heat stress was significantly higher than the mean monthly heat stress [p < 0.03]. The same findings were noted between the difference of the fifth night wet and fourth night dry temperatures, which were higher than those on the day of the attack [p < 0.05 and p < 0.03 respectively]. These weather changes were not specific to a certain month. Weather changes which occur four to five days before an acute gouty attack may play a significant role in precipitating the attack.

Takayasu's arteritis is a chronic inflammatory arteriopathy of unknown cause. The pulseless phase of Takayasu's arteritis is preceded by a period of "prepulseless disease" when the patients suffer from systematic symptoms without obvious evidence of obstruction of larger arteries. Herein we report a unique case of Takayasu's arteritis presenting as sarcoidosis manifested by restrictive lung disease, hilar adenopathy and non-caseating granulomas of the skin. We are aware of only one report in which non-caseating skin granulomas were evident at the prepulseless phase of Takayasu's arteritis. However, in our patient the clinical picture was typical of sarcoidosis. Increased awareness of this possibility will lead to more frequent skin biopsies in patients with Takayasu's arteritis and nodular skin lesions, which may increase the number of reported cases with this combination.

Typhoid fever remains a major cause of mortality in developing countries, with a case-fatality rate (CFR) of 12%-32%, whereas in developed countries this rate has successfully been reduced to < 2%. The cause of this high CFR in developing countries was investigated by studying two populations of patients who had typhoid fever during the years 1984-1985: Ethiopian Jews who were infected in Africa (a region with a high CFR) and treated in Israel (a region with a low CFR) and native-born Israelis. The causative organisms were of similar phage types. Among 121 Ethiopian Jews there were two fatalities (CFR, 1.65%), and among 204 native-born Israelis there were three fatalities (CFR, 1.47%). Findings of the clinical course and treatment were similar for 15 Ethiopian Jews and 14 native-born Israelis and consistent with those of reports from developed countries. We conclude that the high CFR for typhoid fever in Africa is due to delayed hospitalization and treatment rather than to differences in host factors or in the virulence of the pathogen and that mortality can be reduced by hastening hospitalization and treatment.

OBJECTIVE: To report a case of erythromycin base-induced rash and liver function disturbances.CASE SUMMARY: A patient with erythema nodosum and high antistreptolysin-O titers was treated with erythromycin on the assumption that occult streptococcal infection was the cause of the erythema nodosum. Forty-eight hours after the initiation of therapy the patient developed fever, severe generalized rash, pruritus, and cholestatic and hepatocellular liver function disturbances. Extensive evaluation to determine the cause of liver function disturbances was unrevealing. Marked improvement was noticed within days after cessation of erythromycin.DISCUSSION: Case reports in the literature on the adverse effects of erythromycin and its derivatives were reviewed. The possible immunologic mechanism involved is postulated.CONCLUSIONS: Erythromycin base must be added to the list of erythromycin derivatives that can cause rash and liver function disturbances. The concomitant appearance of fever, rash, jaundice, and liver function disturbances raises the possibility of hypersensitivity as the mechanism for the liver disturbances.

Many experiments have shown convincingly that natural killer (NK) cell activity against viral infections is an important early defence mechanism in mice. Since the NK response occurs soon after infection, often long before clinical signs of disease become manifest, it has been difficult to design studies to monitor accurately NK cell kinetics following infection, without actually administering pathogens to volunteers. There is therefore little data pertaining to the role of NK cells in humans. Nevertheless, a number of studies have shown elevated NK activity in response to herpes simplex and influenza virus infections in humans. Our study was designed to show that NK activity could be provoked in humans by exposure to viral particles without actual live viral infection. The development of NK cell response in the peripheral blood of volunteers shortly after vaccination with killed influenza trivalent vaccine was studied. The results demonstrate that killed virus vaccine induces and augments NK cell activity for relatively long periods. Such data may prove valuable for designing possible modes of augmenting NK activity as a therapeutic tool.