Olanzapine in the treatment of hallucinosis in idiopathic Parkinson's disease: a cautionary note

BACKGROUND: Hallucinosis is a dopaminergic dose limiting complication of the treatment of idiopathic Parkinson's disease. Typical neuroleptic medications cannot be used for suppressing hallucinosis because the extrapyramidal side effects worsen parkinsonian motor control. Olanzapine is a novel atypical antipsychotic drug with few reported extrapyramidal side effects which may be more suitable for controlling hallucinosis in these patients. METHODS: Olanzapine was given to five patients with idiopathic Parkinson's disease and the dosage was titrated until a clinically meaningful reduction in hallucinosis was achieved. The commercially available 5 mg, 7.5 mg and 10 mg tablets were used. RESULTS: After an initial 9 days of treatment, hallucinosis frequency was significantly reduced, an effect which was maintained with continued treatment. However, during this early phase of treatment, parkinsonian motor disability increased, which resulted in two of the patients discontinuing medication. CONCLUSIONS: Olanzapine is effective in the suppression of hallucinosis in patients with idiopathic Parkinson's disease but the currently available dose increments may result in an unacceptable exacerbation of motor disability.     

Effects of regular exercise in management of chronic idiopathic constipation

Regular physical exercise has long been considered in the management of chronic constipation. This recommendation is probably based on the assumption that exercise shortens the transit time through the gastrointestinal tract. However, on the basis of previous studies, the effect of exercise on the transit remains controversial at best. Therefore, it was the goal of the present study to assess the influence of regular physical exercise, what average people may consider routine exercise, in the management of chronic idiopathic constipation. The study population consisted of eight patients, seven women and a man, with chronic idiopathic constipation. They were studied for six weeks, including two weeks of rest and four weeks of regular exercise. Patients had a submaximal exercise test, before and after the exercise period, to determine their rate of perceived exertion (RPE), the target heart rate, and the intensity of exercise they can perform. In addition to their routine daily activities, they exercised 1 hr a day, five days a week according to their performance at the initial exercise tolerance test. They kept a daily activity log and maintained their normal dietary intake during this period. The patients overall physical activity was assessed by a pedometer. They also maintained a diary of the number and consistency of their bowel movements and the amount of straining required for defecation. The impact of exercise on constipation was assessed by utilizing an index that took into consideration all three parameters of bowel function. Results of the study revealed that patients covered 1.8+/-0.33 and 3.24+/-0.28 miles/day in the rest period and during the exercise period, respectively (P = 0.007). The intensity of exercise may have improved the level of training as reflected on the mean maximum time before and after exercise period (P = 0.039). This level of exercise did not improve their constipation indices, which were 9.11+/-0.65 and 8.57+/-1.08 in the rest and exercise periods, respectively (P = 0.68). In conclusion, physical activity, to the extent that people consider "regular exercise," does not play a role in the management of chronic idiopathic constipation.     

Motor sequencing deficits in schizophrenia: A comparison with Parkinson's disease.

Motor abnormalities occur in schizophrenia (SZ) and may arise from striatal dysfunction. This study examined whether the pattern of performance on simple and complex motor abilities in SZ was similar to that of patients with Parkinson's disease (PD). Quantitative tests of speeded movement and motor and cognitive sequencing were used to assess 25 SZ, 16 PD, and 84 normal controls (NCs). Sequencing performance was also examined with motor rigidity taken into account. Compared with the NC group, the SZ and PD groups were impaired on measures of motor rigidity and motor sequencing. With rigidity accounted for, the SZ group was significantly more impaired than the PD group on motor sequencing; cognitive and motor processes contributed to the motor deficit. Cognitive sequencing performance predicted motor sequencing performance in PD but not SZ. Although both SZ and PD resulted in significant motor and cognitive sequencing deficits, the pattern and correlates of these deficits differ, suggesting that the affected neural systems underlying motor deficits in SZ are different from those involved in PD. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Parkinson's disease: The psychological aspects of a chronic illness.

In a review of the literature on the psychological and social aspects of Parkinson's disease, it is noted that since the discovery of the underlying neuropathology of parkinsonism, research on its psychological aspects has had a biomedical orientation and has focused almost exclusively on the depression and cognitive impairment observed in a substantial proportion of Parkinson's patients. Present evidence does not permit firm conclusions about the relative contributions of neurological and psychosocial factors to these symptoms. Methodological problems, reliance on indirect evidence, and the paucity of psychosocial data all contribute to the inconclusiveness of the findings. It is argued that a comprehensive understanding of the psychological aspects of Parkinson's disease depends on combining the investigation of how individual patients experience and adapt to their illness with the prevailing biomedical approach to research. (117 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Parkinson's disease: improved function with GM1 ganglioside treatment in a randomized placebo-controlled study

BACKGROUND/OBJECTIVE: Studies in animal models of Parkinson's disease (PD) suggest that GM1 ganglioside treatment can restore neurologic and dopaminergic function. In view of positive preclinical findings and the results of a previous open-label study demonstrating efficacy of GM1 in PD patients, this study compared effects of GM1 ganglioside and placebo on motor functions in PD patients. METHODS: Forty-five patients with mild to moderate PD were studied. The primary efficacy measure was change in the Unified Parkinson's Disease Rating Scale (UPDRS) motor score. After three independent baseline assessments, patients received IV infusion of the test drug (1,000 mg GM1 or placebo) and then self-administered either GM1 or placebo twice daily (200 mg/day, subcutaneously) for 16 weeks. Patients were examined during monthly follow-up visits. RESULTS: There was a significant difference between groups in UPDRS motor scores at 16 weeks (p=0.0001). The activities of daily living portion of the UPDRS (off-period assessment) also showed a significant effect in favor of the GM1-treated patients (p=0.04). GM1-treated patients also had significantly greater mean improvements than placebo-treated patients in performance of timed motor tests including tests of arm, hand, and foot movements, and walking. GM1 was well tolerated and no serious adverse events were reported. CONCLUSIONS: This study demonstrates that GM1 ganglioside treatment enhances neurologic function significantly in PD patients. Further study is warranted to evaluate long-term effects of GM1 in PD patients and to elucidate further the mechanisms underlying patient improvements.     

Esophageal manometry: a comparison of findings in younger and older patients

OBJECTIVE: We sought to determine the utility of esophageal manometry in an older patient population. METHODS: Consecutively performed manometry studies (470) were reviewed and two groups were chosen for the study, those > or = 75 yr of age (66 patients) and those < or = 50 years (122 patients). Symptoms, manometric findings (lower esophageal sphincter [LES], esophageal body, upper esophageal sphincter [UES]) and diagnoses were compared between the groups. RESULTS: Dysphagia was more common (60.6% vs 25.4%), and chest pain was less common (17.9 vs 26.2%) in older patients. In the entire group, there were no differences in LES parameters. Older patients with achalasia had lower LES residual pressures after deglutition (2.7 vs 12.0 mm Hg), but had similar resting pressures (31.4 vs 35.2 mm Hg) compared with younger achalasia patients. Duration and amplitude of peristalsis were similar in both groups, whereas peristaltic sequences were more likely to be simultaneous in the older group (15% vs 4%). The UES had a lower resting pressure in the older patients (49.6 vs 77.6 mm Hg) and a higher residual pressure (2.0 vs -2.7 mm Hg). The older patients were less likely to have normal motility (30.3% vs 44.3%) and were more likely to have achalasia (15.2% vs 4.1%) or diffuse esophageal spasm (16.6% vs 5.0%). When only patients with dysphagia were analyzed, achalasia was still more likely in the older group (20.0% vs 12.9%). CONCLUSION: When older patients present with dysphagia, esophageal manometry frequently yields a diagnosis to help explain their symptoms.     

Dynamic anal manometry in the assessment of patients with obstructed defecation

Patients with obstructed defecation show no consistent abnormalities when assessed by standard anorectal physiologic methods. With a recently developed technique for dynamic anal manometry, we studied 13 female patients with obstructed defecation and 20 healthy volunteers. Seven parameters of anal function were measured. There were no differences between the median values for the two groups. Seven patients (54 percent; 95 percent confidence limits, 25-81 percent) had anal compliance below the normal range, either during opening or closing of the sphincter at rest (five patients), during squeeze (one patient), or both (one patient). Opening and closing pressures of the sphincter at rest, maximal closing pressure during squeeze, and anal hysteresis were normal. Standard anal manometry did not show any differences between patients and controls. Rectal compliance was lower in patients with obstructed defecation, median difference 5 ml/cm H2O (95 percent confidence limits, 1-9 ml/cm H2O). In conclusion, the more detailed method of dynamic anal manometry shows that some patients with obstructed defecation have a less compliant anal sphincter and a less compliant rectum, but in many patients no abnormal findings can be made.     

Dietary and nutritional abnormalities in alcoholic liver disease: a comparison with chronic alcoholics without liver disease

OBJECTIVE: To document the profile and role of malnutrition in alcoholic hepatitis, compared with chronic alcoholics and nonalcoholic chronic liver disease. METHODS: To this end, we studied 67 patients with alcoholic liver disease (ALD) (group I), 52 chronic alcoholics without histological evidence of liver disease (group II), 44 nonalcoholic cirrhotics (group III), and 52 healthy controls (group IV). Alcoholic and nonalcoholic calories were calculated and percentage dietary and nutritional deficiencies computed. Anthropometric indices, nitrogen balance, and immune status of the patients were assessed. RESULTS: Alcohol constituted about 48% of daily caloric intake in patients with ALD. The percentage mean intake of carbohydrate, protein, and energy was decreased in all three study groups compared with controls. The deficiencies were more pronounced in patients with severe than with moderate ALD. These deficiencies were more severe in the group III patients. Whereas body fat stores were maintained in groups I and II, reduction in lean body mass and serum transferrin was significant in patients in groups I and III. In group II patients compared to group I patients, the body mass index (19.9 +/- 4.0 vs. 22.3 +/- 3.4) and triceps skinfold thickness (6.1 +/- 4.8 vs. 10.2 +/- 5.6 mm) were significantly lower. CONCLUSIONS: 1) protein energy malnutrition is common in both alcoholic and nonalcoholic cirrhotics, but is more pronounced in the latter; 2) the degree and profile of malnutrition in chronic alcoholics and in alcoholic cirrhotics are comparable; 3) based on our results, we hypothesize that malnutrition may not play a primary role in the pathogenesis of ALD.     

Palliative care in chronic obstructive airways disease: a needs assessment

The oral administration of mofezolac, [3,4-di(4-methoxyphenyl)-5-isoxazolyl]acetic acid, resulted in the suppression of writhing induced by the intraperitoneal injection of phenyl-p-benzoquinone (phenylquinone, PQ) in mice. The analgesic activity of mofezolac was almost as potent as that of indomethacin, and more potent than that of sodium diclofenac, zaltoprofen, NS-398, and etodolac when their 50% effective doses were compared. The in vitro inhibitory activity of mofezolac against ovine cyclooxygenase (COX)-1 was also more potent than that of any other non-steroidal anti-inflammatory drugs (NSAIDs) tested, whereas the activity of mofezolac against COX-2 was relatively weak. A Western analysis revealed COX-1 to be constitutively expressed, whereas COX-2 was hardly expressed until 30 min after the PQ-injection in the peritoneal cells. Because the writhing terminated within 30 min after PQ-injection, the prostaglandins involved in the induction of writhing seem to be derived from COX-1. These data thus indicate that potent analgesic activity of mofezolac against the present model to be more closely related to its potent inhibitory activity against COX-1 but not against COX-2.     

The effect of cisapride on delayed colonic transit time in patients with idiopathic Parkinson's disease

Disorders of autonomic regulation are common in patients with Parkinson's disease (PD). Patients most frequently complain of dysphagia and therapy resistant constipation, as far as the gastrointestinal tract is concerned. These symptoms have to be attributed to a neuronal degeneration. In a pilot study we therefore investigated the effect of stimulation of the myenteric plexus by cisapride. 11 women and 13 men were examined, the average age was 67.3 years, the Webster rating 17 points. In 2 out of 24 patients, colonic transit was prolonged up to the limit, both with and without therapy. The other 22 patients showed an acceleration in transit on response to cisapride. On average the colonic transit of 130 hours was reduced to 79 hours. This objective improvement was associated with a subjective improvement. Central side effects or a worsening of Parkinsonian symptoms were not found. We conclude that cisapride is effective in the treatment of constipation in idiopathic PD.     

Intact colonic motor response to sudden awakening from sleep in patients with chronic idiopathic (slow-transit) constipation

PURPOSE: There are few data about the relationships between colonic motor behavior and higher brain functions, such as sleep. Previous studies were done in healthy subjects, and it is unknown whether patients with functional motor disorders of the colon behave differently. This study was designed to characterize colonic motor activity in patients with constipation, both during sleep and after sudden awakening, and to compare it with that of healthy subjects. Our working hypothesis was that patients with constipation would have an impaired response to sudden awakening. PATIENTS AND METHODS: Twelve chronically constipated women, 22 to 49 years old, were recruited for the study, and their data were compared with those obtained from 12 healthy female volunteers, 21 to 38 years old. Manometric studies were performed in the descending and sigmoid colon for 30 minutes during sleep (immediately before awakening) and 30 minutes after being awakened suddenly. A motility index was calculated before and after the stimulus. RESULTS: In both groups motility in the descending and the sigmoid colon was almost absent during sleep and significantly increased after sudden awakening. No difference in postawakening values was found between patients with constipation and controls. CONCLUSIONS: In patients with chronic constipation, the brain-gut control of some fundamental mechanisms governing colonic motility is preserved. These data suggest that the alterations of colonic motility described in chronic constipation may be caused by an intrinsic dysfunction of the viscus.     

Benzodiazepine receptors in chronic cerebrovascular disease: comparison with blood flow and metabolism

The brain benzodiazepine (BZD) receptor distribution in patients with chronic cerebrovascular disease was assessed with 123I-iomazenil (IMZ) SPECT, and the findings were compared with the data for the cerebral blood flow (CBF) and cerebral metabolism. METHODS: We examined nine patients with chronic cerebrovascular diseases, six patients with cerebral infarction and three with moyamoya disease. Iodine-123-IMZ SPECT images were obtained for 15 min, 3 hr after the administration of 167 or 222 MBq 123I-IMZ. In seven patients, the CBF and oxygen metabolism were measured by the 50 steady-state method. In two patients, the CBF and glucose metabolism were measured by 99mTc-HMPAO SPECT and 18F-fluoro-2-deoxy-D-glucose-PET, respectively. The brain was initially classified into 18 regions, and abnormalities in the BZD receptor distribution, CBF and cerebral metabolism were visually evaluated. The count ratio of lesion-to-contralateral normal region (L-to-C ratio) was then used for comparison. RESULTS: In the core of the infarct, the 123I-IMZ uptake decreased (L-to-C ratios of the blood flow 0.42 +/- 0.26; metabolism 0.45 +/- 0.24; and 123I-IMZ uptake 0.46 +/- 0.14). In the peri-infarct region, the 123I-IMZ uptake slightly decreased (L-to-C ratios of 0.81, 0.82 and 0.89, respectively). In the region of misery perfusion, the 123I-IMZ uptake was preserved (L-to-C ratios of 0.73, 1.07 and 1.02, respectively). In the remote deafferentiated areas in the ipsilateral cerebrum, the 123I-IMZ uptake was preserved (L-to-C ratios of 0.76 +/- 0.10, 0.75 +/- 0.04 and 0.98 +/- 0.05, respectively). In the remote areas in the contralateral cerebellum, the 123I-IMZ uptake was preserved (L-to-C ratios of 0.84 +/- 0.08, 0.85 +/- 0.04 and 0.94 +/- 0.05, respectively). CONCLUSION: The BZD receptor distribution, as measured by 123I-IMZ SPECT, is not considered to reflect neuronal function, but it may reflect neuronal cell viability. Iodine-123-IMZ SPECT may, therefore, hold promise as a potential probe for neuronal damage.     

A comparison of transesophageal and transthoracic echocardiographic assessment of left ventricular function in pediatric patients with congenital heart disease

OBJECTIVE: To determine the quantitative utility of transesophageal echocardiographic assessments of left ventricular function in pediatric patients with congenital heart disease by evaluating the variability between observers and between echocardiographic windows. DESIGN: Retrospective, blinded analysis. SETTING: University-associated pediatric hospital. PARTICIPANTS: Transthoracic and transesophageal echocardiographic images of 25 pediatric patients with congenital heart disease were reviewed. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: End-diastolic area, end-systolic area, and fractional area change were measured from short-axis images of the left ventricle at the midpapillary level by two separate investigators. These measurements were compared by the method of Bland and Altman and Sheiner and Beal. Significant differences in measurements of end-diastolic and end-systolic area by different observers were noted, but they were systematic. A similar situation was noted for the comparison of transthoracic and transesophageal measurements of end-diastolic and end-systolic area. In the comparison of fractional area change between observers or windows, bias and absolute prediction error were lower, with 95% confidence limits of bias or absolute prediction error of 10% or less. CONCLUSIONS: The potential error in the measurement of fractional area change in 10% under optimal conditions. This would suggest that the assessment of ventricular function in the operating room or intensive care unit, under less than optimal conditions, should be viewed as a qualitative, rather quantitative, measurement. There may be significant interobserver and interwindow variability.     

Autonomic nervous function in progressive supranuclear palsy--comparison with Parkinson's disease and healthy controls

This study evaluated the autonomic nervous function in 6 patients with progressive supranuclear palsy (PSP). The autonomic nervous functions in PSP patients were compared with those in 17 patients of Parkinson's disease (PD) and 9 age-matched healthy control subjects. Results were that all PSP patients and 59% of PD patients had sympathetic skin response (SSR) abnormalities. Significant abnormalities in cardiovascular response observed in PD patients suggested the presence of sympathetic and parasympathetic disturbances. There were no significant differences between PSP patients and control subjects in cardiovascular responses. But some of PSP patients showed abnormal cardiovascular responses compared with the results from the control subjects. In PSP patients mild disturbances in cardiovascular responses and sudomotor dysfunction were suggested. We consider that the high incidence of SSR abnormality is at least partially related to the presence of disturbances in the frontal lobes.     

Parkinson's disease in populations of African origin: a review

Several studies have reported a lower prevalence of Parkinson's disease (PD) in populations of African origin than in populations of European origin, raising the possibility that the former are protected against PD. However, the confounding effects of low case ascertainment and high selective mortality on PD prevalence estimates in populations of African origin cannot be ruled out at this time. One hypothesis consistent with available data is that populations of African origin are vulnerable to vascular parkinsonism, which is associated with high mortality.     

A histopathological study of alcoholics with chronic HCV infection: comparison with chronic hepatitis C and alcoholic liver disease

To clarify the relationship between hepatitis C virus infection and excessive alcohol intake, we carried out histological examination of the liver in 46 alcoholics with chronic hepatitis C virus infection and compared the findings in 55 patients with chronic hepatitis C, 38 with alcoholic liver disease, and 27 with chronic hepatitis B. The majority of alcoholics with chronic hepatitis C virus infection displayed virus-related histological changes very similar to those in chronic hepatitis C, including frequent lymphoid follicles (34.7%) or aggregates (93.3%) in the portal tracts, mild necroinflammatory change (76.1%) in the parenchyma, and lymphocytosis in sinusoids (83.7%). Liver cell dysplasia and irregular regenerative activity of hepatocytes were rarely observed. The effects of alcohol on the liver were found to be minimal in the majority. These findings could suggest that the hepatic injury in the majority of alcoholics with chronic hepatitis C virus infection in Japan is due to persistent hepatitis C virus infection rather than to alcoholic injury. In addition, our study disclosed that the perivenular fibrosis which is designated as a histological characteristic of alcoholic liver disease is frequently observed in chronic hepatitis C. These similarities suggest that a similar fibrogenesis is present in chronic hepatitis C and alcoholic liver disease.     

Misoprostol in the treatment of chronic refractory constipation: results of a long-term open label trial

BACKGROUND: Misoprostol is known to be effective in stimulating intestinal transit both in healthy individuals and in patients with chronic constipation when evaluated in short-term trials. The aim of this study was to determine the utility of misoprostol in the long-term management of patients with chronic refractory constipation. METHODS: Eighteen patients were offered misoprostol (600-2400 microg/day) as adjunctive therapy in an open-ended, non-blinded trial. All patients were encouraged to continue the drug for a minimum of 4 weeks, after which time the effect on bowel movement patterns was evaluated and continued use of misoprostol was offered to those patients who demonstrated a clinical benefit. RESULTS: Six patients withdrew prior to 4 weeks because of side-effects. In the 12 patients who continued the treatment and were evaluated at 4 weeks, the mean interval between bowel movement frequency had decreased from a baseline of 11.25 to 4.8 days (P = 0.0004). Eight patients continued the long-term treatment, with sustained response seen in six. In a subset of patients (n = 4) the effect of single-dose misoprostol (400 microg) was evaluated compared to healthy controls (n = 5) on post-prandial segmental colonic motility. Misoprostol augmented the colonic motility response to a meal throughout the colon, and this was significantly greater in the left versus right colonic segments (P < 0.05). CONCLUSIONS: Misoprostol can be effective as part of the long-term medical treatment of patients with chronic refractory constipation, but side-effects are observed at higher doses and can be a limiting factor. Part of misoprostol's action may be mediated through the augmentation of colonic motility, particularly of the left colon.