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Biomedical subjects

M D Holmes

Publications and source records attributed to M D Holmes.

69 records · Page 4Linked to original sources
PubMed1989

Chlamydia trachomatis cervical infection in women seeking routine gynecologic care: criteria for selective testing.

PURPOSE: Chlamydia trachomatis infection is one of the most common sexually transmitted diseases. Developing methods to identify patients who are at higher risk would enable clinicians to perform selective testing for C. trachomatis infection, which may reduce morbidity, sequelae, and overall costs. Risk factors for C. trachomatis infection of the cervix in women seen for routine gynecologic care were therefore analyzed. PATIENTS AND METHODS: Extensive clinical data and cervical cultures were obtained from 1,141 women between the ages of 18 and 50. Multivariate techniques were used to develop and prospectively test a model to predict infection. RESULTS: In the model development series of 530 patients seen in a hospital-based practice, 24 (4.5%) had a positive culture result. In the validation series of 611 patients seen in private practice, 17 (2.8%) had positive culture results. The majority of infected patients (61%) were asymptomatic. For sexually active women 18 to 35 years of age, the optimal predictive model was based on three factors: level of education (high school or less), a sex partner with other partners during the prior three months, and endocervical bleeding induced by the initial swab. In the validation series, the prevalence of infection for women with one or more of these factors was 5.8% (95% confidence interval, 4.0 to 8.6) compared with 0.9% in patients without these factors (p = 0.005). CONCLUSION: Clinical information can be used in a low-prevalence population to predict a patient's risk for C. trachomatis infection and to select patients for testing.

Adolescent↗
PubMed1989

Ribonuclease A cleavage combined with the polymerase chain reaction for detection of the Z mutation of the alpha-1-antitrypsin gene.

Homozygous inheritance of the Z mutation (exon V, Glu342GAG----Lys342AAG), the most common cause of alpha-1-antitrypsin (alpha 1AT) deficiency, is associated with a high risk for emphysema and liver disease. This study presents a rapid and accurate approach to definitive genotypic diagnosis of the Z homozygous state using a combination of polymerase chain reaction amplification of exon V of the alpha 1AT gene and ribonuclease cleavage of an exon V-specific antisense RNA probe. Taking advantage of the concept that ribonuclease A will cleave at points of mismatch of RNA-DNA hybrids, a 0.79 kb antisense RNA probe was designed with complementarity to the sense strand of exon V of the alpha 1AT gene (the site of the Z mutation) along with small regions of the 5' and 3' flanking sequences. After amplification of exon V of the alpha 1AT gene from genomic DNA by the polymerase chain reaction, the amplified DNA was analyzed by hybridization to a 32P-labeled exon V antisense RNA probe followed by digestion with RNase A. Any substitution mutations resulting in DNA-RNA mismatch were detected by evaluation with polyacrylamide gel electrophoresis under denaturing conditions followed by autoradiography (expected fragment lengths: 0.33 kb when the exon V probe hybridized to the normal amplified genomic DNA, 0.25 and 0.08 kb fragments when the exon V probe hybridized to the amplified genomic DNA with the Z mutation). Double-blinded evaluation of genomic DNA of 36 individuals (phenotypes MM n = 14, MZ n = 5, ZZ n = 16, ZNull n = 1; included among the "M" alleles were representatives of all the major normal M alleles) demonstrated definitive diagnosis of the Z mutation with absolute specificity for all 36 specimens, i.e., ZZ homozygotes, MZ heterozygotes, and normals were all detected accurately. This approach should be useful not only for screening for the Z mutation of the alpha 1AT gene, but by this type of analysis, mutational alterations of the alpha 1AT gene can be screened for without prior knowledge of the sequence changes and without complex cloning and sequencing methods.

Alleles↗
PubMed1989

An analytic review of current therapies for obesity.

Weight control is a cornerstone objective for many diseases common in medicine. Substantial, prolonged weight loss is difficult to achieve. Nutrition counseling, very low calorie diets, behavior modification, exercise, intragastric balloon, and gastric restriction surgery are interventions that physicians may recommend for obese patients. This paper analyzes the efficacy of these methods with attention to attrition rates, maximum weight loss, long-term maintenance of weight loss, and morbidity. Strategies for intervention for various classes of obese patients are recommended.

Humans↗
PubMed1989

Rapid, nonradioactive detection of mutations in the human genome by allele-specific amplification.

A simple, rapid, nonradioactive method has been developed to facilitate the direct detection of point mutations that cause genetic disease. The method operates on the basis of the specific amplification of a target allele by the polymerase chain reaction with extension primers designed such that their 3' end is placed at the mutation site. When this base is complementary to that of the specific allele, the DNA segment is amplified; when it is not complementary, the polymerase chain reaction cannot proceed. When alpha 1-antitrypsin (alpha 1AT) deficiency was used as a model, the technique of allele-specific amplification was capable of selective detection of five different mutations that cause the alpha 1AT deficiency state, including three different naturally occurring single-base substitution mutations (alleles Z, S, and Nullbellingham), an insertion mutation (Nullmattawa), and a deletion mutation (Nullgranite falls). Double-blind evaluation of 47 samples of genomic DNA demonstrated 100% accuracy of the method. The technique of allele-specific amplification is rapid, simple, and does not require the existence of a convenient restriction endonuclease site or the use of radioactive materials, and thus should have broad applicability for the detection of known genetic diseases in a highly sensitive and specific fashion.

Alleles↗
PubMed1988

Structure of the human neutrophil elastase gene.

The gene for human neutrophil elastase (NE), a powerful serine protease carried by blood neutrophils and capable of destroying most connective tissue proteins, was cloned from a genomic DNA library of a normal individual. The NE gene consists of 5 exons and 4 introns included in a single copy 4-kilobase segment of chromosome 11 at q14. The coding exons of the NE gene predict a primary translation product of 267 residues including a 29-residue N-terminal precursor peptide and a 20-residue C-terminal precursor peptide. Analysis of the N-terminal peptide sequence suggests it contains a 27-residue "pre" signal peptide followed by a "proN" dipeptide, similar to that of other blood cell lysosomal proteases. The sequences for the mature 218-residue NE protein are included in exons II-V. The 5'-flanking region of the gene includes typical TATA, CAAT, and GC sequences within 61 base pairs (bp) of the cap site. The sequence 1.5 kilobases 5' to exon I contains several interesting repetitive sequences including six tandem repeats of unique 52- or 53-bp sequences. The 5'-flanking region also contains a 19-bp segment with 90% homology to a segment of the 5'-flanking region of the human myeloperoxidase (MPO) gene, a gene also expressed in bone marrow precursor cells and a protein stored in the same neutrophil granules as NE. In addition, like the MPO gene, the NE 5'-flanking region has several regions with greater than or equal to 75% homology to sequences 5' to c-myc, but there is no overlap between the NE-c-myc and MPO-c-myc homologous sequences.

Amino Acid Sequence↗
PubMed1988

Complex partial seizures. Correlation of clinical and metabolic features.

We compared metabolic patterns on 18F-2-deoxyglucose positron emission tomography (PET) with closed circuit television and simultaneous electroencephalographic ictal recordings of complex partial seizures in 48 patients. Closed circuit television and electroencephalographic data and PET scans were scored by "blinded" raters. Of the 48 patients, 26 had unilateral temporal; three, frontal; ten, ipsilateral frontotemporal; one, frontoparietal; and five, temporoparietal hypometabolism; and three had widespread hypometabolism affecting frontal, temporal, and parietal lobes. patients with frontal hypometabolism alone had shorter ictal and postictal durations, but involvement of multiple regions was associated with prolonged seizures. Auras were more likely to be present in patients with temporal hypometabolism alone, but an initial motionless stare did not distinguish this group. However, other metabolic patterns did not predict specific ictal clinical features. Vocalizations (formed or unformed) were not more closely associated with frontal involvement. When hypometabolism is multilobar, it may be difficult to use PET to distinguish between complex partial seizures of frontal and temporal origin.

Brain↗
PubMed1984

Clinical features of meningovascular syphilis.

Meningovascular syphilis presents as a subacute encephalitic syndrome with superimposed cerebrovascular events that may evolve gradually. This picture differs from the more common cases of thrombotic or embolic stroke. Optimal treatment is uncertain, and requires monitoring of spinal fluid abnormalities until they return to normal.

Adult↗
PubMed1981

Endosalpingiosis.

The origin of psammoma bodies in cul-de-sac fluid must always be explained. Multiple, histologically benign, predominantly peritoneal foci of tubal-like epithelium are described in a woman with endometriosis and psammoma bodies in the cul-de-sac fluid. Because no primary ovarian neoplasm was present, the diagnosis of endosalpingiosis was made. The pathogenesis and significance of endosalpingiosis are discussed.

Adult↗
PubMed1979

Enhancement of healing in osteochondral defects by collagen sponge implants.

Implants of porous, highly cross-linked collagen sponge (CS) were tested for their capacity to enhance the healing of osteochondral defects in rabbits. Comparison was made to the healing of similar defects with polyvinyl alcohol sponge (PVAS) implants and with no implants (CONT). Evaluation was carried out up to 44 weeks following implantation and included observation of host cellular response, biodegradability of implant, gross appearance of restored joint surface, collagenous architecture of repair tissue, and properties of the junctions of implants and host articular cartilage, subchondral bone, and medullary bone. Collagen sponge proved most effective in promoting healing of osteochondral defects with fibrous and fibrocartilaginous tissue over restored subchondral bone. Collagen sponge showed many desirable properties as a potential material for biologic resurfacing of damaged joints. These properties included porosity, biodegradability, biocompatability, ability to mechanically protect cells and matrix while directing cell ingrowth, and an available chemical technology for modifying its biomechanical and biological properties. Comparative analysis of results of healing of CS, PVAS, and CONT osteochondral defects suggest rational design criteria for implant materials to improve their effectiveness in restoration of articular surfaces.

Animals↗
PubMedDate not supplied

MR imaging and positron emission tomography of cortical heterotopia.

Heterotopia of the gray matter is a developmental malformation in which ectopic cortex is found in the white matter of the brain. A case of a 33-year-old man with cortical heterotopia who had a lifelong history of seizures and psychomotor retardation is reported, including the results of cerebral CT, magnetic resonance imaging, and positron emission tomography using 18F-2-deoxyglucose.

Adult↗
PubMedDate not supplied

Role of tachykinins in bronchial hyper-responsiveness.

1. Sensory afferent fibres mediate important protective reflexes in the lung. Small, unmyelinated C-fibre nerves have both sensory afferent and effector functions. C-fibres contain a number of neuropeptides, including the tachykinins, which have pro-inflammatory effects in the airways. Following stimulation with capsaicin and other stimuli, neuropeptides are released from the nerve endings, either directly or by axonal reflexes. 2. Important tachykinin effects include smooth muscle contraction, vasodilatation and oedema, mucus secretion and inflammatory cell activation. There are also trophic effects, including proliferation of fibroblasts, smooth muscle and epithelial cells. 3. Tachykinins mediate their effects by binding to G-proteinlinked receptors. Receptor-specific agonists and antagonists are available, which have helped clarify the effects of tachykinins. These agents may have therapeutic potential. 4. Tachykinins are degraded by the enzyme neutral endo-peptidase. 5. Studies in humans in vivo show an increase in airways resistance following challenge with tachykinins. There is some evidence for an increase in tachykinins and their receptors in airway inflammation, but this has not been found in all studies. A reduction in neutral endopeptidase has been seen in some animal models of airway inflammation, but this has not been shown in human disease. 6. Trials of tachykinin receptor antagonists in human asthma have begun, but it is too early to say what their therapeutic impact will be.

Airway Obstruction↗
PubMedDate not supplied

Complex partial seizures: cerebral structure and cerebral function.

We studied the relationships between cerebral structure and function in 10 patients with complex partial seizures who had major cerebral lesions, including porencephalic cysts, tuberose sclerosis, agenesis of the corpus callosum, and cerebral hemiatrophy. Evaluation included computed tomography (CT) and magnetic resonance imaging (MRI) scanning, EEG, and positron emission tomography (PET) using [18F]-2-deoxyglucose. Surface EEG usually showed widespread, bilateral epileptiform discharges even if pathology was clearly restricted to one hemisphere. In several cases, interictal PET hypometabolism was more widespread than structural changes seen on CT and MRI, extending to involve the ipsilateral temporal lobe in patients with extratemporal lesions. This study shows that patterns of metabolic and electrophysiologic dysfunction may not be predicted by structural lesions in patients with partial seizure disorders.

Agenesis of Corpus Callosum↗