Israel Medical Association Journal

Between the 1960s and 1980s, the main focus of biological research was nucleic acids and the translation of the coded information into proteins. Protein degradation was a neglected area and regarded by many as a scavenger, non-specific and end process. While it was known that proteins are turning over, the large extent and high specificity of the process - where distinct proteins have half-lives that range from a few minutes to several days - have not been appreciated. The discovery of the lysosome by Dr. Christian de Duve did not change this view significantly, as this organelle is involved mostly in the degradation of extra- and not intracellular proteins, and it was clear that lysosomal proteases, similar to those of the gastrointestinal tract, cannot be substrate specific. The discovery of the complex cascade of the ubiquitin pathway has changed this view dramatically. It is now clear that degradation of cellular proteins is a highly complex, temporally controlled, and tightly regulated process that plays major roles in a broad array of basic pathways during cell life and death. With the multitude of substrates targeted and processes involved, it is not surprising that aberrations in the pathway have been recently implicated in the pathogenesis of many diseases, certain malignancies and neurodegeneration among them. Degradation of a protein via the ubiquitin pathway involves two successive steps: a) conjugation of multiple ubiquitin moieties to the substrate, and b) degradation of the tagged protein by the downstream 263 proteasome complex with release of free and re-utilizable ubiquitin. Despite intensive research, the unknown still exceeds what we currently know on intracellular protein degradation and major key problems remain unsolved. Among these are the modes of specific and timed recognition of the myriad substrates of the system and the nature of the mechanisms that underlie aberrations in the system and pathogenesis of diseases.

Background: Between 1970 and 1979, there was an increase in the incidence of viral hepatitis in Israel with a shift of peak incidence to an older age in the Jewish population, followed by a declining trend during the early 1980s. In July 1999 universal immunization of infants against hepatitis A was introduced.

Objective: To evaluate the chan-ges in the epidemiology of viral hepatitis A in Israel during the past decade.

Methods: Viral hepatitis is a notifiable disease in Israel and cases are reported to the regional health offices, which in turn provide summary reports to the Ministry of Health's Department of Epidemiology. The data in this study were derived from the summary reports and from results of seroprevalence studies.

Results: Following the increase in the incidence of reported viral hepatitis (mainly due to type A) between 1970 and 1979, the rates then stabilized and around 1984 began to decline until 1992. Since then there has been a slight increase. Whereas until 1987 the rates were consistently higher in the Jewish population. since then they are higher in the Arab population. The shift in the peak age-specific incidence from the 1-4 to the 5-9 year age group observed in the Jewish population around 1970 occurred 20 years later in the Arab population. The previously described seasonality is no longer evident. Recent seroprevalence studies indicate that by age 18 years only about 30-40% of the Jewish population have anti-hepatitis A antibodies.

Conclusions: The decline in the incidence of hepatitis probably reflects the changing socioeconomic condition occurring at different times in the two major population groups. Since hepatitis A accounts for almost all the acute viral hepatitis in Israel, the universal vaccination of infants introduced in 1999 should substantially lower the morbidity within the next few years.

Background: Patients who feel involved in their treatment have better outcomes than those who do not.

Objective: To identify determinants of perceived patient involvement in obstetric care.

Methods: A retrospective study was undertaken in 1,452 (83%) of 1,750 women sampled in November 1995 from maternity wards of 14 general hospitals in Israel. A postal and telephone survey using a self-administered questionnaire included the following variables: hospital (identity number), patients' age, self-reported complications, previous deliveries, education, ethnicity, and number of obstetric interventions performed and/or considered. The main outcome measured was the reported involvement in decisions for obstetric interventions.

Results: Reported full involvement varied from 72% for epidural analgesia to 13% for forceps/vacuum extraction. Factor analysis identified two dimensions of perceived involvement: one for routine” interventions (enema, monitor­ing, IV line and episiotomy), which are performed in Israel mostly by midwives, and another for "special" interventions (forceps/vacuum extraction, epidural or other analgesia, and cesarian section) performed by physicians. Logistic regression identified hospitals, younger age, number of interventions, and Arab ethnicity as correlates of a perceived non-involvement in decisions for "special" interventions.

Conclusions: Clinical setting, age and ethnicity affected patient perception of involvement in decisions for obstetric interventions.

The hepatitis C virus is an enveloped positive-sense single-stranded RNA virus, which has been classified into 6 major genotypes and over 100 subtypes. HCV replicates mainly in the hepatocyte. Recently, infectious HCV cDNA clones have been generated. Despite evidence that innate and adaptative humoral and cellular immune responses are activated as part of an antiviral defense, HCV has a remarkable ability to establish persistent infection. The analysis of viral kinetics using mathematical modeling shows a relative steady state without treatment, while an immediate biphasic HCV decline occurs in blood during successful treatment, the latter being predictive of clearance of HCV by the end of treatment.

Sex steroid hormones (estrogens, progestagens and androgens) have been associated with healthy and neoplastic pancreatic biology, although the precise significance of the findings has not been well established. Receptors for the three different types of SSH are expressed in normal and tumoral pancreatic tissue with varying profiles related to cell origin (exocrine or endocrine), to type of neoplasm. and probably even to tumoral behavior. The activity of specific enzymes involved in the synthesis and transformation of SSH are increased in some neoplastic pancreatic tissues, which may influence the circulating concentrations of these hormones, such as the low serum testosterone: dihydrotestosterone ratio described in male patients with pancreatic carcinoma. Different patterns of age and gender-related incidence and growth of neoplasms have been identified. Experimental studies have shown that pancreatic carcinogenesis is promoted or inhibited by SSH. At present, the data supporting hormonal manipula­tion for the treatment of these tumors are non-conclusive. Normal and tumoral pancreatic tissues may be regarded as a target for SSH and an additional site of biosynthesis. The influence of these hormones on physiological activities is not well known but should be further explored. The study of SSH in pancreatic neoplasms will provide clues about its origin, development, tumoral behavior, prognosis and more specific hormonal therapy. We review here the evidence favoring the role of SSH and their possible clinical implications in pancreatic function.

Background: Case-control and prospective studies indicate that an elevated plasma homocysteine level is a powerful risk factor for atherosclerotic vascular diseases. Certain medications can induce hyperhomocystinemia, such as methotrexate, trimethoprim and anti-epileptic drugs. There are few reports indicating an interaction between lipid-lowering drugs (cholestyramine and niacin) and homocysteine. Recently, an interaction was shown between fenofibrate and benzafibrates (a fibric acid derivative) and homocysteine plasma levels.

Objectives: To evaluate the effects of different fibrates on plasma homocysteine levels and to measure the reversibility of this effect.

Methods and Results: We investigated the effects of ciprofibrate and bezafibrate on homocysteine levels in patients with type IV hyperlipidemia and/or low high density lipoprotein levels. While a 57% increase in homocysteine was detected in the ciprofibrate-treated group (n=26), a 17% reduction n homocysteine was detected in the group treated with bezafibrate (n=12). The increase in homocysteine in the ciprofibrate-treated group was sustained for the 12 weeks of treatment and was partially reversible after 6 weeks of discontinuing the ciprofibrate therapy.

Conclusions: These results indicate that an increase In plasma homocysteine levels following administration of flbrates is not a class effect, at least in its magnitude. Moreover, it is reversible upon discontinuation of the treatment.
 

Background: Alkaline tide is the transient increase in blood and urine pH following stimulation of gastric acid secretion. It is attributed to HC0₃ release from parietal cells in parallel with H+ secretion. The enzyme carbonic anhydrase is thought to be responsible for HC0₃ production from CO₂ and 0H in the parietal cell.

Objective: To examine the effect of pretreatment with the carbonic anhydrase inhibitor, acetazolamide, on the alkaline tide phenomenon.

Methods: Ten patients with dyspepsia and demonstrable alkaline tide were tested on three separate days. The pH and base excess were determined in arterialized venous blood before and 45 minutes after an intramuscular injection of pentagastrin. The pH of the urine was measured before and 120 mm after pentagastrin injection. Measurements were performed after pentagastrin alone on day 1 following pretreatment with acetazolamide 60 mm before pentagastrin on day 2, and after the administration of acetazolamide alone on day 3.

Results: Following the administration of pentagastrin alone, the blood base excess increased by 1.61 +0.2 mEq/L (mean + standard deviation) and the calculated alkaline tide at 45 mm was 33.99 ±4.49 mEq. On day 2 with prior adminis­tration of acetazolamide, base excess decreased by 0.21 + 0.39 mEq/L, and the calculated alkaline tide was -3.28±7.57 mEq, which was significantly lower than on day 1 (P=0 0001). On day 3, following acetazolamide alone, the base excess values decreased by 0.53~0.2 mEq/L and the alkaline tide was -10.05 +3.33 mEq there was no significant difference compared with day 2 (P= 0.44).

Conclusion: Pretreatment with acetazolamide abolished the alkaline tide induced by pentagastrin. This finding supports the view that carbonic anhydrase has a major role in the alkaline tide phenomenon.