Israel Medical Association Journal

Israel has a National Screening Program for early detection of breast cancer. The need to continue and even expand this program was recently stressed in light of the high risk in the population. However, the optimal modalities for breast cancer screening are controversial, especially for women at risk. Mammography, the established screening method, is critically examined, and molecular imaging techniques, such as magnetic resonance spectroscopy and spectroscopic imaging are explored, especially for primary breast cancer detection. MRS[1] and MRSI[2] are currently limited by their reliance on the conventional framework for data analysis in biomedical imaging, i.e., the fast Fourier transform. Recent mathematical advances in signal processing via the fast Pade transform can extract diagnostically important information, which until now has been unavailable with in vivo MRS. A clinical MRS signal illustrates the rapid and stable convergence provided by FPT[3], yielding accurate information about key metabolites and their concentrations at short acquisition times. We suggest that the next step would be to apply the FPT to in vivo MRS/MRSI signals from patients with breast cancer and to compare these to findings for normal breast tissue. The potential implications of such an optimized MRS/MRSI for breast cancer screening strategies are discussed, especially for younger women at high risk.

The ubiquitin-proteasome pathway has a central role in selective degradation of intracellular proteins. Among the key proteins degraded by the system are those involved in the control of inflammation, cell cycle regulation and gene expression. With numerous important cellular pathways affected, derangements in the ubiquitin system were shown to result in a variety of human diseases including malignancies, neurodegenerative diseases and hereditary syndromes, and proteasome inhibition was implicated as a potential treatment for cancer and inflammatory conditions. Two proteasome inhibitors are currently under clinical evaluation for multiple myeloma and acute ischemic stroke. The ubiquitin system also has an important function in the immune and inflammatory response. It is involved in antigen processing and presentation to cytotoxic T cells, and the activation of nuclear factor-kappa B – the central transcription factor of the immune system. Since the proteasome is the central source of antigenic peptides that are presented to the immune system, some viruses, such as the Epstein-Barr virus, developed escape mechanisms that manipulate the ubiquitin-proteasome system in order to persist in the infected host. Understanding the mechanisms underlying the production of viral antigens by the ubiquitin-proteasome system may have therapeutic applications such as future development of vaccines.

Background: Since the early 1970s testicular scintigraphy has been used to diagnose the cause of acute scrotal pain. The advent of Doppler sonography further enhances diagnosis by  providing simultaneous real-time scrotal imaging with superimposed testicular blood flow information.

Objectives: To assess the diagnostic value of Doppler sonography in patients with acute scrotal pain and scintigraphic findings suggestive of testicular torsion.

Methods: Seventy-five patients with acute scrotal pain underwent testicular scintigraphy and Doppler sonography. All patients who had scintigraphic findings suggestive of testicular torsion were included in the study and their files were retrospectively reviewed.

Results: Twenty-seven patients had scintigraphic findings suggestive of testicular torsion. Radionuclide scintigraphy accurately detected all cases of testicular torsion. However, abscess, hematoma, hydrocele and other conditions simulated testicular torsion on scintigraphy, lowering the test specificity. These pathologies were clarified by Doppler sonography that was 95% specific and 86% sensitive for testicular torsion.

Conclusions: Doppler sonography should be used as the first-line modality in the evaluation of patients with suspected testicular torsion. Scintigraphy should be performed only in certain settings of equivocal sonographic findings to prevent false negative sonographic diagnosis.
 

Background: The Dead Sea in Israel has a very high mineral content. Near-drowning in the Dead Sea is expected to result in severe electrolyte abnormalities and respiratory failure. Previous limited studies reported a high mortality rate.

Objective: To evaluate the clinical and biochemical manifestations and disease outcome of near-drowning in the Dead Sea.

Methods: Data were abstracted from the archives of Soroka University Medical Center. The cohort comprised 69 patients who nearly drowned in the Dead Sea.

Results: The median age of the patients was 68 years (range 21–84). There were two major manifestations of near-drowning in the Dead Sea: electrolyte imbalance and acute lung injury. Serum calcium, magnesium and phosphorus (but not sodium, potassium and chloride) were abnormal in most patients. Median serum electrolyte levels (and range) on admission were 10.9 mEq/dl (9–24) for calcium, 4.3 mEq/dl (1–30) for magnesium, and 4.1 mEq/dl (2–9) for phosphorus. These levels quickly normalized with forced diuresis within 24 hours. Acute lung injury – namely, hypoxic bilateral pneumonitis – occurred in 29 patients. Mechanical ventilation was required in 11 patients. Sixty-five patients recovered fully, while the remaining 4 had minor sequelae.

Conclusions: Near-drowning in the Dead Sea is a syndrome of severe electrolyte abnormalities and lung injury. Early treatment, with forced diuresis and supportive care, results in prompt recovery.

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: Little information is available on the clinical practice and implementation of guidelines in treating acute myocardial infarction patients in Israel.

Objective: To assess patient characteristics, hospital course, management, and 30 day clinical outcome of all AMI[1] patients hospitalized in Israel during a 2 month period in 2000.

Method: We conducted a prospective 2 month survey of consecutive AMI patients admitted to 82 of 96 internal medicine departments and all 26 cardiac departments operating in Israel in 2000. Data were collected uniformly by means of a hospital and 30 day follow-up form.

Results: During the survey 1,683 consecutive patients with a discharge diagnosis of AMI were included. Their mean age was 66 years; 73% were male. The electrocardiographic pattern on admission revealed ST elevation, non-ST elevation and an undetermined ECG[2] in 63%, 34% and 4% of patients respectively. Aspirin and heparin were given to 95% of patients. Beta-blockers and angiotensin-converting enzyme inhibitors were given to 76% and 65% of patients respectively. Among hospital survivors, 45% received lipid-lowering drugs. Thrombolytic therapy was administered in 28% of patients, coronary angiography was used in 45%, and 7% of patients underwent primary percutaneous coronary intervention. The 7 and 30 day mortality rates were 7% and 11% respectively.

Conclusions: This nationwide survey shows that one-third of the AMI patients in Israel are elderly (≥ 75 years). The survey suggests that clinical guidelines for the management of patients with AMI are partially implemented in the community. Data from large surveys representing the "real world" practice are of utmost importance for the evaluation of clinical guidelines, research and educational purposes.

Background: Acute renal infarction is an oft-missed diagnosis. As a result; its true incidence, although presumed to be low, is actually unknown. Surprisingly, the medical literature on the subject, other than anecdotal case reports, is scarce.

Objectives: To increase physician awareness of the diagnosis and to identify predictive clinical and laboratory features of the entity.

Method: Between 1 November 1997 and 31 October 2000, 11 cases of acute renal infarction in 10 patients were diagnosed in our center by contrast-enhanced computerized tomography. The medical charts of these patients were reviewed regarding risk factor, clinical presentation, possible predictive laboratory examinations, and out-come.

Results: During the 36 month observation period, the incidence of acute renal infarction was 0.007%. The mean age of the patients (5 men and 5 women) was 67.4 + 21.1 (range 30-87 years). In four cases the right and in five the left kidney was involved; in the other. two cases bilateral:involvement was seen. In 7/10 patients, an increased risk for thromboembolic events was found. Six had chronic atrial fibrillation and one had a combined activated protein C resistance and protein S deficiency, Three patients had suffered a previous thromboembolic event. Two cases were receiving anticoagulant therapy with an INR of 1.6 and 1.8, respectively. On admission, flank pain was recorded in 10/11, fever in 5 and nausea/vomiting in 4 cases. Hematuria was detected in urine reagent strips in all cases; Serum lactate dehydrogenase and white blood cell count were elevated in all cases (1,570 + 703 IU/L and 12,988 + 3,841/ l, respectively). In no case was the diagnosis of acute renal infarction  initially entertained. The working diagnoses were .renal colic in 2 pyelonephritis in 3, renal carcinoma, digitails intoxication, and suspected endocarditis in one patient each, and an acute abdomen in 3. Time from admission to definitive CT diagnosis ranged from 24 hours to 6 days; Three patients were treated with intravenous heparin and another with a combination of IV heparin and renal intra-arterial urokinase infusion with, in the latter case, no recovery of function of the affected kidney. With the exception of this one patient (with a contralateral contracted kidney) who required maintenance dialysis, in all other cases serum creatinine levels. remained unchanged or reverted to the baseline mean of 1.1 mg/dl (0.9-1.2).

Conclusions: Acute renal infarction is not as rare as previously assumed. The entity is often misdiagnosed. Unilateral flank pain in a patient with an increased risk for thromboembolism should raise the suspicion of renal infarction. In such a setting, hematuria, leuaocytosis and an elevated LDH level are strongly supportive of the diagnosis.

Background: Eldercare often necessitates the presence of a family caregiver at the senior's visit to a doctor’s office. Studies indicate that some caregivers are not satisfied with these encounters or with as An understanding of the dynamics of these complex interactions is required.

Objectives: To explore family physicians’ attitudes to interfacing family caregivers of the elderly, to identify factors within the family patient-caregiver encounters in the office setting that for physicians,  to ascertain factors that might be problematic for physicians, to ascertain factors that might contribute to doctors’ behaviors and concerns, and to propose possible solutions for optimizing the outcomes of these visits.

Method: A questionnaire for self-administration was mailed to 200 family physicians in Montreal, Canada who are affiliated with two community secondary care and one tertiary care hospital and involved in geriatric office practice. The survey focused on family physician attitudes, concerns and observations on the interactions among themselves, elderly patients and their family caregivers during office visits.

Results: A total of 142 completed questionnaires were returned with a 71% response rate. Most family doctors felt that it was their responsibility to respond to caregiver concerns (90.6%) and that they were generally meeting their needs (94.2%). In contrast, 81% found this activity stressful and that as few as three such encounters per day were sufficient to generate stress. Causes of stress included: a) concern regarding misdiagnosis, b) different agendas or conflicting responses of patient and caregiver to doctors’ suggestions, and c) reluctance of the elderly or the caregiver to use community resources. A common physician strategy was reliance on acquired professional experience to solving problems of the elderly or of their caregivers.

Conclusions: Despite the stress involved, physicians are interested in assisting caregivers in the management of the elderly. Many doctors lack adequate knowledge about or confidence in community resources. Clinicians may require enhanced skills in conflict resolution necessary to achieve optimal outcomes.

Background: Colorectal cancer is the second leading cause of cancer mortality in Israel. Unfortunately, compliance  with annual fecal occult blood testing is very low.

Objective: To assess the effectiveness of interventions to increase FOBT[1] screening in primary care clinics in Israel.

Methods: A prospective, randomized study included all 50–75 year old enrollees of six family physicians in two primary care clinics. The register of two physicians, one from each clinic, was allocated to one of three groups. Two FOBT reminder strategies were tested: a physician reminder (753 patients), and a patient reminder that was either a phone call (312 patients) or a letter (337 patients). The control group (913 patients) of physicians continued administering their regular level of care. The main outcome measure was the percentage of patients undergoing FOBT screening in each study arm at the conclusion of the one year study period.

Results: In the intervention groups 14.3% (201/1,402) were screened using the FOBT over the course of the study year. Using an intent-to-screen analysis, the screening rate in the physician and patient reminder groups was significantly higher than in the control group(16.5 and 11.9%,vs. 1.2% respectively, P < 0.0001). Phone reminders were significantly more efective as compared to letters (14.7 vs. 9.2%, P = 0.01).

Conclusions: Our study has shown the benefit of various FOBT reminder systems, especially those centered around the family physician. Further research should focus on this area, in conjunction with other novel approaches.

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[1] FOBT = fecal occult blood testing