Neuroleptic sensitivity in Parkinson's disease and parkinsonian dementias

BACKGROUND: Severe sensitivity to neuroleptic agents is a major clinical problem in dementia with Lewy bodies (DLB), but has not been determined in Parkinson's disease (PD) and PD with dementia (PDD). METHOD: Severe neuroleptic sensitivity reactions (NSRs) were evaluated according to an operationalized definition blind to clinical and neuropathologic diagnoses in prospectively studied patients exposed to neuroleptics from 2 centers. The study was conducted from June 1995 to May 2003. RESULTS: Ninety-four patients were included (15 with DLB, 36 with PDD, 26 with PD, 17 with Alzheimer's disease, all diagnosed with various operational criteria). Severe NSR only occurred in patients with Lewy body disease: DLB (8 [53%]), PDD (14 [39%]), and PD (7 [27%]), but did not occur in Alzheimer's disease (p = .006). Severe NSR was not associated with other clinical or demographic features. In DLB, severe NSR was not associated with neuropathologic indices (Consortium to Establish a Registry for Alzheimer's Disease staging, Braak staging, or cortical distribution of Lewy bodies). CONCLUSIONS: An operationalized evaluation of severe NSR blind to diagnosis confirmed the high prevalence in DLB and identified high frequencies in Parkinson's disease and PDD with important implications for clinical practice.     

Chronic mucocutaneous candidiasis and primary hypothyroidism in two families

We describe the clinical and immunological features of two families with chronic mucocutaneous candidiasis (CMC) and primary hypothyroidism. Family A includes three siblings with both candidiasis and hypothyroidism and four individuals with hypothyroidism only. Family B includes four members with candidiasis, of whom one (a male child) also had hypothyroidism. All individuals affected with CMC had suffered from oral candidiasis and onychomycosis since infancy. Facial seborrhoic dermatitis, general folliculitis and scaling blepharitis were main manifestations. Hypothyroidism became evident during childhood. No thyroid antibodies were present in the affected siblings in family A, while the male in family B with hypothyroidism had antibodies against thyroid peroxidase at diagnosis. Immunological evaluation revealed intra-individual variations in serum immunoglobulin levels, lymphocyte subsets and proliferative responses, but there were no consistent abnormalities. Vaccine responses were normal. AIRE gene region microsatellite markers did not segregate with disease nor were autoantibodies typical for autoimmune polyendocrine syndrome type 1 detected in the families. Conclusion: the link between hypothyroidism and chronic mucocutaneous candidiasis remains to be identified.Abbreviations AADC aromatic l -amino acid decarboxylase - APS 1 autoimmune polyendocrine syndrome type 1 - CMC chronic mucocutaneous candidiasis - GAD glutamic acid decarboxylase - MBL mannose-binding lectin - 17OH 17-hydroxylase - 21OH 21-hydroxylase - SCC side-chain cleaving enzyme - TG-Ab anti-thyroglobulin antibodies - TPO-Ab anti-thyroperoxidase antibodies     

Factors affecting increasing radiation dose for mammography in North Carolina from 1997 through 2001: an analysis of Food and Drug Administration annual surveys

RATIONALE AND OBJECTIVES: To determine which factors affected the increase in average glandular dose recorded at the annual US Food and Drug Administration Mammography Quality Standards Act inspections of mammography equipment in North Carolina from 1997 to 2001. MATERIALS AND METHODS: Average glandular dose, HVL, kVp, ambient light, luminance, equipment age, processing speed, and system speed for every mammography unit at all facilities in the state were collected by state inspectors. A mixed-effect model was used to assess the average changes of glandular dose over time and to identify the factors associated with these changes. RESULTS: There was a statistically significant increase in the average glandular dose in North Carolina in 1999, 2000, and 2001 when compared with the baseline year of 1997. Factors that were statistically significantly linked to this effect were changes in kVp, processing speed, and system speed. CONCLUSION: Average glandular dose for mammography has recently increased in North Carolina. This change is likely caused by changes in screen-film products and processing techniques.     

Association analysis of the lymphocyte-specific protein tyrosine kinase (LCK) gene in type 1 diabetes

Prior data associating the expression of lymphocyte-specific protein tyrosine kinase (LCK) with type 1 diabetes, its critical function in lymphocytes, and the linkage of the region to diabetes in the nonobese diabetic (NOD) mouse model make LCK a premier candidate for a susceptibility gene. Resequencing of LCK in 32 individuals detected seven single nucleotide polymorphisms (SNPs) with allele frequencies >3%, including four common SNPs previously reported. These and six other SNPs from dbSNP were genotyped in a two-stage strategy using 2,430 families and were all shown not to be significantly associated with type 1 diabetes. We conclude that a major role for the common LCK polymorphisms in type 1 diabetes is unlikely. However, we cannot rule out the possibility of there being a causal variant outside the exonic, intronic, and untranslated regions studied.     

Analysis of the vitamin D receptor gene sequence variants in type 1 diabetes

Vitamin D is known to modulate the immune system, and its administration has been associated with reduced risk of type 1 diabetes. Vitamin D acts via its receptor (VDR). Four single nucleotide polymorphisms (SNPs) of the VDR gene have been commonly studied, and evidence of association with type 1 diabetes has been reported previously. We sequenced the VDR gene region and developed its SNP map. Here we analyzed association of the 98 VDR SNPs in up to 3,763 type 1 diabetic families. First, we genotyped all 98 SNPs in a minimum of 458 U.K. families with two affected offspring. We further tested eight SNPs, including four SNPs associated with P < 0.05 in the first set and the four commonly studied SNPs, in up to 3,305 additional families from the U.K., Finland, Norway, Romania, and U.S. We only found weak evidence of association (P = 0.02-0.05) of the rs4303288, rs12721366, and rs2544043 SNPs. We then tested these three SNPs in an independent set of 1,587 patients and 1,827 control subjects from the U.K. and found no evidence of association. Overall, our results indicate that common sequence variation in the VDR gene has no major effect in type 1 diabetes in the populations tested.     

Cumulative deprivation and cause specific mortality. A census based study of life course influences over three decades

OBJECTIVE: To examine whether increasing cumulative deprivation has an incremental effect on total as well as cause specific mortality. DESIGN: Census data on housing conditions as indicators of deprivation from 1960, 1970, and 1980 were linked to 1990-98 death registrations. Relative indices of inequalities were computed for housing conditions to measure the cumulative impact of differences in social conditions. PARTICIPANTS: 97 381 (71.1%) 30-49 year old and 70701 (80.0%) 50-69 year old inhabitants of Oslo, Norway, in 1990 with census information on housing conditions and recorded length of education. MAIN RESULTS: Mortality risk was increased when all censuses' housing conditions were summed in both age groups and sex. The cause specific analysis indicated such an effect particularly for coronary heart disease, chronic obstructive lung disease, and smoking related cancers. Violent deaths were essentially associated with housing conditions closer to the time of death in men in both age groups and in young women. CONCLUSIONS: To fully account for socially mediated risk of death, a full life course approach should be adopted. The relative importance of each stage seems to vary by cause of death.     

Pleurodesis in recurrent pleural effusions: a randomized comparison of a classical and a currently popular drug

STUDY OBJECTIVES: Pleurodesis is generally regarded to give the best palliation in recurrent pleural effusion. Talc is now increasingly recommended but in our department quinacrine has been used successfully for many decades with good results and only minor side effects. It was therefore decided to make a prospective randomized clinical study comparing quinacrine (500 mg) with talc (5 g) with regard to efficacy and safety. METHODS: One hundred and ten eligible consecutive patients with recurrent and or malignant effusions, from 1 March 1996 till 31 March 1999 were randomized to chemical pleurodesis with either talc or quinacrine through a chest drainage tube after medical thoracoscopy. Patients were evaluated with chest radiographs at 2 weeks and 2, 4, and 6 months after pleurodesis. RESULTS: Chi-square test showed 84% power to distinguish between the groups and 10% to determine the primary endpoint. Primary success (fluid production < 50ml/24h within the first 6 days) was 96% of 56 patients with talc and 91% of 54 patients with quinacrine, a non-significant difference (P = 0.46). Quinacrine patients needed a repeated treatment in 31% (17 patients) and talc patients in 7% (4 patients) (P < 0.05). Side effects were minor with no significant difference between the substances. CONCLUSIONS: Both substances are effective. Talc treatment had less often to be repeated. This indicates that the recommendation of talc for pleurodesis is well founded. However, quinacrine is a good alternative.     

Levodopa infusion therapy in Parkinson disease: state of the art in 2004

Orally administered levodopa, in combination with a decarboxylase inhibitor, is the gold standard therapy for Parkinson disease (PD). The problems in management of motor fluctuations in the advanced stages of the disorder are due to the close relationship between plasma levodopa levels and availability of dopamine at striatal receptor sites. The fluctuating levodopa concentrations are mainly explained by the fact that levodopa absorption only occurs in the proximal small intestine. The patient's motor function thus depends on gastric emptying, which is erratic and may even be delayed in PD. Oral therapy with sustained-release formulations and COMT inhibitors have not solved the problems satisfactorily. Therefore, infusions of levodopa by intravenous and enteral (duodenal/jejunal) routes of administration have been studied. In this review of the literature on clinically relevant levodopa infusion studies, it is shown that improvements regarding fluctuations in both plasma levodopa levels and motor performance have been repeatedly reported. The results acquired so far suggest that levodopa infusion is a safe and efficacious therapy. Recent drug delivery development and long-term studies have shown that infusion is a clinically feasible alternative to treat advanced PD.     

Pentagon drawing and neuropsychological performance in Dementia with Lewy Bodies, Alzheimer's disease, Parkinson's disease and Parkinson's disease with dementia

OBJECTIVES: Early and accurate diagnosis of Dementia with Lewy Bodies (DLB) to allow the appropriate clinical treatment is a priority, given reports of severe neuroleptic sensitivity and a preferential response to cholinesterase inhibitors in these patients. There have been suggestions that constructional apraxia is prevalent in DLB, and may provide a sensitive marker of the disease. METHODS: This study examined the pentagon drawings of 100 DLB patients, 50 Alzheimer's disease (AD) patients, 81 Parkinson's disease (PD) patients of whom 36 suffered from dementia (PDD). Performance on this task was correlated with cognitive performance on the MMSE and CAMCOG scales. RESULTS: Patients with DLB were found to draw significantly worse pentagons than those with AD or PD, but not those with PDD. Drawing scores were significantly correlated with MMSE scores for the AD and PDD groups but not those with DLB. More detailed analysis of the neuropsychological correlates of constructional performance for patients with AD and DLB, revealed that those with AD showed a broad cognitive basis to their impairment, in DLB drawing was linked only to perception and praxis. CONCLUSIONS: This study has suggests that DLB subjects show an impairment of pentagon copying that is dissociable from more global cognitive impairments, whereas PD patients are relatively unimpaired on pentagon copying and AD and PDD patients show a linkage of their impairment in copying with more global cognitive deficits.