Body weight in patients with Parkinson's disease.

There is some evidence suggesting that Parkinson's disease (PD) patients exhibit lower body weight when compared to age-matched healthy subjects. Low body mass index (BMI) is correlated with low bone mineral density, both of which are major risk factors for hip fractures. Possible determinants of weight loss in PD patients include hyposmia, impaired hand-mouth coordination, difficulty chewing, dysphagia, intestinal hypomotility, depression, decreased reward processing of dopaminergic mesolimbic regions, nausea, and anorexia as the side effects of medication, and increased energy requirements due to muscular rigidity and involuntary movements. It is unclear whether PD patients in general, or only a subgroup of those affected, definitely show lower BMI in the advanced stages of the disease. We therefore recommend that the body weight of PD patients be monitored monthly as the disease progresses, and that a patient's nutrition should be supplemented with sufficient amounts of vitamin D and calcium to reduce the risk of hip fractures and strengthen bone density. Because meal times may coincide with unpredictable off periods associated with akinesia and impaired hand-mouth coordination, PD patients also need flexible food schedules that accommodate the associated symptoms of this disease.     

Patients' experience of epilepsy and health care

OBJECTIVE: The aim of this study was to assess the severity of epilepsy and its effect on patients lives, and to describe patients' use of and attitudes to health care. METHOD: A questionnaire was sent to 595 people with epilepsy identified from 14 general practices in north-west Bristol. All patients aged 16 years and over receiving anti-epileptic medication for their epilepsy were included in the study. Areas investigated included severity of epilepsy and its effect on quality of life, anti-epileptic medication and its perceived effect, health care utilization and preferences for health care. RESULTS: Seizure frequency was strongly associated with adverse effects of epilepsy. Attacks of epilepsy were experienced at least monthly by 20.4% (95% confidence intervals (Cl) 17.0-23.7%) of patients, 29.4% (25.4-33.4%) took more than one anti-epileptic drug, 56.1% (50.1-62.2%) reported drug side effects, 74.1% (70.3-77.8%) would prefer to receive all or most of their epilepsy care in a general practice setting, and 69.8% (63.5- 76.2%) would like contact with a primary care-based epilepsy specialist nurse. During the previous year 42.4% (35.9-48.8%) of patients had not seen a doctor about their epilepsy. Of patients who had attended the general practice only 13.4% (9.6-17.2%) had regular arrangements to see their GP about epilepsy. Patients receiving both primary and secondary care had the greatest needs and wants for improved care. CONCLUSIONS: Structured care, including regular appointments, co-ordination of primary and secondary care, and increased monitoring and discussion, may improve the quality of life of people with epilepsy, but requires evaluation.      

A simple mechanical model using a piston to produce localized cerebral contusions in pigs

Summary A simple mechanical model using a piston to produce localized cerebral contusions in pigs, is presented.The precision and reproducibility of the method are described by the biomechanical and pathological results.There are only pathological changes with haemorrhage and laceration close to the place of entry of the piston. The changes in the physiological parameters also indicate that the damage is focal.In this model, when kept intact, the dura mater offers considerable protection as no pathological changes in the brain are observed even when the energy at the time of the contusion is increased to twice the values which, when the dura is open, cause considerable damage.     

Comparative investigation of the influence of nizatidine, ranitidine, and cimetidine on the steady-state pharmacokinetics of theophylline in COPD patients.

The influence of usual regimens of the H2 blocking drugs, cimetidine, ranitidine, and nizatidine on the steady-state plasma concentrations and pharmacokinetic characteristics of theophylline was studied in seventeen patients with chronic obstructive pulmonary disease (COPD). Patients were dosed to steady-state with an oral, sustained-release formulation of theophylline given in therapeutic doses twice daily for 2 weeks. Over the next 4 weeks, each patient received a week-long regimen of each H2 blocker concomitantly with theophylline, and a week-long regimen of theophylline alone (control). At the end of each of the latter 4 weeks the steady-state pharmacokinetics of theophylline were assessed. Neither ranitidine nor nizatidine treatment altered the steady-state pharmacokinetics of theophylline relative to the control phase (i.e. no H2 blocker treatment). Values for theophylline C(ave), Cssmax, AUC0-12, and CLoral were significantly different during cimetidine treatment compared with all other treatments (ranitidine, nizatidine, and control). Cimetidine increased theophylline Cssmax, AUC0-12 and Cave by approximately 32%, and decreased theophylline oral clearance by approximately 23%. The authors conclude that cimetidine alters the steady-state pharmacokinetics of theophylline in COPD patients, whereas ranitidine and nizatidine are without effect.     

In vivo evidence that ethosuximide is a substrate for cytochrome P450IIIA.

The role of various subfamilies of rat hepatic cytochrome P450 in the oxidation of ethosuximide was evaluated by comparing ethosuximide clearance in control rats and those pretreated with relatively selective P450 inducers and/or inhibitors. Clotrimazole pretreatment increased ethosuximide clearance threefold (p less than 0.005). Dexamethasone increased ethosuximide clearance twofold (p less than 0.001), and the dexamethasone effect was completely abolished by a single dose of triacetyloleandomycin. These results suggest a prominent role for cytochrome P450IIIA in ethosuximide metabolism in the rat. Isoniazid increased ethosuximide clearance twofold (p less than 0.001), and this effect was abolished by a single dose of diallylsulfide, suggesting that ethosuximide is also processed by cytochrome P450IIE1 in rats. Phenobarbital pretreatment increased ethosuximide clearance 2-2.7 fold (p less than 0.001); an effect that was only partially reversed by orphenadrine, an inhibitor of cytochrome P450IIB/IIC enzymes. This suggests a quantitatively less important role for the IIB/IIC subfamilies in processing ethosuximide, since phenobarbital is an inducer of P450 subfamilies IIB, IIC, IIE, and IIIA. Neither the cytochrome P450IA inducer, beta-naphthoflavone, nor the inhibitor, alpha-naphthoflavone altered ethosuximide clearance. Ajmaline, an inhibitor of cytochrome P450IID, had no effect on ethosuximide clearance. Together, these findings suggest that ethosuximide is principally oxidized by cytochrome P450IIIA, and that cytochrome P450IIE may play an important role. Cytochromes P450IIB/C play less prominent roles in ethosuximide oxidation, and neither cytochrome P450IA nor cytochrome P450IID is involved.     

Interaction of thiamine deficiency and voluntary alcohol consumption disrupts rat corpus callosum ultrastructure.

The relative roles of alcohol and thiamine deficiency in causing brain damage remain controversial in alcoholics without the Wernicke-Korsakoff syndrome. Experimental control over alcohol consumption and diet are impossible in humans but can be accomplished in animal models. This experiment was designed to differentiate the separate and combined effects on the macro- and ultrastructure of the corpus callosum of thiamine deficiency and voluntary alcohol consumption. Adult male alcohol-preferring (P) rats (9 chronically alcohol-exposed and 9 water controls) received a thiamine-deficient diet for 2 weeks. There were four groups: five rats previously exposed to alcohol were treated with pyrithiamine (a thiamine phosphorylation inhibitor); five rats never exposed to alcohol were treated with pyrithiamine; four alcohol-exposed rats were treated with thiamine; and four rats never exposed to alcohol were treated with thiamine. On day 14, thiamine was restored in all 18 rats; 2 weeks later the 10 pyrithiamine-treated rats received intraperitoneal thiamine. The rats were perfused 61 days post-pyrithiamine treatment at age 598 days. Brains were dissected and weight and volumes were calculated. Sagittal sections were stained to measure white matter structures. The corpus callosum was examined using transmission electron microscopy to determine density of myelinated fibers, fiber diameter, and myelin thickness. The corpus callosum in the alcohol/pyrithiamine group was significantly thinner, had greater fiber density, higher percentage of small fibers, and myelin thinning than in the alcohol/thiamine and water/thiamine groups. Several measures showed a graded effect, where the alcohol/pyrithiamine group had greater pathology than the water/pyrithiamine group, which had greater pathology than the two thiamine-replete groups. Across all 16 rats, thinner myelin sheaths correlated with higher percentage of small fibers. Myelin thickness and axon diameter together accounted for 71% of the variance associated with percentage of small fibers. Significant abnormalities in the alcohol/pyrithiamine group and lack of abnormality in the alcohol-exposed/thiamine-replete group indicate that thiamine deficiency caused white matter damage. The graded abnormalities across the dually to singly treated animals support a compounding effect of alcohol exposure and thiamine depletion, and indicate the potential for interaction between alcohol and thiamine deficiency in human alcohol-related brain damage.     

Differential effect of catechol-O-methyltransferase Val158Met genotype on emotional recognition abilities in healthy men and women.

The catechol-O-methyltransferase (COMT) Val158Met polymorphism modulates executive functions and working memory and recent neuroimaging studies implicate an association with emotional processing. We examined the relationship between the COMT Val158Met polymorphism and facial emotion recognition and differentiation in 100 healthy individuals. Compared to Met homozygosity, Val homozygosity was associated with better and faster recognition of negative facial expressions such as anger and sad. Our study provides evidence for a possible influence of the COMT polymorphism on emotion recognition abilities in healthy subjects. Additional research is needed to further define the neurocognitive phenotypes associated with COMT polymorphisms.