Outcome of Silicone Ring Vertical Gastroplasty in Patients Aged 50 Years and Older

Background: The authors studied the results of silicone ring vertical gastroplasty (SRVG) in patients aged 50 years and older. Methods: The early and late postoperative results in 28 patients aged 50 years or older undergoing SRVG were reviewed retrospectively. The results were compared to those of 370 patients younger than 50 years operated during the same period. Results: There was no postoperative mortality among patients aged 50 years and older. There was a significantly higher incidence of pulmonary embolus and wound infection among patients aged 50 years and older (p < 0.05). The weight loss did not differ significantly between the two studied age groups. Conclusion: SRVG may be performed on patients aged 50 years or older with acceptable complication rate and favourable postoperative results.     

Familial adenomatous polyposis at the Tel Aviv Medical Center: demographic and clinical features

Familial adenomatous polyposis (FAP) is an uncommon, but widespread genetic disorder that develops multiple colonic adenomatous polyps and, if untreated, can lead to large bowel cancer. Little is known about its occurrence and characteristics in the Israeli population. Aims: To evaluate FAP prevalence, phenotypic manifestations and compliance for diagnosis and follow-up in our registry. Methods: Since 1993 approximately one-half of FAP patients in Israel have been seen and followed-up by us before and/or after colectomy. They and their families were encouraged to have mutation analysis, genetic and/or endoscopic screening. Results: 37 pedigrees were identified, including 2 non-Jewish. The Jewish ethnic distribution was similar to that of the general population and the point prevalence rate estimated as 28.4/one million Jewish inhabitants. There were 461 first-degree relatives at-risk for FAP. Genetic screening was completed and successful in 28 pedigrees (87.5%), and 73 FAP patients entered the registry. Marked intra-familial phenotypic variations with minimal disease manifestation were noted in 11 patients belonging to 4 pedigrees. Cancer occurred in 15.1% (11 patients), in 10 before FAP diagnosis or during follow-up elsewhere, but one non-compliant patient developed duodenal cancer. One other patient died from a massive, neglected, intra-abdominal desmoid. Compliance for evaluation and follow-up of pedigree members and individual FAP patients was inadequate in 29% and 27%, respectively. Conclusions: FAP occurs in the Israeli Jewish population at the expected rate, but is inadequately recognized in non-Jews. The inadequate compliance for screening and post-surgical follow-up needs to be addressed by educating the public, health care workers and Health Insurers.     

Eliminating the Need for Dietary Restrictions When Using a Sensitive Guaiac Fecal Occult Blood Test

When using the peroxidase-sensitive guaiac fecaloccult blood test, Hemoccult Sensa (HOS), dietaryrestrictions are recommended so as to reduce its falsepositivity from ingested peroxidases. As dietary restrictions could reduce compliance for annualretesting, we reexamined their need. HOS was given to944 persons in an endoscopic screening/follow-upprogram. Only the first 403 received instructionsregarding a low peroxidase-containing diet for three daysbefore and during HOS collection. Development wasdelayed 3-14 days after HOS preparation, and there wereno significant differences in duration before HOS development in examinees with or withoutcolorectal neoplasia and having or not having a positivetest. Of the 901 persons without endoscopic evidence ofneoplasia, 377 had received and 524 had not received instructions on dietary restrictions. Their HOSpositivity was 7.2% and 5.5%, respectively (P = 0.26).When using HOS, delaying development by 3-14 days allowsbreakdown of ingested peroxidases, so dietary restrictions are not needed in our population,which has a low red meat intake.     

Incidence and risk factors for surgical infection after total knee replacement

Surgical site infection (SSI) after total knee replacement (TKR) is a devastating complication. We performed a retrospective study of all consecutive TKRs performed during a 2-y period. Surgical site infection (SSI) was defined by standard criteria. All patients were examined 1 y following surgery. Of 180 patients undergoing TKR, 10 (5.6%) developed a superficial (3, 1.7%) or deep (7, 3.9%) SSI. Two independent risk factors for SSI were detected: left knees became infected more often (9/ 92, 9.8%) than right knees (1/88, 1.1%) (Relative Risk 6.7 +/- 95% CI 1.7-26.8); and 7/72 (9.7%) patients receiving a type-1 prosthesis developed infection versus 3/104 (3.1%) receiving a type-2 prosthesis (RR 4.7, 95% CI 1.18-18.4). Investigation of the operating room revealed 3 problems: there was significant traffic through the door on the left of the patient; a nonstandard horizontal-flow air conditioner had been installed above that door; a tool-washing sink was in use on the other side of that door. Infection control guidelines were rehearsed: the sink was removed, the air conditioner was disconnected, and the door was locked. In a prospective survey performed 2 y later only 1/45 patients (2.2%) undergoing TKR developed a superficial SSI (p = 0.5). Correction of independent risk factors for infection following TKR led to a decrease in SSI rate.     

The Ras inhibitor S-trans, trans-farnesylthiosalicylic acid exerts long-lasting neuroprotection in a mouse closed head injury model.

Traumatic brain injury activates N-methyl-d-aspartate receptors (NMDAR) inducing activation of the Ras protein (a key regulator of cell growth, survival, and death) and its effectors. Thus, trauma-induced increase in active Ras-GTP might contribute to traumatic brain injury pathology. Based on this hypothesis, a new concept of neuroprotection is proposed, examined here by investigating the effect of the Ras inhibitor S-trans, trans-farnesylthiosalicylic acid (FTS) in a mouse model of closed head injury (CHI). Mice subjected to CHI were treated systemically 1 h later with FTS (5 mg/kg) or vehicle. After 1 h, Ras-GTP in the contused hemisphere showed a significant (3.8-fold) increase, which was strongly inhibited by FTS (82% inhibition) or by the NMDA-receptor antagonist MK-801 (53%). Both drugs also decreased active (phosphorylated) extracellular signal-regulated kinase. FTS prevented the CHI-induced reduction in NMDAR binding in cortical, striatal, and hippocampal regions, measured by [3H]-MK-801 autoradiography, and decreased lesion size by 50%. It also reduced CHI-induced neurologic deficits, indicated by the highly significant (P < 0.0001) 60% increase in extent of recovery. Thus, FTS provided long-term neuroprotection after CHI, rescuing NMDAR binding in the contused hemisphere and profoundly reducing neurologic deficits. These findings suggest that nontoxic Ras inhibitors such as FTS may qualify as neuroprotective drugs.     

Suppression of lung cancer tumor growth in a nude mouse model by the Ras inhibitor salirasib (farnesylthiosalicylic acid)

Aberrant Ras pathway functions contribute to the malignant phenotype of lung cancers. Inhibitors of Ras might therefore be considered as potential drugs for lung cancer therapy. Here, we show that the Ras inhibitor farnesylthiosalicylic acid (salirasib) inhibits proliferation of human lung cancer cells harboring a mutated K-ras gene (A549, H23, or HTB54) or overexpressing a growth factor receptor (H1299 or HTB58) and enhances the cytotoxic effect of the chemotherapeutic drug gemcitabine. Salirasib inhibited active K-Ras in A549 cells, reversed their transformed morphology, and inhibited their anchorage-independent growth in vitro. Tumor growth in A549 and HTB58 cell nude mouse models was inhibited by i.p. administration of salirasib. P.o. formulated salirasib also inhibited A549 cell tumor growth. Our results suggest that p.o. salirasib may be considered as a potential treatment for lung cancer therapy.     

Dialysis in Israel, 1989-2005--time trends and international comparisons.

BACKGROUND: A universal increase in the incidence of renal replacement therapy (RRT) was reported in developed countries during the 1990s, especially among the elderly and diabetic patients. We studied trends in RRT incidence and mortality in Israel between 1989 and 2001-2005. METHODS: The end-stage renal disease (ESRD) registry holds data on all RRT patients in Israel. Age-adjusted incidence rate ratios (RRs) were estimated comparing 2001-2005 with 1989. We compared incidence data between Israel and elsewhere using standardized incidence ratios (SIRs). Survival analysis was conducted by the Kaplan-Meier method and Cox's proportional hazards regression was used to compare survival of diabetic with non-diabetic ESRD patients. RESULTS: The mean incidence rates per million population increased from 99 in 1989-1991 to 179 in 2003-2005. In 2000, Israel was the second leading country for incidence of RRT. Age-adjusted incidence rates increased by 67% [95% confidence interval (CI): 49-87%], from 1989 to 2001, but the trend was attenuated between 2002 and 2005. The increase in incidence was positively associated with age, the largest increase being among the elderly aged > or = 75 years (RR: 3.18, 95%CI: 2.72-3.70). Diabetes accounted for 41% of RRT in 2001 vs only 19% in 1989. There was no increase in 1-year survival between the beginning and the end of the study period. Patients with diabetes-associated RRT had 57% increased risk of 1-year mortality (adjusted HR: 1.57 95% CI: 1.51-1.63). CONCLUSIONS: Despite a similar proportion of RRT attributed to diabetes in Israel and other countries, the age-adjusted incidence in Israel is considerably higher than most countries.     

Methylation of 21-23 kD membrane proteins by a membrane-associated protein carboxyl methyltransferase in neuroblastoma cells. Increased methylation in differentiated cells

Membranes of neuroblastoma N1E-115 cells contain a specific protein carboxyl methyltransferase that methylates a 70 kD protein and a group of 21-23 kD proteins which are tightly bound to the membranes. The enzyme catalyzes the transfer of [methyl-3H] groups from [methyl-3H]S-adenosyl-L-methionine (Km = 0.22 microM) to these proteins to form base-labile carboxymethylesters. These protein methylesters are relatively stable compared to other protein methylesters, as shown by the ability of the 21-23 kD methylated proteins to retain their [methyl-3H] groups at pH values of 7 to 8.5 for at least 12 hr at room temperature. The extent of methylation of the 21-23 kD proteins, but not that of the 70 kD protein, was increased in membranes of cells induced to differentiate by 2% dimethyl sulfoxide (from a basal level of 0.1-0.2 to 0.9-1.2 pmol [methyl-3H] groups incorporated per mg membrane protein). This increase appeared after a lag period of 3 days of growth in the presence of the dimethyl sulfoxide and developed in parallel with the appearance of neurite-like processes in the cells. Kinetic experiments suggest that the amounts of 21-23 kD proteins available for methylation in the membranes of the undifferentiated and of the differentiated cells are limited. This and the previously observed low turnover of methylated 21-23 kD proteins in the intact cells suggest that the differentiated cells express and methylate more 21-23 kD proteins than the undifferentiated cells. These methylated proteins may be involved in differentiation or other functions of the differentiated cell membranes.     

Performance Characteristics and Comparison of Two Immunochemical and Two Guaiac Fecal Occult Blood Screening Tests for Colorectal Neoplasia

A new immunochemical test for stool Hb, FlexSureOBT, was compared with the immunochemical HemeSelect andguaiac Hemoccult II and Hemoccult SENSA tests. Blindeddevelopment of test cards smeared with stools having added human blood showed betteranalytical sensitivity of FlexSure OBT (0.2 ml blood/100g feces), than Hemoccult SENSA (0.5 ml) or HemoccultII (1.0 ml). All four stool tests were prepared by 403 subjects having endoscopic examinations.The guaiac tests and FlexSure OBT were easy to prepareand develop. The positivity rate of Hemoccult SENSA was8.7%, Hemoccult II 6%, FlexSure OBT 4.2%, and HemeSelect 3.4%. In this mainly asymptomatic(97%) population, 98% were free of clinicallysignificant neoplasia (five had cancers, three hadadenomas 1.0 cm). Sensitivity for cancers oradenomas 1.0 cm was similar for all tests (62.5-86%, NS) andHemoccult SENSA had the lowest specificity (92% vs95-98%, P < 0.05); but both Hemoccult II andHemoccult SENSA had significantly lower predictivepositive values (21% and 14%) than either FlexSure OBT(29%) or HemeSelect (50%) (P < 0.05). If bothHemoccult SENSA and FlexSURE OBT were positive in thesame subjects (1.7%), sensitivity for cancer or adenomas 1.0 cm (50%) was not significantly betterthan guaiac tests, but specificity (99.2%) andpredictive positive (57%) values were improved (P <0.05). In this population, guaiac tests were assensitive as immunochemical tests for clinically significantcolorectal neoplasia, but with significantly lowerpredictive positive values. A combination of a sensitiveguaiac test (Hemoccult SENSA) and a specificconfirmatory test for human Hb (FlexSure OBT) provided highspecificity, comparable to HemeSelect.