Israel Medical Association Journal

Background: Genetic hemochromatosis leads to iron overload in many tissues and may lead to liver cirrhosis and hepatocellular carcinoma. Early diagnosis and therapy are crucial. Since 80–100% of hemochromatosis patients of European origin are homozygous for a cysteine to tyrosine exchange in the HFE gene at codon 282, genetic screening might be useful. Representative population studies are needed to evaluate the phenotype of people heterozygous and homozygous for the C282Y mutation.

Objective: To determine the correlation between parameters of iron metabolism and the hemochromatosis genotype in a large population-based study.

Methods: A representative population-based survey, the Diabetomobil study, analyzed 5,083 German probands. Serum transferrin saturation and ferritin levels were determined, and the C282Y mutation of the HFE gene was analyzed by restriction fragment length polymorphism- polymerase chain reaction analysis.

Results: Nine of 373 probands with a transferrin saturation > 55% (2.4%) and none of 264 randomly selected probands with a transferrin saturation £ 55% (0%) were homozygous for the C282Y mutation. Three of the nine homozygous probands had ferritin values less than 250 µg/L. The frequency of the heterozygous genotype was 8.8%, and the percentage of heterozygous probands increased with increasing levels of transferrin saturation.

Conclusion:We propose a population screening strategy with an initial transferrin saturation test, followed by genotyping for the C282Y mutation if the transferrin saturation is above 55%, regardless of the ferritin level. Heterozygous individuals with higher transferrin saturation values may be protected against iron loss but may also be more susceptible for certain liver diseases, depending on the simultaneous prevalence of other diseases.
 

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: Despite the controversy regarding the risks and benefits of hormone replacement therapy, studies in various countries indicate a two- to threefold increase in the use of HRT[1] during the last decade.

Objectives: To estimate the prevalence of HRT use among post-menopausal Jewish women in Israel and to determine the variables predicting current HRT use.

Methods: A cross-sectional telephone survey was conducted in 1998 on a random sample of Jewish women aged 45–74. Of 935 women who were located and eligible, 704 (75%) were interviewed by means of a structured questionnaire.

Results: A total of 589 women (85%) were peri-menopausal or post-menopausal.  Ninety-nine of them (16.8%) were currently using HRT and 78 (13.2%) were past users. Higher rates of current use were found among women who had undergone hysterectomy and/or oophorectomy (38%) than among all other women (13.5%).  Among naturally menopausal women the highest rate of current use (25.6%) was found in those aged 55–59.  A multiple logistic regression showed that the variables associated with current HRT use among naturally menopausal women  were: having a regular gynecologist (odds ratio 3.6, 95% confidence interval 1.7–7.5), visiting a gynecologist during the past year (OR[2] 2.9, 95% CI[3] 1.4–6.0), experiencing symptoms of menopause (OR 2.0, 95% CI 1.01–3.8), having more than a high-school education (OR 1.9, 95% CI 1.04–3.6), and a lower body mass index (OR 0.91, 95% CI 0.85–0.99).

Conclusions: The factors associated with HRT use may be markers for other socioeconomic or psychological characteristics. The disparities noted between population subgroups may be indicative of differences in awareness or in the delivery of preventive healthcare services to women in Israel, and as such need to be addressed by the health system.

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Background: Multiple factors are involved in the pathogenesis of hypertension in the obese individual.

Objective: To evaluate the role of a decrease in sympathetically mediated thermogenesis and the effect of the correlation between the plasma leptin and daily urinary nitric oxide levels on obesity-related hypertension.

Methods: We evaluated three groups: 25 obese hypertensive patients (age 45.7±1.37 years, body mass index 34.2±1.35 kg/m², systolic/diastolic blood pressure 155±2.9/105±1.3, mean arterial pressure 122±1.50 mmHg); 21 obese normotensive patients (age 39.6±1.72, BMI[1] 31.3±0.76, SBP/DBP[2] 124±2.1/85.4±1.8, MAP[3] 98.2±1.80); and 17 lean normotensive subjects (age 38.1±2.16, BMI 22.1±0.28, SBP/DBP 117±1.7/76.8±1.5, MAP 90.1±1.50). We determined basal resting metabolic rates, plasma insulin (radioimmunoassay), norepinephrine (high performance liquid chromatography) in all subjects. Thereafter, 14 obese hypertensives underwent a weight reduction diet. At weeks 6 (n=14) and 14 (n=10) of the diet the above determinations were repeated. Plasma leptin (enzyme-linked immunosorbent assay) and UNOx[4] (spectrophotometry) were assayed in 17 obese hypertensives and 17 obese normotensives, and in 19 obese hypertensives versus 11 obese normotensives, respectively.

Results: Obese hypertensive patients had significantly higher basal RMR[5] and plasma NE[6] levels. Insulin levels were lower in the lean group, with no difference between the hypertensive and normotensive obese groups. At weeks 6 and 14, BMI was significantly lower, as were insulin and NE levels. RMR decreased to values of normotensive subjects. MAP normalized but remained significantly higher than that of obese normotensives. Leptin blood levels and the leptin/UNOx ratio were significantly higher in the obese hypertensive compared to the obese normotensive patients. Both these parameters were strongly correlated to BMI, MAP⁵, RMR, and plasma NE and insulin .Obese hypertensive patients excreted less urinary NO metabolites. A strong correlation was found between MAP and the leptin/UNOx ratio.  

Conclusions: A reduction of sympathetically mediated thermogenesis, as reflected by RMR, results in normalization of obesity-related hypertension. In contrast, insulin does not seem to play a major role in the pathogenesis of hypertension associated with obesity. Increased leptin levels in conjunction with decreased NO production in the presence of enhanced sympathetic activity may contribute to blood pressure elevation in the obese.

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[1] BMI = body mass index

[2] SBP/DBP = systolic blood pressure/diastolic blood pressure

[3] MAP = mean arterial pressure

[4] UNOx = urinary nitric oxide

[5] RMR – resting metabolic rate

[6] NE = norepinephrine

Background: Primary aldosteronism is a common cause of non-renal secondary hypertension. A correct diagnosis results in curing the hypertension or targeting appropriate pharmacotherapy. In patients with low renin resistant hypertension (after treatment with three or more different anti-hypertensive drugs the blood pressure remains above 140/90 mmHg), screening for aldosteronism is mandatory.

Objectives: To demonstrate that normal blood levels of potassium in resistant hypertensive patients do not exclude the possible presence of hyperaldosteronism, and to suggest the use of the plasma aldosterone concentration (ng/dl)/plasma renin activity (ng/ml/hour) ratio in screening for hyperaldosteronism.

Methods: Blood tests, suppression and stimulation tests (2 L normal saline IV/4 hours and 20 mg furosemide IV for 60 minutes in a standing position) were systematically performed in 20 low renin normokalemic resistant hypertensive patients. None had renal disorders, known endocrine abnormalities or heart failure. They did not receive anti-hypertensive drugs affecting PAC[1] or PRA[2]. Basal PRA and PAC were measured twice: PAC after saline infusion and PAC/PRA after stimulation.

Results:. PAC/PRA above 50 was used to denote hyperaldosteronism. Serum K was 4 ± 0.07 mM/L, PAC 22.8 ± 1.8 ng/dl, PRA 0.13 ± 0.02 ng/ml/hour, PAC/PRA 190 ± 22 (above 100 in 17). After suppression PAC decreased from 25 ± 1.8 to 11 ± 1 ng/dl (normal <5 ng/dl). Stimulation did not affect PRA and PAC/PRA. Abdominal computed tomography scan revealed normal adrenal glands in 15 patients. Spironolactone (116 ± 60 mg/day) normalized blood pressure in all patients; it was used as a single therapy in 8, and in association with only one anti-hypertensive drug in the remaining 12 patients. In one patient the treatment was discontinued due to the presence of hyperkalemia.

Conclusions: Low renin resistant hypertension associated with normokalemia may be due to hyperaldosteronism. Normal aldosterone levels in the basal condition do not exclude the possibility of hyperaldosteronism. Using a PAC/PRA ratio above 50 as a screening test can aid the physician in deciding when to perform dynamic tests, thus increasing the sensitivity of the diagnosis of hyperaldosteronism. CT scan is frequently normal. Targeted pharmacotherapy leads to a normalization of blood values.

Background: Low birth weight has been shown to be strongly related to hypertension in adult life.

Objective: To determine whether blood pressure is higher in children with intruterine growth retardation than in control subjects.

Methods: Blood pressure was measured in 58 children aged 4-6 years with IUGR and in 58 age-matched controls. The control children, whose birth weight was appropriate for gestational age, were also matched for gestational age.

Results: The children with IUGR had significantly higher mean values of systolic (p<0.05) and diastolic blood pressures (p<0.05) and mean arterial pressure (p<0.05). Significant differences in blood pressure values were found between preterm IUGR (n=21) and preterm controls (p<0.05).

Conclusion: These data indicate that children with IUGR may be at higher risk of hypertension already in childhood.

Background: Fasting is required by the Jewish and Islamic religions, and may sometimes be necessary for non­religious reasons as well. Very little empiric data are available on the effect of 24 hours of food and water deprivation.

Objectives:  To compare the effects of the dietary composition of different pre-fast meals on subjective discom­fort and various other parameters of a 24 hour food and water fast.

Methods: Thirteen volunteers of both genders participated in a non-randomized crossover study. Each consumed three different equicaloric pre-fast meals in which the main source of calories was protein (49% of calories), carbohydrate (86%), or fat (69%). Weight, heart rate, blood pressure, blood and urine were tested before and after 24 hours of fasting, and the subjective evaluations of the discomfort during the three fasts were compared.

Results: After the protein-rich meal greater discomfort and more side effects were reported. Weight and blood pressure decreased at the end of the fasts that followed each of the three meals heart rate increased after the high fat and carbohydrate meals but not after the protein meal. The main laboratory findings were a 40% increase in blood urea nitrogen and higher urine osmolarity after the protein-rich meal than after the other meals.

Conclusion: A protein-poor pre-fast meal is likely to be followed by easier fasting.
 

Background: When encountering complaints of pain in the area of the Achilles tendon, the clinician seldom reaches a correct and precise diagnosis based solely on the grounds of physical examination and standard X-rays.

Objectives: To assess the usefulness of ultrasound in diagnosing pathologies of the Achilles tendon.

Methods: We conducted a retrospective review of patients presenting at our orthopedic clinics.

Results: Sonography was used to evaluate 41 patients with achillodynia. This modality enabled the diagnoses of 19 abnormal tendons (46%), peritendinous and other lesions a complete rupture in two patients (5%) a partial rupture of the Achilles tendon in 3 (7%) various degrees of calcification of the tendon in 7 (17%) and peritendinous lesions discerned by the tendon’s hypoechoic regions with disorganized arrange­ment of collagen fibrils in 4 patients (10%). Other lesions included tendonitis (3 patients, 7%), retrocalcaneal bursitis (3 patients, 7%), lipoma (1 patient, 2%), and foreign bodies (2 patients, 5%). The mean diameter of the pathological tendons was 10.4 +2.7 mm, while normal tendons measured 5.2 +0.8 mm (P<0.001).

Conclusion: As in many other soft tissue lesions, ultrasonography is a useful tool in the evaluation of the underlying pathology in patients presenting with achillodynia.

Background: Foreign bodies are sometimes overlooked in the initial evaluation of soft tissue wounds in the emergency room setting. The physical examination identifies foreign bodies that are superficial enough to be seen or palpated, while radiographs reveal those that are radio-opaque. If these two criteria are not met, however, the foreign body may remain undetected. These patients present later with long-standing pain in the area of penetration sometimes associated with localized tenderness.

Objectives: To assess the role of ultrasonography in the diagnosis and management of patients with a suspected retained foreign body.

Methods: Ultrasound was used in 21 patients with suspected retained foreign bodies and the diagnosis was positive in 19. Fifteen underwent a surgical exploration in which the ultrasound was used as an adjunctive modality either pre- or intraoperatively to assist in the localization of the foreign body.

Results: All procedures were successful. No postoperative complications were recorded at an average follow-up of 2 years. Three patients gradually became asymptomatic and were left untreated. One patient was lost to follow-up.

Conclusion: Sonography is an extremely effective tool for the late diagnosis of retained foreign bodies in the soft tissues. We suggest that its availability in the emergency room may decrease the rate of misdiagnosis and avoid these unfortunate cases, although this remains tc be proven.