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Biomedical subjects

M Roth

Publications and source records attributed to M Roth.

592 records · Page 33Linked to original sources
PubMedDate not supplied

Validation of the full and short forms of the CAMDEX interview for diagnosing dementia: evidence from a one-year follow-up study.

The sensitivity and specificity of the two forms of the CAMDEX interview for dementia diagnosis were assessed in a 1-year follow-up study. At the beginning of the study, 60 patients (22 males and 38 females) who met DSM-IV criteria for dementia and 60 matched controls (15 males and 45 females), were administered the short form of the CAMDEX (short CAMDEX) 3 months after the full one (full CAMDEX). At the follow-up, all patients were administered both the full and short CAMDEX (again with a 3-month interval), whereas controls were administered either CAMDEX form (in any case, at a 12-month interval from initial testing). Upon initial testing, the sensitivity of the full CAMCOG proved to be significantly higher than that of the short CAMCOG, while the opposite trend was observed for specificity, that is the sensitivity of the full Organicity was lower than that of the short Organicity, with specificity remaining equal in the two forms. Upon follow-up, the specificity and sensitivity levels of the two forms did not significantly differ for the CAMCOG and Organicity indices. Moreover, in detecting mildly demented patients, the full CAMCOG proved to be more accurate than the short one, while the opposite trend was observed for Organicity. Among the dementia subjects, significant correlations were found between the homologous indices of the two forms for both test sessions. On the whole, the short CAMDEX appears to maintain most of the psychometric properties of the full version and therefore the two CAMDEX forms can be considered to be interchangeable.

Aged↗
PubMedDate not supplied

Presence of the apolipoprotein E type epsilon 4 allele is not associated with neurofibrillary pathology or biochemical changes to tau protein.

Alzheimer's disease (AD) represents a heterogeneous disorder, and several factors have been associated with its development. The presence of the apolipoprotein E type (APOE) epsilon 4 allele has been proposed as a risk factor for AD, but how it influences the development of the characteristic hallmarks of the disease remains unknown. In the present study, the neuropathological changes and levels of both core PHF-tau and normal tau protein in 4 neocortical areas, cerebellum and medial temporal cortex were determined in 18 AD cases. The extent of these changes was compared between 10 cases possessing an epsilon 4 allele and 8 cases without. These two groups were indistinguishable in terms of neurofibrillary pathology, whereas cases with an epsilon 4 allele had more diffuse plaques, particularly in the temporal neocortex. Biochemically, there was no difference in the levels of PHF-tau protein between the two groups. These data indicate that APOE epsilon 4 allele may influence deposition of diffuse amyloid, but altered tau protein processing, which underlies the development of the neurofibrillary pathology in AD, is not influenced by this allele.

Aged↗
PubMedDate not supplied

Senile dementia of Lewy body type and Alzheimer type are biochemically distinct in terms of paired helical filaments and hyperphosphorylated tau protein.

We have used biochemical assays to examine cingulate and occipital cortices from age-matched cases of Alzheimer's disease (AD; n = 12), senile dementia of the Lewy body type (SDLT; n = 13), Parkinson's disease (PD; 5 non-demented cases and 7 cognitively impaired cases) and controls (n = 11) for paired helical filaments (PHFs), phosphorylated and normal tau protein and beta/A4-protein. Whereas cingulate cortex is characterised by relatively high densities of cortical Lewy bodies in the SDLT cases and lower numbers in PD, these inclusion bodies were absent in the cingulate cortex from AD and control cases. Protease-resistant PHFs and hyperphosphorylated tau protein were found in AD and, at low levels, in a minority of SDLT cases. Qualitatively, both of these preparations were indistinguishable in SDLT from those found in AD but levels of both parameters in SDLT were less than 5% of those in AD. SDLT, PD and control groups did not differ from each other in terms of the quantity of protease-resistant PHFs or the level of hyperphosphorylated tau. Furthermore, PHF accumulation did not distinguish between PD cases with or without dementia. The levels of normal tau protein did not differ between the four groups. beta/A4 protein levels did not distinguish between PD and control groups, between AD and SDLT groups, or between SDLT and control groups for either cingulate or occipital cortices. Thus extensive accumulation of PHFs in either neurofibrillary tangles or dystrophic neurites is not a feature of either SDLT or PD. Our findings provide molecular support for the neuropathological and clinical separation of SDLT as a form of dementia that is distinct from AD.

Aged↗
PubMedDate not supplied

Validation of the full and short forms of the CAMDEX interview for diagnosing dementia. Cambridge Examination for Mental Disorders of the Elderly.

The present study compares the sensitivity and specificity of the short and full forms of the Cambridge Examination for Mental Disorders of the Elderly (CAMDEX) interview in diagnosing dementia. We tested 73 subjects meeting DSM-IIIR criteria for dementia and 61 matched controls. The short version was applied 3 months after the full one to guarantee a relative stability of the tested functions. Referred to an independent clinical rating made at the beginning of the study, the levels of sensitivity and specificity were not significantly different in the two forms and fully comparable with those of the original full English version. Moreover, the scores on analogous sections of the two versions were highly correlated in the demented and control groups. These findings support the hypothesis that the short form of the CAMDEX maintains the psychometric properties of the full one, and consequently can be used in diagnostic routines for a variety of clinical and research purposes.

Dementia↗
PubMedDate not supplied

Alterations in tau protein metabolism during normal aging.

It is unknown whether aging and Alzheimer's disease (AD) are on the same continuum, or whether they are qualitatively distinct. Tau protein has been identified as a major constituent of paired helical filaments (PHFs) and AD is characterised by a major redistribution of the normal tau protein pool into PHFs. Little is known about the changes in tau protein distribution that occur in the course of normal aging. We have examined PHF-bound and normal tau fractions in frontal, temporal, parietal and occipital neocortex, cerebellum, hippocampus and entorhinal cortex in 15 cognitively unimpaired individuals aged 19-88 years at death. Insoluble tau protein in the PHF fraction did not increase with aging in any brain region, despite the appearance of neurofibrillary pathology at low density in the more elderly cases. By contrast, normal tau protein decreased with aging (r = 0.32, p < 0.001), with an average loss of 14% of soluble tau per decade after the age of 20 years. This was unrelated either to neurofibrillary or beta-amyloid pathology. Frontal grey matter and hippocampus were most vulnerable to age-related tau loss, decreasing by as much as 90% in the older subgroup. These findings contrast with those we have previously reported in AD, where the redistribution of tau protein into the PHF-bound fraction was highly correlated with the extent of neurofibrillary pathology, and suggest that the mechanisms of tau loss in aging and AD are distinct. Age-related tau loss may underlie the neuropsychological impairments seen in the non-demented elderly.

Adult↗
PubMedDate not supplied

Functional mapping of the EcoRV DNA methyltransferase by random mutagenesis and screening for catalytically inactive mutants.

M.EcoRV is an alpha-adenine DNA methyltransferase. According to structure predictions, the enzyme consists of a catalytic domain, which has a structure similar to all other DNA-methyltransferases, and a smaller DNA-recognition domain. We have investigated this enzyme by random mutagenesis, using error-prone PCR, followed by selection for catalytically inactive mutants. 20 single mutants were identified that are completely inactive in vivo as His6- and GST-fusion proteins. 13 of them could be overexpressed and purified. All of these mutants are also inactive in vitro. 5 of the mutations are located near the putative binding site for a flipped adenine residue (C192R, D193G, E212G, W231R, N239H). All of these variants bind to DNA, demonstrating the importance of this region of the protein in catalysis. Only the W231R mutant could be purified with high yields. It binds to DNA and AdoMet and, thus, behaves like a bona fide active site mutant. According to the structure prediction Trp231 corresponds to Val121 in M.HhaI, which forms a hydrophobic contact to the flipped target cytosine. 4 of the remaining purified variants are located within a small region of the putative DNA-recognition domain (F115S, F117L, S121P, C122Y). F117L, S121P and C122Y are unable to bind to DNA, suggesting a critical role of this region in DNA binding. Taken together, these results are in good agreement with the structural model of M.EcoRV.

Catalysis↗
PubMedDate not supplied

Cannibalism in a population of the medicinal leech (Hirudo medicinalis L.).

Medicinal leeches (Hirudo medicinalis L.) were maintained in large ponds in a commercial leech farm at Biebertal, Germany. The feeding of hungry adult leeches was performed on representative individuals that were placed on cloth soaked with mammalian blood obtained from a local butchery (pig, Sus scrofa). In a second set of experiments, cane toads (Bufo marinus) were used as host organisms. The leeches rapidly attached to the toads, explored the body and sucked blood. After feeding, the fully engorged leeches were placed into the pond or an aquarium. In this artificial habitat, the satiated leeches were attacked by hungry conspecifics, sucked off and killed. This observation demonstrates that H. medicinalis must be classified as a cannibalistic annelid.

Animals↗
PubMedDate not supplied

Comments on AOAC dry ash method for digestion of mineral-mix feeds.

Phosphorus in feeds or mineral mixes containing monobasic calcium phosphate cannot be determined accurately if the sample is subjected to the dry ash procedure described in AOAC method 7.125-7.128. HCl-insoluble calcium metaphosphates are formed at the high temperature required for ashing.

Animal Feed↗
PubMedDate not supplied

Stimulation of UV-induced DNA excision repair by chemotherapeutic drugs in cancer patients.

We have used a monoclonal antibody specific for UV-induced 6-4 photoproducts in an ELISA assay to determine the kinetics of loss of antigenicity from the DNA of lymphocytes obtained from four groups of people; normal controls and cancer patients who had either received chemotherapy, hormone therapy or no treatment at all. This result was confirmed on a matched pairs analysis of 12 breast cancer patients sampled before and after chemotherapy. We conclude, that chemotherapeutic treatment with alkylating agents modulate the capacity of UV-induced DNA-repair in human lymphocytes in a yet unknown way.

Alkylating Agents↗
PubMedDate not supplied

No evidence for abnormal gallbladder emptying in Crohn's disease.

BACKGROUND/AIMS: An increased risk of gallstone development has been found in patients with Crohn's disease. This has been suggested to be due to abnormal bile acid metabolism. We investigated the possibility that Crohn's disease might alter gallbladder mechanical function and predispose to gallstone formation by incomplete emptying or prolonged contraction time of the gallbladder. MATERIALS AND METHODS: Seventeen patients with Crohn's disease (CD) and 20 healthy controls (CO) of similar age and sex (CD: 7 males, 31 +/- 13 years; 10 females, 30 +/- 9; CO: 10 males, 26 +/- 12; 10 females, 26 +/- 9) were compared. None of the patients or controls had gallstones. Using ultrasonography with computed volume calculation, the gallbladder was assessed in fasting state and every 10 min for 70 minutes after ingestion of a standard fatty meal. RESULTS: Neither maximum volume (CD: 22 +/- 9 ml, CO: 25 +/- 15), residual volume after stimulation (CD: 3 +/- 2 ml, CO: 6 +/- 6 ml), volume decrease in % (CD: 83 +/- 5%, CO: 78 +/- 9%), nor rate constants of emptying (CD: = 0.034/min, CO: = 0.033/min) were different between patients and controls. CONCLUSION: Abnormal gallbladder contractility does not seem to be a major cause of an increased risk of gallstone formation in Crohn's disease.

Adult↗
PubMedDate not supplied

Treatment of active and postactive ileal and colonic Crohn's disease with oral pH-modified-release budesonide. German Budesonide Study Group.

BACKGROUND/AIMS: Budesonide is a glucocorticoid with a high topical anti-inflammatory but low systemic activity due to its rapid hepatic inactivation. The aim of this open, multicenter study was to investigate efficacy and safety of oral pH-modified-release budesonide in patients with active Crohn's disease of the ileum and colon and in maintaining budesonide-induced remission in postactive Crohn's disease. MATERIALS AND METHODS: 81 patients (intention-to-treat) received 3 x 3 mg budesonide/day for 6 weeks, followed by 3 x 2 mg budesonide for another 6 weeks in case of response to initial treatment. Clinical and laboratory parameters were assessed at study entry as well as after 2, 4, 6 and 12 weeks of treatment. RESULTS: On an intention-to-treat basis remission was induced in 54.3% of 81 patients with active Crohn's disease, 71.4% of 35 patients stayed in remission after the acute-phase treatment until the end of the trial. Typical steroid-related side effects were observed during the acute-phase treatment in only 18% of the patients. Duration, severity and extent of disease at study entry played no significant role in the outcome of the trial, but there was a tendency towards better results during the acute-phase treatment in patients with moderate disease activity and affection of the terminal ileum and proximal colon. CONCLUSIONS: Budesonide could be an alternative to conventional steroid treatment in patients with active Crohn's disease.

Administration, Oral↗
PubMedDate not supplied

State health department and university evaluation of North Carolina's Maternal Outreach Worker Program.

INTRODUCTION: The Maternal Outreach Worker (MOW) Program is a social support intervention using lay helpers to provide support, health education, and outreach to Medicaid eligible women at risk for poor pregnancy and parenting outcomes. State Health Department and University collaborators designed a two-pronged evaluation comprised of programwide and interview study components to assess the impact of the program on pregnancy outcomes, health behaviors, and infant health status. METHODS: Programwide evaluation data are based on 1992-1995 N.C. birth files for the original 24 participating counties and include 1,726 MOW participant births and 12,988 comparison births whose records were linked to birth files and met the study criteria. For the interview study 373 MOW participants and 332 comparison women were personally interviewed three times: during pregnancy, one month postpartum, and one year after delivery. RESULTS: Risk factors associated with poor pregnancy and parenting outcomes were greater among MOW participants than comparisons in both the programwide and intensive study components. Caucasian MOW participants had slightly higher rates of adequate prenatal care. African Americans were found to have less adequate prenatal care. Fewer than expected LBW and VLBW births were observed for African-American MOW participants. MOW Program participation did not affect the utilization of health and social services for infants. African Americans, regardless of whether they received MOW services, fared better than Caucasians in terms of having their pregnancy needs fulfilled. CONCLUSIONS: Findings show the need to further explore appropriate measures of maternity support program outcomes and indicate inconsistent program benefit among subpopulations.

Adolescent↗
PubMedDate not supplied

Computer-supported identification and intervention for diabetic patients at risk for amputation.

We used the fully automated medical record system at Kaiser Permanente of Ohio to direct appropriate interventions to diabetic patients at risk for amputation. The computer identified all patients with a diagnosis of diabetes, reminded physicians, at the moment of care, of the need to enter the patient's risk status for amputation, and kept track of patients at medium or high risk for amputation who were due for an evaluation with education in the podiatry department. Two years and four months after activation of this reminder system, the risk level had been determined for 76% of the diabetic population (n = 10,000), and two thirds of those at medium or high risk had received the appropriate intervention. In patients in the medium and high risk groups, the risk ratio for amputation was 17.5.

Amputation, Surgical↗