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Biomedical subjects

M D Holmes

Publications and source records attributed to M D Holmes.

At least 55 records · Page 3Linked to original sources
PubMed1996

Neuronal activity in human right lateral temporal cortex related to visuospatial memory and perception.

Neuronal activity was recorded extracellularly from 22 neurons in the right lateral temporal cortex of 12 patients undergoing awake craniotomy for surgical treatment of epilepsy during tests of visuospatial function. These included: measures of short-term visuospatial memory; face, complex figure and line matching; labeling of facial emotional expressions; and a language task, object naming. Six neurons demonstrated significant changes during one or more of the three 1.3-s epochs following test presentation. All 6 of these neurons demonstrated inhibition during short-term visuospatial memory entry, or retrieval, or both. Four of the neurons also showed significant changes during one or more matching tasks; 8 of 10 of these changes were excitatory. One neuron also demonstrated excitation with labeling of facial emotional expression and another with naming. These data demonstrate in human right lateral temporal cortex a pattern of inhibition of neuronal activity during short-term visuospatial memory that contrasts with excitation during other functions, particularly figure matching.

Adult↗
PubMed1996

Unilateral focal preponderance of interictal epileptiform discharges as a predictor of seizure origin.

OBJECTIVE: To test the hypothesis that seizure origin may be predicted from scalp-recorded electroencephalographic interictal epileptiform patterns that occur exclusively or preponderantly over a single focal region. PATIENTS AND METHODS: Fifty-nine of 98 patients (>=16 years old) with intractable epilepsy who underwent sphenoidal/scalp electroencephalographic video monitoring were identified as having interictal epileptiform discharges preponderantly (>=75% of all discharges) or exclusively over a single unilateral region (basal-temporal, midposterior temporal, frontopolar, superior frontal, central). Ictal recordings in 48 patients could be interpreted as demonstrating focal origins, and the ictal findings were compared with the interictal findings. Eleven patients had uninterpretable ictal recordings or no seizures during monitoring and were not further considered. RESULTS: All seizures arose from the expected region in 39 of the 48 patients (Fisher's exact test, P<.001). Interictal discharges occurred exclusively over a single region in 23 of the 48 patients, and all seizures arose from the expected region in 22 of the 23 patients (P<.001). Seventeen patients among this group of 23 had exclusively unilateral basal-temporal discharges, and all seizures arose from the expected side, with the exception of one seizure that arose from the opposite side in one patient, with her other seizure arising from the expected side (P<.001). All seizures arose from the expected region in three patients who exhibited all interictal discharges arising from a single superior frontal region, in two patients with discharges only over a single midposterior temporal region, and in one patient with exclusively unilateral frontopolar discharges. CONCLUSIONS: Interictal discharges that demonstrate a consistent unilateral focal preponderance over a single region, regardless of location, generally predict seizure origin. If the discharges are exclusive to a single region, there is a greater than 95% probability that all recorded seizures will originate from the expected region.

Adolescent↗
PubMed1996

Five-year outcome after epilepsy surgery in nonmonitored and monitored surgical candidates.

PURPOSE: We wished to compare outcome 5 years after temporal lobectomy in 28 patients selected for surgery on the basis of interictal EEG patterns with that in 46 patients who underwent EEG-video monitoring studies as part of their preoperative evaluation during the same era. METHODS: The 28 nonmonitored patients had interictal EEG patterns that demonstrated a consistent, unilateral, anterior-midtemporal epileptiform focus, without discordant findings from other studies. Outcomes were assessed for years 4 and 5 after operation. RESULTS: Twenty-six of 28 (92.9%) nonmonitored patients were seizure-free or had at least 75% reduction in seizures. Twenty-nine of 46 (63.0%) monitored patients were seizure-free or had at least 75% reduction in seizures. Preoperative interictal EEGs of 29 of these patients showed independently localized bitemporal, extratemporal, midposterior temporal, or diffuse epileptiform patterns. The remaining 17 monitored patients had preoperative strictly unilateral anterior-midtemporal interictal discharges, and their outcome was comparable to the nonmonitored group, with 15 (88.8%) seizure-free or with at least 75% reduction in seizures. CONCLUSIONS: A proportion of candidates for epilepsy surgery can be selected without ictal recordings provided that interictal EEGs demonstrate consistent unilateral anterior-midtemporal epileptiform discharges and that other data are not discordant.

Adolescent↗
PubMed1996

Preferred sources of AIDS information, risk perceptions, and risk behaviors among inner-city community college students.

To understand preferred sources of acquired immunodeficiency syndrome (AIDS) information and level of worry about human immunodeficiency virus (HIV) among community college students, a survey of 102 students in an inner-city community college was conducted. The survey requested information on preferred sources of information about AIDS, risk behaviors, and level of worry about HIV infection compared with other life risks. Forty-six per cent of respondents had engaged in risk behaviors for AIDS. Of those who were sexually active, 81% acknowledged not always using a condom. Students noted that they were more likely to believe AIDS information from a health professional than from a friend, relative, teacher, clergy, or celebrity. Overall, getting AIDS ranked third on a list of life worries, ranking only behind getting bad grades and the death of a family member. For students who identified themselves as black or Latino, however, getting AIDS ranked first on a list of life risks. For those students who reported highrisk behavior for getting HIV, getting AIDS also ranked first on a list of life worries. We conclude that those students at whom messages about risk status have been targeted are most likely to report being more worried about getting AIDS than about other adverse life events. It remains unclear, however, whether heightened levels of worry about HIV actually translate into changes in risk behavior.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Mortality rates among 15- to 44-year-old women in Boston: looking beyond reproductive status.

Mortality rates were examined for Boston women, aged 15 to 44, from 1980 to 1989. There were 1234 deaths, with a rate of 787.8/100,000 for the decade. Leading causes were cancer, accidents, heart disease, homicide, suicide, and chronic liver disease. After age adjustment, African-American women in this age group were 2.3 times more likely to die than White women. Deaths at least partly attributable to smoking and alcohol amounted to 29.8% and 31.9%, respectively. Mortality was found to be related more directly to the general well-being of young women than to their reproductive status, and many deaths were preventable. African-American/White disparities were most likely linked to social factors. These findings suggest that health needs of reproductive-age women transcend reproductive health and require comprehensive interventions.

Adolescent↗
PubMed1994

Peripheral intravenous line survival and phlebitis prevention in patients receiving intravenous antibiotics: heparin/hydrocortisone versus in-line filters.

OBJECTIVE: To compare the use of in-line filtration with the addition of heparin/hydrocortisone (hep/hc) to the infusate for both phlebitis prevention and intravenous (i.v.) line survival in peripheral i.v. catheters. This study was specific for a patient group receiving prolonged courses of i.v. antibiotics. Analysis of the two endpoints for conventional short i.v. catheters (short lines) versus long (30 cm) i.v. catheters (long lines) was also performed. METHODS: Patients with cystic fibrosis receiving intermittent i.v. antibiotics were randomly allocated to receive their drugs either through an in-line filter using a drug-free infusate or with no filter and an infusate containing heparin 500 units and hydrocortisone 10 mg/L. Infusion sites were assessed daily. RESULTS: Both the hep/hc and filter groups were similar in terms of phlebitis incidence and i.v. line survival when analyzed separately for both short and long lines. Long lines displayed markedly prolonged survival times and reduced phlebitis compared with short lines. CONCLUSIONS: The effectiveness of i.v. filters in excluding the large particle load introduced by i.v. antibiotics and hence in reducing the subsequent phlebitis makes them a useful alternative to the use of hep/hc. The use of filters in this patient group may offer advantages in terms of ease of use and a possible decrease in hep/hc-related problems. Long lines offer practical advantages over short lines for patients requiring longer term i.v. access.

Anti-Bacterial Agents↗
PubMed1993

Cochlear implants.

Explore the source record for details and available documents.

Child, Preschool↗
PubMed1993

Chlamydial cervical infection in jailed women.

OBJECTIVES: The prevalence of Chlamydia trachomatis cervical infection in incarcerated adult women has not been reported. To develop a policy for testing and treatment, we determined the prevalence of and risk factors for chlamydial infection in women in a New York City jail. METHODS: Interviews and cervical cultures for C trachomatis were obtained from 101 consenting female inmates. RESULTS: Positive cultures for C trachomatis were found in 27% of the participants. Mucopurulent cervical discharge and education of 8 years or less were two independent risk factors for infection, but only 63% of the infected women had one or both of these factors. If pelvic tenderness were considered as a third factor, an additional 7% of the infected women would have been identified. CONCLUSIONS: The prevalence of chlamydial infection in this population was as high as that in populations for which presumptive treatment is recommended. Although the optimal policy for detection and treatment of chlamydial infection may vary depending on practical considerations, we suggest that women entering correctional facilities should be screened or offered presumptive therapy for C trachomatis infection.

Adult↗
PubMed1991

Vaginal douching. Who and why?

Despite the long history of vaginal douching and its estimated practice by more than 67 million U.S. women, little is known about who those women are or why they douche. We addressed these questions by studying 618 women from urban gynecology practices. Fifty-nine percent had douched at some time, with the most frequent reason given as hygiene. The solutions used were evenly divided between commercial and home preparations. Three characteristics stood out among the women who douched: lower socioeconomic status, greater risk of sexually transmitted diseases and symptoms suggestive of vaginal infection. These characteristics were most common among women who douched frequently. The results suggest that douching has a strong cultural component but also raise the possibility that douching may be done in response to a perceived infection, possibly one transmitted through sexual contact.

Adolescent↗
PubMed1990

Alpha 1-antitrypsin Wbethesda: molecular basis of an unusual alpha 1-antitrypsin deficiency variant.

Molecular analysis of alpha 1-antitrypsin (alpha 1AT) Wbethesda revealed that it differs from the normal M1 (Ala213) allele by a single base mutation causing an amino acid substitution Ala336 GCT----Thr ACT. Evaluation of alpha 1AT biosynthesis directed by the Wbethesda allele showed that although Wbethesda alpha 1AT mRNA was translated normally in vitro, transfection of the Wbethesda cDNA into COS-I cells was associated with human alpha 1AT secretion of 50% that of cells transfected with a normal alpha 1AT cDNA. The pattern of alpha 1AT biosynthesis was not intracellular accumulation as observed with the common Z alpha 1AT deficiency allele, but reduced intracellular alpha 1AT, suggesting intracellular degradation of the newly synthesized Wbethesda molecule. Together these observations suggest that in heterozygous combination with a Z or Null alpha 1AT allele, the Wbethesda variant causes "alpha 1AT deficiency", thus classifying it as an alpha 1AT "at risk" allele for emphysema.

Alleles↗
PubMed1990

Molecular analysis of the heterogeneity among the P-family of alpha-1-antitrypsin alleles.

The rare P-family of alpha 1-antitrypsin (alpha 1AT) variants is defined by the position of migration of the alpha 1AT protein on isoelectric focusing of serum (IEF) between the common M and S variants. To begin to examine the molecular heterogeneity among the P-type alleles, two unrelated subjects and their families identified by IEF to be carrying a P allele were analyzed. The first, Plowell, is a deficiency allele associated with reduced serum alpha 1AT levels, and the second, Psaint albans, is associated with normal serum levels. DNA sequence analysis of Plowell, the more anodal of the two variants on IEF analysis, showed that if differed from the normal M1(Val213) allele by a single base and amino acid substitution Asp256 GAT----Val GTT. In contrast, Psaint albans, a slightly more cathodally positioned variant on IEF analysis, differed from the coding exons of the normal M1(Val213) allele by two mutations, Asp341 GAC----Asn AAC, and a silent substitution in the same codon as the Plowell variant, Asp256 GAT----Asp GAC. Evaluation of Plowell mRNA transcripts by Northern and cytoblot analyses demonstrated they were of normal size and amount, and Plowell mRNA transcripts could be translated normally in vitro. Retroviral insertion of the Plowell cDNA into the genome of 3T3 fibroblasts demonstrated that it directed the synthesis of alpha 1AT, but at levels 24% that of the Psaint albans cDNA or the normal M1 (Val213) cDNA, with a pattern of biosynthesis consistent with the concept that the Plowell alpha 1AT deficiency state results from intracellular degradation of the newly synthesized Plowell protein.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1990

Characterization of the normal alpha 1-antitrypsin allele Vmunich: a variant associated with a unique protein isoelectric focusing pattern.

alpha 1-Antitrypsin (alpha 1AT), the major serum inhibitor of neutrophil elastase, is a highly polymorphic protein associated with isoelectric focusing (IEF) patterns typical for each variant. alpha 1AT Vmunich, a previously unreported normal alpha 1AT variant, has a unique IEF banding pattern in which the 7 and 8 alpha 1AT protein bands focus with the normal M-type 7 and 8 bands, despite the fact that the major fraction of the Vmunich protein focuses in the "V" region of the IEF gel. To characterize the molecular basis of this variant and its unique IEF pattern, DNA sequence analysis of the coding exons of the Vmunich alpha 1AT gene was carried out using the polymerase chain reaction. The Vmunich allele differed from the common normal M1(Val213) alpha 1AT allele by a single nucleotide substitution of cytosine for adenosine, with the resultant amino acid change Asp2 GAT----Ala GCT. Inheritance of the allele was confirmed by family analysis using allele-specific amplification with the polymerase chain reaction. The Asp2----Ala mutation explains the cathodal position of the Vmunich protein on IEF, as there is a substitution of a negatively charged amino acid by a neutral one.(ABSTRACT TRUNCATED AT 250 WORDS)

Alleles↗
PubMed1989

Characterization of the coding sequence of the normal M4 alpha 1-antitrypsin gene.

The nucleotide sequences of the common normal "M" family of alpha 1-antitrypsin (alpha 1AT) variants are known, including M1(Val213), M1(Ala213), M2 and M3. Less common, but also migrating with the "M" family on isoelectric focusing gels, is the normal M4 allele. Being relatively rare, the M4 allele is usually found in heterozygous combination with another alpha 1AT allele making sequence characterization more difficult. To facilitate analysis of the coding exons of the alpha 1AT M4 allele, a method was developed to combine blood monocyte RNA extraction, reverse transcription of the alpha 1AT mRNA, amplification with the polymerase chain reaction and direct sequencing. This analysis demonstrated that the M4 allele differs from the M1(Val213) allele by a single nucleotide substitution G--greater than A, causing the amino acid substitution Arg101 CGT--greater than His101 CAT. This same mutation is also a part of the M2 gene suggesting that this region of the alpha 1AT gene may be one of increased mutational activity.

Alleles↗
PubMed1989

Molecular basis of the liver and lung disease associated with the alpha 1-antitrypsin deficiency allele Mmalton.

Alpha 1-Antitrypsin (alpha 1AT) deficiency is characterized by reduced serum levels of alpha 1AT and a risk for the development of emphysema and liver disease. However, whereas there is an increased risk for emphysema associated with at least 10 alpha 1AT deficiency and null alleles, the hepatic disease is observed only in a subset of these alleles, suggesting that it is not the reduced serum levels of alpha 1AT per se which cause the liver disease. The present study characterizes the alpha 1AT deficiency allele Mmalton, an allele that like the common Z deficiency mutation (Glu342----Lys) is associated with both alpha 1AT deficiency and hepatic disease. Capitalizing on the identification of the homozygous inheritance of the rare Mmalton alpha 1AT deficiency allele, it was demonstrated that although caused by a very different mutation, the Mmalton allele shares with the Z allele the association of liver disease with the same type of abnormalities of alpha 1AT biosynthesis. Cloning of the Mmalton gene and sequence analysis demonstrated that it differs from the normal alpha 1AT M2 allele by deletion of the entire codon (TTC) for residue Phe52. Liver biopsy of the Mmalton homozygote revealed inflammation, mild fibrosis, and intrahepatocyte accumulation of alpha 1AT. Evaluation of de novo alpha 1AT biosynthesis in alpha 1AT-synthesizing cells of this individual demonstrated normal levels of alpha 1AT mRNA transcripts but abnormal intracellular accumulation of newly synthesized alpha 1AT at the level of the rough endoplasmic reticulum with consequent reduced alpha 1AT secretion. Finally, retroviral gene transfer of a normal alpha 1AT cDNA and an alpha 1AT cDNA with the Mmalton Phe52 deletion into murine cells demonstrated that the Mmalton cells reproduced the abnormal accumulation of newly synthesized alpha 1AT, thus directly demonstrating that the deletion mutation is responsible for the intracellular accumulation of the newly synthesized alpha 1AT. Thus, not only is the liver disease associated with alpha 1AT deficiency restricted to a subset of alpha 1AT deficiency alleles, it appears to be restricted to those alleles associated with intracellular accumulation of newly synthesized alpha 1AT, suggesting that it is the abnormal intrahepatocyte alpha 1AT accumulation which incites the liver injury.

Alleles↗
PubMed1989

Carbamazepine and its epoxide: relation of plasma levels to toxicity and seizure control.

We studied the relation of plasma levels of carbamazepine (CBZ) and carbamazepine 10,11 epoxide (CBZ-E), and their ratio to drug toxicity and seizure control in 7 patients with complex partial seizures. CBZ-E/CBZ increased with increasing CBZ levels and was higher when patients were taking phenytoin or valproic acid. There were weak correlations between CBZ, CBZ-E levels, toxicity scores, and seizure control when patients were taking CBZ alone, but not when other drugs were given as well. There were no significant differences in the correlation with toxicity score or seizure frequency between CBZ, CBZ-E, or their sum. Measurement of CBZ-E levels did not provide additional information useful for monitoring clinical response to CBZ therapy.

Carbamazepine↗