Israel Medical Association Journal

Background The temporal behavior of the coronary microcirculation in acute myocardial infarction may affect outcome. Diastolic deceleration time and early systolic flow reversal derived from coronary artery blood flow velocity patterns reflect microcirculatory function.

Objectives To assess left anterior descending coronary artery flow velocity patterns using Doppler transthoracic echocardiography after primary percutaneous coronary intervention, in patients with anterior AMI[1].

Methods Patterns of flow velocity patterns of the LAD[2] were obtained using transthoracic echocardiography-Doppler in 31 consecutive patients who presented with anterior AMI. Measurements were done at 6 hours, 36–48 hours, and 5 days after successful PPCI[3]. Measurements of DDT[4] and pressure half times (Pt½), as well as observation for ESFR[5] were performed.

Results In the first 2 days following PPCI, the average DDT, 600 ± 340 msec, were shorter than on day 5, 807 ± 332 msec (P < 0.012). FVP[6] in the first 2 days were dynamic and bidirectional: from short DDT (< 600 msec) to long DDT (> 600 msec) and vice versa. On day 5 most DDTs became longer. Pt½ at 6 hours was not different than at day 2 (174 ± 96 vs. 193 ± 99 msec, P = NS) and became longer on day 5 (235 ± 98 msec, p = 0.012). Bidirectional patterns were also observed in the ESFR in 6 patients (19%) at baseline, in 4 (13%) at 36 hours, and in 2 (6.5%) on day 5 after PPCI.

Background: Skin basal and squamous cell carcinomas together account for over half of all newly diagnosed cancer cases. Frozen  section control of surgical margins is often required in the head and neck region. A paraffin permanent section does not always confirm the results of a frozen section.

Objectives: To test the diagnostic accuracy of frozen section histopathological analysis in determining the free margins of excised tumors.

Methods: This was a retrospective study of 169 cutaneous basal and squamous cell carcinomas excised with surgical margins diagnosed by frozen section and confirmed by permanent paraffin sections. The data included patients' age, gender, clinical and histopathological diagnosis, as well as characteristics of the lesions.

Results: There were 149 (88%) basal cell carcinomas and 20 (12%) squamous cell carcinomas. False negative margins were found in 19 cases (11.2%) and false positive margins in 11 cases (6.6%). We did not find any correlation between false positive or false negative margins and patients' age, gender, tumor size, tumor location, or the presence of sun-damaged skin. A significantly lower rate of false negative results was found in the residual tumor group.

Conclusions: Our findings show support the use of frozen section margin control in selected patients suffering from non-melanoma skin cancer of the head and neck.
 

Background: Carotid artery stenting is used as an alternative to surgical endarterectomy.

Objectives: To determine the outcome of CAS[1] in a retrospective cohort of patients.

Methods: Between July 1999 and March 2003, 56 consecutive patients with carotid artery stenosis who were considered ineligible for surgery were treated (45 male, 11 female, mean age 69). All cases were performed prior to the introduction of distal protective devices in Israel.

Results: Intraprocedural complications included transient neurological findings in 5 patients (8%), cerebrovascular accident in 2 (3%), hemodynamic changes in 11 (18%), and 4 procedural failures. Post-procedural complications included transient ischemic attack in 3 patients and cardiovascular accident in 6 (10%). At 30 days follow-up, three patients (5%) remained with signs of CVA[2]. Two patients (3%) died during the post-procedural period and 16 (28%) during the 5 year follow-up, one due to recurrent CVA and the remainder to non-neurological causes. Five-year carotid Doppler follow-up was performed in 25 patients (45%), which revealed normal stent flow in 21 (84%), 50–60% restenosis in 3 patients (12%) and > 70% restenosis in one patient (4%).

Conclusions: This study confirms that stent procedures are beneficial for symptomatic carotid stenosis in patients not eligible for surgery.

Background: Systemic lupus erythematosus is an autoimmune disease with diverse clinical manifestations that cannot always be regulated by steroids and immunosuppressive therapy. Intravenous immunoglobulin is an optional immunomodulatory agent for the treatment of SLE[1], but the appropriate indications for its use, duration of therapy and recommended dosage are yet to be established. In SLE patients, most publications report the utilization of a high dose (2 g/kg body weight) protocol.

Objectives: To investigate whether lower doses of IVIg are beneficial for SLE patients.

Methods: We retrospectively analyzed the medical records of 62 patients who received low dose IVIg[2] (approximately 0.5 g/kg body weight).

Results: The treatment was associated with clinical improvement in many specific disease manifestations, along with a continuous decrease in SLEDAI scores (SLE Disease Activity Index). However, thrombocytopenia, alopecia and vasculitis did not improve following IVIg therapy.

Conclusions: Low dose IVIg is a possible therapeutic option in SLE and is associated with lower cost than the high dose regimen and possibly fewer adverse effects.

Background: The prevalence of obesity among children and adolescents in the western world has increased dramatically.

Objective: To assess the efficiency of routine childhood obesity screening by primary physicians in the pediatric population in Israel and the utilization of health services by overweight children.

Methods: The electronic medical records of children aged 60–83 months registered in 39 pediatric primary care centers between January 2001 and October 2004 (n=21,799) were reviewed. Those in whom height and weight were documented during a clinic visit (index visit) were classified as overweight, at risk of overweight, and normal weight by body mass index percentiles. The number of visits to the pediatrician, laboratory tests and health care costs 12 months after the index visit were calculated.

Results: Anthropomorphic measurements were performed in 1556 of the 15,364 children (10.1%) who visited the clinic during the study period. Of these, 398 (25.6%) were overweight, 185 (11.9%) were at risk of overweight, and 973 (62.5%) were normal weight. Children in the first two groups visited the clinic slightly more often than the third group, but the differences was not statistically significant (P = 0.12), and had significantly more laboratory tests than the rest of the children visiting the clinics (P = 0.053). Health care costs were 6.6% higher for the overweight than the normal-weight children.

Conclusions: Electronic medical records are a useful tool for population-based health care assessments. Current screening for obesity in children during routine care in Israel is insufficient and additional education of community pediatricians in diagnosis and intervention is urgently needed.

Background: Percutaneous tracheostomy has largely replaced surgical tracheostomy in the intensive care unit setting. Although it seems logical that surgeons continue to do tracheostomies, anesthesiologists and intensive care specialists are familiar with airway control and guide wire techniques and could replace surgeons in the performance of PDT.

Objectives: To assess the safety and effectiveness of bedside PDT[1] in the ICU[2].

Methods: We conducted a retrospective chart review of 207 patients in the ICU who underwent PDT by an intensive care physician.

Results: Subcutaneous emphysema without pneumothorax occurred in one patient. Four patients underwent surgical revision following PDT. Early bleeding (during the first 48 hours following the procedure) was the indication in two patients and late bleeding, on the 10th post-PDT day, in one. In one case PDT was converted to surgical tracheostomy due to inadvertent early decannulation. There was one death directly related to the procedure, due to an unrecognized paratracheal insertion of the tracheostomy tube followed by mechanical ventilation, which led to bilateral pneumothorax, pneumomediastinum and cardio-circulatory collapse. No infectious complications were seen at the stoma site or surrounding tissues.

Conclusions: PDT by intensive care physicians appears to be safe and should be included in the curriculum of intensive care residency.

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.
 

Quantitative chimerism testing has become an indispensable tool for following the course and success of allogeneic hematopoietic stem cell transplants. In this paper, we describe the current laboratory approach to quantitative chimerism testing based on an analysis of short tandem repeats, and explain why performing this analysis longitudinally is important and feasible. Longitudinal analysis focuses on relative changes appearing in the course of sequential samples, and as such exploits the ultimate potential of this intrinsically semi-quantitative platform. Such an analysis is more informative than single static values, less likely to be confused with platform artifacts, and is individualized to the particular patient. It is particularly useful with non-myeloablative conditioning, where mixed chimerism is common. When longitudinal chimerism analysis is performed on lineage-specific subpopulations, the sensitivity, specificity and mechanistic implications of the data are augmented. Importantly, longitudinal monitoring is a routinely feasible laboratory option because multiplex STR-PCR[1] kits are available commercially, and modern software can be used to perform computation, reliability testing, and longitudinal tracking in a rapid, easy to use format. The ChimerTrack© application, a shareware program developed in our laboratory for this purpose, produces a report that automatically summarizes and illustrates the quantitative temporal course of the patient’s chimeric status. Such a longitudinal perspective enhances the value of quantitative chimerism monitoring for decisions regarding immunomodulatory post-transplant therapy. This information also provides unique insights into the biological dynamics of engraftment underlying the fluctuations in the temporal course of a patient’s chimeric status.

Rembrandt van Rijn (1606–1669) left behind the largest collection of self-portraits in the history of art. These portraits were painted over a period of 41 years, using a realistic technique. To evaluate Rembrandt's aging process we studied 25 uncontested Rembrandt oil self-portraits by means of objective and descriptive techniques. By measuring brow position changes through the years, we demonstrated that brow descent started in the second half of the third decade and began to level out in the fourth decade. Based on Rembrandts' aging physiognomy, from age 22 to 63, we believe that Rembrandt did not suffer from temporal arteritis, hypothyroidism, rosacea, or rhynophima and that no other facial signs of systemic diseases are evident, contrary to the opinions expressed by other medical professionals. We suggest that Rembrandt suffered from melancholia or mild depression, and propose the possibility of chronic lead poisoning as a theoretical illness that he might have had.

Background: The model for end-stage liver disease is the best available predictor of waiting list mortality among liver transplant candidates.

Objectives: To validate the applicability of MELD[1] in Israel.

Methods: All candidates awaiting liver transplantation in our institution were followed prospectively since 2002. We measured the concordance (c-statistic) equivalent to the area under the receiver operating characteristic curve in order to assess the predictive power of MELD. Other independent mortality risk factors were identified by a separate multivariate analysis. Mortality rates within different MELD and Child‑Pugh‑Turcotte scores were compared to the original (United States) MELD data.

Results: Of 86 patients listed for transplantation, 40 were transplanted (36 in Israel and 4 abroad). Of the other 46 patients, 24 are alive and still listed, and 22 died (25%, ~7%/year). The area under the ROC[2] curve for MELD score was 0.79 (0.83 USA) compared to a CPT[3] score of 0.71 (O.76 USA). High MELD scores, occurrence of spontaneous bacterial peritonitis, and diagnosis of hepatocellular carcinoma were independent risk factors of mortality. Death rates per mid MELD score (20–29) were significantly higher than the USA results.

Conclusions: MELD is valid in Israel and superior to CPT in predicting waiting list mortality. Although longer waiting time due to organ scarcity is a key factor, death rates in the mid-range (10–29) MELD groups indicate further audit of the care of patients with end‑stage liver disease.

Background: Dyspnea may be a presenting symptom of type I food hypersensitivity, and bronchial hyper-reactivity, without known asthma, can coexist in patients with food allergy.

Objective: To evaluate airway involvement in young adult patients with food allergy and no asthma and compare the findings to those of patients with food allergy and asthma, with food allergy and allergic rhinitis, with asthma and no food allergy, and of apparently healthy controls.

Methods: The evaluation involved prick skin test to food (65 allergens) and inhalants (24 allergens), spirometry, methacholine inhalation challenge, and induced sputum for cell analysis. The five groups consisted of 18 patients with food allergy alone, 11 with food allergy and asthma, 13 with food allergy and allergic rhinitis, 10 with asthma alone, and 10 controls.

Results: Patients with food allergy alone were mainly (86%) skin sensitive to pollens. Those with either asthma or allergic rhinitis were mainly (95%) sensitive to mites. BHR was detected in 40% of the patients with food allergy alone, 55% of the patients with allergic rhinitis, and 100% of the patients with asthma. Cell counts in the sputum of patients with asthma and in those with food allergy and asthma showed higher eosinophil counts compared to those with food allergy and allergic rhinitis. Patients with food allergy and no asthma, regardless of BHR status, had mainly neutrophils in the sputum.

Conclusions: Patients with food allergy are highly likely to have concomitant asymptomatic BHR. Mite sensitivity in patients with food allergy predicts respiratory allergy (either asthma or allergic rhinitis). High eosinophil levels in the sputum of food allergy patients predict respiratory involvement.

Objectives: To evaluate the accuracy of 16-slice multi-detector CT angiography in the diagnosis of coronary artery disease, and assess coronary bypass grafts and coronary anomalies.

Methods: We conducted a retrospective study of 223 patients who were examined at our medical center over a period of 2 years with a 16-slice CT angiography scanner and retrospective electrocardiographic gating.

Results: There were no significant complications, and good visualization of the coronary arteries was achieved in all but eight patients. A high correlation with the results of the invasive angiography was noted (sensitivity 85%, specificity 93%, negative predictive value 98%). Altogether, 131 bypass conduits were examined with excellent graft visualization. Several coronary anomalies were detected, as were significant extra-cardiac findings.

Conclusions: Multi-slice CT angiography is a reliable non-invasive diagnostic procedure for demonstration of the coronary arteries and bypass grafts. In the future it will probably replace part of the diagnostic invasive coronary angiography and, as a result, a large proportion of coronary angiography procedures will be therapeutic.

Objective: To investigate the effectiveness of preoperative chemoradiation in increasing the resectability rates of rectal cancer and increasing the anal sphincter preservation rate.

Methods: The study group included 66 patients aged 33–84 years with T₂–T₃ rectal carcinoma who were treated in our institute from 1997 to 2002 with preoperative chemoradiation followed by surgery 6 weeks later. All patients underwent preoperative transrectal endoscopic ultrasound for tumor staging and localization. The duration of follow-up was 25 months.

Results: Chemoradiation led to tumor downstaging in 61 patients (92.4%), all of whom underwent low anterior resection. Only 11.4% of this group needed a temporary (6 weeks) loop colostomy/ileostomy. None of the 16 patients with post-treatment T₀ tumors had evidence of malignant cells on pathologic study. Five patients (7.6%) failed to respond to chemoradiation and underwent APR[1]. There were no major complications, such as leakage, and no deaths.

Conclusions: Neoadjuvant chemoradiation is an effective modality to downstage advanced rectal cancer, improving patient quality of life by significantly reducing the need for a terminal permanent colostomy, or even a temporary one.

Objective: To investigate hemodynamic variables, including small and large artery compliance, in cirrhotic patients during total paracentesis.

Methods: The study included 15 cirrhotic patients admitted for an episode of tense diuretic-resistant ascites. Hemodynamic variables including vascular compliance were measured using an HDI pulse wave cardiovascular profiling instrument CR-2000. The variables were measured in these patients before, immediately after and 24 hours following large volume (mean 5.6 L) paracentesis.

Results: Cardiac output increased immediately after paracentesis due to increment in stroke volume, with no change in heart rate. However, 24 hours later the cardiac output decreased to below the basal level. The fluctuation was statistically significant (P < 0.05). There was no change in large artery compliance, but small artery compliance increased after paracentesis (P < 0.05) and partially returned to the basal level after 24 hours. Systemic vascular resistance measurement showed the same pattern of change: vasodilatation occurred during paracentesis and was attenuated 24 hours later.

Conclusions: Large volume paracentesis with albumin replacement caused an accentuation of the vasodilatation (small but not large artery) already present in these patients. This may be the first sign of enhanced vasodilatation due to large volume paracentesis before the clinical expression of impaired hemodynamics and deterioration of renal function.

The complexity of medical problems is a well-recognized phenomenon. In the presence of economic and cultural restrictions, medical decision-making can be particularly challenging. This paper outlines a system of analysis and decision-making for solving such problems, and briefly describes a case study in which the method was used to analyze the case of antibiotic overprescribing in a large health maintenance organization. The purpose of the study was to determine if a technique for problem-solving in the field of engineering could be applied to the complex problems facing primary care. The method is designated Systematic Inventive Thinking and consists of a three-step procedure: problem reformulation, general search-strategy selection, and an application of idea-provoking techniques. The problem examined is the over-prescribing of antibiotics by general practitioners working in Maccabi Healthcare Services, an HMO[1] serving one and a half million patients in Israel. The group of healthcare professionals involved in the discussions generated 117 ideas for improving antibiotic use. Six of these ideas were then implemented in a national campaign in the winter of 2000/1 and 2001/2. During this period, a significant reduction in per-visit antibiotic purchasing was observed for influenza visits (from 79.2 per 1,000 to 58.1 per 1,000, P < .0001), but not for other categories of visits. The SIT[2] methodology is a useful technique for problem-solving and idea generation within the medical framework.