Israel Medical Association Journal

Background: Transcobalamin II is a serum transport protein for vitamin B₁₂. Small variations in TC-II[1] affinity were recently linked to a high homocysteine level and increased frequency of neural tube defects. Complete absence of TC-II or total functional abnormality causes tissue vitamin B₁₂ deficiency resulting in a severe disease with megaloblastic anemia and immunologic and intestinal abnormalities in the first months of life. This condition was described in hereditary autosomal-recessive form. Low serum TC-II without any symptoms or clinical significance was noted in relatives of affected homozygotes.

Objectives: To study 23 members of a four-generation family with hereditary vitamin B₁₂ deficiency and neurologic disorders.

Methods: Thorough neurologic, hematologic and family studies were supplemented by transcobalamin studies in 20 family members.

Results: Partial TC-II deficiency was found in 19 subjects. Apo TC- II (free TC-II unbound to vitamin B₁₂) and total unsaturated B₁₂ binding capacity were low in all tested individuals but one, and holo TC-II (TC-II bound by vitamin B₁₂) was low in all family members. The presentation of the disease was chronic rather than acute. Early signs in children and young adults were dyslexia, decreased IQ, vertigo, plantar clonus and personality disorders. Interestingly, affected children and young adults had normal or slightly decreased serum vitamin B₁₂ levels but were not anemic. Low serum B₁₂ levels were measured in early adulthood. In mid-late adulthood megaloblastic anemia and subacute combined degeneration of the spinal cord were diagnosed. Treatment with B₁₂ injections resulted in a significant improvement. The pedigree is compatible with an autosomal-dominant transmission. This family study suggests a genetic heterogeneity of TC-II deficiency.

Conclusions: We report the first family with a hereditary transmitted condition of low serum TC-II (partial TC-II deficiency) associated with neurologic and mental manifestations in childhood. Partial TC-II deficiency may decrease the amount of stored cobalamin, resulting in increased susceptibility to impaired intestinal delivery of cobalamin and predisposing to clinically expressed megaloblastic anemia at a later age. Partial TC-II deficiency should be suspected in families with megaloblastic anemia and in individuals with neurologic and mental disturbances – despite normal serum vitamin B₁₂ levels. Low serum UBBC[2] and apo TC-II should confirm the diagnosis. Early vitamin B₁₂ therapy may prevent irreversible neurologic damage.

The human placenta is the interface between the mother and fetus in the uterus. Until recently it was generally believed that the uterus provides a protective environment for the fetus. It is now accepted that any chemical substance, including any therapeutic agent, administered to a mother is able to permeate across the placental barrier. Unfortunately, the placental transfer of substances and their distribution in the placenta is not well established. Understanding the structure of placental transporters and their function may serve as the ideal tool for drug development and the cure of mother and fetus during pregnancy.
 

Background: The lack of lactobacilli in the vagina of postmenopausal women due to estrogen deficiency plays an important role in the development of bacteriuria. In the last few years, the use of lactobacilli for the prevention of genitourinary infections has been explored using different probiotic strains.

Objectives: To evaluate the vaginal colonization by Lactobacillus rhamnosus GG in postmenopausal healthy women following oral administration of the bacteria in a yogurt base for 1 month, as a first step in evaluating the potential probiotic role of LGG[1] in the prevention of recurrent urinary tract infections.

Methods: One or two doses per day of yogurt containing 10⁹ colony forming units of LGG were administered orally to 42 postmenopausal healthy women for 1 month. Vaginal and rectal swabs were cultured at the beginning and end of the study.

Results: At the end of the study, the vaginas of only four women (9.5%) were colonized with LGG, at a very low number of bacteria, despite the fact that the gastrointestinal tracts of 33 women (78.6%) were colonized. There were no significant differences between one or two doses daily.

Conclusions: LGG should not be considered as a probiotic agent in urinary infections since it does not attach well to the vaginal epithelium.

Background:  Physicians’ decisions regarding provision of life-sustaining treatment may be influenced considerably by non-medical variables.

Objectives: To examine physicians’ attitudes towards end-of-life decisions in Israel, comparing them to those found in the United States.

Methods: A survey was conducted among members of the Israel Society of Critical Care Medicine using a questionnaire analogous to that used in a similar study in the USA.       

Results: Forty-three physicians (45%) responded, the majority of whom hold responsibility for withholding or withdrawing life-sustaining treatments. Preservation of life was considered the most important factor by 31 respondents (72%). The quality of life as viewed by the patient was generally considered less important than the quality of life as viewed by the physician. Twenty-one respondents (49%) considered withholding treatment more acceptable than withdrawing it. The main factors for decisions to withhold or withdraw therapy were a very low probability of survival of hospitalization, an irreversible acute disorder, and prior existence of chronic disorders. An almost similar percent of physicians (93% for Israel and 94% for the U.S.) apply Do Not Resuscitate orders in their intensive care units, but much less (28% vs. 95%) actually discuss these orders with the families of their patients.

Conclusions:  Critical care physicians in Israel place similar emphasis on the value of life as do their U.S. counterparts and assign DNR[1] orders with an incidence equaling that of the U.S. They differ from their U.S. counterparts in that they confer less significance to the will of the patient, and do not consult as much with families of patients regarding DNR orders.

Background: Among the various new technologies in the field of parathyroid surgery are intraoperative quick parathormone measurements.

Objectives: To evaluate the contribution of QPTH[1] measurements during parathyroidectomy to the achievement of higher success rates. 

Methods: QPTH assay using Immulite Turbo Intact PTH[2] was measured in 32 patients undergoing parathyroidectomy: 30 for primary and 2 for secondary hyperparathyroidism.  QPTH levels were measured at time 0 minutes (before incision) and at 10, 20, and 30 minutes after excision of the hyperfunctioning gland.  Only a drop of 60% or more from the 0’ level was considered to be a positive result.

Results: The mean QPTH level at time 0’ for PHPT[3] patients was 38.12 ± 25.15 pmol/L (range 9.1–118 pmol/L).  At 10 minutes post-excision of the hyperfunctioning gland (or glands), QPTH dropped by a mean of 73.80% to 9.89 ± 18.78 pmol/L. 

Conclusions: Intraoperative QPTH level measurement is helpful in parathyroid surgery.  A drop of 60% or more from 0’ level indicates a successful procedure, and further exploration should be avoided.

Background: Leukotriene antagonist therapy in asthmatic patients alleviates symptoms and improves exercise tolerance, however the effect of these drugs on bronchial provocation tests and exhaled nitric oxide levels are less clearly established.

Objective: To determine the effect of montelukast treatment on airway hyperresponsiveness to exercise, methacholine and adenosine-5’-monophosphate and on exhaled nitric oxide levels in steroid-naive asthmatics.

Methods: Following a 2 week run-in period, 20 mild to moderate asthmatics were enrolled in an open label 6 week trial of oral montelukast-sodium therapy. Bronchial hyperreactivity (exercise, methacholine and adenosine-5’-monophosphate challenges) and exhaled nitric oxide levels were measured before and after the 6 week period.

Results: Montelukast treatment resulted in a significant improvement in exercise tolerance: median DFEV₁ 20.0% (range 0–50) prior to treatment vs. 15.0% (range 0–50) post-treatment (P = 0.029). A significant difference was also observed for exhaled NO[1] following therapy: median NO 16.0 ppb (range 7–41) vs. 13.0 (range 4.8–26) (P = 0.016). No change was seen in baseline lung function tests (FEV₁, MEF₅₀) or in the bronchial responsiveness (PC₂₀) for methacholine and adenosine-5’-monophosphate.

Conclusions: This study demonstrates that the leukotriene antagonist, montelukast-sodium, reduces bronchial hyperreactivity in response to exercise and reduces exhaled nitric oxide levels but has little effect on bronchial responsiveness to methacholine and adenosine challenges.

Background: In the emergency department the physician is often confronted with the decision of where to hospitalize a patient presenting with chest pain and a possible acute myocardial infarction – in the cardiac care unit or in the internal medicine ward.

Objective: To characterize the clinical factors involved in the triage disposition of patients hospitalized with AMI[1] in Israel to either CCUs[2] or IMWs[3] and to determine to what extent the perceived probability of ischemia influenced the disposition decision.

Methods: During a 2 month nationwide prospective survey in the 26 CCUs and 82 of the 94 IMWs in Israel, we reviewed the charts of 1,648 patients with a discharge diagnosis of AMI. The probability of ischemia at admission was determined retrospectively by the Acute Coronary Ischemia Time-Insensitive Predictive Instrument. Co-morbidity was coded using the Index of Coexistent Diseases.

Results: The ACI-TIPI[4] score for patients admitted to CCUs or to IMWs was 76.2% and 57.7% respectively (P < 0.001). Multivariate analysis showed that young patients with a high probability of ischemia and low co-morbidity or functional impairment were more likely to be hospitalized in CCUs than in IMWs.

Conclusion: In Israel, the factors that strongly influence the initial triage disposition of patients with AMI to CCUs or IMWs are age, perceived probability of ischemia, status of co-morbid conditions and functional impairment.

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