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Biomedical subjects

M Eaton

Publications and source records attributed to M Eaton.

At least 19 recordsLinked to original sources

Dactylitis: implications for clinical practice.

OBJECTIVES: To assess the specificity of dactylitis for the diagnosis of spondyloarthropathy, sarcoidosis, and gout; and to characterize dactylitis specifically associated with gout. METHODS: Dactylitis was prospectively assessed among all individuals presenting to the Arthritis Center of Northeast Ohio from 1986 to 1996. RESULTS: Dactylitis was observed in 12% of individuals with spondyloarthropathy, 17% with sarcoidosis, and 5% with gout, but not in 96 patients with rheumatoid arthritis or in 2,434 patients with osteoarthritis, neck or back pain, or collagen vascular diseases. Among individuals with spondyloarthropathy, dactylitis was present in 22% with psoriatic, 28% with Reiter's syndrome, and only 7% with undifferentiated spondyloarthropathy. Gouty dactylitis was found only in individuals with polyarticular disease. CONCLUSIONS: Dactylitis is a valuable clue in the differential diagnosis of arthritis. Compared with the wider spectrum in children, sausage-shaped digits have only a few known causes in adults: Reiter's syndrome, psoriatic arthritis, sarcoidosis, flexor tendon sheath infections, and gout. In our series, the presence of dactylitis eliminated rheumatoid arthritis from the differential diagnosis.

Adult

Self-reported stress and reproductive health of female lawyers.

We studied the prevalence and relationship of stress and working conditions with adverse reproductive outcomes in a cohort of female US law-school alumnae. A total of 584 female lawyers (74% response), aged 25 to 63, responded to a mailed questionnaire. Job hours per week was a strong predictor of job stress. In a logistic regression analysis, women working > 45 hours/week were five times as likely to report high stress as those working < 35 hours/week. Marriage and length of time on the job showed a small inverse association with stress. Women who worked more than 45 hours/week during their first trimester of pregnancy were more likely to report high stress at work during pregnancy. After being adjusted for confounding factors, weekly job hours during the first trimester of pregnancy showed a strong independent association with spontaneous abortion risk (odds ratio [OR], 3.0; 95% confidence interval [CI], 1.4 to 6.6). Seven or more alcohol drinks/week was also independently associated with spontaneous abortion risk (OR, 4.8; 95% CI, 1.5 to 18.1). Self-reported stress during pregnancy was positively but not statistically significantly associated with spontaneous abortion (OR, 1.4; 95% CI 0.8 to 2.3).

Abortion, Spontaneous

Report of the Northern California Conference for Guidelines on Aid-in-Dying: definitions, differences, convergences, conclusions.

In September 1996, the Stanford University Center for Biomedical Ethics convened a conference entitled "Comprehensive Care of the Terminally Ill: The Northern California Consensus Development Conference for Guidelines on Aid-in-Dying." The regionally based, multidisciplinary conference gathered people from a variety of disciplines and diverse perspectives on physician aid-in-dying. This report documents important points of convergence, disagreement, and uncertainty that emerged from the conference and provides commentary on crucial issues: the definition of terminal illness, ensuring adequate palliative care, psychiatric challenges, coping with family pressures, the doctor-patient relationship, the managed care context, the role of ethics committees, and institutional challenges. Should physician aid-in-dying become a legal practice in California, the report will provide guidance to health care organizations, health professionals, and public policy officials engaged in local or state guideline or policy development.

California

Intraperitoneal cell movement during abdominal carbon dioxide insufflation and laparoscopy. An in vivo model.

PURPOSE: Possible mechanisms of movement of malignant cells within the peritoneal cavity during CO2 insufflation and laparoscopy involve direct transfer via laparoscopic instruments or dispersion of cells by CO2 or water vapor. An in vivo model has been developed to study these mechanisms. METHODS: Laparoscopy was performed on an animal model (domestic white pig). Cells derived from colorectal cancer cell line Lim 1215 were injected to lie free within the peritoneal cavity. A polycarbonate filter system with a 5-micron pore diameter was used to examine CO2 expelled from the peritoneal cavity, during laparoscopy and manipulation of abdominal viscera, for malignant cells. Laparoscopic instruments and laparoscopic ports were washed independently, and fluid was centrifuged and examined for malignant cells. RESULTS: Malignant cells were identified on 1 of 30 filters used to examine exhaust carbon dioxide. Malignant cells also were identified from 2 of 10 washings from laparoscopic ports and from 4 of 10 washings of laparoscopic instruments. CONCLUSIONS: These results suggest that movement of cells throughout the peritoneal cavity during laparoscopy is via contaminated instruments, but local cell movement by dispersion possibly within water vapor from the port may also occur.

Animals

The inhibition of antigen-induced eosinophilia and bronchoconstriction by CDP840, a novel stereo-selective inhibitor of phosphodiesterase type 4.

1. The novel tri-aryl ethane CDP840, is a potent and selective inhibitor of cyclic AMP phosphodiesterase type 4 (PDE 4) extracted from tissues or recombinant PDE 4 isoforms expressed in yeast (IC50S: 4-45 nM). CDP840 is stereo-selective since its S enantiomer (CT 1731) is 10-50 times less active against all forms of PDE 4 tested while both enantiomers are inactive (IC50S: > 100 microM) against PDE types 1, 2, 3 and 5. 2. Oral administration of CDP840 caused a dose-dependent reduction of interleukin-5 (IL-5)-induced pleural eosinophilia in rats (ED50 = 0.03 mg kg-1). The eosinophils in pleural exudates from CDP840-treated animals contained higher levels of eosinophil peroxidase (EPO) than cells from control animals, suggesting a stabilizing effect on eosinophil degranulation. CDP840 was approximately equi-active with the steroid dexamethasone in this model and was 10-100 times more potent than the known PDE 4-selective inhibitors rolipram and RP73401. The activity of CDP840 was not influenced by adrenalectomy, beta-sympathomimetics or beta-sympatholytics. 3. Antigen-induced pulmonary eosinophilia in sensitized guinea-pigs was reduced dose-dependently by CDP840 (0.01-1 mg kg-1, i.p.) and intracellular EPO levels were significantly higher. CDP840 was more potent in these activities than CT1731 or rolipram and comparable in potency to RP73401. 4. Rolipram or CDP840 were less active than dexamethasone in preventing neutrophil accumulation, or exudate formation in carrageenan-induced pleurisy in rats and thus do not exhibit general anti-inflammatory activity. 5. In sensitized guinea-pigs, aerosols of the antigen ovalbumin caused a dose-dependent bronchoconstriction demonstrated by an increase in pulmonary inflation pressure. Administration of CDP840 (0.001-1.0 mg kg-1, i.p.), 1 h before antigen challenge, resulted in dose-dependent reduction in response to antigen. This activity was not due to bronchodilatation since higher doses of CDP840 (3 mg kg-1) did not significantly change the bronchoconstrictor response to histamine. Rolipram was approximately 10 times less active than CDP840 in preventing antigen-induced bronchoconstriction. 6. These results confirm the observations that selective PDE 4 inhibitors reduce antigen-induced bronchoconstriction and pulmonary eosinophilic inflammation. CDP840 is more potent than rolipram in inhibiting native or recombinant PDE 4. Unlike the recently described potent PDE 4 inhibitor RP73401, CDP840 is more active than rolipram in the rat IL-5 model following oral administration. The novel series of tri-aryl ethanes, of which CDP840 is the lead compound, could be the basis of an orally active prophylactic treatment for human asthma.

3',5'-Cyclic-AMP Phosphodiesterases

Clinical Importance of Salmonella Paratyphi A Infection to Enteric Fever in Nepal.

Background: Enteric fever in Nepal is caused by infection with Salmonella typhi or Salmonella paratyphi A. The clinical presentation of these two illnesses has never been compared in a population of travelers and expatriates. If the illnesses are clinically comparable, and if S. paratyphi A infection is sufficiently common, the choice of typhoid vaccine for Nepal may have to take into account the vaccine's efficacy in preventing infection with S. paratyphi A. Methods: NonNepalese patients presenting to the CIWEC Clinic with a history of 3 days of fever or greater were considered eligible for the study. Patients with positive blood or stool cultures for S. typhi or S. paratyphi A were entered into the study (along with three patients who had positive Widal titers only). A questionnaire was administered by a physician to determine signs and symptoms. Treatment with oral chloramphenicol was openly compared to treatment with oral ciprofloxacin. Results: Forty-five cases of enteric fever were diagnosed during the 2 years of the study. Infection with S. typhi accounted for 20 cases, and S. paratyphi A was isolated in 22 cases. The illnesses were clinically indistinguishable. Treatment with chloramphenicol and ciprofloxacin was clinically comparable. Conclusions: Infection with S. paratyphi A accounts for a significant percentage of enteric fever presentations among tourists in Nepal, and the illness is comparable to infection with S. typhi. Therefore, the choice of typhoid vaccine for long-term travelers or expatriates in Nepal should take into account the vaccine's potential ability to also prevent S. paratyphi A infection. The only typhoid vaccine that can currently offer this type of cross protection is the whole-cell killed preparation.

Journal Article

Locally advanced breast cancer: is surgery warranted following chemotherapy?

Various methods of management of locally advanced breast cancer have been proposed, including combinations of chemotherapy, surgery, radiotherapy, immunotherapy and hormone manipulation. This retrospective study evaluated the effectiveness of chemotherapy in the management of locally advanced breast cancer in pre- and perimenopausal women by examining the pathology of the mastectomy specimens. Sixteen women who on initial clinical examination had breast cancers measuring 5 cm or greater underwent chemotherapy prior to surgery. Four women were also treated with radiotherapy prior to surgery. All 16 women underwent mastectomy and axillary clearance. All specimens showed residual tumour in the mastectomy specimen or the regional lymph nodes. Chemotherapy is useful in reducing tumour burden to allow surgical resection, but does not produce centripetal shrinkage of tumour, nor sterilize the breast of cancer. In this small series, the addition of radiotherapy also failed to clear the patient of tumour. Wide surgical excision including the original tumour margins is thus required to achieve locoregional control. Until chemotherapy and radiotherapy regimens can be proved to sterilize the breast of tumour, we caution against the use of any surgery less than total mastectomy if optimal local control is to be achieved for locally advanced breast cancer in pre- and perimenopausal women.

Adult

Crystal and molecular structure of a collagen-like peptide at 1.9 A resolution.

The structure of a protein triple helix has been determined at 1.9 angstrom resolution by x-ray crystallographic studies of a collagen-like peptide containing a single substitution of the consensus sequence. This peptide adopts a triple-helical structure that confirms the basic features determined from fiber diffraction studies on collagen: supercoiling of polyproline II helices and interchain hydrogen bonding that follows the model II of Rich and Crick. In addition, the structure provides new information concerning the nature of this protein fold. Each triple helix is surrounded by a cylinder of hydration, with an extensive hydrogen bonding network between water molecules and peptide acceptor groups. Hydroxyproline residues have a critical role in this water network. The interaxial spacing of triple helices in the crystal is similar to that in collagen fibrils, and the water networks linking adjacent triple helices in the crystal structure are likely to be present in connective tissues. The breaking of the repeating (X-Y-Gly)n pattern by a Gly-->Ala substitution results in a subtle alteration of the conformation, with a local untwisting of the triple helix. At the substitution site, direct interchain hydrogen bonds are replaced with interstitial water bridges between the peptide groups. Similar conformational changes may occur in Gly-->X mutated collagens responsible for the diseases osteogenesis imperfecta, chondrodysplasias, and Ehlers-Danlos syndrome IV.

Alanine

Construction of a Helicobacter pylori genome map and demonstration of diversity at the genome level.

Genomic DNA from 30 strains of Helicobacter pylori was subjected to pulsed-field gel electrophoresis (PFGE) after digestion with NotI and NruI. The genome sizes of the strains ranged from 1.6 to 1.73 Mb, with an average size of 1.67 Mb. By using NotI and NruI, a circular map of H. pylori UA802 (1.7 Mb) which contained three copies of 16S and 23S rRNA genes was constructed. An unusual feature of the H. pylori genome was the separate location of at least two copies of 16S and 23S rRNA genes. Almost all strains had different PFGE patterns after NotI and NruI digestion, suggesting that the H. pylori genome possesses a considerable degree of genetic variability. However, three strains from different sites (the fundus, antrum, and body of the stomach) within the same patient gave identical PFGE patterns. The genomic pattern of individual isolates remained constant during multiple subcultures in vitro. The reason for the genetic diversity observed among H. pylori strains remains to be explained.

Base Sequence

Genome maps of Campylobacter jejuni and Campylobacter coli.

Little information concerning the genome of either Campylobacter jejuni or Campylobacter coli is available. Therefore, we constructed genomic maps of C. jejuni UA580 and C. coli UA417 by using pulsed-field gel electrophoresis. The genome sizes of C. jejuni and C. coli strains are approximately 1.7 Mb, as determined by SalI and SmaI digestion (N. Chang and D. E. Taylor, J. Bacteriol. 172:5211-5217, 1990). The genomes of both species are represented by single circular DNA molecules, and maps were constructed by partial restriction digestion and hybridization of DNA fragments extracted from low-melting-point agarose gels. Homologous DNA probes, encoding the flaAB and 16S rRNA genes, as well as heterologous DNA probes from Escherichia coli, Bacillus subtilis, and Haemophilus influenzae, were used to identify the locations of particular genes. C. jejuni and C. coli contain three copies of the 16S and 23S rRNA genes. However, they are not located together within an operon but show a distinct split in at least two of their three copies. The positions of various housekeeping genes in both C. jejuni UA580 and C. coli UA417 have been determined, and there appears to be some conservation of gene arrangement between the two species.

Bacterial Proteins

An alga-like organism associated with an outbreak of prolonged diarrhea among foreigners in Nepal.

An unidentified organism was found in the stools of 55 immunocompetent patients who presented to the CIWEC Clinic in Kathmandu, Nepal between June and November 1989. The microscopic features of the organism share characteristics of both coccidia and cyanobacteria species. From June 26, 1989 to November 17, 1989, 55 persons were identified as having the organism in at least one stool sample. The illness was characterized by prolonged watery diarrhea, anorexia, fatigue, and weight loss. The mean +/- SD duration of illness was 43 +/- 24 days (range 4-107). Thirty-four patients received a total of 78 courses of antimicrobial treatment (2.3 courses/patient). The mean +/- SD duration of illness in 34 treated patients was 46 +/- 24 days. In 14 untreated patients, the mean +/- SD duration of illness was 35 +/- 23 days. The organism is 8.0-9.0 microns in diameter, floats in Sheather's solution, and stains red with the modified acid-fast stain. Since the agent was closely associated with a prolonged, self-limited diarrheal illness, it could easily have been misdiagnosed as Cryptosporidium. The organism should be looked for in the stools of patients with persistent diarrhea and a history of foreign travel.

Adolescent

The effect of oral and parenteral typhoid vaccination on the rate of infection with Salmonella typhi and Salmonella paratyphi A among foreigners in Nepal.

We studied the incidence of enteric fever among travelers and foreign residents who attended an expatriate clinic in Kathmandu, Nepal, from February 1987 to June 1988. There were 42 cases of enteric fever; 20 were caused by Salmonella typhi and 22 by Salmonella paratyphi A. Among 18 unvaccinated foreigners who had enteric fever, S typhi was isolated from 67%, and S paratyphi A from 33%, a ratio similar to the local Nepalese population. Among 22 vaccinated foreigners, S typhi was isolated from 35%, compared with 65% with S paratyphi A. Nine percent of tourists had received the oral Ty21A typhoid vaccine. However, among seven vaccinated tourists who became infected with S typhi, four (57%) had received the oral vaccine. Typhoid vaccine efficacy for tourists was calculated and showed an overall protective rate of 90% against enteric fever in general, 95% protection against S typhi, and 72% to 75% protection against S paratyphi A. We conclude that typhoid vaccine should be recommended to all travelers to the Indian subcontinent, and since S paratyphi A is the predominant cause of enteric fever among vaccinated travelers, consideration should be given to an effective vaccine against S paratyphi A when that becomes available.

Administration, Oral

The effect of touch on nutritional intake of chronic organic brain syndrome patients.

Inadequate nutrition, a major cause of illness and complications among elderly adults, is of particular import for those who cannot provide for themselves. We evaluated the effect of gentle touch during eating on nutritional intake (NI) of 42 institutionalized chronic organic brain syndrome (COBS) patients. Patients were randomly assigned to experimental or control groups. NI was evaluated for 3 consecutive weeks. During Weeks 1 and 3 all patients were encouraged verbally to eat. In the treatment week experimental group members were touched gently during this verbal encouragement. Repeated measures analyses of variance were used to evaluate the effect of touch on NI. In the first week NI for the groups did not differ. NI was significantly greater in the experimental than in the control group (p less than .01) during the other 2 weeks. Tactile stimulation, a simple intervention, may be an important adjunct to verbal encouragement to improve NI in COBS patients.

Aged

Seven-year follow-up of workers exposed to 1,2-dibromo-3-chloropropane.

A follow-up report was done of workers exposed to 1,2-dibromo-3-chloropropane (DBCP) 7 years after termination of exposure. A 1977 study of male pesticide workers exposed to DBCP in a California agricultural chemical plant identified many who were azoospermic or oligospermic. Sperm concentration and serum follicle-stimulating hormone (FSH) levels in 44 of these workers were reassessed 5 to 8 years after exposure was terminated in 1977. Two of the eight originally azoospermic workers produced sperm during the follow-up, although only one had normal sperm counts. No increase in sperm production could be detected in men who had low sperm counts in 1977, and elevated serum FSH levels did not drop in oligospermic or azoospermic men. These results suggest that permanent destruction of germinal epithelium occurs in most DBCP-sterile persons.

Follicle Stimulating Hormone