Stimulation of kainate toxicity by zinc in cultured cerebellar granule neurons and the role of mitochondria in this process

Zinc chloride (0.01 mM kept for 3 h) is not toxic to cultured cerebellar granule neurons (CGNs) while kainate (0.1 mM kept for 3 h) demonstrates some but very low toxicity towards these cells.Measurements of the relative intraneuronal zinc ion concentration showed that increase in [Zn²⁺]_i under the simultaneous action of ZnCl₂ and kainate was significantly stronger compared to their separate action. Simultaneous treatment of CGNs with kainate and zinc chloride caused the swelling of neuronal mitochondria and consequent intensive neuronal death, which was totally prevented by NBQX (an AMPA/kainate-receptors blocker) or ruthenium red (a mitochondrial Ca²⁺ uniporter blocker). These data imply that Zn²⁺ synergistically to kainate increase their separate toxic effects on mitochondria leading to rapid neuronal death.     

Restless legs syndrome: an early manifestation of Huntington’s disease?

Background – Far from being uniform, Huntington’s disease (HD)’s phenotype encompasses a large variety of motor and non‐motor symptoms which occur in various combinations in individual patients. Aim – To describe an unusual association between restless legs syndrome (RLS) and HD. Methods and results – We report a patient with an atypical presentation of genetically demonstrated HD, who developed typical RLS a few years prior to and during the course of HD. Common causes of RLS were excluded and the polysomnography confirmed frequent and severe periodic limb movements during sleep and while awake. Conclusions – We propose RLS as an uncommon but early feature of HD in some patients, and suggest adding HD to the already long list of RLS secondary to neurodegenerative conditions.     

Transforaminal Doppler: an alternative to transtemporal approach for right-to-left cardiac shunt assessment

BACKGROUND: Paradoxical thrombotic embolism via right-to-left shunt is a risk factor for ischemic stroke, especially in younger subjects. Transtemporal Doppler shows a sensibility and specificity in the detection of patent foramen ovale comparable to that of transesophageal echocardiography, but even younger patients may not have a sufficient acoustic temporal bone window (up to 10%). METHODS AND RESULTS: We thus studied prospectively in 74 patients subsequent to a recent stroke of undetermined origin whether transforaminal (foramen magnum) Doppler is an alternative to transtemporal Doppler in the detection and quantification of right-to-left cardiac shunt. We found a highly significant correlation between the two methods. CONCLUSIONS: We conclude that transforaminal Doppler may be a complement and alternative to transtemporal Doppler and thus improve its value as a screening method for right-to-left cardiac shunt due to patent foramen ovale.     

Impact of Toll‐like receptor‐4 and tumour necrosis factor gene polymorphisms in patients with hidradenitis suppurativa

Background Recent evidence has suggested that deranged immune responses play a role in the pathogenesis of hidradenitis suppurativa (HS). Objectives To investigate the role of single nucleotide polymorphisms (SNPs) of the tumour necrosis factor (TNF) and Toll‐like receptor 4 (TLR4) genes in the physical course of HS; these genes encode for proteins implicated in the immune response of the host. Methods DNA was isolated from 190 patients with HS and 84 healthy controls. SNPs at the promoter regions ?376G/A, ?238G/A and ?308G/A of the TNF gene and the Asp299Gly and Thr399Ile SNPs of the TLR4 gene were determined by polymerase chain reaction (PCR) and digestion of the PCR product by restriction enzymes; after electrophoresis on 2·0% agarose gel, products were visualized on under ultraviolet radiation. Results The presence of the ?238 TNF gene polymorphism was associated with a predisposition to HS (P = 0·027). Susceptibility to the disease was strongly correlated with the presence of AGG/GGA/AGA/GAA TNF haplotypes in 32 (17%) patients compared with two (2%) controls (P < 0·001, odds ratio 8·30, 95% confidence interval 1·94–35·52). The frequency of HS exacerbations and disease severity were greater in patients carrying any of the GAG/AGG/GGA/AGA/GAA haplotypes of the TNF gene. Thirty‐two patients were given TNF antagonists. Nineteen of these patients were carriers of the GGG haplotype of the TNF gene, whereas 13 were carriers of other haplotypes; favourable responses as evidenced by the Sartorius score were registered in 15 (79%) and five (38%, P = 0·025), respectively. Carriage of the TLR4 gene alleles was not associated with any disease parameter. Conclusions A significant role of SNPs at the promoter region of the TNF gene is indicated for susceptibility to HS and for response to TNF antagonists.     

Bone mineral density and its correlation with clinical and laboratory factors in chronic peritoneal dialysis patients

The aim of this study was to assess the clinical and laboratory correlations of bone mineral density (BMD) measurements among a large population of patients on chronic peritoneal dialysis (PD). This cross-sectional, multicenter study was carried out in 292 PD patients with a mean age of 56 ± 16 years and mean duration of PD 3.1 ± 2.1 years. Altogether, 129 female and 163 male patients from 24 centers in Canada, Greece, and Turkey were included in the study. BMD findings, obtained by dual-energy X-ray absorptiometry (DEXA) and some other major clinical and laboratory indices of bone mineral deposition as well as uremic osteodystrophy were investigated. In the 292 patients included in the study, the mean lumbar spine T-score was −1.04 ± 1.68, the lumbar spine Z-score was −0.31 ± 1.68, the femoral neck T-score was −1.38 ± 1.39, and the femoral neck Z score was −0.66 ± 1.23. According to the WHO criteria based on lumbar spine T-scores, 19.2% of 292 patients were osteoporotic, 36.3% had osteopenia, and 44.4% had lumbar spine T-scores within the normal range. In the femoral neck area, the prevalence of osteoporosis was slightly higher (26%). The prevalence of osteoporosis was 23.3% in female patients and 16.6% in male patients with no statistically significant difference between the sexes. Agreements of lumbar spine and femoral neck T-scores for the diagnosis of osteoporosis were 66.7% and 27.3% and 83.3% for osteopenia and normal BMD values, respectively. Among the clinical and laboratory parameters we investigated in this study, the body mass index (BMI) (P < 0.001), daily urine output, and urea clearance time × dialysis time/volume (Kt/V) (P < 0.05) were statistically significantly positive and Ca × PO₄ had a negative correlation (P < 0.05) with the lumbar spine T scores. Femoral neck T scores were also positively correlated with BMI, daily urine output, and KT/V; and they were negatively correlated with age. Intact parathyroid hormone levels did not correlate with any of the BMD parameters. Femoral neck Z scores were correlated with BMI (P < 0.001), and ionized calcium (P < 0.05) positively and negatively with age, total alkaline phosphatase (P < 0.05), and Ca × P (P < 0.01). The overall prevalence of fractures since the initiation of PD was 10%. Our results indicated that, considering their DEXA-based BMD values, 55% of chronic PD patients have subnormal bone mass—19% within the osteoporotic range and 36% within the osteopenic range. Our findings also indicate that low body weight is the most important risk factor for osteoporosis in chronic PD patients. An insufficient dialysis dose (expressed as KT/V) and older age may also be important risk factors for osteoporosis of PD patients.     

Radical versus postoperative radiotherapy for localized prostate cancer: a 10-year experience of an academic hospital

This study is a presentation of our department’s experience in the treatment of localized prostate cancer with either radical or postoperative radiotherapy (RT). Fifty-five patients with clinical localized prostate cancer were reviewed. Thirty-three patients (T1-T2AN0M0 stage) were treated with radical RT and 22 (T2B-T3N0M0 stage) with postoperative RT. All patients received hormonal therapy. Primary end points of the study were the incidence of clinical and biochemical recurrences and death in the whole group and according to treatment modality. Within a median follow-up of 18 months the overall incidence of clinical relapse was 16.9%, of biochemical relapse 12.7% and of death 10.9%. Both treatment options achieved similar outcomes despite the fact that the patients in the postoperative RT group were of higher stage. Radical RT group tended to have better overall and disease-free survival compared to postoperative RT group, but there was no statistically significant evidence. Long-term toxicity was negligible.     

Gastric phytobezoars may be treated by nasogastric Coca-Cola lavage

Large gastric phytobezoars may occur in patients with gastric dysmotility disorders. Treatment options include dissolution with enzymes, endoscopic fragmentation with removal or aspiration, and surgery. We report our experience with nasogastric cola lavage therapy. Over an 8-year period, five consecutive patients were referred to our unit for endoscopic treatment of large gastric phytobezoars. They included one patient with lobectomy for lung cancer and four patients with diabetic gastroparesis. An initial attempt of endoscopic fragmentation and removal was unsuccessful. Patients were treated with 3 l of Coca-Cola nasogastric lavage over 12 h. Nasogastric lavage was very well tolerated by the patients. Complete phytobezoar dissolution was achieved in one session in all cases. There were no procedure-related complications. The dissolution of large gastric phytobezoars with cola nasogastric lavage is a safe, rapid and effective method. Patients may be treated in the medical ward, avoiding therapeutic endoscopy or surgery.     

Anticholinergic medication use and cognitive impairment in the older population: the medical research council cognitive function and ageing study

OBJECTIVES: To determine whether the use of medications with possible and definite anticholinergic activity increases the risk of cognitive impairment and mortality in older people and whether risk is cumulative. DESIGN: A 2‐year longitudinal study of participants enrolled in the Medical Research Council Cognitive Function and Ageing Study between 1991 and 1993. SETTING: Community‐dwelling and institutionalized participants. PARTICIPANTS: Thirteen thousand four participants aged 65 and older. MEASUREMENTS: Baseline use of possible or definite anticholinergics determined according to the Anticholinergic Cognitive Burden Scale and cognition determined using the Mini‐Mental State Examination (MMSE). The main outcome measure was decline in the MMSE score at 2 years. RESULTS: At baseline, 47% of the population used a medication with possible anticholinergic properties, and 4% used a drug with definite anticholinergic properties. After adjusting for age, sex, educational level, social class, number of nonanticholinergic medications, number of comorbid health conditions, and cognitive performance at baseline, use of medication with definite anticholinergic effects was associated with a 0.33‐point greater decline in MMSE score (95% confidence interval (CI)=0.03–0.64, P=.03) than not taking anticholinergics, whereas the use of possible anticholinergics at baseline was not associated with further decline (0.02, 95% CI=?0.14–0.11, P=.79). Two‐year mortality was greater for those taking definite (OR=1.68; 95% CI=1.30–2.16; P<.001) and possible (OR=1.56; 95% CI=1.36–1.79; P<.001) anticholinergics. CONCLUSION: The use of medications with anticholinergic activity increases the cumulative risk of cognitive impairment and mortality.     

Obesity in children and adolescents in Cyprus. Prevalence and predisposing factors

OBJECTIVE: To estimate the prevalence of childhood and adolescent obesity in Cyprus and define possible associated risk factors. STUDY DESIGN: Cross-sectional study of a representative sample of children 6-17 y of age performed during October 1999 to June 2000. METHODS: Anthropometric data were taken using standard methods, from 2467 children. Certain diet and physical activities as well as other socioeconomic family parameters were assessed with the aid of a questionnaire. Obesity and overweight were defined using both the National Health and Nutrition Examination Survey (NHANES) I definition and the newer International Obesity Task Force (IOTF) definition. Logistic regression analyses were performed to estimate the influence of various parameters. RESULTS: The prevalence of obesity in males was 10.3% and in females 9.1% using the NHANES I definition and 6.9 and 5.7%, respectively, using the IOTF definition. The percentages presented a decreasing trend with age. There were an additional 16.9% of males and 13.1% of females defined as overweight with the NHANES I definition and 18.8 and 17.0%, respectively, using the IOTF definition. The most significant associated factor for obesity was parental obesity status. The odds ratio for offspring obesity when both parents were obese ranged from 11.34 (95% CI 1.83-75.50) in females 6 to 11-y-old to 18.09 (95% CI 2.06-158.81) for males 12 to 17-y-old. CONCLUSIONS: The prevalence of childhood and adolescent obesity was estimated for the first time in a representative sample from Cyprus, and this rate is comparable to that observed in North America. These results indicate the need for individual and population measures for the treatment and prevention of pediatric obesity. The rate of obesity differs significantly depending on the method of estimation.     

Coincidental Malabsorption of Lactose, Fructose, and Sorbitol Ingested at Low Doses Is Not Common in Normal Adults

Normal subjects may incompletely absorb either lactose, fructose, or sorbitol and may therefore have abdominal symptoms. The frequency of coincidental malabsorption of these sugars is not known. This is clinically important, since we often ingest them during the same day and malabsorption may cause abdominal symptoms. To shed light on this issue we studied 32 normal subjects. Volunteers drank in random order the following solutions: 20 g lactulose, 50 g sucrose, 50 and 25 g lactose, 50 and 25 g fructose, 20 and 10 g sorbitol. Semiquantitative carbohydrate malabsorption was estimated with lactulose standards. Frequency of 50-g lactose (69%), 50-g fructose (81%), and 20-g sorbitol (84%) malabsorption was not significantly different (P = 0.3). The estimated median fraction of the ingested high dose malabsorbed was 42, 19, and 68% for lactose, fructose, and sorbitol, respectively. At low challenging doses, 63% of the volunteers absorbed two of three or all three sugars, and 88% were asymptomatic to two or all three sugars. In conclusion, the frequency of coincidental malabsorption of lactose, fructose, and sorbitol and intolerance to these sugars is not common, when normal adults ingest them at low doses.