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Biomedical subjects

A Regev

Publications and source records attributed to A Regev.

At least 37 records · Page 2Linked to original sources

Necrotizing fasciitis caused by Staphylococcus aureus.

Two patients with rapidly progressive necrotizing fasciitis of a lower extremity due to Staphylococcus aureus as a single pathogen are described. In both patients the portal of entry was attributed to needle puncture (intra-articular injection and intravenous catheter, respectively), followed by bacteremia. Necrotizing fasciitis occurred in a site remote from the needle puncture, suggesting metastatic infection. One patient developed toxic shock syndrome and the other a sunburn-like rash and erythematous mucosae with strawberry tongue. One patient died, and the other required above-knee amputation due to secondary infectious complications. Staphylococcus aureus may mimic the presentation of invasive group A streptococcal infections. A history of needle puncture should alert the physician to the possibility of Staphylococcus aureus infection.

Aged↗

Comparison of two bowel preparations for colonoscopy: sodium picosulphate with magnesium citrate versus sulphate-free polyethylene glycol lavage solution.

OBJECTIVES: Adequate preparation of the bowel is essential for accurate colonoscopic examination. We compared colonic preparation with sodium picosulphate plus magnesium citrate (SPS-Mg) with sulphate-free polyethylene glycol electrolyte lavage (PEG-EL) solution before colonoscopy, for quality of bowel cleansing, patient discomfort, and side effects. METHODS: Sixty-eight consecutive patients were randomly assigned to receive either 3 sachets of SPS-Mg (16.5 g each) (n = 39) or 3 L of PEG-EL (n = 29) on the day before colonoscopy. Shortly before the procedure each patient was interviewed to determine the degree of discomfort (1 = none or mild, 2 = moderate, 3 = severe) and side effects. The quality of bowel cleansing was graded by a gastroenterologist who was unaware of the method of preparation (from 1 = poor to 4 = excellent). RESULTS: Of the 29 PEG-EL patients, four (14%) did not complete the preparation because of side effects. The degree of discomfort was significantly greater with PEG-EL (mean score, 2.3 +/- 0.7) than with SPS-Mg (mean score, 1.4 +/- 0.5; p < 0.01). Nausea and vomiting were significantly more common in the PEG-EL group (38% vs 13%; p < 0.05). Using intention-to-treat analysis, bowel cleansing proved to be significantly better with SPS-Mg than with PEG-EL (mean score +/- SD, 3.05 +/- 0.9 and 2.57 +/- 1.0, respectively; p = 0.036). CONCLUSIONS: Colonic preparation with SPS-Mg is better tolerated, associated with significantly fewer side effects, and results in higher quality bowel cleansing than preparation with PEG-EL.

Adult↗

Is greater than normal nocturnal heart rate in children with renal scars a predictor of reflux nephropathy?

BACKGROUND: The existence of renal scars constitutes the major etiologic factor for the development of hypertension during childhood. Elevated blood pressure in this setting can be considered a secondary form of hypertension. Certain forms of secondary hypertension have been associated with a lower than normal nocturnal fall in blood pressure. Resting heart rate per se has recently been reported to be an independent predictor of risk for cardiovascular mortality irrespective of age and the presence or lack of hypertension. OBJECTIVE: To ascertain the responses of heart rate and blood pressure in normotensive children with renal scars without, however, proteinuria and renal failure. METHODS: Ten children with renal scars documented by a 99Tc dimercaptosuccinic acid (DMSA) scan were subjected to ambulatory blood pressure monitoring. Ten age-matched and sex-matched healthy children served as the control group. Serum urea and creatinine levels, calculated rate of clearance of creatinine, microalbuminuria, plasma renin activity, and levels of aldosterone and catecholamines were determined for each subject. RESULTS: Average daytime and night-time systolic and diastolic blood pressures for the two groups did not differ. Subjects in both groups demonstrated the physiologic decrease in blood pressure during sleep (normal 'dipper' response), which was of equal magnitude for these two groups. Mean daytime heart rates were 92+/- 13 beats/min in children with renal scars versus 80+/-11 beats/min in controls (NS). Mean and minimal heart rates during night-time in children with renal scars were found to be significantly greater [79+/-6 versus 65+/-5 beats/min (mean) and 61+/-10 versus 56+/-7 beats/min (minimal), P < 0.01]. Parameters of renal function, plasma renin activity, and levels of aldosterone and catecholamines were similar for these two groups. CONCLUSION: Despite their having an equivalent physiologic dip in blood pressure during night-time, normotensive children with renal scars have a significantly greater nocturnal heart rate than do control subjects.

Child↗

[Disappointing response of chronic C hepatitis to interferon].

From February 1990 to August 1995 we treated 58 patients with chronic hepatitis C alfa-interferon, 3 million units 3 times weekly for 6 months. Of the 48 patients with adequate follow-up, 34 did not respond to treatment at all. 10 patients responded, but within a few months hepatic enzymes again increased. These 2 groups can be considered failures of interferon treatment. In 4 patients enzymes remained normal for the duration of follow-up, (10-34 months). Even in this small group, 1 patient had a positive test for HCV RNA after completion of treatment. A partial explanation of our disappointing results may be the high prevalence of a subtype of C hepatitis-subtype 1b, which has recently been reported in Israel. This strain is particularly resistant to interferon. The means to define subtypes were not, and as far as we know are not yet available in Israel. Various groups have attempted to improve the outcome of treatment of hepatitis C, which in other hands too was still far from satisfactory. Thus, regimens of interferon utilizing higher doses and longer periods of treatment are being evaluated, as well as the addition of Ribavirin, which hopefully will improve results.

Antiviral Agents↗

Small polydispersed circular DNA (spcDNA) in human cells: association with genomic instability.

Small Polydispersed Circular DNA (spcDNA) was suggested to be associated with genetically unstable cells. However, until now, qualitative and quantitative research has been limited due to the lack of efficient methods for detection and analysis. We developed a two-dimensional (2-D) neutral-neutral gel electrophoresis assay for the identification, characterisation and quantitation of spcDNA. Using this method, we established the relation of spcDNA to genetic and induced genomic instability in human cells, both in vitro and in vivo. Enhanced amounts of spcDNA were found in genetically unstable cells and tissues. spcDNA was detected in a tumor cell-line (HeLa) and in tumor tissue (colon carcinoma) as well as in fibroblasts derived from patients suffering from the genomic instability disease, Fanconi's Anemia. We failed to detect spcDNA in the genetically stable normal human fibroblasts. However, following treatment with the initiating carcinogen MNNG, an induction of spcDNA was observed. The level of spcDNA was quantified according to mitochondrial DNA (mtDNA) standards. In light of these findings, we discuss the possible role of spcDNA as a marker and an enhancer of genomic instability.

Carcinogens↗

Thrombotic complications in essential thrombocythemia with relatively low platelet counts.

Essential thrombocythemia (ET) is often associated with thrombotic and hemorrhagic complications, mostly at platelet counts exceeding 600 x 10(9)/L. There are, however, a few reports of such complications in ET at considerably lower platelet levels and the therapeutic approach to affected patients with relatively low platelet counts is still controversial. In the present study, the first to directly address the issue of hemostatic manifestations at relatively low platelet counts, we have determined the lowest platelet counts associated with such manifestations in 56 consecutive ET patients. Clinical manifestations related to ET were recorded in 46 (82%) patients. Of the symptomatic patients, 32 (70%) had symptoms at platelet counts lower than 600 x 10(9)/L, 23 (50%) at counts lower than 500 x 10(9)/L, 10 (22%) at counts lower than 400 x 10(9)/L, and 6 patients (13%) at platelet counts as low as 300-350 x 10(9)/L. Severe complications occurred at platelet counts lower than 600 x 10(9)/L in 10 patients (22%), lower than 500 x 10(9)/L in 7 (15%), and at lower than 400 x 10(9)/L in 2 (4%). Thrombotic neurologic symptoms were the most common (31 patients, 67%), followed by peripheral vascular symptoms (17 patients, 37%); hemorrhagic complications were relatively rare (3 patients, 7%). In most cases, cessation or improvement of clinical manifestations was observed only after further reduction in platelet counts. In conclusion, thrombotic manifestations, including severe ones, are not uncommon in ET at relatively low platelet counts. We recommend that symptomatic patients with relatively low platelet counts be treated and the platelet counts further reduced well into the lower normal range.

Adult↗

Effect of androgen substrates on the steroidogenic pattern of cumulus cells: correlation with cumulus culture morphology.

BACKGROUND: In previous studies, higher progesterone secretion was observed in mature versus immature cumulusoocyte complexes. In mature cumulus mass that become homogeneously spread in culture (type C/D) progesterone secretion was higher than in partially (type B) or totally (type A) aggregated morphology. In sharp contrast, estradiol-17 beta secretion was significantly higher in type A than type C/D cumulus. PURPOSE: Our purpose was to assess whether the decreased estradiol-17 beta level in type C/D cumulus culture is caused by deficiency of substrates. METHODS: The different cumulus types were incubated with or without 10(-7) M dehydroepiandrosterone, 4-androstane-3, 17-dione, or testosterone. The levels of estradiol-17 beta, testosterone, and progesterone, were measured after 24 hr of culture. RESULTS: The addition of dehydroepiandrosterone or 4-androstane-3, 17-dione significantly increased the estradiol-17 beta levels in all types of cumulus cells, whereas the addition of testosterone was less effective. In all types of cumulus cells the testosterone levels increased significantly on adding these androgen substrates. In the type C/D cumulus, the testosterone increased to lower levels compared to type A cumulus cells. In the presence of these androgens progesterone secretion is significantly reduced in type A cumulus cells. In type C/D cumulus cells, however, progesterone levels were significantly higher than in type A. The estradiol-17 beta/ testosterone and progesterone/estradiol-17 beta ratios, which partially resemble the degree of aromatase activity and the degree of selectivity for progesterone secretion, respectively, were higher in type C/D than in type A cumulus cells. CONCLUSIONS: In type C/D cumulus the significant increase in estradiol-17 beta secretion in the presence of various androgens suggests that, under basal conditions, androgen is less available for estradiol-17 beta biosynthesis compared to type A cumulus. Furthermore, the higher progesterone secretion in type C/D cumulus may suggest that the follicles yielding type C/D cumulus cells are more mature than the follicles yielding type A cumulus.

Androgens↗

Mapping of the entomocidal fragment of Spodoptera-specific Bacillus thuringiensis toxin CryIC.

Insecticidal CryI protoxins of Bacillus thuringiensis are activated by proteolysis in the midgut of insects. A conservation of proteolytic cleavage sites in the CryI proteins facilitates the expression of active toxins in transgenic plants to obtain protection from various insects. However, the engineering of CryIC toxins has, thus far, failed to yield applicable resistance to armyworms of Spodoptera species representing common insect pests worldwide. To improve the production of recombinant CryIC toxins, we established a CryIC consensus sequence by comparative analysis of three cryIC genes and tested the stability and protease sensitivity of truncated CryIC toxins in Escherichia coli and in vitro. In contrast to previous data, the boundaries of trypsin-resistant CryIC core toxin were mapped to amino acid residues I28 and R627. Proteolysis of the truncated CryIC proteins showed that Spodoptera midgut proteases may further shorten the C-terminus of CryIC toxin to residue A615. However, C-terminal truncation of CryIC to residue L614, and a mutation causing amino acid replacement I610T, abolished the insecticidal activity of CryIC toxin to S. littoralis larvae, as well as its resistance to trypsin and Spodoptera midgut proteases. Because no CryIC toxin carrying a proteolytically processed N-terminus could be stably expressed in bacteria, our data indicate that, in contrast to other CryI proteins, an entomocidal fragment located between amino acid positions 1 and 627 is required for stable production of recombinant CryIC toxins.

Amino Acid Sequence↗

Influence of diabetes mellitus and glycaemic control on the characteristics and outcome of common infections.

The aim of the present study was to elucidate the effect of diabetes and metabolic control on the presentation, sources, pathogens and outcome of common infections. Of 515 patients admitted to three departments of internal medicine because of a suspected acute infection, 132 (26%) had diabetes mellitus. Osteomyelitis was diagnosed in 3% of the diabetic patients and in 1% of patients without diabetes, and infection of the extremities in 7% and 0%, respectively (p = 0.003). Klebsiella sp. caused 24% of urinary tract infections in diabetic patients, versus 13% in patients without diabetes (p = 0.1). The percentage of Staphylococcus aureus infections in diabetic patients was 10% versus 5% in non-diabetic patients (p = 0.06). The gross mortality rate in the diabetic patients was 10%, and in patients without diabetes, 12%. In patients without fatal underlying disorders, mortality in the diabetic patients was 10% (2% in patients with glycosylated haemoglobin (GHb) lower than median, and 17% in patients with GHb higher than median) and in the non-diabetic patients 4% (p = 0.04). Five factors were independently and significantly related to mortality in diabetic patients: acute respiratory distress (very large odds-ratio [OR]), coma (OR 3.8, 95% confidence interval [CI] 1.0-14.3), GHb above the median (OR 3.3, 95% CI 1.8-6.2), the interaction between GHb and absence of a severe underlying disorder (OR 12.0, 95% CI 2.9-50.7) and duration of diabetes (OR of 1.072 for 1-year increment, and 1.42 for a 5-year increment). Choice of empiric antibiotic treatment in diabetic patients with suspected bacterial infection should take into account the preponderance of Klebsiella sp. and Staphylococcus aureus infections. The present results favour an association between poor glycaemic control and a fatal outcome of infectious diseases in diabetic patients.

Aged↗

Two rules for early prediction of bacteremia: testing in a university and a community hospital.

BACKGROUND: Two rules (model 1 and model 2) were previously derived and prospectively validated at the same institution to predict the likelihood of bacteremia. The objective of the present study was to test and compare the performance of the rules in patients admitted to two sites of inpatient care: a university hospital and a community hospital. METHODS: Clinical and laboratory data (including the variables contained in the two models) were collected within 24 hours in all patients admitted to the Department of Medicine of the Beilinson Medical Center, a university hospital in central Israel, and Emek Hospital, a community hospital in northern Israel, because of an acute infectious disease. The scores of the models were compared with the results of blood cultures. RESULTS: The percentage of bacteremia was 15% in the university and 18.5% in the community hospital. The area under the receiver-operating characteristic curve was 0.56 + or - 0.04 SE for model 1, and 0.67 + or - 0.04 SE for model 2 in the university hospital; and 0.59 + or - 0.05 SE versus 0.63 + or - 0.04 SE, respectively, in the community hospital. At the best calibration, model 1 defined low-risk groups of 205 patients in the university hospital, and 66 patients in the community hospital, with prevalences of bacteremia of 13% and 15%. The high-risk groups defined by model 1 had prevalences of 30% and 32%. Model 2 defined low-risk groups with prevalences of bacteremia of 7% (8 of 114) and 8% (6 of 76); and high-risk groups with percentages of 29% and 38%. CONCLUSIONS: The overall accuracy of the two models deteriorated significantly. Both models defined groups at high risk of bacteremia, but the percentages of bacteremia and of death in the low-risk groups do not encourage withholding blood cultures in these patients. The failure of the two models points toward the need for external validation, and for monitoring performance of prediction models over time.

Adolescent↗

Digestion of delta-endotoxin by gut proteases may explain reduced sensitivity of advanced instar larvae of Spodoptera littoralis to CryIC.

The present study describes the correlation between gut protease activity of lepidopteran larvae of different instars, the inactivation of Bacillus thuringiensis delta-endotoxins in crystalline and noncrystalline forms, and the reduced susceptibility of advanced larval instars of Spodoptera littoralis to the toxin. The original assembly of delta-endotoxins in a crystal structure is essential for causing efficient larval mortality. Denaturation and renaturation (D/R) of delta-endotoxin crystals increased the vulnerability of the toxin molecules to proteolysis, reduced their capability to kill neonate larvae of S. littoralis, but sustained most of their larval growth-inhibition activity. E. coli-produced CryIC delta-endotoxin applied as a fraction of inclusion bodies exerted a growth inhibition effect, similar to the molecules released from the crystals by denaturation and subsequent renaturation. Incubation of CryIC with gut juice of 1st or 2nd instar larvae, left part of the CryIC toxin intact, while the toxin was completely degraded when incubated with gut juice of 5th instar larvae. The degradation rate was consistent with the increase of protease specific activity of the gut juice during larval development. This increase in toxin degradation may account for the loss of sensitivity of 5th instar larvae to CryIC. Specific protease inhibitors such as PMSF and Leupeptin were shown to inhibit gut proteases activity in all instar larvae, while, 1,10 phenanthroline, TLCK and TPCK were effective only in young instar larvae. The differential effect of protease inhibitors on proteases obtained from different larval instars indicated that gut juice protease profiles change with larval age. The observed quantitative and qualitative differences in degradation of delta-endotoxin by larval gut proteases that occur during larval maturation may account for the difference in susceptibility to the delta-endotoxin. This finding should be taken into consideration when designing strategies for the development of transgenic crops expressing delta-endotoxins as potent insecticidal proteins.

Animals↗

Synergistic activity of a Bacillus thuringiensis delta-endotoxin and a bacterial endochitinase against Spodoptera littoralis larvae.

In an attempt to increase the insecticidal effect of the delta-endotoxin crystal protein CryIC on the relatively Cry-insensitive larvae of Spodoptera littoralis, a combination of CryIC and endochitinase was used. CryIC comprising the first 756 amino acids from Bacillus thuringiensis K26-21 and endochitinase ChiAII encoded by Serratia marcescens were separately produced in Escherichia coli carrying the genes in overexpression vectors. The endochitinase on its own, even at very low concentrations (0.1 microgram/ml), perforated the larval midgut peritrophic membrane. When applied together with low concentrations of CryIC, a synergistic toxic effect was obtained. In the absence of chitinase, about 20 micrograms of CryIC per ml was required to obtain maximal reduction in larval weight, while only 3.0 micrograms of CryIC per ml caused a similar toxic effect in the presence of endochitinase. Thus, a combination of the Cry protein and an endochitinase could result in effective insect control in transgenic systems in which the Cry protein is not expressed in a crystalline form.

Animals↗

Clomiphene citrate reduces procarbazine-induced sterility in a rat model.

Chemotherapy with the cytotoxic drug procarbazine (PCB) causes permanent infertility in most male patients. Since many patients treated with this cytotoxic drug are of reproductive age, it is important to develop a method to protect spermatogenesis and fertility. It has been hypothesised that 'spermatogenic arrest' by pharmacological intervention may render the testes less susceptible to the effects of chemotherapy. The present study investigated whether recovery of fertility in a male rat model could be achieved by suppression of spermatogenesis with high doses of clomiphene citrate (CC) prior to PCB administration. It was demonstrated that young male rats treated with a combination of CC and PCB partially recovered spermatogenesis and achieved almost normal fertility. In contrast, animals treated with PCB alone exhibited abnormal spermatogenesis and remained infertile.

Animals↗

Noninvasive determination of neonatal hyperbilirubinemia: standardization for variation in skin color.

The estimation of plasma bilirubin concentration in neonates, using a transcutaneous, noninvasive jaundice meter, is significantly affected by many factors, such as gestational age, birthweight, phototherapy, and skin pigmentation. In an attempt to minimize the influence of skin color and hence circumvent the need for standardization curves for different ethnic populations, we obtained noninvasive jaundice meter readings from the infant's midsternum within 4 hours of birth and subtracted this measurement from subsequent reading in infants with hyperbilirubinemia. These results were correlated with simultaneous plasma bilirubin determinations. By this method, a single standardization curve and improved sensitivity, specificity, and predictive values for the noninvasive determination of neonatal hyperbilirubinemia in a population of mixed ethnic origin was obtained.

Bilirubin↗