Hirschsprung's disease in cartilage-hair hypoplasia has poor prognosis

Purpose: Cartilage-hair hypoplasia (CHH) is a chondrodysplasia with growth failure, impaired immunity, and high incidence of Hirschsprung disease (HD). This study describes the outcome of CHH patients with HD. Methods: Among 147 patients with CHH, 13 were identified to have HD. Their medical records were analyzed for treatment, outcome, and complications of HD and compared with a control group of 169 patients with HD but not CHH. Results: Eight CHH patients had classic HD with rectosigmoid involvement, 2 had long segment colonic disease, and 3 patients had total colonic aganglionosis. Six of the 13 CHH patients (46%) had episodes of enterocolitis before the first surgery. Enterocolitis was complicated by colonic perforation in 2 cases. Eleven CHH patients (85%) had at least one episode of postoperative enterocolitis. Five patients (38%) with CHH and HD had died; 4 of enterocolitis-related septic infection and one of non-Hodgkin's lymphoma. In the control group, preoperative enterocolitis occurred in 14% and postoperative enterocolitis in 8%. Two controls (1.2%) had died. Conclusions: HD associated with CHH has poor prognosis in terms of postoperative morbidity and risk of death. These patients require particular attention during postoperative follow-up to detect potentially lethal complications.     

Effect of spinal cord abnormalities on the function of the lower urinary tract in patients with anorectal abnormalities

PURPOSE: We evaluated the effect of spinal cord abnormalities on lower urinary tract function in patients with anorectal abnormalities. MATERIALS AND METHODS: We examined 30 patients with anorectal anomalies mainly because of fecal or urinary incontinence. All patients underwent spinal magnetic resonance imaging and urodynamic investigation. RESULTS: Major lumbosacral abnormalities were detected in 57% of patients, including 13, 4 and 3 with a tethered cord, syringomyelia and caudal regression, respectively. Significant dysfunction of the lower urinary tract in 57% of the cases involved an overactive detrusor in 11, detrusor-sphincter dyssynergia in 4, distended bladder in 4 and lazy bladder in 1. When the spinal cord was normal, 54% of the patients had abnormal urodynamic findings but when the spinal cord was abnormal, 59% had abnormal urodynamics. When the bony spine was normal, 33% of the patients had an abnormal spinal cord but when the bony spine was abnormal, 69% had an abnormal spinal cord. CONCLUSIONS: Patients with anorectal abnormalities and fecal or urinary incontinence problems often have an abnormal spinal cord and abnormal urodynamic findings. However, the state of the spinal cord is not the only factor explaining lower urinary tract function. Thus, the possibility of lower urinary tract dysfunction should be considered in each patient with anorectal abnormalities. If the patient has symptoms or findings suggesting abnormal lower urinary tract function urodynamic evaluation should be performed.     

Postpartum bone mineral density in women treated for thromboprophylaxis with unfractionated heparin or LMW heparin

Venous thromboembolism remains an important cause of maternal mortality. In a randomised open study, 44 pregnant women with confirmed previous or current thromboembolism were randomised to receive either low-molecular-weight heparin, dalteparin (N = 21) once daily subcutaneously or unfractionated sodium heparin (UF heparin, N = 23) twice daily subcutaneously for thromboprophylaxis during pregnancy and puerperium. Bone mineral density (BMD) in the lumbosacral spine was measured with dual X-ray absorptiometry (DEXA) 1, 6, 16, 52 weeks and, if possible, 3 years after delivery. BMD values were also compared with those of healthy, delivered women (N = 19). Mean BMD of the lumbar spine was significantly lower in the unfractionated heparin group compared with the dalteparin and with the control groups (repeated measures ANOVA p = 0.02). BMD in the dalteparin group did not differ from BMD of healthy delivered women. Multiple logistic regression analysis revealed that therapy was the only independent factor influencing BMD at weeks 16 and 52. Therefore we recommend use of dalteparin instead of UF heparin for long-term thromboprophylaxis during and after pregnancy.     

Event-related potential features indexing central auditory discrimination by newborns

Behavioral research has produced little evidence on sound feature discrimination in neonates. Sensory processes underlying sound perception can be studied using the mismatch negativity (MMN) component of auditory event-related potentials (ERPs), which is not contingent on conscious perception and response. Thus, MMN is suitable for studying newborns, who are difficult to obtain behavioral responses from. The present study thus utilized spectrally rich sounds, known to elicit the most replicable MMN in adults, to investigate newborns' preattentive analysis of sound duration and frequency changes. An attempt was also made to control for the obligatory ERP effects on the MMN. Three-partial harmonic tones were presented in Duration and in Frequency oddball conditions to 55 newborns. In the other two, Equiprobable duration and Equiprobable frequency, conditions frequency and duration deviants of the oddball paradigms were presented with equal probabilities among sounds of other durations and frequencies. MMN was elicited in 81% of newborns in Frequency oddball condition and in 78% of newborns in Duration oddball condition. No significant amplitude differences between the duration and frequency MMNs were found, but MMN latency was delayed in Duration condition. The obligatory components seemed to contribute significantly to the deviant-standard difference in Duration but not in Frequency condition. The majority of neonates appear to possess effective sound frequency and duration discrimination mechanisms. Their preattentive sound discrimination is facilitated by spectrally rich sound content. The present findings support a change-detection nature of MMN in neonates; however, sound duration-related obligatory effects need to be taken into account in infant MMN studies.     

Effects of ergonomic intervention in work with video display units

OBJECTIVES: This study evaluated the effect of an intensive ergonomic approach and education on workstation changes and musculoskeletal disorders among workers who used a video display unit (VDU). METHODS: A randomized controlled design was used. The subjects (N=124) were allocated into three groups (intensive ergonomics, ergonomic education, reference) using stratified random sampling. The evaluation involved questionnaires, a diary of discomfort, measurements of workload, and an ergonomic rating of the workstations. The assessments were made 2 weeks before the intervention and after 2 and 10 months of follow-up. RESULTS: The intensive and training groups showed less musculoskeletal discomfort than the reference group after 2 months of follow-up. Positive effects on discomfort were seen primarily for the shoulder, neck, and upper back areas. No significant differences were found for the strain levels or prevalence of pain. After the intervention the ergonomic level was distinctly higher in the intensive ergonomic group than in the education or reference group. CONCLUSIONS: Both the intensive ergonomics approach and education in ergonomics help reduce discomfort in VDU work. In attempts to improve the physical ergonomics of VDU workstations, the best result will be achieved with cooperative planning in which both workers and practitioners are actively involved.     

Evidence of benefit from centralised treatment of ovarian cancer: a nationwide population-based survival analysis in Finland

To assess the effect of different hospital types or surgical volume on the survival of ovarian cancer patients, a nationwide and population-based analysis was carried out in Finland. The study included all 3,851 ovarian cancer patients operated from 1983-94. The patients were classified according to the hospital of the first surgery. The hospitals were categorized by type (university, central or other hospital) and, separately, into quartiles by the number of operated patients (surgical volume). The patients operated at university hospitals had better survival than those operated in central hospitals, the 5-year relative survival rates (RSR) being 45% (95% CI = 42-48%) and 37% (34-40%), respectively. RSR in the 'other hospital' category was 45% (42-48%). The RSR for the patients operated in the highest volume hospitals was 47% (43-50%), and by decreasing volume (quartile) the RSR was 40% (36-43%), 40% (36-43%) and 42% (38-45%), respectively. After controlling for potential confounding by stage and age using regression models, the results remained practically the same. The results indicate that further centralizing of operative treatment of ovarian cancer may still improve survival rates on a population level in Finland.     

The combination of HSV-tk and endostatin gene therapy eradicates orthotopic human renal cell carcinomas in nude mice

BACKGROUND AND METHODS: Gene therapy may offer a new tool for the treatment of renal cell carcinoma (RCC). We have tested a combination of cytotoxic and antiangiogenic gene therapy for wild-type orthotopic human RCC xenografts in nude mice using intratumoral adenovirus-mediated herpes simplex virus thymidine kinase (HSV-tk) and endostatin (ES) gene therapy. In vivo magnetic resonance imaging, morphometry, immunocytochemistry, and survival were used to evaluate the treatment effect. Adenovirus-mediated marker gene transfers (GFP) were used as controls. Results: In vivo transduction efficiency, measured using GFP gene transfer, was 27+/-7%. The combination gene therapy with HSV-tk and ES adenoviruses resulted in a significant antitumor effect (P<.01) compared to single HSV-tk (n.s.) or ES (n.s.). In the survival study, all tumors with single gene therapy using HSV-tk, ES, and marker gene adenoviruses showed progression in magnetic resonance imaging. In contrast, the majority of the tumors in the combination treatment group remained dormant or were eradicated (57%). Survival of these mice equaled healthy nude mice, and was significantly prolonged (P<.0001) compared to HSV-tk (P<.028) and ES (n.s.) groups. Conclusions: It is concluded that the inhibition of angiogenesis using ES gene transfer together with the cytotoxic HSV-tk gene therapy results in a significantly improved treatment effect in RCC compared to the single gene treatments.     

Treatment of deep venous thrombosis with low-molecular-weight heparin during pregnancy

Low-molecular-weight (LMW) heparins have been shown to be at least as effective as unfractionated (UF) heparin in the treatment of deep venous thrombosis (DVT) in nonpregnant subjects. LMW heparins have been shown to be safe when used during pregnancy as they do not cross the placenta. Up to now, they have been used mainly in thromboprophylaxis during pregnancy and rarely in the treatment of acute DVT in pregnant women. In a prospective observational study, we compared the effectiveness and safety of the LMW heparin, dalteparin, with UF heparin in the initial treatment (first week) of DVT during pregnancy. After confirmation of DVT by ultrasonography, 10 women were treated with UF heparin (25,430 IU/day, mean) and 21 women with dalteparin (16,000 IU/day, mean) for 7 days and, thereafter, all women were given treatment doses of LMW heparin for another 2 weeks. The dose was then gradually decreased and kept at a high prophylactic dose until delivery. One patient in the dalteparin group had recurrence of DVT 2 weeks after starting the treatment. No differences were observed between the groups in symptoms or bleeding complications during pregnancy and delivery. Our results indicate that LMW heparin is as effective and safe as UF heparin for the first week of treatment, but LMW heparin has the advantage of being easily administered and few laboratory controls are required.     

Evaluation of cocktail approach to standardise Caco-2 permeability experiments.

The purpose of this study was to investigate the suitability and reliability of n-in-one approach using FDA suggested compounds for standardising Caco-2 permeability experiments. Special attention was paid to the evaluation of rank order correlation and mechanistic insights of compound permeability. Transport studies with antipyrine, metoprolol, ketoprofen, verapamil, hydrochlorothiazide, ranitidine, mannitol and fluorescein were performed in 12- and 24-well formats, as single compounds and in cocktails under iso-pH 7.4 and pH-gradient (pH 5.5 vs. 7.4) conditions. Compounds were quantified using n-in-one LC/MS/MS analysis. The cocktail-dosing proved to be a feasible method to determine the permeability of the Caco-2 cell line and to introduce external standards for permeability tests. Even though sink conditions were lost in cocktail experiments for highly permeable compounds, the rank order of compound permeability and the classification to low and high permeability compounds remained unchanged between single and cocktail studies and permeability values of 12- and 24-well formats were directly comparable. Under pH-gradient conditions the margin between high and low permeability compounds was narrower due to the lower permeability (higher fraction of ionisation) of basic molecules. Of the compounds studied, antipyrine, metoprolol, hydrochlorothiazide and mannitol are suitable for evaluation and standardisation purposes of passive permeability, while fluorescein would function as paracellular marker under iso-pH 7.4. As efflux activity may vary between cell batches, verapamil is a useful marker for P-glycoprotein.