Israel Medical Association Journal

Background: Cystinuria is an autosomal recessive disease that is manifested by kidney stones   and is caused by mutations in two genes: SLC3A1 on chromosome 2p and SLC7A9 on chromosome 19q. Urinary cystine levels in obligate carriers are often, but not always, helpful in identifying the causative gene.

Objectives: To characterize the clinical features and analyze the genetic basis of cystinuria in an inbred Moslem Arab Israeli family.

Methods: Family members were evaluated for urinary cystine and amino acid levels. DNA was initially analyzed with polymorphic markers close to the two genes and SLC7A9 was fully sequenced.

Results: Full segregation was found with the marker close to SLC7A9. Sequencing of this gene revealed a missense mutation, P482L, in the homozygous state in all three affected sibs.

Conclusions: A combination of urinary cystine levels in obligate carriers, segregation analysis with polymorphic markers, and sequencing can save time and resources in the search for cystinuria mutations.
 

Background: Radiofrequency ablation has been suggested as first-line therapy in the management of accessory pathways. There are limited data on the results of ablation over years of experience.

Objectives: To assess the results and complications following RFA[1] of APs[2] performed in our institution over a 14 year period.

Methods: RFA was performed using deflectable electrode catheters positioned at the mitral or tricuspid annulus. The site of the AP was localized by electrophysiological study and radiofrequency energy was applied via the tip of the catheter

Results: The study cohort comprised 508 consecutive patients (64.2% males, mean age 33.6 ± 15.1 years) who underwent 572 RFA procedures for ablating 534 APs. A single AP was found in 485 (95.5%) patients while multiple APs were noted in 23 patients (4.5%). The APs were manifest, concealed or intermittent in 46.8%, 44.4% and 8.8% of cases, respectively. AP distribution was as follows: left free wall (56.6%), posteroseptal (23%), right anteroseptal (7.9%), right free wall (6.2%), midseptal (3.4%) and right atriofascicular (3.0%). Acute successful rates for a first or multiple ablation attempts were 93.1% and 95.3%, respectively. At a first ablation attempt, acute success and failure rates were the highest for midseptal (100%) and right atriofascicular (12.5%) APs respectively. Right anteroseptal APs were associated with the highest rate (23.9%) of discontinued or non-attempted procedures. Recurrent conduction in an AP after an initial successful ablation was observed in 9.9% of cases; it was the highest (24.2%) for right free wall APs and the lowest (5.0%) for left free wall APs. During follow-up (85 ± 43 months), definite cure of the AP was achieved in 94.9% of cases following a single or multiple procedures: midseptal (100%), left free wall (98%), right free wall (97%), posteroseptal (92.7%), right atriofascicular (87.5%) and right anteroseptal (78.5%). A non-fatal complication occurred in 18 patients (3.5%), more frequently in females (6.6%) than in males (1.8%) (P < 0.01). The two major complications (pericardial effusion and myocardial ischemic events) mainly occurred during RFA of a left free wall AP using a retrograde aortic approach. Catheter-induced mechanical trauma to APs was observed in 56 cases (10.5%). Mechanical trauma mainly involved right atriofascicular (43.8%) and right anteroseptal (38.1%) APs and contributed to the low success rate of RFA at these AP locations. During the 14 year period, our learning curve was achieved quickly in terms of success rate, although the most significant complications were observed at the beginning of our experience.

Conclusions: The results of this study confirm the efficacy and safety of RFA and suggest that it is a reasonable first-line therapy for the management of APs at any location.

Objectives: To review our experience with cricotracheal resection and to assess related pitfalls and complications.

Methods: We examined the records of all patients who underwent CTR[1] in a tertiary referral medical center during the period January 1995 to April 2005.

Results: The study included 61 patients (16 women and 45 men) aged 15–81 years. In 17 patients previous interventions had failed, mostly dilatation and T-tube insertion. Complete obstruction was noted in 19 patients and stenosis > 70% in 26. Concomitant lesions included impaired vocal cord mobility (n=8) and tracheo-esophageal fistula (n=5). Cricotracheal anastomosis was performed in 42 patients, thyrotracheal in 12 and tracheotracheal in 7. A staged procedure was planned for quadriplegic patients and for three others with bilateral impaired vocal cord mobility. Restenosis occurred in six patients who were immediately revised with T-tube stenting. Decanulation was eventually achieved in 57 patients (93.4%). Complications occurred in 25 patients, the most common being subcutaneous emphysema (n=5). One patient died of acute myocardial infarction on the 14th postoperative day.

Conclusions: CTR is a relatively safe procedure with a high success rate in primary and revised procedures. A staged procedure should be planned in specific situations, namely, quadriplegics and patients with bilateral impaired vocal cord mobility. 

Objective: To study the attitude of physicians to obesity by examining discharge letters of overweight patients with ischemic heart disease.

Methods: We used the HOLEM database for this analysis. The HOLEM project was designed to study the NCEP (National Cholesterol Education Program) guideline implementation among patients with IHD[1] at hospital discharge. We documented the recording of risk factors and treatment recommendations for IHD by reviewing the discharge letters of 2994 IHD patients admitted to four central hospitals in Israel between 1998 and 2000. A follow-up visit was held 6–8 weeks after discharge, at which time the diagnosis of IHD was verified, risk factor status was checked, height and weight were measured and drug treatment was reviewed.

Results: Mean body mass index was 28.3 kg/m² and 32% were obese (BMI[2] ³ 30 kg/m²). Only 39.6% of the obese patients and 65.8% of the morbidly obese patients (BMI ³ 40 kg/m²) had "obesity" noted in their discharging letters, and weight loss recommendation was written in only 15% of the obese patients' discharge letters. Acute episodes like acute myocardial infarction and unstable angina did not influence the notation of obesity, and only BMI and the number of additional risk factors were positively correlated with the notation of this risk factor.

Conclusions: Despite the importance of obesity, weight status was not noted and weight loss was not recommended in most of the discharge letters of obese IHD patients.

Tumor necrosis factor-associated fever syndrome is an autosomal dominant disorder caused by mutations of the TNFRSF 1A gene encoding the 55 kD TNF receptor (p55 TNF-RI).

Although the airway granulomata in Wegener's granulomatosis were stressed initially by Friedrich Wegener himself, in the last few decades systemic lesions mainly caused by acute vasculitis have received the most attention. However, recently, the implication of granulomatous manifestations in WG[1] has raised much interest. The present data suggest that an aberrant Th1-type response might play a role in the initiation of WG, clinico-pathologically characterized by granulomatous inflammation rather than vasculitis. Disease progression to generalized WG with the predominance of vasculitic manifestations is associated with a “switch” or further complexity of the collective T cell response with the appearance of another subset of Th2-type cells and a less prominent Th1-type cytokine production in the granulomatous lesions of the upper respiratory tract. However, the clinical significance of the granulomatous inflammation is not yet completely understood. Further research will also have to focus on the role of the granulomata during relapsing disease. We review present knowledge of granulomatous inflammation in WG. Morphologic aspects, the scale of cytokine alterations as well as the variety of clinical manifestations are discussed.

Objectives: To present a variety of radiologic findings on high resolution computerized tomography in eight sequential patients with COP[1], together with clinical and pathologic correlation.

Methods: Sequential HRCT[2] examinations of eight patients (four males) aged 53–80 years (mean 65.5 years) with pathologically proven COP were retrospectively analyzed by a consensus of two experienced chest radiologists for the existence and distribution of airspace consolidation, ground-glass opacities, nodular thickening along bronchovascular bundles, small (<1 cm) and large (>1 cm) nodules. The distribution of radiologic findings was classified as unilateral or bilateral, located in the upper, lower or middle lobe, and central or peripheral. Also recorded was the presence or absence of mediastinal lymphadenopathy and pleural effusion. Correlation with clinical symptoms was analyzed.

Results: All eight patients had bilateral airspace consolidations: in two cases consolidations were limited to central fields, in four they were peripheral, and in the remaining two cases they were both central and peripheral. Small nodules were noted in six cases and large nodules in three. Ground-glass opacities were found in four cases. All patients had enlarged lymph nodes (1–1.5 cm) in the mediastinum. Radiologic abnormalities resolved or improved after steroid treatment in all patients.

Conclusions: HRCT findings of bilateral multiple heterogenic lung infiltrates and nodules associated with mild mediastinal lymphadenopathy in a patient with non-specific clinical symptoms are suggestive of COP; in such cases, lung biopsy is indicated. Radiologic resolution of abnormalities correlates well with clinical improvement under adequate steroid treatment.

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[1] COP = cryptogenic organizing pneumonia

[2] HRCT = high resolution computerized tomography

Objectives: To examine whether the treatment recommendations given to ischemic heart disease patients at hospital discharge are compatible with the guidelines of the Israeli Medical Societies and the U.S. National Cholesterol Education Program for coronary artery disease prevention; and to study the effects of brief educational sessions on the adherence of physicians with the guidelines.

Methods: We included consecutive IHD[1] patients admitted to four central hospitals in Israel between 1998 and 2000. The study was conducted in two phases. In phase 1, we reviewed discharge letters to document treatment recommendations given to each patient. In phase 2 we educated the practitioners by reviewing the Israeli Medical Societies and the NCEP[2] guidelines and the quality of their recommendations in phase 1, after which we reevaluated the discharge letters.

Results: The study included 2,994 patients: 627 in phase 1 and 2,367 in phase 2. Of the patients who needed cholesterol-lowering according to their low density lipoprotein levels, 37.4% were not prescribed such drugs at discharge (under-treatment group). This proportion was reduced by education to 26.6% (P < 0.001) in phase 2. Of the treated patients, 65.6% did not reach the target LDL[3] goal in phase 1 (under-dosage group) as compared to 60.2% in phase 2 (P = 0.23). In phase 2 there was an increase in the percent of patients reaching LDL levels <130 mg/day (69.3% vs. 63.8% of patients prescribed medication, P = 0.01), but the percent of patients reaching LDL levels <100 was not different in phase 2 after adjusting for age and gender (the odds ratio for reaching target LDL was 1.16, with 95% confidence interval of 0.95–1.43).

Conclusions: Physician recommendations to IHD patients discharged from hospital were suboptimal. We documented a high proportion of under-treated and under-dosage patients. Brief educational sessions have a beneficial effect on the usage of statins; however, additional effort in guideline implementations is needed.

Objective: To reexamine the impact of prolonged nasogastric tube feeding on the oral microbiota and to explore the salivary flow and composition in elderly patients in long-term care.

Methods: We compared a group of elderly patients fed by nasogastric tube with a control group of elderly patients in long-term care who are fed orally. Bacteriologic studies were performed by culturing samples from the oropharynx. Saliva studies included quantitative and biochemical analysis of basal and stimulated salivary flow.

Results: Bacteriologic studies performed in 90 patients revealed a significantly higher prevalence of gram-negative bacteria in nasogastric tube-fed patients (73% vs. 13%, P < 0.001). It is emphasized that Pseudomonas aeruginosa and Klebsiella pneumoniae were commonly and exclusively isolated from the oral flora of the nasogastric tube-fed patients (P < 0.001, P < 0.05). In the saliva studies performed on 23 nasogastric tube-fed and 21 control patients, basal and stimulated salivary flow was not significantly different in the two groups, however the ratio of stimulated to basal flow was reduced in the nasogastric tube-fed group (P < 0.05). Significant differences were also found in the concentrations of sodium, amylase, phosphor and magnesium. Noteworthy was the concentration of uric acid, the main non-enzymatic antioxidant of saliva, which was significantly lower in nasogastric-tube fed patients (P < 0.002).

Conclusions: These findings suggest that prolonged nasogastric tube feeding is associated with pathologic colonization of the oropharynx and with alterations in the saliva that are related to the risk of aspiration pneumonia. Further research is called for, as well as a thorough revision of the existing oral cleansing procedures in these patients.