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.     

BDNF regulates the expression of fragile X mental retardation protein mRNA in the hippocampus

Both fragile X mental retardation protein (FMRP) and brain-derived neurotrophic factor (BDNF) are implicated in the maturation of neurons and in the higher cognitive functions. We have investigated whether FMRP and BDNF are reciprocally regulated in neurons. Exposure of cultured hippocampal neurons to BDNF, but not to NT-3, reduced FMR1 mRNA levels to 84.8% of control at 4 h and the levels were back to baseline by 24 h or 4 days. Furthermore, expression of FMR1 mRNA was reduced (82.4% of control) in vivo in the hippocampus of transgenic mice overexpressing TrkB receptors, and a small but significant (5.1%) decrease was also detected in FMRP protein levels. In contrast, the expression patterns of BDNF and TrkB mRNAs were not altered in FMRP-deficient mice compared to wild-type mice. Our data provide evidence that BDNF via TrkB signaling decreases FMRP expression and suggest a role for FMRP in BDNF-induced synaptic plasticity.     

Relationships of in vitro sensitivities tested with nine drugs and two types of irradiation in chronic lymphocytic leukemia

Extensive research into mechanisms of cytotoxic drug and irradiation resistance have produced few clinically encouraging results. In this report, we apply correlation analyses to drug and irradiation response results from a cohort of 36 classical B chronic lymphocyte leukemia (CLL) patients. Nine drugs and two types of irradiation were selected according to their usefulness in CLL therapy or on the basis of their otherwise interesting mechanisms of action. Part of the results concerning individual drugs have been previously published, but new correlation analyses are presented in this paper. Altogether 2376 duplicate cultures were performed in order to determine ID(80) values, i.e. doses causing an 80% inhibition in 4-day cultures when leucine incorporation was used as an indicator of cells vitality. Non-parametric Spearman's rank order correlation confirmed a tight relationship between 2-chlorodeoxyadenosine and fludarabine, as expected. Surprisingly, correlation between two P-glycoprotein-dependent drugs, vincristine and doxorubicin, was not demonstrable. A number of entirely unexpected correlations were identified between drugs with very different mechanisms of action: (i) chlorambucil and gamma-irradiation; (ii) 2-chlorodeoxyadenosine and vincristine; (iii) 2-chlorodeoxyadenosine and gamma-irradiation; (iv) fludarabine and cis-platin; (v) doxorubicine and gamma-irradiation; (vi) prednisolone and cyclosporin A; (vii) vincristine and verapamil. Our findings emphasize: (i) the usefulness of fresh tumor cells instead of cell lines in cytotoxicity studies; (ii) the great variation in cytotoxicity in individual patients, i.e. tumor cell heterogeneity, as well as patient heterogeneity; and (iii) an entirely unexpected finding that there were tight relationships in drug and irradiation responses between substances supposed to act with very different mechanisms.     

Treatment of late Lyme borreliosis

The aim of this study was to develop a treatment for late Lyme borreliosis and to compare the clinical results with serological findings before and after treatment. It was done in the land Islands (population 25000), a region endemic for Lyme borreliosis. The patients were the first consecutive 100 patients from the land Islands with late Lyme borreliosis. They were followed for at least 1 year after treatment. The clinical results of treatment were compared with results of analyses of flagellar IgG antibodies to Borrelia burgdorferi done at the time of diagnosis before treatment and up to 12 months afterwards. Short periods of treatment were not generally effective. The outcome was successful in four of 13 treatments with 14 days of intravenous ceftriaxone alone, in 50 of 56 assessable treatments with ceftriaxone followed by 100 days of amoxycillin plus probenecid, and in 19 of 23 completed treatments with ceftriaxone followed by 100 days of cephadroxil. Titres of IgG antibodies to B. burgdorferi flagella declined significantly after 6 and 12 months in the patients who had successful treatments. All patients whose final titres were less than 30% of the initial titre were in the successful group. Their titres usually remained above the upper limit of normal for a long time but a decline to a value of less than 30% of that before treatment was always a sign of cure.     

Serum concentrations of oestrone,oestradiol and oestriol during various oestrogen treatments

Serum oestradiol/oestrone ratios were measured during various oestrogen treatments in castrated women. Oral oestriol succinate therapy (8 mg/day) caused little change in the pre-treatment oestradiol/oestrone ratio. During oestradiol valerianate therapy (2 mg/day) serum total oestrogens and the E₂/E₁ ratio were considerably increased. One day after the injection of 10 mg of oestradiol valerianate and 2.5 mg of oestradiol benzoate + 10 mg of oestradiol phenylpropionate the E₂/E₁ ratio was similar to the ratio in the middle of the normal ovulatory cycle. The change in serum oestriol was rather small after oral doses of 8 mg of oestriol succinate 15, 30 and 120 min after the application.     

Indentation stiffness of repair tissue after autologous chondrocyte transplantation

Our main hypothesis was that indentation stiffness of the repair tissue approaches the values of adjacent cartilage 1 year after autologous chondrocyte transplantation. We also wanted to investigate the differences between osteochondritic lesions and full-thickness lesions. Thirty patients with cartilage lesions were operated on with autologous chondrocyte transplantation. The repair was evaluated arthroscopically, indentation stiffness was measured, and clinical evaluations were done. The stiffness of the repair tissue improved to 62% (mean 2.04 +/- 0.83 N, mean +/- SD) of adjacent cartilage (3.58 +/- 1.04 N). Fifty-three percent of the patients graded their knee as excellent or good and 47% of the patients graded their knee as fair at the followup. In six patients the normalized stiffness was at least 80%, suggesting hyaline-like repair. The indentation stiffness of the osteochondritis dissecans lesion repairs (1.45 +/- 0.46 N; n = 7) was less than that of the nonosteochondritis dissecans lesion repair sites (2.37 +/- 0.72 N; n = 19). Gadolinium-enhanced magnetic resonance imaging of the cartilage (dGEMRIC) during followup of four patients suggested proteoglycan replenishment, although all grafts showed low indentation values. Low stiffness values may indicate incomplete maturation or predominantly fibrous repair. The indentation analysis showed that the repair tissue stiffness could, in some cases, reach the same level as the adjacent cartilage, but there was a large variation among the grafts.     

Sentinel node metastasectomy in thin ≤1-mm melanoma

Background and aims Sentinel lymph node biopsy (SLNB) has been widely accepted as a precise tool to stage melanoma. In thin T1 melanomas (1 mm), the indication of SLNB is controversial since the risk of nodal metastasis is low. The aim of this study was to assess if SLNB detects occult nodal metastases among patients with thin melanomas.Patients and methods SLNB was performed prospectively in 135 patients with invasive melanoma in any depth category, including 56 T1 melanomas.Results Nodal metastases were detected in 18% by SLNB, and there were three sentinel-positive thin melanomas, constituting 5% of the T1 cases. Histopathologically, there were no factors of the primary tumors that would have predicted these metastases.Conclusion SLNB is a precise method to detect clinically silent nodal metastases in thin invasive melanoma. Certain histopathologic features of a thin primary lesion may correlate with the predictive probability of the sentinel node status. We were unable to identify these predictors, but the conclusions from this study are limited by the small sample size. Advanced melanoma is a lethal disease, and accurate staging is essential also in the T1 group. For stage III patients with occult nodal metastases, metastasectomy is a better option for cure than observation.     

Effects of home strength training and stretching versus stretching alone after lumbar disk surgery: a randomized study with a 1-year follow-up

OBJECTIVE: To assess the adherence to and effects of a 12-month combined strength and stretching home exercise regimen versus stretching alone, on patient outcome after lumbar disk surgery. DESIGN: Randomized controlled trial. SETTING: Departments of physical medicine and rehabilitation and orthopedics at a Finnish hospital. PARTICIPANTS: Patients (N=126) were randomized into either a combined strength training and stretching group (STG, n=65) or a control group (CG, n=61). INTERVENTION: The STG was instructed to perform strength training and both the STG and CG were instructed in the same stretching and stabilization exercises for 12 months. MAIN OUTCOME MEASURES: Pain on the visual analog scale (VAS), the Oswestry and the Million disability indexes, isometric and dynamic trunk muscle strength, mobility in the lumbar spine, and straight-leg raising were measured. RESULTS: The trial was completed by 71% and 77% of the patients from the STG and the CG, respectively. The mean strength training frequency decreased from 1.5 to 0.6 times a week in the STG during the intervention. The mean stretching frequency decreased from 3.7 to 1.6 times a week in both groups. Median back and leg pain varied between 17 and 23 mm (VAS), and the Million and Oswestry indices varied between 14 and 23 points 2 months postoperatively. No statistically significant changes took place in these outcome measures during the 12-month follow-up in both groups. The changes in isometric trunk extension favored the STG ( P =.016) during the first 2 months. However, during the whole 12-month training period, both dynamic and isometric back extension and flexion strength, as well as mobility of the spine and repetitive squat-test results, improved significantly in both groups, and no differences were found in any of the physical function parameters between the STG and CG. CONCLUSIONS: At the 12-month follow-up, no statistically significant changes were found in the physical function, pain, or disability measures between the groups. In the STG, training adherence with regard to training frequency and intensity remained too low to lead to specific training-induced adaptations in the neuromuscular system. Progressive loading, supervision of training, and psychosocial support is needed in long-term rehabilitation programs to maintain patient motivation.     

Bilateral hemodynamic responses to auditory stimulation in newborn infants

We studied hemodynamic auditory evoked responses of 20 healthy full-term neonates with near-infrared spectroscopy. The instrument used allows the measurements to be performed simultaneously above both auditory cortices. The stimulation consisted of 5-s trains of sound (700-ms interstimulus interval) with a 25-s silent interval. In response to the stimulation, a significant increase in concentration of oxygenated hemoglobin was detected in 14 out of 21 measurements. The mean latency of the largest response was 9.63+/-2.20 s (mean+/-SD) and the mean amplitude was 1.02+/-0.53 microM. The response amplitude was significantly larger in active (1.28+/-0.59 microM) than in quiet sleep (0.76+/-0.32 microM). The latency of the oxygenated hemoglobin concentration response was significantly shorter (r=-0.70 and p=0.0023) for infants with higher gestational age.     

Asthma, airway inflammation and treatment in elite athletes

Highly trained athletes are repeatedly and strongly exposed to cold air during winter training and to many inhalant irritants and allergens all year round. Asthma occurs most commonly in athletes engaging in endurance events such as cross-country skiing, swimming, or long-distance running. As well as the type of training, a major risk factor is atopic disposition. A mixed type of eosinophilic and neutrophilic airway inflammation has been shown to affect elite swimmers, ice-hockey players, and cross-country skiers. The inflammation may represent a form of repeated thermal, mechanical, or osmotic airway trauma resulting in a healing or remodelling process. Elite athletes commonly use antiasthma drugs to treat exercise-induced bronchial symptoms. Only a few controlled studies have been conducted on the effects of antiasthma drugs on asthma symptoms, bronchial hyperresponsiveness and airway inflammation in elite athletes. Inhaled beta(2)-adrenoceptor agonists are effective against exercise-induced bronchospasm. In contrast, airway inflammation, bronchial hyperresponsiveness and symptoms have responded poorly to inhaled corticosteroids and leukotriene antagonists. As discontinuing high-level exercise has proved effective in reducing eosinophilic airway inflammation, exercise or training should be restricted in athletes having troublesome symptoms and sputum eosinophilia. Switching training to less irritating environments should be considered whenever possible. It appears to be difficult to change the 'natural course' of asthma in athletes by anti-inflammatory treatment.