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עמוד בית
Thu, 18.07.24

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July 2002
Rami Sagi, MD, Eyal Robenshtok, MD, Lior H. Katz, MD, Shmuel Reznikovich, MMHF, Israel Hendler, MD, Lior Poles, MD, Ariel Hourvitz, MD, Boaz Tadmor, MD, Meir Oren, MD, Giora Martonovich, MD and Boaz Lev, MD

The threat of a disease outbreak resulting from biologic warfare has been of concern for the Israeli health system for many years. In order to be prepared for such an event the health system has formulated doctrines for various biologic agents and defined the logistic elements for the procurement of drugs. During the last 4 years, and especially after the West Nile fever epidemic in 2000, efforts to prepare the healthcare system and the relevant organizations were accelerated. The Director-General of the Ministry of Health nominated a Supreme Steering Committee to fill in the gaps and upgrade the preparedness of the health system for an unusual disease outbreak. This committee and its seven subcommittees established appropriate guidelines, communication routes among different organizations, and training programs for medical personnel. The anthrax outbreak in the United States found the healthcare system in the hub of the preparation process, and all modes of action were intensified. Further work by hospitals, primary care clinics and all other institutes should be initiated to maintain a state of proper preparedness.

May 2002
Adi Friedman, MD, Yizhar Floman, MD, Shabtai Sabatto, MD, Ori Safran, MD and Rami Mosheiff, MD

Background: As air travel increases and the number of commercial and non-commercial flights rises so does the number of aircraft accidents. The improved safety standards of the aviation industry result in a growing number of survivors of aircraft crashes, but there are no management guidelines for the treatment of aircraft crash survivors.

Objectives: To present our experience in treating five survivors of a light aircraft crash that occurred in August 1995 near Jerusalem.

Results: All five survivors sustained vertebral column injuries, which was the only injury in most of the survivors. We discuss the mechanism of injury.

Conclusions: Investigation of injuries’ pattern in survivors of aircraft crash is important for establishing management protocols in trauma centers.
 

Michael Eckstein, MSc, Iris Vered, MD, Sophia Ish-Shalom, MD, Anat Ben Shlomo, MD, Avraham Shtriker, MD, Nira Koren-Morag, PhD and Eitan Friedman, MD, PhD

Background: Genetic factors have been shown to play a major role in the development of peak bone mass, with hereditability accounting for about 50-85% of the variance in bone mass. Numerous candidate genes were proposed to be involved in osteoporosis, but the precise genes and their relative contribution remain unknown.

Objectives: To gain insight into the genetic basis of idiopathic low bone mineral density in Israeli patients by analyzing the impact of two candidate genes: polymorphism of the vitamin D receptor gene and polymorphism A986s in the calcium-sensing receptor gene.

Methods: We analyzed 86 Jewish Israeli patients with LBMD[1]: 38 premenopausal women and 48 men, and compared the allelic pattern distribution with that of the general population (126 men and 112 women). Genotyping of the VDR[2] gene was performed in three polymorphic sites using restriction enzymes, and allelic analysis of A986s polymorphism in the CaSR[3] gene was performed using the denaturing gradient gel electrophoresis technique.  

Reaults: In LBMD women the distributions of VDR alleres in Apal polymorphism were AA=7/28, Aa=16/28 and aa=5/28; in TaqI polymorphism TT=10/31, Tt=16/31 and tt=5/31; and in BsmI polymorphism BB=7/32, Bb=14/32 and 11/32. In LBMD men the distributions were AA=17/39, Aa=21/39 and aa=1/39; in TaqI polymorphism TT=12/42, Tt=23/42 and tt=7/42; and in BsmI polymorphism BB=12/41 Bb=18/41 and bb=11/41. The distributions of all these polymorphisms in the control groups were not significantly different. Adjusting for the independent age and gender parameters confirmed that these three polymorphisms of the VDR gene did not have a significant effect on bone mineral density. Thirty percent (24/79) of LBMD patients of either sex displayed heterozygosity of the CaSR A986s polymorphism, compared with 40 of 203 controls (19.7%) (P=0.059). Adjusting for age and gender in these patients revealed a significant difference in the femoral neck BMD[4] between homozygotes and heterozygotes (P=0.002). The age at menarche of the LBMD women was found to predict 61% of the variance of femoral neck BMD.

Conclusions: In Israeli Jewish men and premenopausal women VDR gene alleles do not seem to be associated with lower lumbar spine or femoral neck BMD. A trend towards heterozygosity for a CaSR polymorphism missense mutation was noted in the LBMD patients. Age at menarche in the LBMD women was found to be an important predictor of BMD. A significant difference was found between LBMD women and healthy control women towards heterozygosity for a CaSR polymorphism, as well between homozygotes and heterozygotes for a CaSR polymorphism in BMD. The significance of these findings and their applicability to a larger population awaits further studies.

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[1] LBMD = low bone mineral density


[2] VDR = vitamin D receptor


[3] CaSR = calcium-sensing receptor


[4] BMD = bone mineral density




Tatiana Fadeeva, MD, Yair Levy, MD, Gisele Zandman-Goddard, MD, Segal Tal, MD and Marina Perelman, MD
April 2002
Eyal Meltzer, MD and Shmuel Steinlauf, MD

Background: Lithium has been a part of the psychiatric pharmacopoeia for more than half a century. Its efficacy is marred by a narrow therapeutic index and significant toxicity.

Objectives: To increase physicians’ awareness of the various manifestations of lithium intoxication.

Methods: We reviewed the clinical data of cases of lithium poisoning occurring in a municipal hospital during a 10 year period.

Results: Eight patient records were located. The mortality rate was 12.5%. All patients were women and the mean age was 66.4 years. The most common symptoms were neurological. One illustrative case is described in detail with lithium serum levels showing the usual two-phase decline.

Conclusions: Lithium poisoning can present in many forms. Increased physician awareness and the early use of effective treatment, mainly hemodialysis, will prevent mortality and protracted morbidity associated with this condition.
 

March 2002
Zeev Rotstein, MD, MHA, Rachel Wilf-Miron, MD, MPH, Bruno Lavi BA, Daniel S. Seidman, MD, MMSc, Poriah Shahaf, MD, MBA, Amir Shahar, MD, MPH, Uri Gabay, MD, MPH and Shlomo Noy, MD, MBA

Background: The emergency department is one of the hospital’s busiest facilities and is frequently described as a bottleneck. Management by constraint is a managerial methodology that helps to focus on the most critical issues by identifying such bottlenecks. Based on this theory, the benefit of adding medical staff may depend on whether or not physician availability is the bottleneck in the system.

Objective: To formulate a dynamic statistical model to forecast the need for allocating additional medical staff to improve the efficacy of work in the emergency department, taking into account patient volume.

Methods: The daily number of non-trauma admissions to the general ED[1] was assessed for the period 1 January 1992 to 1 December 1995 using the hospital computerized database. The marginal benefit to shortening patient length of stay in the ED by adding a physician during the evening shift was examined for different patient volumes. Data were analyzed with the SAS software package using a Gross Linear Model.

Results: The addition of a physician to the ED staff from noon to midnight significantly shortened patient LOS[2]: an average decrease of 6.61 minutes for 80–119 admissions (P<0.001). However, for less than 80 or more than 120 admissions, adding a physician did not have a significant effect on LOS in the ED.

Conclusions: The dynamic model formulated in this study shows that patient volume determines the effectiveness of investing manpower in the ED. Identifying bottleneck critical factors, as suggested by the theory of constraints, may be useful for planning and coordinating emergency services that operate under stressful and unpredictable conditions. Consideration of patient volume may also provide ED managers with a logical basis for staffing and resource allocation.






[1] ED = emergency department



[2] LOS = length of stay


Alexander Kagan, MD, Nurit Haran, PhD, Ludmila Leschinsky, MD, PhD, Ruty Sarafian, RN, BA, Dan Aravot, MD, Jaffa Dolberg, RN, Ziv Ben-Ary, MD and Jason Rapoport, MB, BS, MRCP

Background: Leptin is a 16 kDa hormone synthesized by adipocytes and involved in body weight regulation.

Objectives: To determine serum leptin concentrations in heart, liver and kidney transplant recipients.

Methods: We investigated 57 patients: 18 male heart transplant recipients (age 25-69 years) at 1-66 months after transplantation, 6 female and 8 male liver transplant recipients (age 33-70) at 11-73 months after transplantation, and 10 female and 15 male kidney transplant recipients (age 20-61) at 3-138 months after transplantation. All recipients were receiving immunosuppressive therapy, including prednisone 0-20 mg/day, azathioprine 75-125 mg/day, cyclosporin 100-250 mg/day or tacrolimus 2-10 mg/day. The results were compared to those of 10 female and 10 male healthy controls. Morning serum concentrations of leptin were measured with a commercial radioimmunoassay (Linco Research Inc., USA), and serum insulin and cortisol levels were measured by radioimmunoassay.

Results: Patients (both men and women) after heart, liver and kidney transplantation exhibited significantly higher serum concentrations of leptin and leptin/body mass index ratios than controls. Serum leptin concentrations were significantly higher in women than in men and correlated very significantly with BMI[1] in all cases. The multivariate stepwise analyses showed that among parameters including BMI, gender, age, time after transplantation, prednisone dose, hematocrit, serum concentrations of glucose, albumin, creatinine, cortisol and insulin, only BMI, gender, cortisol and insulin were significant independent determinants of serum leptin levels in these patients.

Conclusions: This is the first report showing that, in addition to body mass index and gender, basal cortisol and insulin levels affect the hyperleptinemia in transplant patients. The clinical relevance of hyperleptinemia in these patients will require further investigation.






[1] BMI = body mass index



 
Giselle Zandman-Goddard, MD and Sigal Tal, MD
February 2002
Leah Peleg, PhD, Rachel Pesso, PhD, Boleslaw Goldman, MD, Keren Dotan, Merav Omer, Eitan Friedman, MD, PhD, Michal Berkenstadt, PhD, Haike Reznik-Wolf, PhD and Gad Barkai, MD

Background: The Bloom syndrome gene, BLM, was mapped to 15q26.1 and its product was found to encode a RecQ DNA helicase. The Fanconi anemia complementation group C gene was mapped to chromosome 9q22.3, but its product function is not sufficiently clear. Both are recessive disorders associated with an elevated predisposition to cancer due to genomic instability. A single predominant mutation of each disorder was reported in Ashkenazi Jews: 2281delATCTGAinsTAGATTC for Bloom syndrome (BLM-ASH) and IVS4+4A®T for Fanconi anemia complementation group C.

Objectives: To provide additional verification of the mutation rate of BLM and FACC[1] in unselected Ashkenazi and non-Ashkenazi populations analyzed at the Sheba Medical Center, and to trace the origin of each mutation.

Methods: We used polymerase chain reaction to identify mutations of the relevant genomic fragments, restriction analysis and gel electrophoresis. We then applied the ProntoTM kit to verify the results in 244 samples and there was an excellent match.

Results: A heterozygote frequency of 1:111 for BLM-ASH and 1:92 for FACC was detected in more than 4,000 participants, none of whom reported a family history of the disorders. The ProntoTM kit confirmed all heterozygotes. Neither of the mutations was detected in 950 anonymous non-Ashkenazi Jews. The distribution pattern of parental origin differed significantly between the two carrier groups, as well as between each one and the general population.

Conclusions: These findings as well as the absence of the mutations in non-Ashkenazi Jews suggest that: a) the mutations originated in the Israelite population that was exiled from Palestine by the Roman Empire in 70 AD and settled in Europe (Ashkenazi), in contrast to those who remained; and b) the difference in origin distribution of the BS[2] and FACC mutations can be explained by either a secondary migration of a subgroup with a subsequent genetic drift, or a separate geographic region of introduction for each mutation.

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[1] FACC = Fanconi anemia complementation group C


[2] BS = Bloom syndrome

Imad R. Makhoul, MD, DSc, Polo Sujov, MD, Leon Ardekian, DDS, Imad Kassis, MD, Tatiana Smolkin, MD, Imad Abu-Elnaa'j, DMD, Ada Tamir, DSc and Dov Laufer, DMD

Background: Factors influencing the oral flora of premature infants have not been adequately investigated.

Objective: To investigate the effects of gestational age and of anti-bacterial therapy on the oral flora of premature infants.

Methods: Oral cultures were obtained at age 1 day and age 10 days from 65 premature infants, divided into three groups: a) 24 neonates of 30-34 weeks gestation who did not receive ABT, b) 23 neonates of 30-34 weeks gestation who received ABT, and c) 18 neonates < 30 weeks gestation who received ABT.

Results: Oral bacterial colonization increased from day 1 to day 10 of life. In 24-34 week neonates, gestational age did not affect early bacteremia or oral colonization at birth. Neither gestational age nor ABT affected late bacteremia or oral colonization at day 10. In 30-34 week neonates with ABT, the oral flora consisted mainly of non-Escherichia coli gram-negative bacteria, whereas those who did not receive ABT grew mainly alpha-hemolytic streptococci, Klebsiella pneumoniae and E. coli in neonates < 30 weeks who received ABT the oral flora were mainly coagulase-negative staphylococci. Oral colonization with anearobes was zero and colonization with fungi was minimal.

Conclusions: Acquistion of oral bacteria rose from day 1 to day 10 of life, regardless of gestational life or ABT. On day 10 of life, the spectrum of oral bacterial flora changed following ABT and consisted mainly of coagulase-negative Staphylococcus and non E. coli garm-negative bacteria. Oral colonization showed few fungi but no anaerobes. These microbiologic observations merit attention when empirical anti-microbial therapy is considered in premature infants suspected or having late-onset sepsis.

December 2001
Martine Granek-Catarivas, MD

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.
 

Avraham Friedman, MD and Amnon Lahad, MD, MPH

Background: Alternative medicine use is increasing worldwide and the associated expenditures are significant. In Israel 19% of patients who consulted their family physician had also sought treatment by an alternative medicine practitioner.

Objectives: To explore the correlation between different modalities of healthcare utilization, health behavior, and health belief among adult members of a kibbutz. This unique study population enabled the use of a simplified quantitative model due to the minimal individual differences in cost and access.

Methods: Healthcare utilization data were obtained for 220 kibbutz members aged 15–70 years from patient medical files and self-administered questionnaires over a 45 month period. Patient visits to the family practitioner and other specialist physicians were tallied, and individuals reported alternative medicine consultations during the previous year. Multiple regression analysis was used to control for age, chronic disease, and other background characteristics.

Results: The mean number of patient FP visits was 3.6 per patient per year. Women and chronic disease sufferers visited the doctor more frequently. A patient’s number of FP visits and other specialist physician visits were closely correlated, with each specialist physician consult resulting in an additional 0.64 FP visit for a given individual (P=0.007). Our analysis indicated that self-reported alternative therapy utilization was positively associated with the number of FP visits; patients reporting alternative therapy use visited their primary care physician once additionally per year (P=0.03). Low self-rated health status was correlated with increased likelihood of alternative therapy use (borderline significance).

Conclusion: These results suggest that a patient who seeks treatment from one type of healthcare practitioner will seek out other practitioners as well. This study supports the notion that unconventional therapies are used in conjunction with, rather than instead of, mainstream medical care.

October 2001
Efraim Aizen, MD, Rachel Swartzman, MD and A. Mark Clarfield, MD, FRCPC

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.
 

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