Israel Medical Association Journal

Background: Alteration of innate and acquired immunity can play a role in the mechanism involved in the development of dementia. Epidemiologic studies indicate that the use of non-steroidal anti-inflammatory drugs can delay the onset or slow progression of Alzheimer disease.

Objectives: To determine whether the use of NSAIDs[1] is associated with natural killer activity alteration in AD[2] and multi-infarct vascular dementia patients, as compared with non-demented elderly and healthy young people.

Methods: In this prospective open study four groups of subjects (AD, VD[3], non-demented elderly, and healthy young people) were treated with an NSAID drug (rofecoxib 12.5 mg/day or ibuprofen 400 mg twice daily) for 7 days. Natural killer cell cytotoxicity was measured after flow cytometry analysis before and after treatment.

Results: Of the 49 subjects studied, 15 had a diagnosis of AD (3 men, 12 women; mean age 83.5 ± 8.1 years), 15 had a diagnosis of multi-infarct VD (7 men, 8 women; mean age 75.5 ± 8.4), 13 were non-demented elderly (1 man, 12 women; mean age 80.2 ± 7.2), and 6 were healthy young volunteers (3 men, 3 women; mean age 36.8 ± 4.4). While all examined subjects showed decreased NK[4] cell cytotoxicity after treatment, this decrease was most prominent and statistically significant in elderly patients suffering from vascular dementia –  from an average of 30.5 ± 11.8% before treatment to 22.5 ± 16% after treatment (P = 0.04). The decrease in NK cell cytotoxicity was only moderate and not statistically significant in all other elderly and young subjects. Young healthy volunteers exhibited a significantly higher total NK cytotoxicity before and after treatment compared to all age groups (P < 0.001).

Conclusion: These findings suggest that NSAIDs decrease NK activity in vascular dementia patients. Our findings also suggest that natural killer activity alteration cannot explain the ability of anti-inflammatory drugs to delay the onset or slow the progression of AD.

Background: Restorative proctocolectomy eliminates the risk of colorectal cancer in patients with familial adenomatous polyposis. Complications and extra‑intestinal manifestations are inherent to the procedure.

Objectives: To evaluate operative procedures, complications, early and late results and long-term functional outcome in FAP[1] patients operated in our department.

Methods: The study group included all patients with FAP who were operated between 1988 and 2003. Demographic data, length of follow‑up, complications, colorectal cancer, pouch function and extracolonic manifestations were recorded.

Results: Median age at surgery was 33 years (range 13–61 years). The final operative breakdown was: 48 proctocolectomies, 41 ileal pouch-anal anastomoses, 2 Kock’s pouch, 5 permanent ileostomies, and 2 colectomies with ileorectal anastomosis. There was no perioperative mortality. Early and late complications occurred in 20 and 9 patients, respectively. Twelve patients required re‑operation. Colorectal carcinoma was diagnosed in eight patients, three of whom were in an advanced stage. The mean follow‑up was 74 months (range 3–288 months). Four patients were lost to follow‑up. Extracolonic manifestations developed in 38 patients, including desmoid tumors (in 12), duodenal adenomas (in 9), pouch adenomas (in 5), and rectal stump adenomas (in 3). Two patients died (4%) because of desmoid tumor and malignant fibrous histiocytoma. At last follow‑up, 37 IPAA[2] patients have (median) six bowel movements/24 hours and good fecal control.

Conclusions: Restorative proctocolectomy can be performed with low mortality, acceptable morbidity, and good functional results. Patients should be closely followed after surgery for development of other manifestations of the syndrome. Relatives of the affected patients should be referred to a specialist multidisciplinary clinic.

Background: Road traffic accidents are the leading cause of accidental injury and death for persons under the age of 35. The medical literature presents surprisingly little information on the general characteristics of such accidents in the urban setting.

Objectives: To characterize RTA[1] patients arriving at an urban trauma center.

Methods: We prospectively examined the charts of all patients admitted to the Tel Aviv Sourasky Medical Center due to RTA injuries during two periods in 1995.

Results: Of the 1,560 patients examined, the male:female ratio was 1:1 and median age was 27 years (47% aged 20–30 years); 51% of the accidents took place between 8 a.m. and 4 p.m. and on working week days; automobiles comprised 47.1% of the vehicles involved, motorized two-wheel vehicles 37.1%, bicycles 3.8%, and pedestrians 12%. The Glasgow Coma Scale was 15 on arrival in 98.7% of the patients. The trunk was the most commonly injured body part (84.7%); whiplash injury to the neck was diagnosed in 343 patients (22%), and brain concussion in 183 (11.7%). Computed tomography studies were performed in 34 patients (2.2%). The vast majority of patients (1,438, 92.2%) was discharged home; 14 (0.9%) were admitted to the intensive care unit, and 2 (0.13%) died during hospitalization. The average time spent in the emergency department in the morning shift was 2.1 hours.

Conclusions: We could identify distinguishing factors of this population: equal gender distribution, peak RTA incidence in the young adult working population during working hours, automobile drivers being the most injured subgroup, a disproportionate number of motorcycle and motor scooter involvement, and a relatively extensive amount of time and resources spent treating these injuries despite their generally minor nature.



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[1] RTA = road traffic accidents

Background: Continuous positive airway pressure is the treatment of choice for patients with obstructive sleep apnea syndrome.

Objective: To determine the factors influencing treatment initiation with a CPAP[1] device in a healthcare system in which co-payment is required.

Methods: A total of 400 adult patients with OSAS[2] who required CPAP therapy completed questionnaires at three different stages of the diagnostic and therapeutic process: CPAP titration study (stage 1), patient adaptation trial (stage 2), and purchase of a CPAP device (stage 3). Logistic regression was used to analyze the variables influencing CPAP use at the different stages of the diagnostic and therapeutic processes.

Results: Only 32% of the patients who underwent CPAP titration study purchased a CPAP device. The number of subjects who purchased a CPAP device increased gradually as monthly income increased, 28% vs. 62% in the “very low” and “very high” income levels respectively. Reporting for the titration increased in patients with excessive daytime sleepiness and an Epworth Sleepiness Scale score above 9 (odds ratio = 1.9, P = 0.015). Higher socioeconomic status increased reporting to stage 2 (OR[3] = 1.23, P = 0.03) and CPAP purchase (stage 3, OR = 1.35, P = 0.002). Excessive daytime sleepiness increased reporting to stage 2 (OR = 2.28, P = 0.006). Respiratory disturbance index above 35 increased CPAP purchasing (OR = 2.01, P = 0.022). Support from the bed partner, referring physician and sleep laboratory team increased CPAP purchasing.

Conclusions: A supportive environment for a patient with OSAS requiring CPAP is crucial to increase initiation of CPAP treatment. Minimizing cost sharing for the CPAP device will reduce inequality and may increase CPAP treatment initiation.

Background: Restorative proctocolectomy with ileal pouch-anal anastomosis has become the surgical procedure of choice for patients with ulcerative colitis and familial adenomatous polyposis.

Objectives: To evaluate the long-term functional outcome of patients who underwent this surgical procedure.

Methods: We performed this observational study in 174 consecutive patients: 146 with UC[1] and 28 with FAP[2]. The patients, 91 males and 83 females with a mean age of 34.1 ± 10.6 years (range 6–67 years), underwent the procedure between January 1984 and January 2004 (mean follow-up 64.8 months, range 1–240 months). The indications for surgery were intractable disease in 124 patients (71%), dysplasia in 36 (21%), severe bleeding in 8 (5%), and perforation in 6 (3%).

Results: A protective ileostomy was performed in 140 patients (96%) with UC and 12 (43%) with FAP. An urgent three-stage procedure was necessary in 14 patients (8.4%). A mucosal proctectomy was performed in 94 (54%), and a double stapling technique in 80 (46%). Mean length of hospital stay was 9.4 ± 6.6 days (range 5–34 days, median 8). Complications included pelvic sepsis in 7 patients (4.2%), anastomotic leakage in 8 (4.8%), bowel obstruction in 22 (13.2%), incisional hernia in 12 (7.2%), anastomotic stenosis that usually responded to manual dilatation in 46 (27.6%), pouchitis in 106 (61%), recto-vaginal fistula in 3 (1.8%), retrograde ejaculation in 3 (1.8%), and impotence in 2 (1.2%). There was no mortality in this group of patients. The median number of bowel movements per 24 hours was six in UC patients and five in FAP patients, with at least one bowel movement during the night. Complete daytime and night-time continence was documented in 124 patients (71%). Overall satisfaction was 95%.

Conclusions: Restorative proctocolectomy with ileal pouch-anal anastomosis confers a long-term good quality of life to both UC and FAP patients, and the majority of patients are fully continent with five to six bowel movements per day. 

Background: Many medical school curricula include training for ethical considerations, legal comprehension, implementation of patients' rights, awareness of cultural differences and communication skills (ELCE).

Objectives: To explore medical students' perceptions of their ELCE training during the clinical phase as well as the relationship between humanistic practice skills' experiences and the quality of clinical training.

Methods: A cross-sectional survey was carried out in two cohorts during their clinical year period at Tel Aviv University's Sackler Faculty of Medicine at the end of their internal medicine and surgery clerkships in the 2002 academic year. The research tool was an 18 item Likert-type questionnaire (ELCEQ), based on the literature of biomedical ethics, legal aspects and behavior of practice skills. The content validation of the questionnaire was established by consulting experts among the school's faculty. It was circulated among the students by representatives of the Unit of Medical Education.

Results: The response rate was 88%. Students reported only a few opportunities for gaining experience in humanistic practice skills. A weak correlation was found between students' assessment of the quality of clinical training and their experiences in humanistic practice skills.

Conclusions: A wider and more relevant range of active experiences in humanistic practice skills should be available to students during the clerkships. Correspondingly, there is a need for the clinical faculty to find innovative ways to internalize their task as role models and ensure that students acquire and are able to practice those skills.
 

Background: Food intake has an immediate effect on the cardiovascular system. However, the effect of a large meal as an immediate trigger for the acute coronary syndrome has not been assessed.

Objectives: To assess the relative risk for an ACS[1] within a few hours after the ingestion of a heavy meal.

Methods: In a case-crossover study 209 patients were interviewed a median of 2 days after an ACS. Ingestion of a large meal in the few hours immediately before the onset of ACS was compared with the comparable few hours the day before and with the usual frequency of large meals over the past year. Large meals were assessed by a 5 level scale.

Results: The relative risk of an acute coronary event during the first hour after a heavy meal ingestion was RR[2] = 7 (95% confidence interval 0.75–65.8) when the day before the ACS served as the control data and RR = 4 (95% CI[3] 1.9–8.6) when the usual frequency of heavy meals ingestion during the previous year served as the control data. 

Conclusions: The ingestion of heavy meals can trigger the onset of an ACS. Education of the population to avoid heavy meals, especially in people at high risk for coronary heart disease, should be included in the prevention of ACS. Research on specific nutrients that may act as potential triggers for ACS should be considered.

Background: Oral anticoagulation with warfarin can lead to life-threatening events as a result of either over-anticoagulation or undertreatment. One of the main contributors to an undesirable warfarin effect is the need to adjust its daily dose for a specific patient. The dose is adjusted empirically based on the experience of the clinician, a method that is often imprecise. There is currently no other well-accepted method for predicting the maintenance dose of warfarin.

Objective: To describe the application of an artificial neural network to the problem of warfarin maintenance dose prediction.

Methods: We designed a neural network that predicts the maintenance dose of warfarin. Data on 148 patients attending a large anticoagulant clinic were collected by file review. Using correlational analysis of the patients' data we selected the best input variables. The network was trained by using the back-propagation algorithm on a subset of our data and the results were validated against the rest of the data. We used a multivariate linear regression to create a comparable model.

Results: The neural network generated reasonable predictions of the maintenance dose (r = 0.823). The results of the linear regression model were similar (r = 0.800).

Conclusion: Neural networks can be applied successfully for warfarin maintenance dose prediction. The results are promising, but further investigation is needed.
 

Background: Hypertension is considered resistant if blood pressure cannot be reduced to <140/90 mmHg with an appropriate triple-drug regimen, including an oral diuretic, with all agents administered at maximal dosages. This definition has evolved with the development of new therapies and evidence-based data supporting treatment to lower BP[1] goals.

Objective: To assess whether vitamin C and atorvastatin improve endothelial function and blood pressure control in subjects with resistant arterial hypertension and dyslipidemia.

Methods: Forty-eight hyperlipidemic subjects with RH[2] (office systolic BP >140 mmHg and/or office diastolic BP >90 mm/Hg notwithstanding antihypertensive treatment with three medications in maximal doses) were randomized into three groups to receive additional medication for 8 weeks. Group VTC (n = 17) – mean 24 hour SBP[3] 150.6 ± 5.2 mmHg, DBP[4] 86.1 ± 3.3 mmHg, low density lipoprotein 158.1 ± 24.5 mg/dl) – received vitamin C 500 mg per day; Group ATR (n = 15) – mean 24 hour SBP 153.1 ± 4.8 mmHg, DBP 87.1 ± 6.7 mmHg, LDL[5] 162.6 ± 13.6 mg/dl) – received atorvastatin 20 mg/day; and Group PLA (n = 16) – mean 24 hour SBP 151.1 ± 7.4 mmHg, DBP 84.8 ± 5.9 mmHg, LDL 156.7 ± 26.1 mg/dl – received a placebo. High resolution ultrasound was used to calculate brachial artery flow-mediated dilation, and 24 hour ambulatory BP monitoring was performed at study entry and after 8 weeks.

Results: In the ATR group there were significant reductions of SBP (DSBP1-2: 13.7 ± 5.6 mmHg, P < 0.001), DBP (DDBP1-2: 7.8 ± 5.7 mmHg, P < 0.01), LDL (DLDL1-2: 67.7 ± 28.3 mg/dl, P < 0.001) and improvement of brachial artery FMD[6] (DFMD2-1: 4.2 ± 2.6%). No significant changes in BP, LDL and FMD were observed in the other two groups.

Conclusions: In subjects with RH and dyslipidemia, atorvastatin 20 mg/day compared to vitamin C 500 mg/day may help to achieve better BP control and improve endothelial function in a finite period. A larger trial is needed to assess the drug's efficacy in this population for longer periods.