David Modai

Hereditary Hypophosphatemic Rickets with Hypercalciuria

We studied a new hereditary syndrome of hypophosphatemic rickets and hypercalciuria in six affected members of one kindred. In all patients, the manifestations of disease began in early childhood. The characteristic features are rickets, short stature, increased renal phosphate clearance (the ratio between the maximal tubular reabsorption rate for phosphorus and the glomerular filtration rate [TmP/GFR] is 2 to 4 S.D. below the age-related mean), hypercalciuria (8.6 mg of urinary calcium per kilogram of body weight per 24 hours vs. the upper normal value of 4.0), normal serum calcium levels, increased gastrointestinal absorption of calcium and phosphorus, an elevated serum concentration of 1,25-dihydroxyvitamin D (390 +/- 99 pg per milliliter vs. the upper normal value of 110), and suppressed parathyroid function (an immunoreactive parathyroid hormone level of 0.33 +/- 0.1 ng per milliliter and a cyclic AMP level of 1.39 +/- 0.12 nmol per deciliter of glomerular filtrate vs. the lower normal values of 0.3 and 1.5, respectively). Long-term phosphate supplementation as the sole therapy resulted in reversal of all clinical and biochemical abnormalities except the decreased TmP/GFR. We propose that the pivotal defect in this syndrome is a renal phosphate leak resulting in hypophosphatemia with an appropriate elevation of 1,25-dihydroxyvitamin D levels, which causes increased calcium absorption, parathyroid suppression, and hypercalciuria. This syndrome may represent one end of a spectrum of hereditary absorptive hypercalciuria. Our observations support the importance of phosphate as a mediator in controlling 1,25-dihydroxyvitamin D production in human beings.

Warfarin for Stroke Prevention Still Underused in Atrial Fibrillation: Patterns of Omission

BACKGROUND AND PURPOSE The value of warfarin in preventing stroke in patients with chronic atrial fibrillation is well established. However, the prevalence of such treatment generally lags behind actual requirements. The aim of this study was to evaluate doctor- and/or patient-related demographic, clinical, and echocardiographic factors that influence decision for warfarin treatment. METHODS Between 1990 and 1998, 1027 patients were discharged with chronic or persistent atrial fibrillation. This population was composed of (1) patients with cardiac prosthetic valves (n=48), (2) those with increased bleeding risks (n=152), (3) physically or mentally handicapped patients (n=317), and (4) the remaining 510 patients, the main study group who were subjected to thorough statistical analysis for determining factors influencing warfarin use. RESULTS The respective rates of warfarin use on discharge in the 4 groups were 93.7%, 30.9%, 17.03%, and 59.4% (P=0.001); of the latter, an additional 28.7% were discharged on aspirin. In the main study group, warfarin treatment rates increased with each consecutive triennial period (29.7%, 53.6%, and 77.1%, respectively; P=0.001). Age >80 years, poor command of Hebrew, and being hospitalized in a given medical department emerged as independent variables negatively influencing warfarin use: P=0.0001, OR 0.30 (95% CI 0.17 to 0.55); P=0.02, OR 0.59 (95% CI 0.36 to 0.94); and P=0.0002, OR 0.26 (95% CI 0.12 to 0.52), respectively. In contrast, past history of stroke and availability of echocardiographic information, regardless of the findings, each increased warfarin use (P=0.03, OR 1.95 [95% CI 1.04 to 3.68], and P=0.0001, OR 3.52 [95% CI 2.16 to 5.72], respectively). CONCLUSIONS Old age, language difficulties, insufficient doctor alertness to warfarin benefit, and patient disability produced reluctance to treat. Warfarin use still lags behind requirements.

Type II diabetes mellitus, congestive heart failure, and zinc metabolism

Zinc status was assessed in patients with type II diabetes mellitus and congestive heart failure (CHF). Three groups of patients were enrolled into the study: Group 1: 15 patients with type II diabetes mellitus and CHF; Group 2: 20 patients with isolated type II diabetes mellitus; and Group 3: nine patients with isolated CHF. Twenty-four-hour urine was measured for creatinine, protein, and zinc, and blood was drawn for creatinine, proteins, liver enzymes, hemoglobin A1c, and zinc. Insulin treatment and hemoglobin A1c were comparable in the diabetic patients of groups 1 and 2, but group 1 was also treated with captopril and diuretics like the CHF patients of group 3. Plasma zinc levels were statistically similar in all three groups, but urinary zinc excretion (μmol/24 h) and urinary zinc: creatinine (μmol/mmol) ratio were significantly higher in the type II diabetics and CHF group (27.2±1.5; 1.69±0.6, respectively) compared to the diabetic patients alone (19.4±0.76; 0.97±0.3, respectively) and the CHF patients (9.7±0.3; 0.62±0.3, respectively). Patients with type II diabetes mellitus and CHF were treated with higher doses of captopril than the CHF patients (56.25±24 mg vs 18.8±11 mgP<0.05). Thus, patients with type II diabetes mellitus and CHF excrete larger amounts of zinc, which may eventually lead to zinc deficiency.

Dietary Intake of Various Nutrients in Older Patients with Congestive Heart Failure

Background and Aims: Anorexia, nausea and premature satiety with eating, prevalent in congestive heart failure (CHF), have been held responsible for reduced dietary intake and deficiency of magnesium, potassium and probably other nutrients. Since solid data is not available, this study was undertaken with the following aims (1) to assess dietary intake in CHF, (2) to compare dietary intake in older CHF patients with a similar patient population free of CHF (control group), and (3) to evaluate these data in patients with moderate versus severe CHF. Methods and Results: Dietary intake of 57 consecutively hospitalized furosemide-treated CHF patients over the age of 60 was compared with that of 40 similar patients free of CHF. In addition, a statistical analysis was performed comparing the data of the 37 patients with moderate versus the 20 patients with severe CHF. Dietary content of various nutrients was assessed with the food frequency recall technique. Dietary intake was comparable in the two respective pairs of groups. However, the intake of magnesium, calcium, zinc, copper, manganese, energy, thiamin, riboflavin, and folate in all subgroups fell short of recommended levels for intake, while vitamins A, C and niacin contents exceeded those recommended. Intakes of potassium andproteins were within the recommended values. Conclusions: CHF per se, even severe CHF, is not responsible for a reduced dietary intake of various nutrients. A population-related dietary culture, old age or other chronic conditions, rather than CHF, might be mainly involved. The increased intake of vitamins A, C and niacin in our patients may be attributed to the high content of fruits and vegetables in the Mediterranean diet. Insufficient intake of the above-mentioned group of electrolytes and essential nutrients may contribute to the frequently observed negative balance of some of them. This is especially relevant in furosemide-treated CHF patients. Therefore, supplementation should be considered.

Elevated Serum 1,25-Dihydroxyvitamin D Concentrations in Siblings with Primary Fanconi's Syndrome

THE de Toni–Debre–Fanconi syndrome,1 2 3 or Fanconis syndrome, is characterized by multiple abnormalities in renal tubular function. Defective handling of phosphate, glucose, and amino acids is th...

Pulse oximetry in the evaluation of the painful hand after arteriovenous fistula creation

Five patients with a side-to-side arteriovenous fistula complaining of pain, numbness, and cold sensation were evaluated by pulse oximetry. Low SaO2 was noticed in all five. Closure of a major proximal venous collateral vessel eliminated the steal and resulted in SaO2 correction and was followed by clinical amelioration. Pulse oximetry proved to be a helpful adjunct in the evaluation of the painful hand after creation of an arteriovenous fistula. By applying the pulse oximeter to the patients affected limb, we were able to determine whether the pain was a result of ischemia and if the correction of the steal improved oxygenation.

Contrast media augmented apoptosis of cultured renal mesangial, tubular, epithelial, endothelial, and hepatic cells.

Peer A, Averbukh Z, Berman S, et al. Contrast Media Augmented Apoptosis of Cultured Renal Mesangial, Tubular, Epithelial, Endothelial, and Hepatic Cells. Invest Radiol 2003;38:177–182. Rationale and Objective. Nephrotoxicity of contrast media, resulting in apoptosis and acute necrosis of tubular cells, is well documented. No studies concerning mesangial cells apoptosis have been published yet. Aim Apoptosis of cultured mesangial, tubular, and hepatic cell lines was investigated following exposure to different contrast media. Methods. Apoptosis was assessed by TUNEL assay and verified by Mayer Hematoxylin staining. Results. Iopromide, Ioxaglate, and Ioxatalamate induced apoptosis in all cell cultures at final concentrations ranged from 0.1% to 10.0%. However, only 1% to 10% Iomeprol elicited a significant apoptosis. Moreover, at 10% concentration, Iomeprol induced significantly less apoptosis than Iopromide, Ioxaglate, or Ioxatalamate. Conclusions. First, Iomeprol, which has a different physico-chemical properties, proved to be less proapoptotic compared with other contrast compounds. Second, all types of cells similarly respond by apoptosis to contrast media induced injury. However, apoptosis of mesangial cells might generate additional deleterious effects in vivo.

Hereditary angioneurotic edema with severe hypovolemic shock

Hereditary angioneurotic edema (HAE) is characterized by recurrent attacks of edema of the upper airways, face, and limbs, and/or abdominal pains sometimes mimicking surgical abdomen. Our patient, a 24-year-old woman, had undergone laparotomy on a previous attack, at which a large amount of serious peritoneal fluid and edema of the intestinal wall were found. This time she presented with severe abdominal pain and profound hypovolemic shock requiring replacement of great amounts of fluids in addition to fresh frozen plasma. There was no evidence of bleeding, and the patient recovered rapidly. Based on clinical and ultrasonographic grounds and findings on previous laparotomy, we concluded that the shock was produced by fluid sequestration in the peritoneal cavity and intestinal wall. We propose that patients with HAE who present with abdominal pain, hypotension, hemoconcentration, and leukocytosis form a distinct subgroup with a high risk of hypovolemic shock. This dangerous development should be anticipated in these patients.

Acute inflammatory myopathy with severe subcutaneous edema, a new variant? Report of two cases and review of the literature

Abstract. Acute inflammatory myopathy with severe subcutaneous edema is extremely rare and has been reported in only a handful of cases. We describe two similar patients presenting with this disorder and generalized rash. Unlike the five previously reported cases, the clinical and histologic features of our two patients are more suggestive of dermatomyositis than polymyositis. Nevertheless, scrutinizing all seven reported patients, a number of specific characteristics could be defined. All patients were adult males. Dysphagia was present in four. In six patients, acute inflammatory myopathy was idiopathic while malignancy was present in one. Two patients died despite intensive therapy, three improved on corticosteroid treatment, and two recovered spontaneously. In all patients, limb involvement with marked subcutaneous edema was present, clinically mimicking deep vein thrombosis in both our patients. The presence of severe subcutaneous edema may be a hallmark of a distinctive variant of acute inflammatory myopathy. More cases are needed to discern subtypes of this general entity and to establish guidelines for treatment and prognosis.

Seating-Induced Postural Hypotension Is Common in Older Patients with Decompensated Heart Failure and May Be Prevented by Lower Limb Compression Bandaging

Background: Postural hypotension induced by transition from supine to sitting position and measures for its prevention in heart failure has not been investigated. Objective: Our purpose was to evaluate the prevalence of postural hypotension and associated clinical manifestations as well as the contribution of various risk factors for postural hypotension on transition from lying to sitting in older patients with decompensated heart failure, and to study the eventual preventive effect of leg bandaging. Methods: Seating-induced postural hypotension (≥20 mm Hg systolic and/or ≥10 mm Hg diastolic blood pressure fall) was assessed on the first study day in 108 patients aged ≥60 years, hospitalized for acutely decompensated heart failure. On the next day, in patients manifesting postural hypotension, compression bandages were applied along both legs before seating. Blood pressure, heart rate, O2 saturation, and the occurrence of dizziness or palpitations were recorded prior to and 1, 3 and 5 min following seating. Results: Postural hypotension occurred in 49.1% of patients. Dizziness and/or palpitations manifested in 25%. Diastolic (36.1%) versus systolic (23.1%) postural hypotension prevailed (p = 0.05). On univariate analysis, postural hypotension was associated with female sex (p = 0.03), more severe heart failure (p = 0.05), longer bedrest (p = 0.04), higher supine systolic (p = 0.01) or diastolic (p = 0.002) blood pressure, nonischemic heart failure (p = 0.002), and not using nitrates (p = 0.01). On multivariate analysis, longer bedrest (OR = 1.58, 95% CI = 1.13–2.2, p < 0.001), higher supine diastolic blood pressure (OR = 1.33, 95% CI = 1.1–1.61, p = 0.001), and nonischemic heart failure (OR = 3.48, 95% CI = 1.4–8.63, p = 0.009) were the most predictive of postural hypotension. Compression bandages prevented postural hypotension in 21 of 49 patients and decreased the degree of postural blood pressure fall (p < 0.001). Conclusion: Seating-induced postural hypotension is common among older inpatients with decompensated heart failure, especially with longer bedrest, higher supine diastolic blood pressure and non-ischemic etiology. Leg compression bandaging may be useful for the prevention of postural hypotension in these patients.