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Biomedical subjects

M Davidson

Publications and source records attributed to M Davidson.

At least 181 records · Page 10Linked to original sources

Incidence of invasive cervical cancer preceded by negative screening in high-risk Alaska Native women.

BACKGROUND: Alaska Native women experience higher invasive cervical cancer incidence and mortality rates than US whites despite a long-standing cancer screening programme including recommendations for annual Pap smears. METHODS: To determine the frequency and results of cytological screening preceding their diagnoses, a histological and medical record review was completed for 44 of 46 Alaska Native cases of invasive cervical cancer from a defined population. An interval cancer (no prior dysplasia and a negative screening report within 3 years of diagnosis) was determined for 23 women. Mean number of negative reports during the 3- and 5-year intervals before diagnosis was 1.7 and 2.6 respectively. The age-adjusted incidence rate for all cervical cancer was 24.0/100,000 women/year and for interval cancer with single and multiple negative reports during the 3-year interval before diagnosis it was 11.6, and 9.6 respectively. Sensitivity of a Pap smear to demonstrate dysplasia during the year before diagnosis was 51%. CONCLUSIONS: Annual cytological screening of all Alaska Native women with current methods would provide earlier diagnoses for only an additional 15% of cervical cancer cases. Plausible but unproven explanations include rapid progression through precursor stages of neoplasia or random screening errors. Improved or ancillary screening methods appear necessary.

Adolescent↗

The prevalence of cervical infection with human papillomaviruses and cervical dysplasia in Alaska Native women.

Alaska Native women historically have high rates of sexually transmitted diseases (STDs) and invasive cervical cancer. Their prevalence of cervical infections with human papillomavirus (HPV) in relation to cervical dysplasia was determined with a commercial dot hybridization test for seven HPV genotypes. Type-specific HPV DNA, similarly distributed between genotype groups 16/18 and 31/33/35, was detected in 234 cervical specimens (21%) from 1126 Alaska Native women seeking routine care and colposcopy or from population-based lists. The prevalence of HPV DNA declined with age and increased with sexual activity and cigarette smoking. It was unrelated to use of oral contraceptives or condoms or to STDs. Relative risks associating HPV with increasing severe grades of cervical dysplasia increased markedly with HPV infection, up to 7.1 for high-risk genotypes 16/18 and 14.4 for coinfection with 31/33/35. These genotypes were detected in 8% of women without dysplasia seeking routine care. Screening for strain-specific HPV DNA may identify women at highest risk for cervical neoplasia.

Adolescent↗

The epidemiology of invasive pneumococcal disease in Alaska, 1986-1990--ethnic differences and opportunities for prevention.

To assess prevention strategies for pneumococcal disease in Alaska, prospective surveillance during 1986-1990 identified 672 invasive pneumococcal infections, including 315 among Alaska Natives. Age-adjusted annual incidence was 74 per 100,000 for Alaska Natives and 16 per 100,000 for nonnatives. The annual incidence in Alaska Native children < 2 years old was 624 per 100,000; rates of 84 per 100,000 for meningitis and 290 per 100,000 for bacteremic pneumonia were 8-10 times higher than for other US groups. By age 75, cumulative incidence (7%) and mortality (1%) in Alaska Natives were almost 4 times higher than for nonnatives. Only 17% of Alaska Native adults with predisposing conditions and invasive infections previously received pneumococcal vaccine. For Alaska Natives, a proposed heptavalent conjugate pneumococcal vaccine will include serotypes responsible for 85% of invasive isolates from children < 2 years but only 32% of those from adults. The 23-valent polysaccharide pneumococcal vaccine, which contains > 94% of serotypes identified in Alaska Native toddlers and adults, should be used more widely.

Adolescent↗

Serotype distribution and antimicrobial resistance patterns of invasive isolates of Streptococcus pneumoniae: Alaska 1986-1990.

From January 1986 through December 1990, 672 cases of invasive pneumococcal disease were identified. From these, 574 pneumococcal isolates were recovered from normally sterile sites (blood, cerebrospinal and pleural fluid); 92% were serotypes represented in the 23-valent pneumococcal polysaccharide vaccine. The most common serotypes from children < 2 years old were 4, 6B, 9V, 14, 18C, 19F, and 23F, recovered from 83% of Alaska Native and 75.1% of nonnative children with invasive disease. Moderate penicillin resistance (MIC, 0.1-1.0 micrograms/mL) was found in 3.8% of isolates. All were sensitive to chloramphenicol, vancomycin, rifampin, ceftriaxone, cefotaxime, cephalothin, and cefaclor. However, in the Yukon-Kuskokwim Delta region, 16.9% of isolates were moderately resistant to penicillin, and 10.8% were resistant to erythromycin and 6.2% to trimethoprim-sulfamethoxazole; the number resistant to two or more antibiotics increased significantly during surveillance. All multiply resistant isolates were serotype 6B, and all were from Alaska Native patients < 2 years old.

Adolescent↗

Effect of age on the immunogenicity of yeast recombinant hepatitis B vaccines containing surface antigen (S) or PreS2 + S antigens.

A single-blind, multicenter, phase II trial of yeast recombinant hepatitis B virus (HBV) vaccines containing surface antigen (S) alone or with PreS2 (PreS2 + S) was conducted in 282 healthy HBV-seronegative adults aged 20-59 years. Each volunteer was randomly assigned to receive HBV vaccine containing 10 micrograms of S or one of three doses of PreS2 plus S: 2 + 10 micrograms, 4 + 20 micrograms, or 8 + 40 micrograms. The level of antibody to HBV surface antigen reached depended on the dose of S, not PreS2, received. In each vaccine group, volunteers 20-39 years old had higher titers of anti-PreS2 and antibody to S than those 40-59 years old. The age-related effect on immune response to HBV vaccination suggests that adults should be immunized against hepatitis B at as early an age as possible and that older persons may need a higher dose or booster immunizations to achieve durable immunity.

Adult↗

Early response to clozapine in schizophrenia.

Forty schizophrenic patients were treated with clozapine for 5 weeks. Patients were then classified as treatment responders or nonresponders according to a priori established criteria. After only 1 week of treatment, the responders showed a significant decrease on the Brief Psychiatric Rating Scale (BPRS) total score and the psychosis and tension subscale scores. Higher BPRS scores at baseline and larger improvements in BPRS scores after the first week predicted a more favorable outcome in this trial and yielded good classification accuracy.

Clozapine↗

A longitudinal study of Alzheimer's disease: measurement, rate, and predictors of cognitive deterioration.

OBJECTIVE: This study measured the annual rate of cognitive change in patients with Alzheimer's disease and determined the effects of clinical variables on that rate. It also compared the ability of two cognitive scales to measure change over the entire range of dementia severity. METHOD: The cognitive subscale of the Alzheimer's Disease Assessment Scale and the Blessed test for information memory and concentration were given to 111 patients with Alzheimer's disease and 72 nondemented elderly comparison subjects at 6-month intervals for up to 90 months. Longitudinal changes in scores on the cognitive subscale were measured with several different methods of data analysis. RESULTS: For the patients with Alzheimer's disease, the annual rate of change in cognitive subscale scores showed a quadratic relationship with dementia severity in which deterioration was slower for mildly and severely demented patients than for patients with moderate dementia. Gender, age at onset, and family history of dementia had no effect on the rate of cognitive deterioration. The comparison group showed a slight improvement in cognitive performance over time. All data analytic methods gave similar results. The cognitive subscale of the Alzheimer's Disease Assessment Scale was more sensitive to change in both mild and severe dementia than was the Blessed test. CONCLUSIONS: These results suggest that cognitive deterioration is slow during the early and very late stages of Alzheimer's disease and more rapid during the middle stages. No clinical variables other than degree of cognitive impairment and previous rate of cognitive decline predicted rate of deterioration. These results have implications for treatment trials and attempts to identify subgroups.

Adult↗

Characterization of cadherin-4 and cadherin-5 reveals new aspects of cadherins.

Several properties of cadherin-4 and cadherin-5 were characterized by using the cDNA transfection approach. The proteins of both cadherins had a relative molecular mass of about 130 kDa and were present at the cell periphery, especially at cell-cell contact sites. These cadherins were easily digested with trypsin, and Ca2+ protected cadherin-4, but not cadherin-5, from the digestion. In immunoprecipitation, cadherin-4 co-precipitated with two major proteins of 105 kDa and 95 kDa, respectively. The 105 kDa and the 95 kDa proteins are likely to correspond to alpha- and beta-catenins. Cadherin-5 co-precipitated with only one major protein of 95 kDa, but seems to associate with the 105 kDa protein. On the other hand, plakoglobin or gamma-catenin did not co-precipitate well with either cadherin-4 or cadherin-5 in immunoprecipitation, but plakoglobin also appears to associated weakly with these cadherins. Cadherin-4 transfectants aggregated within 30 minutes in a cell aggregation assay, but cadherin-5 transfectants did not aggregate under the same conditions. Furthermore, the transfectants of chimeric cadherin-4 with cadherin-5 cytoplasmic domain showed cell aggregation activity comparable to that of wild-type cadherin-4 transfectants, whereas the transfectants of chimeric cadherin-5 with cadherin-4 cytoplasmic domain did not show appreciable cell aggregation, suggesting that the extracellular domains of cadherins, in conjunction with their cytoplasmic domains, play an important role in cell aggregation activity. These results show that cadherin-4 is very similar to the classical cadherins, whereas cadherin-5 is functionally as well as structurally distinct from classical cadherins.

Animals↗

Emergency nurses' perceived knowledge and comfort levels regarding pediatric patients.

OBJECTIVE: To assess emergency nurses' levels of preparation and education regarding pediatric patients, their levels of knowledge and comfort with specific medical conditions of these patients, and the need they perceive for special policies for pediatric patients. METHODS: Surveys were mailed to nurse managers and emergency nurses in six diverse counties, including Los Angeles and vicinity. Fifty-one nurse managers and 362 emergency nurses from 51 hospitals responded to the questionnaires. RESULTS: More than half of the emergency nurses had 6 or more years of experience; many had certificates, professional designations, and pediatric nursing education. Those with more pediatric education and those designated Pediatric Advanced Life Support, Certified Emergency Nurse, and Mobile Intensive Care Nurse reported the greatest comfort and knowledge with pediatric patients. The greatest discomfort and least knowledge were associated with neonatal emergencies, major trauma, child abuse or sexual abuse, sudden infant death syndrome, envenomation, psychiatric emergencies, meningococcemia, near-drowning, respiratory arrest, and cardiac arrest. Opinions regarding the need for special pediatric policies differed in some cases from current practice. CONCLUSION: Pediatric medical conditions associated with high nurse discomfort and low knowledge point to areas of need for specific education.

Child↗

Polyamine-enhanced NMDA receptor activity: effect of ethanol.

The effect of ethanol on spermidine-enhanced, N-methyl-D-aspartate (NMDA)-induced seizures and c-fos expression was investigated in the rat brain. The latency of tonic-clonic convulsions induced by i.p. administration of NMDA (50 mg/kg) was decreased by prior i.c.v. injection of spermidine (0.1-2.5 mumol) in a dose-dependent manner. Neither NMDA (50 mg/kg) nor spermidine (up to 2.5 mumol) alone induced c-fos mRNA expression in the brain. When both agents were administered, significant induction of c-fos expression occurred 30 min after the convulsion. Prior treatment with ethanol did not alter the curve of spermidine dose-dependency over most of the range. The c-fos expression induced by a combination of NMDA (50 mg/kg) and spermidine (1.0 mumol) was unaffected by ethanol. Only at a high dose of ethanol (2.0 g/kg) and at minimal spermidine enhancement was NMDA-induced seizure and c-fos expression inhibited. These results suggest that polyamines may have an important role in modulating NMDA receptor function in vivo and that polyamine enhancement of NMDA receptor function is relatively insensitive to the inhibitory effects of ethanol.

Animals↗

Selective loss of dopamine D3-type receptor mRNA expression in parietal and motor cortices of patients with chronic schizophrenia.

The expression of dopamine D3-subtype-receptor mRNA was analyzed in defined anatomic regions of brain obtained postmortem from patients with chronic schizophrenia and from controls. The specific amplification of D3-encoding cDNA by PCR allowed the identification of D3 mRNA expression in a wide variety of anatomic regions in both control brains and brains obtained from schizophrenic patients. However, in the parietal cortex (Brodmann areas 1, 2, 3, and 5) and motor cortex (Brodmann area 4), a selective loss of D3 mRNA expression was found in schizophrenia. A different D3 mRNA species was identified that appears to be widely expressed and that is still found in those regions of schizophrenic brains where D3 mRNA could not be detected. Compared with D3 mRNA this RNA is significantly less abundant, and at present its function (if any) is unclear. Many variables associated with either the course and/or the therapeutic management of the disease may account for the selective loss of D3 mRNA in the motor, somatosensory, and somatosensory association areas of schizophrenic brains.

Aged↗

Atypical human T-cell lymphotropic virus type-I-associated T-cell lymphoma in a low-prevalence Alaska Native population. Implications for disease surveillance.

An atypical case of adult T-cell leukemia/lymphoma (ATL) associated with human T-cell lymphotropic virus type I (HTLV-I) occurred in a 46-year-old Inupiat Eskimo man with no behavioral risk factors for HTLV-I infection. The case was characterized by lack of atypical circulating lymphocytes, hypercalcemia, and opportunistic infections; and by complete remission of the initial renal parenchymal lymphoma. The lymphoma cells had a helper T-cell (CD4) immunophenotype. Serum antibodies to HTLV I/II, detected by Western immunoblot, were identified in specimens collected 31 months before the onset of illness, at the time of diagnosis, and up to 37 months later, shortly before the patient's death. Polymerase chain reaction was used to identify HTLV-I DNA in peripheral blood mononuclear cells and in lymphoma in involved skin. Clinicians should be alert to sporadic cases of both atypical and classic ATL, even in populations in which the prevalence of HTLV-I infection is low.

Alaska↗

NADH oxidase activity of rat liver plasma membrane activated by guanine nucleotides.

The activity of a hormone- and growth-factor-stimulated NADH oxidase of the rat liver plasma membrane responds to guanine nucleotides, but in a manner that differs from that of the classic trimeric and low-molecular-mass monomeric G-proteins. In the absence of added bivalent ions, both GTP and GDP as well as guanosine 5'-[gamma-thio]triphosphate (GTP[gamma-S]) but not guanosine 5'[beta-thio]diphosphate (GDP[beta-S]) stimulate the activity over the range 1 microM to 100 microM. Other di- and tri-nucleotides also stimulate, but only at concentrations of 100 microM or higher. Added bivalent ions are not required either for NADH oxidation or guanine nucleotide stimulation. Bivalent ions (Mg2+ > Mn2+ > or = Ca2+) alone stimulate only slightly at low concentrations and then inhibit at high concentrations. The inhibitions are augmented by GDP or GTP [gamma-S] but not by GTP. Although the activity is the same, or less, in the presence of 0.5 mM MgCl2, GTP at 1-100 nM and other nucleotides at 0.1 mM or 1 mM still stimulate in its presence. The NADH oxidase is activated by mastoparan but aluminum fluoride is weakly inhibitory. Cholera and pertussis toxins elicit only marginal responses. Both the Mg2+ and the GDP and GTP[gamma-S] inhibitions (but not the GTP stimulations) shift to higher concentrations when the membrane preparations are first solubilized with Triton X-100. The results suggest a role for guanine nucleotides in the regulation of plasma membrane NADH oxidase, but with properties that differ from those of either trimeric or the low-molecular-mass G proteins thus far described.

Animals↗

Specialist practice for minor oral surgery: a comparative audit of third molar surgery.

Cost efficiency of removing third molars in a practice specialising in minor oral surgery was compared to that of a hospital oral surgery department. A total of 100 patients treated in each locality were prospectively audited during the financial year 1989-90. Surgical complexity, waiting time, complications and patient satisfaction were compared. The hospital cases were costed individually and compared to fees received for the patients treated in the practice. The practice fees were also compared to average expenses as assessed by the Dental Rates Study Group Inland Revenue Enquiry. Patients were treated more promptly and at a lower cost in the specialist practice with no adverse effect on quality as assessed by complications and patient satisfaction. Surgical complexity was not a contraindication to practice treatment but some patients may be better treated in hospital because of medical or social circumstances. Patient charges for treatment carried out under General Dental Service regulations are a serious impediment to the viability of a specialist oral surgery practice.

Adolescent↗

Severe cognitive impairment in elderly schizophrenic patients: a clinicopathological study.

The severe cognitive impairment that affects many of the elderly schizophrenic patients could represent the outcome of schizophrenia in old age for the very severe and chronically ill patients or may be the result of lengthy institutionalization and somatic treatment. Alternatively, it could be due to the presence of concurrent dementing disorders, such as Alzheimer's disease (AD) or multi-infarct dementia. Using an identical neuropathological protocol, brain specimens from schizophrenic patients who showed evidence of severe cognitive impairment were compared with 12 age-matched control cases and the same number of age-matched cases of neuropathologically confirmed patients with AD. Despite their relatively advanced age (mean age 77.1 years +/- 2.8), none of the schizophrenia cases showed sufficient degree of senile plaques and neurofibrillary tangle formations to confirm a diagnosis of AD. Other neurodegenerative disorders associated with dementia were also not identified. These studies suggest that alternative explanations need to be sought for the severe cognitive impairment commonly encountered in elderly schizophrenic patients.

Age Factors↗

Fine mapping of mitochondrial RNAs derived from the mtDNA region containing a point mutation associated with MELAS.

Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) is a mitochondrial disorder associated with heteroplasmic point mutations in the mitochondrial tRNA(Leu)(UUR) gene. While previous studies have shown that the MELAS mutation at nt-3243 results in impairments in mitochondrial protein synthesis and respiratory chain function, it was not clear whether these were associated with structural alterations in mature RNAs derived from transcription of the region containing the mutation. We have performed fine mapping and high-resolution. Northern analysis of RNAs from cybrids derived from two MELAS patients harboring the nt-3243 mutation. No differences in the size or steady-state levels of transcripts from the 16S rRNA, tRNA(Leu)(UUR), or ND 1 genes (which are contiguous in the mtDNA) were observed between cell lines containing mutated or wild-type mtDNAs. Therefore, it is not likely that the protein synthesis defects observed in cybrids with the MELAS-3243 mutation are directly caused by qualitative alterations in either transcription termination or processing of these mitochondrial RNAs.

Base Sequence↗