Reforms on medical education: the case of Kyrgyzystan.

INTRODUCTION: The Central Asian republics of the former Soviet Union gained their independence in 1991. Soon after this event, reforms in health care were planned in many of these countries. In Kyrgyzistan, the reforms included a mandatory health insurance system, a new provider payment system, licensing and accreditation, a national drug policy and rationalization of ambulatory services. Multi-profile policlinics, or family medicine group practices were established. Reforms in health care are not always accompanied by changes in medical education, and so medical knowledge may lag behind that in other countries. This is especially prominent in rural areas, where new practices and regulations may arrive late, and are often misunderstood. The reforms in Kyrgyzistan necessitated a change in undergraduate medical education. The educational reform consisted of a unification of the separate tracks for pediatrics, medicine and public health into one track of general medicine; the introduction of teaching of patho-physiology according to body systems; the establishment of clinical clerkships; and a proposal for rotating internship. METHODS: World Health Organisation sent teams to Kyrgyzistan to work with the local committees as facilitators for the implementation of the health-care reform. This paper is based on the experience of the authors in conducting two such missions directed at the synergistic reform in medical education. RESULTS: VISIT 1: Changes to the curriculum were suggested. It was decided not to recommend teaching in rural primary care settings at that stage, due to logistical difficulties. This subject was to be addressed at a later stage because medical services in rural areas were scarce. VISIT 2: Among other interventions, the encouragement of doctors to practice in rural areas was discussed in detail, but the teachers of the medical school were not receptive to the idea of sending medical students to rural clinics. This was to be addressed at some time in the future. CONCLUSION: The changes were aimed at facilitating the introduction of family medicine as a specialty and strengthenning primary care, although measures to incorporate rural practice in the reform proved difficult to achieve. Reform in medical education can only be justified if it will contribute to the improvement of the health of the population. In order to achieve this goal, the production of better physicians must be assured. In Kyrgyzistan, it was hoped that improved graduates would be the resource for the development of family medicine as a recognized specialty, with the potential to improve the health status of the whole population.

Genotypic variation of HIV-1 reverse transcriptase and protease: comparative analysis of clade C and clade B.

OBJECTIVE: To compare drug-resistant variants from untreated (naive) and treated patients infected with clade B or C virus. METHODS: Consecutive samples (165) from patients throughout Israel were analyzed. All those in the treated group were failing highly active antiretroviral therapy. RESULTS: There were 87 clade B (14 naive) and 78 clade C (20 naive) [corrected] with significant differences in the prevalence of known drug-resistance mutations between the clades: in naive patients in the protease region M36I 7% and 95% (P < 0.0001), K20R 0% and 27% (P = 0.063), A71V 18% and 0% (P = 0.063), M46I 0% and 13%, and V77I 18% and 0% (P = 0.063), respectively, and in the reverse transcriptase region A98G/S 0% and 20% (P = 0.12), respectively. Most clade C viruses also showed significant differences from clade B consensus sequence at additional protease sites: R41K 100%, H69K/Q 85%, L89M 95% and I93L 80% (P < 0.0001). There were also significant differences (P < 0.03 to < 0.0001) in treated patients in clades B and C: in the protease region L10I 40% and 12%, M36I 26% and 95%, L63P 67% and 40%, A71I 38% and 7%, G73I and V77I 18% and 0%, I84V 16% and 3%, and L90M 40% and 12%, respectively; in the reverse transcriptase M41L 41% and 17%, D67N 41% and12%, K70R 30% and 7%, T215Y 48% and 29%, K219Q 21% and 7%, and A98G/S 3% and 24%, respectively. CONCLUSION: Significantly differences between clade B and C viruses may be associated with development of differing resistance patterns during therapy and may affect drug utility in patients infected with clade C.

Report of a medical mission to Somaliland, 2001.

Somaliland is a self-declared state, not recognized by the nations of the world. Sixty percent of the population are herders or small scale farmers. Gross national product and other data are not available, but it is evident, according to surveys conducted by the United Nations, that most of the population has a low income. The health-care system consists of a public sector, which covers primary care, hospital care, immunizations, and tuberculosis care. The major clinical problems are tuberculosis, malaria and childhood diarrhea. Lack of trained personnel is a major difficulty in the health care system. This paper describes visits to health care facilities in Somaliland, and suggests some improvements for the system.

Changing epidemiology of dengue fever in travelers to Thailand.

A study was conducted to evaluate the incidence and seasonal pattern of dengue fever occurring among Israeli travelers to Southeast Asia. The illness was diagnosed by Israeli physicians stationed abroad and by serological methods carried out in Israel. Between 1994 and 1998 dengue fever was confirmed in 103 travelers, 80 of whom were diagnosed in Israel. A sharp increase in the incidence was noted in 1998 as compared with the previous 4 years. The attack rate during 1998 in a defined group of travelers was 3.4/1,000 and reached a peak of 5/1,000 during the dry season of 1998.

The global medical school, 2020.

With fast-developing technologies and communication, the future of the medical school is not clear. The definition of the graduate is shifting from what was forged in the past to a new doctor. The trends are towards more specialization, mastering of modern technologies and scientific achievements, versus community awareness and a return to family doctors. An innovative approach was taken with the development of a program in International Health and Medicine at Ben Gurion University, supplementing the regular curriculum of the Medical School. Such programs might bridge the gap between the doctor in industrial countries and the physician in Third World countries, by creating a physician who will be able to function in cultural environments other than his/her own.

[Severe psychiatric disorders during trips to the Far East].

8 cases of acute mental disorders among Israelis travelling in the Far East are presented. The most common symptoms were hallucinations, paranoid delusions, agitation and depression. The important precipitating factors were drug abuse, reaction to the foreign environment and malarial prophylaxis. Treatment included creating a nonhostile environment, the presence of a Hebrew-speaking physician, psychopharmacotherapy and prompt evacuation to Israel. Most patients improved markedly and returned to normal functioning.

[Severe pneumonia caused by Bordetella bronchiseptica].

Bordetella bronchiseptica rarely causes disease in man, and is an unusual pathogen in animals. It causes a pertussis-like syndrome, but pneumonia and sepsis have been described in the immunocompromised as well as in the immunocompetent. A 53-year-old man with adult-onset diabetes and healed pulmonary tuberculosis presented with lobar pneumonia and rapidly developed septic shock with adult respiratory distress syndrome. He responded well to the combination of piperacillin-tazobactam.

Serological markers for hepatitis B and treponemal infection among HIV carriers from Ethiopia.

A group of 52 HIV carriers among immigrants who arrived in Israel from Ethiopia in Operation Solomon, 1991, is described. A control group was randomly chosen from the same population. HBV serology and treponemal antibodies were obtained from both groups. The frequency of HBV markers was similar in both groups (70% among the HIV carriers and 78.8% in the controls). HBsAg was more frequently found among HIV carriers (20%) than in the control group (8.6%). Treponemal antibodies were common among HIV carriers (31%), and infrequent in the controls (3%). These data indicate that HIV infection in this community is linked to treponemal infection and that these carriers handle HBV less efficiently then HIV-negative subjects.

PIP: In Jerusalem and the Negev, physicians examined and took blood samples from recent Jewish immigrants older than 10 years who came to Israel from Ethiopia during Operation Solomon in 1991. The physicians and other colleagues compared data on the 52 people who were HIV positive with 139 who were HIV negative to examine HIV's relationships with treponemal infection and hepatitis B infection. The 2 groups were essentially the same age (37 years for cases and 35.5 years for controls). No significant difference in the prevalence of hepatitis B virus (HBV) markers existed between the 2 groups (70% for HIV-positive migrants and 78.8% for HIV-negative migrants). This confirmed other research that HBV is transmitted vertically in developing countries. Yet, HIV-positive migrants were more likely to have markers for hepatitis B surface antigen than HIV-negative migrants (20% vs. 8.6%; p = .018). The HIV-positive migrants had a higher prevalence of treponemal markers than did HIV-negative migrants (31% vs. 3%), indicating that treponemal disease increased their risk of HIV infection. The earlier group of Jewish immigrants from Ethiopia during 1984-1985 (Operation Moses) also had a high prevalence of treponemal antibodies but no one had HIV infection. These immigrants walked through a rural area to a refugee camp in Sudan from which they were taken to Israel by air. The newer immigrants rode buses to Addis Ababa and waited 1 year before they immigrated to Israel. The results of this study suggests that the new immigrants (an ethnic homogenous group just like their earlier counterparts) became infected with HIV during the short period in Addis Ababa. Israeli physicians have designed a study to follow the HIV-positive immigrants to determine whether the environment in Africa is responsible for the different clinical picture of AIDS.

Tuberculosis cases in the Negev 1978-1987: ethnicity, sex, and age.

BACKGROUND: The incidence of tuberculosis (TB) in Sub-Sahara Africa is considered to be one of the highest in the world. During the past decade thousands of Jewish refugees from Ethiopia were settled in the Negev and might constitute a potential reservoir of infection for the indigenous populations. This study provides some baseline information about TB in the Negev just prior to and after an Ethiopian immigration peak. METHODS: The files of every case of TB diagnosed during the decade 1978-1987 at Soroka Medical Center were reviewed and each diagnosis was validated by rigorous clinical and microbiological criteria. The age, gender, and ethnic background of each case were recorded, and approximate population denominators were estimated from Ministry of Health and Census data. Annual and decade incidence rates were then calculated for the different demographic categories. RESULTS: 279 cases of TB were verified. The main 10-year incidence rate per 10,000 Israeli Jews was 0.28; for the Negev Beduins it was 1.52; for the Ethiopian Jews, 91.9. In the Jewish population, cases among males (59) far exceeded those among females (7), but the reverse was observed, both among the Beduins (47 female and 31 male cases) and the Ethiopian immigrants (79 female and 56 male cases). In all three groups TB incidence increased with age, ranging from 0.03 per 10,000 for young non-Ethiopian Jews to a remarkable 623.8 per 10,000 for elderly Ethiopian Jews. CONCLUSIONS: The results of this study indicate the existence of a potentially large TB reservoir in the Negev. Health workers must be alerted to the importance of continued case finding, effective case management, and the control of infection transmission. The unique integration of the Negev Health Delivery System should help monitor intervention strategies.

Extrapulmonary tuberculosis in an immigrant society: clinical and demographic aspects of 92 cases.

Extrapulmonary tuberculosis accounted for 33% of all new cases of tuberculosis identified at the Soroka Medical Center in Beer Sheva, Israel, during a 10-year period. The most common types of extrapulmonary infection diagnosed were genitourinary tuberculosis (54% of patients), lymphadenitis (13%), pleural tuberculosis (9%), and tuberculosis of bones and joints (8%). Of 92 patients, 51% were Jews of Ethiopian origin, 29% were Jews of non-Ethiopian origin, and 20% were Bedouins. Thus, extrapulmonary tuberculosis remains a significant problem for Israel's heterogeneous population.

Benign familial leukopenia and neutropenia in different ethnic groups.

Benign hereditary leukopenia-neutropenia has been reported in several ethnic groups, including Yemenite Jews, Blacks of South African extraction, West Indians and Arab Jordanians. The subjects with BFL were shown not to have an increased incidence of infections, and their response to infection did not differ from subjects having normal white blood cell counts. This study entails the report of two additional unrelated ethnic groups with familial neutropenia - Black Beduin and Falashah Jews. The familial nature of the phenomenon was confirmed. The suggested mechanism of this type of neutropenia is a defect in release of mature WBC from the bone marrow to the peripheral circulation. All ethnic groups thus far reported have tanned or dark skin. The significance of this common feature has still to be elucidated.

Change in degree of type 1 piliation of Escherichia coli during experimental peritonitis in the mouse.

To determine whether expression of type 1 pili varies during the course of Escherichia coli infection in vivo, mice were injected intraperitoneally with 5 X 10(7) CFU of piliated or nonpiliated phase variants per ml, and the degree of piliation was measured in peritoneal exudate by an enzyme-linked immunosorbent assay inhibition method. In the animals challenged with the piliated bacteria, the numbers of organisms increased a log over 9 h and the amount of pilus antigen decreased from 3 to 0.075 micrograms/10 bacteria. After a 4-h delay, nonpiliated bacteria also increased by one log over 9 h; however, the amount of piliation remained virtually undetectable. Piliated E. coli were more virulent than nonpiliated variants in this model (50% lethal dose of 7.5 X 10(6) versus 3 X 10(7), respectively). The difference was significantly reduced by prior passive immunization with rabbit serum containing high titers of antipili antibody. Piliated bacteria adhered in significantly greater numbers to isolated mouse peritoneal membranes than did nonpiliated variants (15,400 +/- 2,700 versus 1,300 +/- 700 bacteria/mm2, respectively; P = 0.05). Adherence was inhibited by the presence of 0.1 M alpha methyl mannose (1,500 +/- 1,800 bacteria/mm2, P = 0.01). These results confirm the results of previous qualitative studies showing that phase variation of type 1 pili occurs in vivo and suggest that these pili may confer an initial advantage for growth of E. coli in the peritoneal cavity, presumably by fostering colonization of the peritoneal serosal surface.

Binding of lipoteichoic acid of group A streptococci to isolated human erythrocyte membranes.

The spontaneous binding of group A streptococcal lipoteichoic acid (LTA) to mammalian cell membranes was studied in isolated membranes of human erythrocytes. The binding of radiolabeled LTA to erythrocyte membranes was dependent on membrane concentration and time. Binding approached a maximum within 30 min of incubation. The bound LTA could be displaced by adding a 50-fold excess of unlabeled LTA. The displaced LTA was eluted from a column of Sepharose 6B in a position identical to that of authentic LTA, suggesting that binding did not alter the size of the molecule. A dissociation constant of 42 micrometers was calculated, and only one population of approximately 5.5 X 10(6) binding sites per erhtyrocyte membrane was detected. Since these results suggested that erythrocyte membranes possess specific binding sites for LTA, an attempt was made to localize the putative receptors to the outside or the inside surface of the erhtyrocyte membrane. Assays of the binding of LTA to resealed right-side-out and inside-out membrane ghosts demonstrated that the outside surface was able to bind over 10 times more LTA than the inside surface. These results support the concept that the membranes possess specific binding sites for LTA and inciate that these binding sites are located almost entirely on the outside surface of erythrocyte membranes.

Suppression of bacterial adherence by subminimal inhibitory concentrations of beta-lactam and aminoglycoside antibiotics.

Nonseptate filaments of Escherichia coli obtained by growth of a temperature-sensitive mutant of the organism at its restrictive temperature in the absence of antibiotics or at its permissive temperature in the presence of approximately one-half the MIC of penicillin (27 micrograms/ml; MIC of penicillin, 50 micrograms/ml) lacked the ability both to bind to mannose and to adhere to host tissues. Addition of low concentrations (0.5-10 micrograms/ml) of streptomycin to cultures of E. coli resulted in marked suppression of the mannose-binding and adhering ability of streptomycin-sensitive E. coli (MIC, 30 micrograms/ml). In contrast, up to 5,000 microgram of streptomycin/ml had no effect on an isogenic streptomycin-resistant mutant of E. coli (MIC, 20,000 micrograms/ml). No concentration of penicillin or streptomycin that was tested was able to suppress either the mannose-binding or the adhering ability of E. coli once those activities had been acquired by the organism. These results suggest that subminimal inhibitory concentrations of antibiotics suppress the ability of bacteria to adhere to cells.

Excretion of lipoteichoic acid by group A streptococci. Influence of penicillin on excretion and loss of ability to adhere to human oral mucosal cells.

Group A streptococci were grown in the presence of [2-(3)H]glycerol. Concentrated suspensions of the labeled organisms were incubated with and without penicillin. [(3)H]Glycerol-labeled material accumulated in the supernates in increasing amounts with increasing concentrations of penicillin, ranging from 0 to 50 U/ml. The excretion of labeled material occurred in the absence of nucleic acid synthesis or bacteriolysis indicating that the phenomenon is independent of cell multiplication or decay. The accumulation of label was paralleled by an accumulation of erythrocyte-sensitizing material measured by passive hemagglutination tests for lipoteichoic acid antigen, indicating that a portion of the labeled material possessed the properties of lipoteichoic acid. Culture supernates were fractionated by column chromatography, and the materials obtained were analyzed by electrophoresis on sodium dodecyl sulfate polyacrylamide, thin-layer chromatography, and paper chromatography. The ability of the same materials to bind to human erythrocytes and epithelial cells was tested. The culture supernate contained lipoteichoic acid, deacylated lipoteichoic acid, glycerol phosphate, and free glycerol. Penicillin caused an increase in the amounts of each of the excreted materials. Streptococci that were stimulated with penicillin to lose their lipoteichoic acid (previously shown to mediate adherence of group A streptococci) lost their ability to adhere to buccal mucosal cells, suggesting that penicillin may influence bacterial ecology by mechanisms other than killing sensitive organisms.

Near drowning in the Dead Sea.

Seven cases of submersion in the Dead Sea are described. The clinical picture varied in severity and consisted of signs of pulmonary edema, chemical bronchitis, hypermagnesemia and hemoconcentration. Two of the patients died of hypotension and cardiac arrhythmia. The clinical findings were similar to those found in cases of drowning in seawather, but the presence of hypermangesemia is unique to this entity. The amount of aspirated water causing severe clinical signs seemed to be much smaller than is seen with ordinary seawater. Therapeutic guidelines, including assisted respiration, infusion of hypotonic solutions and corticosteroid therapy, are suggested.

Chronic eosinophilic leukemia complicated by epidural myeloblastoma.

Epidural myeloblastoma, which compressed the spinal cord, was the first evidence for chronic granulocytic leukemia, eosinophilic type, Ph chromosome negative. This manifestation was preceded by 3 years follow-up of a patient with persistent eosinophilia of 60% mature eosinophils. The only clues for the diagnosis of leukemia were splenomegaly and high serum vitamin B12, most of which was bound to transcobalamin I. The latter finding presents a useful diagnostic criterium in myeloproliferative disorders.