Israel Medical Association Journal

Background: Familial Mediterranean fever is an autosomal recessive disease characterized by sporadic attacks of inflammation affecting the serosal spaces. The gene associated with FMF[1] (MEFV), mainly expressed in neutrophils, was recently found to be expressed also in primary cultures of serosal origin (peritoneal and synovial fibroblasts). A C5a inhibitor, previously detected in normal serosal fluids, was recently identified in serosal cultures as well, and was found to be deficient in serosal fluids and cultures obtained from FMF patients.

Objective: To investigate the effect of colchicine (the main therapeutic agent for FMF patients) and certain inflammatory cytokines (IL-1b, TNF-a, IFN-a, IFN-g) on MEFV expression and C5a inhibitor activity in neutrophils and primary peritoneal fibroblast cultures.

Methods: Human primary peritoneal fibroblast cultures and neutrophils were studied for MEFV expression and C5a inhibitor activity, using reverse transcription-polymerase chain reaction and C5a-induced myeloperoxidase assay, respectively, in the presence and absence of colchicine and cytokines.

Results: MEFV expression in neutrophils was high and could not be induced further. Its expression in the peritoneal fibroblasts was lower than in neutrophils and could be induced using colchicine and cytokines parallel with induction of C5a inhibitor activity. Semi-quantitative RT-PCR[2] assays enabled estimation of MEFV induction by the cytokines at 10–100-fold and could not be further increased by concomitant addition of colchicine.

Conclusion: Serosal tissues, which are afflicted in FMF, express colchicine and cytokine-inducible MEFV and contain inducible C5a inhibitor activity. The relation between colchicine ability to induce MEFV and C5a inhibitor activity, and its efficacy in FMF treatment, require further investigation.

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[1] RT-PCR = reverse transcription-polymerase chain reaction

[2] FMF = familial Mediterranean fever

Background: Primary aldosteronism is a common cause of non-renal secondary hypertension. A correct diagnosis results in curing the hypertension or targeting appropriate pharmacotherapy. In patients with low renin resistant hypertension (after treatment with three or more different anti-hypertensive drugs the blood pressure remains above 140/90 mmHg), screening for aldosteronism is mandatory.

Objectives: To demonstrate that normal blood levels of potassium in resistant hypertensive patients do not exclude the possible presence of hyperaldosteronism, and to suggest the use of the plasma aldosterone concentration (ng/dl)/plasma renin activity (ng/ml/hour) ratio in screening for hyperaldosteronism.

Methods: Blood tests, suppression and stimulation tests (2 L normal saline IV/4 hours and 20 mg furosemide IV for 60 minutes in a standing position) were systematically performed in 20 low renin normokalemic resistant hypertensive patients. None had renal disorders, known endocrine abnormalities or heart failure. They did not receive anti-hypertensive drugs affecting PAC[1] or PRA[2]. Basal PRA and PAC were measured twice: PAC after saline infusion and PAC/PRA after stimulation.

Results:. PAC/PRA above 50 was used to denote hyperaldosteronism. Serum K was 4 ± 0.07 mM/L, PAC 22.8 ± 1.8 ng/dl, PRA 0.13 ± 0.02 ng/ml/hour, PAC/PRA 190 ± 22 (above 100 in 17). After suppression PAC decreased from 25 ± 1.8 to 11 ± 1 ng/dl (normal <5 ng/dl). Stimulation did not affect PRA and PAC/PRA. Abdominal computed tomography scan revealed normal adrenal glands in 15 patients. Spironolactone (116 ± 60 mg/day) normalized blood pressure in all patients; it was used as a single therapy in 8, and in association with only one anti-hypertensive drug in the remaining 12 patients. In one patient the treatment was discontinued due to the presence of hyperkalemia.

Conclusions: Low renin resistant hypertension associated with normokalemia may be due to hyperaldosteronism. Normal aldosterone levels in the basal condition do not exclude the possibility of hyperaldosteronism. Using a PAC/PRA ratio above 50 as a screening test can aid the physician in deciding when to perform dynamic tests, thus increasing the sensitivity of the diagnosis of hyperaldosteronism. CT scan is frequently normal. Targeted pharmacotherapy leads to a normalization of blood values.

Background: Family physicians coordinate the care of their patients and follow them in a longitudinal manner. Do they have a role to play while their patients are hospitalized? Does the system of care expect them to play a role, and how does it support or integrate it?

Objectives: To discuss the various models of relations between hospital and primary care physicians in the world as compared to those in Israel.

Method: Short cases are reported describing the author’s personal experiences and difficulties encountered in a family practice.

Discussion: Identifying and defining problems encountered, as well as their origin and development within the history and evolution of the system of delivery of care in Israel, will lead to some suggestions for a possible solution. Maturation of the system, especially education of the junior staff within the hospital system, is still needed to facilitate the hospital-physician relationship.

Conclusion: More active participation of the family physician offers added value to patients’ management during their hospital stay and is welcomed by them. The full implementation of a system promoting continuity of care requires further attempts at developing suitable models of cooperation between hospital and family physicians.
 

Background: Low birth weight has been shown to be strongly related to hypertension in adult life.

Objective: To determine whether blood pressure is higher in children with intruterine growth retardation than in control subjects.

Methods: Blood pressure was measured in 58 children aged 4-6 years with IUGR and in 58 age-matched controls. The control children, whose birth weight was appropriate for gestational age, were also matched for gestational age.

Results: The children with IUGR had significantly higher mean values of systolic (p<0.05) and diastolic blood pressures (p<0.05) and mean arterial pressure (p<0.05). Significant differences in blood pressure values were found between preterm IUGR (n=21) and preterm controls (p<0.05).

Conclusion: These data indicate that children with IUGR may be at higher risk of hypertension already in childhood.

Background: Concern about the side effects of allogeneic blood transfusion has led to an increased interest in methods of minimizing peri-operative transfusion. Technologies to minimize allogeneic transfusion include drugs such as aprotinin, desmopressin, tranexamic acid and erythropoietin, and techniques such as acute normovolemic hemodilution, cell salvage and autologous pre-donation.

Objective: To survey the current use in Israel of these seven technologies used to minimize allogeneic blood transfusion.

Methods: Our survey was conducted in 1996–97 in all hospitals in Israel with more than 50 beds and at least one of the following departments: cardiac or vascular surgery, orthopedics, or urology. All departments surveyed were asked: a) whether the technologies were currently being used or not, b) the degree of use, and c) the factors influencing their use and non-use. The survey was targeted at the heads of these departments.

Results: Pharmaceuticals to reduce allogeneic blood transfusion were used in a much higher proportion in cardiac surgery departments than in the other three departments. Pre-operative blood donation was used in few of the cardiac, urologic and vascular surgery departments compared to its moderate use in orthopedic departments. The use of acute normovolemic hemodilution was reported in a majority of the cardiac departments only. Moderate use of cell salvage was reported in all departments except urology where it was not used at all.

Conclusion: There is considerable practice variation in the use of technologies to minimize exposure to peri-operative allogeneic blood transfusion in Israel.
 

Background: The evaluation of hospitalized patients with chest pain and non-diagnostic electrocardiogram is problematic and the optimal cost-effective strategy for their management controversial.

Objectives: To determine the utility of myocardial perfusion imaging with thallium-201 for predicting outcome of hospitalized patients with chest pain and a normal or non-diagnostic ECG.

Methods: On pain cessation, 109 hospitalized patients, age 61+14 years (mean+SD), with chest pain and non-diagnostic ECG underwent stress myocardial perfusion SPECT imaging with thallium-201. Costs related to their management were calculated. The occurrence of non-fatal myocardial infarction or cardiac death was recorded at 12+5 months follow-up.

Results: A normal SPECT was found in 84 patients (77%). During one year follow-up, only 1 (1.2%) compared to 7 (28%) cardiac events (6 myocardial infarctions, 1 cardiac death) occurred in patients with normal versus abnormal scans respectively (P < 0.0001). Negative predictive value and accuracy of the method were 99% and 83% respectively. Multivariate regression analysis identified an abnormal SPECT as the only independent predictor of adverse cardiac event (P = 0.0016). Total cost from admission until discharge was 11,193 vs. 31,079 shekels (P < 0.0001) for normal and abnormal scan. Considering its high negative predictive value, shortening the hospital stay from admission until scan performance to 2 days would result in considerably reduced management costs (from NIS 11,193 to 7,243) per patient.

Conclusion: Stress SPECT applied to hospitalized patients with chest pain and a normal or non-diagnostic ECG is safe, highly accurate and potentially cost effective in distinguishing between Iow and high risk patients.
 

Background: Transfer to an emergency room and hospitalization of nursing home residents is a growing problem that is poorly defined and reported.

Objectives: To assess the clinical effectiveness of a pilot project involving hospitalization of nursing home residents directly to an acute-care geriatric department.

Methods: We retrospectively compared the hospitalization in an acute-care geriatric unit of 126 nursing home residents admitted directly to the unit and 80 residents admitted through the emergency room. The variables measured included length of stay, discharge disposition, mortality, cause of hospitalization, chronic medical condition, cognitive state, functional status at admission, and change of functional status during the hospital stay. Follow-up data were obtained from medical records during the 2 year study.

Results: No significant differences between the groups were found for length of stay, mortality, discharge disposition and most characteristics of the hospital stay. The only significant difference was in patients’ mean age, as emergency room patients were significantly older (86 vs. 82.9 years). The most common condition among nursing home patients admitted via the emergency room was febrile disease (36.9%) ,while functional decline was the most common in those coming directly from the nursing home (32.5%). The prevalence of functional dependence and dementia were similar in both groups. Functional status did not change throughout the hospital stay in most patients.

Conclusions: Treatment of selected nursing home residents admitted directly from the nursing home to an acute- care geriatric unit is feasible, medically effective, results in the safe discharge of almost all such patients and provides an alternative to transfer to an emergency room. This study suggests that quality gains and cost-effective measures may be achieved by such a project, although a randomized controlled trial is necessary to support this hypothesis.
 

Background: The method of midline Iaparotomy incision and closure remains a complex surgical problem.

Objective: To compare the mechanical properties at the interface of midline laparotomy incision made by scalpel versus electrocutting current in rats.

Methods: A sharp midline laparotomy incision was made in 60 Wistar female rats using a scalpel or electrocautery to open the fascia. The fascial and skin wounds were closed separately with a continuous nylon. Fascial specimens were analyzed for mechanical properties at the midline incision using a loading machine. The load-extension curve was recorded during tensile loading at a steady extension rate of 15 mm/mm.

Results: There was no statistically significant difference between the two groups in either wound-bursting force (PPEAK) or the strain energy spent until the point of measured PPEAK. Each load-extension curve showed a characteristic pattern in all rats. Tissue stiffness was greater in the scalpel group than in the electrocautery group (P= 0.02). Correlations were found between tissue stiffness and strain energy, between tissue stiffness and bursting force, and between bursting force and strain energy.

Conclusions: While tissue stiffness was greater when a scalpel was used compared to electrocutting to incise the midline abdominal fascia in rats, there was no difference in the bursing force required to disrupt the wound.

Although a depressive state is known to occur following the resolution of an acute psychotic episode, little research has investigated its etiology, course, prognosis and treatment. Very often the depression is mistaken for an extrapyramidal­like syndrome — the secondary effect of antipsychotic medica­tion - as a sense of inevitability assails both the patient and therapist. Post-psychotic depression, far from being an obscure and undefined clinical picture, has the characteristics of a clear-cut syndrome. Nevertheless, it was only recently referred to as a distinct entity in psychiatric classification systems. As a result, different researchers used varying criteria for the definition of the phenomenon, and the data collected in the different studies are therefore difficult to compare. We present a critical review of the data published to date, with emphasis on the importance of early recognition and treatment of post-psychotic depression.

Background: Appropriateness of hospital admission has both clinical and economic relevance, especially in light of the growing pressure for increased efficiency of health services utilization. In Israel, the number of referrals and use of the emergency room continue to rise along with an increase in hospital admissions and the number of inappropriate admis­sions. Using evaluation protocols, such as the Pediatric Appropriateness Evaluation Protocol, international studies have shown that 10-30% of hospital admissions are medically unnecessary. Inappropriate hospitalizations have an economic impact as well as medical and psychological effects on the child and the family.

Objectives: To assess the extent and characteristics of inappropriate pediatric admissions to a tertiary care facility in Israel.

Methods: We conducted a prospective study using chart review of pediatric admissions to Soroka University Medical Center on 18 randomly selected days in 1993, and evaluated the appropriateness of admissions using the PAEP.

Results: Of the 221 pediatric admissions 18% were evaluated as inappropriate. The main reason for such an evaluation was that the problem could have been managed on an ambulatory basis. Inappropriate admissions were asso­ciated with hospital stays of 2 or less days, children older than 1 year of age, Jewish children, and self-referrals to the pediatric emergency room.

Conclusions: The assessment and identification of characteristics of inappropriate hospital admissions can serve as indicators of problems in healthcare management and as a basis for improving quality of care and developing appropriate medical decision-making processes.