Improved diagnostic effectiveness with a sequential diagnostic paradigm in idiopathic pediatric sensorineural hearing loss.

OBJECTIVES: To determine whether a stepwise diagnostic paradigm is more diagnostically efficient and cost-effective than a simultaneous testing approach in the evaluation of idiopathic pediatric sensorineural hearing loss (SNHL). DESIGN: Prospective prevalence study. SETTING: Tertiary referral children's hospital. PATIENTS: Consecutive children (n = 150) presenting with idiopathic SNHL in the last 2 years. INTERVENTIONS: All children were evaluated with full diagnostic evaluations including GJB2 screens, temporal bone computed tomography scans, and laboratory investigations. MAIN OUTCOME MEASURES: 1) Diagnostic yields of GJB2 screens, imaging, and laboratory results per SNHL category; 2) Cost analysis comparing a sequential versus a simultaneous testing approach. RESULTS: Overall, 12.0% of patients had biallelic mutations in the GJB2 gene, whereas 30% of patients had an abnormality on temporal bone scan. Laboratory testing did not reveal the SNHL etiology in any patient. While maintaining diagnostic accuracy, significant cost savings were inferred by using a sequential diagnostic algorithm. Our data show children with severe to profound SNHL should first be tested with a GJB2 screen, as opposed to those with milder SNHL, who should undergo imaging as the initial testing step. In patients with initially positive GJB2 or imaging screens, logistic regression analysis significantly predicted negative results on further testing. CONCLUSIONS: A stepwise diagnostic paradigm tailored to the level of the hearing loss in children with bilateral SNHL is more diagnostically efficient and cost effective than the more commonly used full, simultaneous testing approach. Laboratory investigation should not be routine but based on clinical history.     

Cholecystokinin inhibits DNA alkylation induced by N-nitrosobis (2-oxopropyl)amine (BOP) in hamster pancreas.

Cholecystokinin (CCK) inhibits pancreatic cancer but not hepatic tumor induction by N-nitrosobis (2-oxopropyl) amine (BOP) in hamsters when administered with or shortly before BOP. In this study, we evaluated the capability of sulfated CCK-8 to inhibit DNA alkylation in the hamster pancreas. We examined the pattern of O6-methylguanine (G6-Me) and N7-methylguanine (G7-Me) in pancreatic ductal, acinar and liver tissues from Syrian hamsters treated with a single dose of BOP (20 mg/kg s.c.) and with five s.c. injections of CCK-8 (200 pM/kg, 30 min apart). The first CCK injection was given either 90 min before, or together, or 3 h after POP administration. The amount of G6-Me in liver DNA did not differ significantly. We observed a decrease of G7-Me in the liver of the group treated with CCK together with POP as compared to POP alone (P less than 0.005). Lower amounts of G6-Me were found in ductal preparations (P less than 0.01) of the animals treated with CCK before POP as compared to POP alone. CCK also modified the pattern of alkylation in the acinar tissue, but without a clear relationship with the timing of administration. The results suggest that the inhibitory effect of CCK-8 on pancreatic carcinogenicity of BOP could be related to its capability to modify DNA alkylation by yet unknown mechanisms.     

Evaluation of the Usefulness of Open Lung Biopsies

The role of open lung biopsy (OLB) in the diagnosis of the etiology of lung infiltrates in children was analyzed for a 10-year period 1979-1989 in a tertiary referral center. A total of 18 children had 19 lung biopsies to ascertain the cause of lung infiltrates. Thirteen of these children (72 %) were immunocompromised due to treatment of hematological/solid malignancies and bone marrow transplantation. The clinical diagnosis was bilateral lung infiltrates of unknown etiology in 17 of 18 children. Eight of these children were ventilated for respiratory failure. The biopsy was useful in achieving a histological diagnosis in 18 of 19 samples (diagnostic yield 95%) and an etiological diagnosis in 14 of 19 samples (etiological yield 74 %). Therapeutic strategy was altered in 14 of 18 patients based on the biopsy results. Five of 14 patients responded favorably to a change in specific treatment. The lime interval from onset of respiratory illness to biopsy was 2-60 days (mean 16 days). Despite the critical state of these children there were few complications associated with the biopsy and no mortality directly related to the procedure. We recommend that OLE be undertaken sooner rather than later in immunocompromised children with bilateral pulmonary infiltrates of unknown etiology.     

The thermal effect on the blood flow response to electrical stimulation.

BACKGROUND: Wounds, especially in the elderly, can be life threatening. One modality which allegedly increases blood flow (BF) as an aid to heal chronic wounds is electrical stimulation. This technique applies electrical current (ES) across wounds. However, while many studies show positive findings, others do not. The purpose of this investigation was to investigate some of this inconsistency in results by determining the effect of environmental temperature on the circulation of the skin which may negate the effects of electrical stimulation in a clinical setting. MATERIAL/METHODS: Ten people with no wounds, controls (C), and 12 people with wounds (W) were examined in a thermally neutral or cool room (20 degrees C) and a warm room (34 degrees C) to observe the effect of reducing sympathetic vasoconstrictor activity on the response to 5 and 15 mA sine wave biphasic ES delivered by 2x2 cm surface electrodes. RESULTS: C and W subjects showed a greater BF in the skin in a warm room. In group C, after 30 minutes of stimulation at a current of 15 milliamps, BF increased significantly (p<0.05) but by an average of only 4 flux in the cool room. In the warm environment, BF increased significantly (p<0.01) by 19.3+/-7 flux and increased further during the 60 minute recovery phase. In the W group, BF during ES increased much more during stimulation in a warm room compared to a cool room. CONCLUSIONS: The results show that local vasoconstriction due to exposure to a warm global temperature greatly increases the response of the skin the ES.     

A comparison of technetium-99m-thiodiglycolic acid and iodine-123-hippuran in the evaluation of equivocal upper urinary tract obstruction

In a comparative trial, 21 patients (mean age 43 (range 19-66) years) with dilated upper urinary tracts underwent diuresis renography with both 123I-hippuran and the experimental agent. 99Tcm-thiodiglycolic acid (TDG). Deconvolution analysis of the derived renograms was also performed and the transit times were calculated. Excellent agreement was found between results with the two radiopharmaceuticals. There was complete agreement in interpretation of the response to diuresis with both agents and 84% agreement in the transit time estimations. Good images were produced with both agents and 99Tcm-TDG is considered to be a useful alternative to 123I-hippuran.     

Effects of haloperidol on motor and cognitive functioning in aged mice

The effects of haloperidol on motor and functioning and cognitive functioning were studied in young (3-5 months old) and aged (20-22 months old) male mice by examining haloperidol-induced catalepsy and haloperidol-induced decrements in performance on a radial arm maze. The aged mice were much more sensitive to these adverse effects of haloperidol than were the young mice. Studies of the distribution of radioactivity from [3H]haloperidol to the brain indicated that the differences in sensitivity to this drug were not due to pharmacokinetic differences. The results demonstrate that mice are suitable for studies of aging-induced changes in the behavioral effects of neuroleptic agents.     

Serum ionic fluoride levels in haemodialysis and continuous ambulatory peritoneal dialysis patients

High serum fluoride (F-) in patients with chronic renal failure (CRF) and end-stage renal disease (ESRD) is associated with risk of renal osteodystrophy and other bone changes. This study was done to determine F- in normal healthy controls and patients with ESRD on haemodialysis (HD) or peritoneal dialysis (PD). Seventeen healthy controls (12 males, 5 females) and 39 ESRD patients on dialysis (17 males, 22 females) were recruited in the study in a community with 47.4 +/- 3.28 microM/l (range 44-51 microM/l) of F- content in drinking water. Control subjects showed a mean serum F- concentration of 1.08 +/- 0.350 microM/l. Males in control group showed slightly higher F- levels (1.15 +/- 0.334, range 0.55-1.9 microM/l) than females (0.92 +/- 0.370, range 0.6-1.5 microM/l). Mean serum F- concentration did not correlate significantly with age and sex among control subjects, whereas such correlation was observed in patients with ESRD on dialysis. Mean serum F- concentration was significantly higher in patients on dialysis (2.67 +/- 1.09, range 0.8-5.2 microM/l) than normal controls. When grouped according to sex, the mean serum F- concentration in males (3.05 +/- 1.04, range 1.8-5.2 microM/l) was significantly higher than females (2.38 +/- 1.08, range 0.8-5.2 microM/l). When patients were grouped according to age, it was observed that F- concentration was significantly higher in patients with age groups 21-70 (2.86 +/- 1.05) than those with age group 13-20 years (1.42 +/- 0.531). Thus F- concentration correlated with age and sex, being higher in males and above 20 years. Despite appreciable clearance of F- (39-90%) across the peritoneum, patients on CAPD showed higher serum F- concentration than those on HD (3.1 +/- 1.97 vs 2.5 +/- 1.137 microM/l). Of the total 39 patients on dialysis 39% had their serum F- concentration above 3.0 microM/l, posing the risk of renal osteodystrophy.