Idiopathic hypercalciuria of childhood: 4- to 11-year outcome

Apart from a minority with urolithiasis, the majority of children diagnosed with idiopathic hypercalciuria present with macro- or microhematuria, abdominal or back pain, or voiding symptoms. With dietary and pharmacological interventions, most such children become asymptomatic and are lost to follow-up, hence their long-term outcome is unclear. In the present study, we evaluated the status of 14 males and 19 females aged 8-17 years (mean 11.9 years, median 11.2 years) 4-11 years (mean 6.9 years, median 6.5 years) after the initial diagnosis of idiopathic hypercalciuria not associated with urolithiasis. A questionnaire was answered and two random urine samples provided 3-4 weeks apart were analyzed for calcium (Ca), sodium (Na), potassium (K), and creatinine (Cr). Urine Ca/Cr ratio > or =20.21 (mg/mg) was defined as hypercalciuria. At the time of the study none were under follow-up, although 7 children were still exhibiting voiding symptoms. No child developed clinical urolithiasis. Based on the first urine specimen, 16 of the 33 (48.4%) were hypercalciuric. Their 2nd urinalysis showed persistent hypercalciuria in 8 and normocalciuria in 8. Urine Na/K ratio (mEq/mEq) decreased in the latter 8 from 5.08+/-2.67 to 3.03+/-2.23 (P<0.05). Of the 17 initially normocalciuric children, 5 did not submit a 2nd specimen, 11 remained normocalciuric, and 1 became hypercalciuric with an increase in urine Na/K ratio. Twenty-three children (all 8 persistently and 9 intermittently hypercalciuric plus 6 normocalciuric) were studied by ultrasonography. Only in 1 asymptomatic persistently hypercalciuric child was a single small renal calcification noted. Introduction of a low-Na/high-K diet in 7 persistently hypercalciuric children resulted in a decrease in UNa/K ratio from 7.34+/-2.15 to 4.14+/-3.09 (P<0.01) and UCa/Cr ratio from 0.25+/-0.04 to 0.13+/-0.03 (P<0.01). We conclude that even though over time most hypercalciuric children become asymptomatic, many remain hypercalciuric. Further follow-up is required to ascertain whether these children are at risk of developing kidney stones. If they are at risk then long-term compliance with a low-Na/high-K diet might be beneficial, as it can normalize calciuria in the majority of these children.     

Sieving coefficient inaccuracies during hemodiafiltration in patients with hyperbilirubinemia

Hemodiafiltration has assumed an important role in the supportive therapy of critically ill patients. The viability of the filter used for hemodiafiltration can be monitored by estimating the sieving coefficient of small molecules such as creatinine and/or urea. We report on three patients with severe hyperbilirubinemia whose creatinine sieving coefficient was spuriously elevated as a result of discordance in the accuracy of creatinine measurement in plasma and ultrafiltrate respectively. This discordance was a consequence of lack of bilirubin clearance during hemodiafiltration. As a result, while the plasma creatinine determination by the kinetic Jaffe method was negatively influenced by the hyperbilirubinemia, the ultrafiltrate creatinine was not. This report is the first to document the lack of bilirubin clearance during hemodiafiltration and its impact on the calculation of sieving coefficient based on creatinine. The use of urea as the solute for determining the sieving coefficient allows for an accurate estimate and provides a valid means of monitoring this parameter in the setting of hyperbilirubinemia. Received: 18 April 2000 / Revised: 16 June 2000 / Accepted: 20 June 2000     

The prognostic value of the tumour marker Cyfra 21-1 in carcinoma of head and neck and its role in early detection of recurrent disease

This study examines a new tumour marker, Cyfra 21-1, as a prognostic marker in predicting the survival of H&N cancer patients, and its correlation with clinical outcome during prolonged follow up of these patients. The study included 67 patients with primary detection of carcinoma of H&N. The survival of these patients was evaluated in correlation with the disease stage and Cyfra 21-1 levels at initial diagnosis. 38 patients were followed clinically and with serial assays for at least 12 months, or until recurrence was diagnosed. Cyfra 21-1 levels were determined periodically, using an Elisa kit. Patients with Cyfra 21-1 < 1.5 ng ml(-1)had a higher survival rate compared to patients with Cyfra 21-1 > or = 1.5 ng ml(-1)(63% vs. 20%, respectively). The risk ratio of Ln(Cyfra 21-1) is 1.62 (P = 0.028). In a Cox regression model that included the disease stage and Ln(Cyfra 21-1), Ln(Cyfra 21-1) was preferred as the main parameter for predicting patients survival. In 83% of the 12 patients with recurrent or residual disease, Cyfra 21-1 was elevated before or during clinical detection of the recurrence. Cyfra 21-1 was found to be a prognostic marker for carcinoma of H&N, unrelated to the stage of the disease. Elevated levels of Cyfra 21-1 without clinical evidence of disease can be attributed to the marker's mean lead-time as compared to the clinical appearance of the disease.     

The genetic and clinical outcome of isolated fetal muscular ventricular septal defect (VSD)

Introduction: Our objective was to evaluate the incidence of chromosomal aberration (both microscopic and submicroscopic) and the clinical outcome of fetuses with isolated muscular ventricular septal defect (VSD).

Material and methods: The study included 40 pregnant women whose fetuses were diagnosed with isolated muscular ventricular septal defect (mVSD). Of these, 30 patients underwent amniocentesis and 10 declined. All samples were tested by chromosomal microarray analysis (CMA). Of the 40 women in the study, 32 gave birth and the clinical outcome of the children was retrieved from the patients’ medical records.

Results: Of the 30 patients who underwent amniocentesis, one was detected with mosaic Klinefelter syndrome and one was detected with a pathogenic copy number variant unrelated to the VSD. Clinical follow-up was performed on 26 children after birth. The first postnatal echocardiography did not detect a VSD in 13 (50%) of the followed-up children. Spontaneous closure occurred in another eight (30.8%) children during the postnatal follow-up period. In only five children (19.2%) VSD was still detected by echocardiography after the first year of life.

Discussion: Isolated muscular VSD diagnosed prenatally does not appear to be a significant risk factor for chromosomal abnormalities and has a favorable clinical outcome.     

Cystic fibrosis and neonatal calcified scrotal masses

We report a case of an infant who presented with failure to thrive and in whom the identification of calcified scrotal masses led us to the diagnosis of cystic fibrosis.     

Envenoming by Cerastes vipera—a report of two cases

Two cases of envenoming by Cerastes vipera are described Both were in snake collectors who were accidentally bitten on the finger while handling the snake. In both cases, local signs included a haemorrhagic bulla with fang marks, swelling and tenderness. These signs were mild in one case and moderately severe in the other, necessitating fasciotomy. No systemic signs were observed. Some coagulation abnormalities were found in both cases. In one, prolonged bleeding from the wound and a shortened euglobulin lysis time may suggest activation of the fibrinolytic mechanism. In the other, prolongation of prothrombin time occurred with no haemorrhagic diathesis. Treatment included fasciotomy in one case and elevation of the affected part and antibiotics in the other. It appears that the clinical course of this snakebite is relatively benign.     

Weekly vinblastine in pediatric low-grade glioma patients with carboplatin allergic reaction

BACKGROUND: Carboplatin-based regimens have demonstrated activity in unresectable low-grade glioma (LGG) in children. Despite an interesting toxicity profile, the use of these regimens has been limited by the development of carboplatin hypersensitivity reaction (HSR) in up to 30% of patients. Desensitization has been the recommended approach for HSR. However, no guidelines have existed to aid physicians when carboplatin desensitization techniques fail. METHODS: A pilot study of monotherapy with weekly vinblastine for LGG in 9 children who developed carboplatin HSR on a carboplatin and vincristine regimen was performed. RESULTS: Vinblastine toxicity was moderate and readily manageable. None of the 9 patients had disease progression on therapy. Magnetic resonance imaging evaluation of tumor size from diagnosis to the end of vinblastine treatment showed 1 complete response (CR), 1 partial response (PR), 5 objective effects (OE), and 2 stable diseases (SD). CONCLUSIONS: This experience suggested that weekly vinblastine has a good efficacy to toxicity ratio in the treatment of LGG and can be a valuable option for children who develop severe HSR.     

Association of intentional changes in body weight with coronary heart disease event rates in overweight subjects who have an additional coronary risk factor

Despite evidence that weight loss improves the severity of coronary heart disease (CHD) risk factors, a direct association between weight loss and CHD incidence has not been demonstrated. In 1994-2001, the authors conducted an observational study of intentional weight loss as related to CHD incidence among patients recruited from a network of clinics in Israel who received nutritional counseling from a dietitian to support the medical recommendation to lose weight. Subjects were outpatients aged 50-75 years with a body mass index of > or =27 kg/m(2), without CHD or cancer but with at least one risk factor for CHD in addition to overweight. Outcomes were documented over 4 years by repeated weight measurements and by medical record verification. Among 1,669 patients, 224 (13.4%) incidents of CHD were recorded. For subjects who underwent at least 6 months of dietetic counseling, the risk-factor-adjusted odds ratio for CHD incidence associated with a weight loss of 4.5 kg (the median level of weight loss) was 0.57 (95% confidence interval: 0.39, 0.84). In this, the largest known study of its type reported to date, intentional weight loss from a 6-month diet predicted lower incidence of CHD over 4 years.     

Resolution of medullary nephrocalcinosis in children with metabolic bone disorders

Ultrasonographic resolution of nephrocalcinosis (NC) has been reported in children with furosemide-induced NC, but not in other entities. We report the cases of four children with metabolic bone disease, two with hypophosphatasia and two with X-linked hypophosphatemic rickets, in whom we observed resolution of renal calcifications. At the time of ultrasonographic resolution of NC, 3 of the patients were on anticalciuric diuretics, and all 4 had normal urinalysis, serum creatinine and electrolyte profiles, as well as estimated creatinine clearance. In 3 of the children, evidence of mild tubular dysfunction was found. It thus seems that in some children with bone and mineral disorders who develop NC, ultrasonographic resolution of the renal calcifications can be seen; however, mild tubular dysfunction may remain and require follow-up. Further studies are suggested to explore the possible role of anticalciuric diuretics in promoting the resolution of NC.     

Tumor promoters inhibit spontaneous and induced differentiation of murine erythroleukemia cells in culture.

Addition of the potent tumor promoter, 12-O-tetradecanoyl-phorbol-13-acetate (TPA), to murine erythroleukemia cell lines in suspension cultures inhibited both spontaneous differentiation and differentiation induced by hexamethylene bisacetamide (HMBA), dimethyl sulfoxide, or butyric acid. Inhibition was unrelated to cytotoxicity and was reversible. When several plant diterpenes were tested, there was a positive correlation between tumor-promoting activity and inhibition of differentiation. TPA inhibited HMBA-induced differentiation only if added prior to the time of commitment to differentiation, as assayed by scoring for differentiation after transfer of cells from HMBA to fresh medium without HMBA. TPA-mediated inhibition of differentiation was associated with a decrease in globin mRNA accumulation.