A controlled trial of desmopressin and behavioral therapy for nocturnal enuresis

Erectile dysfunction may have psychological as well as a variety of organic causes. This necessitates in each case a careful medical evaluation. Various commonly used drugs, as well as alcohol and narcotics, may interfere with erection and should, whenever possible, be discontinued before starting treatment. Organic diseases should be identified and, if feasible, specially treated. In the remaining majority of afflicted men, psychological treatment and partner counseling may produce an improvement, but ultimately what is necessary remains an effective and safe medication. The drug, Sildenafil, introduces a new therapeutic principle. During sexual nerve stimulation, nitric oxide (NO) is released from nerves into the cells of the penile erectile bodies. NO activates in turn its "second messenger", the substance cyclic GMP, and the latter induces the vasorelaxation and blood filling of the erectile bodies. Orally administered Sildenafil competitively inhibits phosphodiesterase type 5, which physiologically inactivates cyclic GMP in the erectile bodies. Thus, Sildenafil increases in men with erectile dysfunction the NO-stimulated cyclic GMP concentration and, thereby, improves erection. This new therapy is attractive because 1. Sildenafil is the first pill (for oral use) with established efficacy that benefits most men with insufficient erection; 2. compared with previous therapeutic approaches (such as drug injections in the penis, instillations into the urinary duct, vacuum pumps or even prostheses), Sildenafil is at least as effective, is easy to take and appears well tolerated with no risk of a prolonged erection; 3. remarkably, this medication stimulates erection only during sexual arousal and, thus, has a rather "natural" effect, and 4. side effects (including headache, facial flushing and dyspepsia or epigastric discomfort) were mostly of mild degree and transient, so that only 4% of men interrupted treatment for this reason. Sildenafil does not need to be taken daily, but may be taken, when needed, 1 hour before a planned sexual activity. The new pill has the potential to enliven the boys "wunder horn" with fresh sound.     

S-methylation in Parkinson's disease

We report thiolmethyltransferase (TMT) activity in RBC membrane preparations from patients with Parkinson's disease (PD), normal controls, and patients with symptomatic parkinsonism. Unlike previous reports, our report found no significant decrease in TMT activity in PD patients compared with normal controls. Low S-methylation capacity does not appear to be a risk factor for PD in Japanese patients.     

Dementia in Parkinson's disease

The occurrence of dementia in patients with Parkinson's disease was studied in a Parkinsonian population consisting of all traceable patients residing in a defined area. The prevalence of dementia was found to be 29 per cent in 444 patients studied. The frequency of dementia increased with advancing age and the patients showing signs of clinical arteriosclerosis were more often demented than the patients without arteriosclerosis. There was, however, an evident association between the stage of the disease and the frequency of dementia. The most severely disabled patients displayed dementia more often than the mildly affected, both among the patients with and without arteriosclerosis. The demented patients showed significantly more severe rigidity and hypokinesia when compared with the non-demented. Increasing severity of rigidity and hypolinesia, in particular was found to have a positive correlation with the degree of dementia. The association between dementia and the degree of motor involvement is considered to suggest the role of subcortical structures in the patholophysiology of dementia in Parkinson's disease.     

Genetics of Parkinson's disease

For the past 40 years, research into Parkinson's disease (PD) has been predominantly the province of epidemiologists interested in pursuing the connection between the disease and environmental factors such as viral infection or neurotoxins. Hereditary influences were actually discounted because of a high monozygotic twin discordance rate found in studies that were later shown to be inadequate and inconclusive. There has recently been a resurgence of interest in investigating hereditary factors in PD when it became more and more apparent that a positive family history was a major risk factor for the disease. Meanwhile, it also became increasingly apparent from neuropathological studies that the common, idiopathic form of Parkinson's disease had, in fact, a pathological correlate, i.e., the existence of Lewy bodies, an eosinophilic cytoplasmic inclusion body, distributed diffusely throughout the substantia nigra, hypothalamus, hippocampus, autonomic ganglia and olfactory tracts. Although candidate gene approaches to linkage in PD families have not been rewarding, a genome wide scan mapped PD to 4q21-23 in one large family with PD with diffuse Lewy bodies, where a candidate gene, alpha-synuclein, resides. This gene encodes a presynaptic protein of which a peptide fragment is known to be a constituent of Alzheimer's disease plaques. The identification of a missense mutation in the alpha-synuclein gene in four independent PD families suggests that at least some fraction of familial PD with diffuse Lewy bodies is the result of an abnormal protein that interferes with normal protein degradation leading to the development of inclusions and ultimately neuronal cell death. There may be common pathogenetic mechanisms involved in alpha-synuclein mutations in PD and beta-amyloid and presenilin gene mutations in Alzheimer's disease.     

Sleep benefit in Parkinson's disease

Sleep benefit (SB) In Parkinson's disease (PD) is not well characterized. To determine SB frequency, as well as to characterize and correlate it with other disease variables, we evaluated prospectively a consecutive series of 312 PD patients by means of a structured questionnaire: 55% reported having SB and 35% reported that awakening was their best time of the day. Because of SB, 21% of the entire population were able to skip or delay medication. The mean duration of the phenomenon was 85.4 +/- 67 min. Patients with SB were significantly older (p < 0.0002), had disease longer (p < 0.05), and were often men (chi 2 = 3.5, df 1, p = 0.05). Patients with SB took sleep medication with similar frequency as those without SB. There were no differences in hours of sleep or sleep latency. Sleep problems such as nightmares or somnambulism, but not the number of sleep awakenings, were similar in both groups. In conclusion, SB is a frequent phenomenon, especially in men, elderly patients, and patients with longer disease duration. SB enables the morning L-dopa dose to be postponed in approximately 50% of patients.     

Pharyngo-esophageal dysphagia in Parkinson's disease

The radiologic characteristics of pharyngoesophageal (PE) dysfunction in Parkinson's disease (PD) are not well established, partly because most previous studies have examined only small numbers of patients. We administered a dynamic videofluoroscopic swallowing function study to 71 patients with idiopathic PD. Using the Hoehn and Yahr disease severity scale, patients were subdivided into those with mild/moderate disease, subgroup I (n = 38), and advanced PD disease, subgroup II (n = 33). From pharyngeal ingestion to gastric emptying, bolus transport was normal in only 2 patients. The most common abnormalities occurring during pharyngeal ingestion included impaired motility, vallecular and pyriform sinus stasis, supraglottic and glottic aspiration, and deficient epiglottic positioning and range of motion. Esophageal abnormalities were multiple but most commonly included delayed transport, stasis, bolus redirection, and tertiary contractions. Typical aberrations of lower esophageal sphincter (LES) function included an open or delayed opening of the LES and gastro-esophageal reflux. A pathogenesis linking PE with the pathology of PD is proposed.     

Genetic polymorphisms in Parkinson's disease

The search for genetic polymorphisms relevant to Parkinson's disease etiology and pathogenesis has been motivated by recent thinking emphasizing the potential significance of gene-environment interactions. Especially influential to this research have been the MPTP model of PD induction, hypotheses concerning oxidative stressor reactions, and epidemiological observations of an inverse relation between cigarette smoking and PD risk. This brief review summarizes trends in genetic polymorphism research, with examples provided by investigations of cytochrome P450 enzymes, monoamine oxidase, superoxide dismutase, and mitochondrial genes.     

Memory disturbances in Parkinson's disease

Disturbances in memory belong to the most frequent cognitive impairments in Parkinson patients. This review treats problematical aspects in the clinical diagnosis of these memory disturbances, which are particularly evident in free recall, immediate reproduction, the chronological sequencing of events and the initiation of meaningful strategies. These selective impairments are discussed within a theoretical frame of reference. Finally, considering the time demands and work loading in contemporary psychological practice, recommendations are given for economical and multidimensional routine diagnostic testing.     

A scientific rationale for protective therapy in Parkinson's disease

The desire to introduce neuroprotective therapy for Parkinson's disease has begun to focus attention on pathogenetic mechanisms responsible for cell death. Considerable theory and some evidence have now accumulated to suggest that factors related to oxidative stress, mitochondrial bioenergetic defects, excitatory neurotoxicity, calcium cytotoxicity, and trophic factor deficiencies acting either singularly or in combination may contribute to the development of cell death in Parkinson's disease. A better understanding of the specific pathogenetic mechanism involved in cell degeneration might provide a scientific basis for testing a putative neuroprotective therapy. This chapter reviews the theory and evidence in support of these different mechanisms and possible strategies that might provide neuroprotection and interfere with the natural progression of Parkinson's disease.     

Verb learning in Parkinson's disease.

The relative roles of grammatical processing and memory in the language comprehension difficulties of patients with Parkinson's disease (PD) were evaluated. 20 PD patients who did not have dementia were exposed to a new verb in a naturalistic setting. After 10 min, the semantic and grammatical information that they learned about the new verb was probed. Significant impairments in recalling some aspect of the new verb were seen in 55% of PD patients. Most of these patients demonstrated a language-sensitive deficit in appreciating grammatical information represented in the new verb. A small number of PD patients responded randomly to probes of all information about the new word, which suggests a memory impairment. It is concluded that difficulty in appreciating grammatical information contributes to the language impairments of PD patients. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Movement sequencing disorders in Parkinson's disease

Ten PD patients and ten age-matched normal controls learned a sequence of 3 or 4 different hand movements to a criterion of 5 consecutive correct trials. They also performed a control sequence of 3 or 4 movements which involved the repetition of the same hand posture. Trials to reach criterion, errors, total response time and its components, response time for each movement and inter-response time were examined. There were no group differences in trials to criterion or errors. Total movement time as well as response and inter-response times were significantly longer for the PD patients, however, but only for sequences involving different hand movements not for the repetitive sequences. The relative timing of the responses was also different with the PD patients spending proportionately more time on each response and the controls spending more time between responses. The implications of these findings for understanding the movement sequencing impairments in PD are discussed.     

Patients' experiences of Parkinson's disease

Patients' (n = 101) experiences of Parkinson's disease (PD) were studied through structured interviews. Oblique factor analysis produced three moderately intercorrelated clusters of items reflecting reported severity of motoric, cognitive, and psychological problems, respectively. Scales formed from the factors were correlated with demographic, disease-related, and psychosocial variables. The demographic variables were not significantly correlated with the scales or with any other variables in the set. Hoehn and Yahr staging was significantly related to scores only on the motoric severity scale. Measures of functional capacity, in contrast, were significantly associated with all three scales. Although the addition of the psychosocial variables as a set significantly increased multiple Rs for each of the three scales, the specific patterns of correlation varied from scale to scale. The findings indicate that from the viewpoint of the patient the problems created by PD were not restricted to the motoric domain. Too narrow a focus by clinicians and researchers on medical symptomatology may give insufficient recognition to the multidimensional nature of the patient's experience.