Israel Medical Association Journal

Background: Primary pulmonary hypertension is a rare disorder, characterized by progressive pulmonary hypertension and right heart failure. It may be familial or sporadic. Mutations in bone morphogenetic protein receptor II (BMPR2), a member of the transforming growth factor-beta receptor superfamily of receptors, underlie many cases of the disorder.

Objectives: To perform molecular analysis of a patient with familial PPH[1] and provide her and her family with suitable genetic counseling.

Methods: DNA was extracted from 10 ml whole blood, and the BMPR2 gene was screened for mutations. Individual exons were amplified by polymerase chain reaction and sequenced. Mutation confirmation and molecular characterization of additional family members was performed using restriction enzyme analysis followed by appropriate genetic counseling.

Results: We identified a novel T to C missense mutation expected to result in substitution of arginine for a conserved cysteine in the ligand-binding domain of BMPR2. Screening of family members demonstrated the presence of the mutation in the father and a younger asymptomatic sister of the index patient.

Conclusions: Molecular diagnosis in PPH allows for identification of at-risk family members and raises the option of earlier diagnosis and possibly instituting earlier treatment in affected individuals. However, molecular screening of asymptomatic family members raises difficult ethical questions that can only be resolved by conducting large multicenter prospective studies in BMPR2 carriers.

Background: Increased serum potassium and intraventricular hemorrhage occur frequently in preterm infants.

Objective: To retrospectively analyze data obtained on infants with severe IVH[1] in relation to blood K⁺ concentrations.

Methods: We identified all patients with severe IVH born between July 1997 and July 2000. Each patient was pair-matched with a control infant of the same gestational age (±1 week) without IVH in terms of head ultrasound findings on day 5, and whole blood K⁺ on days 3–5.

Results: There were 24 infants in each group. The IVH group had significantly lower 1 minute Apgar scores and pH and higher blood K⁺ than the control group. Blood pH and K⁺ were inversely correlated. Stepwise regression analysis, taking into account blood pH and 1 minute Apgar score, showed a correlation only between blood K⁺ and IVH status.

Conclusions: Severe IVH is significantly associated with higher blood K⁺ concentrations. A causal relationship cannot be ascertained at this point.

Background: Screening for celiac disease is based on the sequential evaluation of serologic tests and intestinal biopsy; an optimal screening protocol is still under investigation. The screening policy of one of the main healthcare providers in Israel (Maccabi) consists of measuring total immunoglobulin A and tissue transglutaminase IgA[1] antibodies and confirming positive results by endomysial antibodies. For IgA-deficient patients antigliadin IgG is measured.

Objectives: To evaluate the use of tTGA[2] as a first-level screening test in patients suspected of having celiac disease

Methods: The results of tTGA and EMA[3] tests over a 3 month period were obtained from the laboratory computer. Letters were sent to the referring physicians of patients with positive tests, requesting clinical information and small intestinal biopsy results. tTGA was performed using an anti-guinea pig tTG-IgA enzyme-linked immunosorbent assay kit.

Results: Overall, 2,505 tTGA tests were performed: 216 (8.6%) were tTGA-positive of which 162 (75%) were EMA-negative (group 1) and 54 (25%) EMA-positive (group 2). Clinical information was obtained for 91 patients in group 1 and 32 in group 2. Small intestinal biopsy was performed in 33 (36%) and 27 patients (84%) in groups 1 and 2, respectively. Celiac disease was diagnosed in 4 biopsies (12%) in group 1 and 23 (85%) in group 2 (P < 0.0001). The positive predictive value was 45% for tTGA and 85% for EMA.

Conclusions: Symptomatic patients with positive tTGA and negative EMA have a low rate of celiac disease compared to those who are tTGA-positive and EMA-positive. Confirmation with EMA is advised when tTGA is performed as a first-level screening for suspected celiac disease.

Background: The World Health Organization considers a country's morphine consumption to be an important indicator of progress in pain relief. Despite the strong consensus favoring the use of opioids in many types of pain, limited data are available for gauging the trends in opioid usage in specific medical institutions, such as hospitals

Objectives: To assess the possibility that monitoring opioid consumption can shed light on directions and trends in the treatment of pain in a hospital setting.

Methods: Data on opioid consumption, number of inpatient days, and number of operations performed each year during the period 1990–1999 were obtained from records kept in the hospital’s pharmacy and archives.

Results: During that decade the overall opioid consumption in the hospital increased from the equivalent of 3.7 mg of oral morphine per inpatient day to 7.3 mg, and from 56 mg per surgical procedure to 100 mg. In 1990, injected opioids accounted for 93% of the overall consumption, whereas in 1999 they accounted for only 44%. Yet, the proportion of injected meperidine to injected morphine increased only from 43% to 51%.

Conclusions: These results suggest that the ongoing monitoring of opioid consumption can highlight trends and directions and possibly emphasize strengths and weaknesses in the treatment of pain in hospitals.

Background: Corneal erosions, a common and very painful ailment, are traditionally treated with pressure patches and antibiotic ointment but the healing is slow.

Objectives: To report our experience with the use of therapeutic contact lenses for the primary treatment of traumatic corneal erosions.

Methods: During the last 5 years in a single community clinic 65 consecutive patients with traumatic corneal erosions were treated with a corneal contact lens and antibiotic drops as a routine measure. The charts were reviewed for outcome, side effects and complications.

Results: Healing of the corneal erosions occurred within 1 to 3 days in all patients, with minimal or no pain. No corneal infection occurred. One patient had a recurrence that was successfully treated by lens placement.

Conclusions: The therapeutic contact lens with antibiotic drops is a safe and effective method to treat traumatic corneal erosions, and patients can immediately resume their regular activities.

Background: Nasal colonization with methicillin-resistant Staphylococcus aureus in the community is being increasingly reported, but there is a general lack of data on MRSA[1] colonization in children in chronic care institutions and on colonization rates in Israeli children.

Objectives: To define the rate of MRSA nasal colonization in a generally healthy pediatric population in Jerusalem, to compare it with that of children in chronic care institutions, to define risk factors for colonization, and to compare community and hospital-acquired MRSA strains.

Methods: Anterior nares culture for the presence of methicillin-sensitive and methicillin-resistant S. aureus was taken from 831 healthy children attending primary pediatric clinics or emergency department and 118 children hospitalized in three chronic care institutions in Jerusalem.

Results: Of the 831 healthy children, 195 (23.5%) were colonized with S. aureus, as compared to 43 of 118 (36.4%) chronically institutionalized children (P < 0.005). Five of the 195 S. aureus isolates from healthy children (2.6%) were MRSA, as compared to 9 of 43 (21%) from chronically institutionalized children (P < 0.001). Older age and a family member who is a healthcare worker were associated with S. aureus colonization in the population of healthy children, and older age was associated with MRSA colonization in the chronically institutionalized children. The antibiotic susceptibility pattern was similar for both groups, and pulsed field gel electrophoresis of the isolates showed a wide and random distribution in both groups.

Conclusions: MRSA colonization in the studied pediatric community in Jerusalem was very low, whereas that of patients hospitalized in chronic care institutions was significantly higher. In the small number of isolates detected, no significant differences were found in antibiotic susceptibility or PFGE[2] pattern between hospital-acquired and community-acquired strains.

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.