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Biomedical subjects

M McCarthy

Publications and source records attributed to M McCarthy.

At least 91 records · Page 5Linked to original sources

Pre-exposure anti-Campylobacter jejuni immunoglobulin a levels associated with reduced risk of Campylobacter diarrhea in adults traveling to Thailand.

Diarrhea history questionnaires were administered to 369 U.S. military volunteers before and after deployment to Thailand. Additionally, blood samples obtained from a subset of 221 volunteers 1-3 weeks previously and 3-4 weeks after their deployment were tested by enzyme-linked immunosorbent assay for immunoglobulin A to Campylobacter jejuni. Stool samples from personnel (including volunteers) contracting diarrhea in Thailand were cultured for enteric pathogens. Overall, 35.2% (130 of 369) of questionnaire respondents reported one or more diarrhea episodes during their trip. Volunteers with pretravel anti-C. jejuni reciprocal titers < or = 450 were 1.6 times as likely to have had diarrhea during their stay in Thailand compared with those with pretravel titers > 450 (39.7% versus 25.3%; P = 0.05). The symptomatic seroconversion, or attributable Campylobacter diarrhea attack rate, for the 1-month exercise was 12.7% (28 of 221). The symptomatic seroconversion rate in nonimmune (titer < or = 450) volunteers was 17.1%, whereas that in immune volunteers was only 4.0% (P = 0.002). Campylobacter jejuni or C. coli were recovered from 32.9% (56 of 170) of stool samples cultured and were the most commonly identified enteropathogens. Campylobacter diarrhea was associated with elevated temperatures, fecal red cells, and fecal white blood cells. The results of this study show that Campylobacter continues to represent a significant health threat to Western travelers to Thailand, but many of these travelers have preexisting Campylobacter immunity that protects them from clinically significant Campylobacter enteritis.

Adult↗

Pharmacological characterization of ZD6021: a novel, orally active antagonist of the tachykinin receptors.

The tachykinins, substance P, neurokinin A, and neurokinin B, have been implicated in many diseases. The present study evaluated the pharmacological properties of a novel tachykinin antagonist ZD6021 [3-cyano-N-((2S)-2-(3,4-dichlorophenyl)-4-[4-[2-(methyl-(S)-sulfinyl)-phenyl]piperidino]butyl)-N-methyl-]-napthamide]. The affinity (K(i)) of ZD6021 for the cloned human neurokinin (NK)1, NK2, and NK3 receptors was 0.12 +/- 0.01, 0.64 +/- 0.08, and 74 +/- 13 nM, respectively. Mucin secretion by Chinese hamster ovary cells transfected with the human NK1 receptor was dose dependently inhibited by ZD6021: pIC(50) = 7.6 +/- 0.1. For NK1 and NK2 receptors, the agonist concentration-response curves using isolated tissues were displaced rightward in the presence of ZD6021: rabbit pulmonary artery, pA2 = 8.7 and 8.5; human pulmonary artery and bronchus, pKB = 8.9 +/- 0.4 and 7.5 +/- 0.2, at 10(-7) M, respectively. Senktide-induced contractions of isolated guinea pig ileum were also blocked by low concentrations of ZD6021. Oral administration of ZD6021 to guinea pigs dose dependently attenuated tracheal extravasation of plasma proteins induced by the NK1 receptor agonist Ac-[Arg6,Sar9,Met(O2)11]-SP(6-11), ED50 = 0.8 micromol/kg, and bronchoconstriction, elicited by the NK2 receptor agonist [beta-Ala8]-NKA(4-10), ED50 = 20 micromol/kg. Potency was unaffected by feeding. After oral administration of ZD6021, the time to peak activity was 150 min for the NK1 receptor and 60 min for the NK2 receptor with pharmacodynamic half-lives of 280 and 458 min, respectively. These data indicate that ZD6021 is a potent, orally active antagonist of all three tachykinin receptors. This compound may be useful for future studies of tachykinin-related pathology such as asthma.

Administration, Oral↗

Surface keratopathy after penetrating keratoplasty.

PURPOSE: To determine the type and prevalence of epithelial abnormalities in the intermediate postoperative period after penetrating keratoplasty and to define the donor and recipient variables that influence the status of the graft epithelium. DESIGN: Prospective cohort study. METHODS: We prospectively followed the clinical course of 80 patients after penetrating keratoplasty. We monitored the status of the corneal epithelium for 3 months after surgery using slit-lamp biomicroscopy and fluorescein staining of the epithelium. Donor characteristics, recipient preoperative and postoperative variables, and postoperative medications were recorded. Epithelial abnormalities were analyzed against these variables by using univariate and combined statistical models to determine the impact of each variable on postoperative epithelial pathology. Main outcome measures included punctate keratopathy, macro-epithelial defects, hurricane keratopathy, rim defects, and filamentary keratopathy. RESULTS: Sixty-three percent of all patient visits demonstrated punctate epithelial keratopathy (PEK). Hurricane keratopathy (51%) and filamentary keratopathy (14%) constituted the next most commonly observed abnormalities. Older recipient age and the use of topical antibiotics were associated with a higher prevalence of punctate epithelial keratopathy. The odds ratio (OR) for a 1-year increase in age is 1.0276 (95% CI, 1.1013-1.0442), and the OR for using topical antibiotics is 6.9028 (95% CI, 3.1506-15.1239). Use of topical ofloxacin and increased time after surgery were associated with lower prevalence of punctate keratopathy; ORs were 0.9806 (95% CI, 0.9736-0.9876) and 0.3662 (95% CI, 0.1688-0.7943), respectively. Decreased corneal sensation and the presence of anterior blepharitis preoperatively were associated with an increase in hurricane keratopathy; ORs were 8.8265 (CI, 2.3837-32.6835) and 3.2815 (CI, 1.7388-6.1931), respectively. Total storage time for the donor material was also associated with an increased prevalence of hurricane keratopathy (OR, 1.0316; CI, 1.0052-1.0220). Patients with rim defects and macro-epithelial defects were more likely to have antibiotic and topical lubrication prescribed. No specific variable was found to have a significant association with filamentary keratopathy, except possibly for death-to-preservation time, which had a P value of .0587. CONCLUSIONS: Surface keratopathy is one of the most common complications of keratoplasty. Our study demonstrates that older age, preoperative lid disease, and decreased preoperative corneal sensation appear to increase the probability of clinically significant epithelial surface abnormalities after keratoplasty. Recognition of these risk factors in advance of surgery will alert the surgeon to the need for appropriate management.

Adolescent↗

University of Arizona, Cardiac Transplantation: changing patterns in selection and outcomes.

Among 391 patients who received heart transplants at the University of Arizona since 1990, the percentage of bridge-to-transplant device patients receiving donor hearts has increased from 6.7% to 50%. Survival after transplantation in this-bridge-to transplant group and has been consistently 10-15% lower than patients who do not require a device. The result has been that our overall survival rate is beginning to fall. We have come to 2 major conclusions based on these results: First, the current UNOS system ranking candidates as Status 1A, 1B, and 2 may not identify those who are at higher risk for transplantation. It has failed to do so in our program. Rather, by grouping the potential recipients into patients with a device, Status 1 nondevice patients, and Status 2 patients, we have found a significantly lower survival rate after transplantation in the device group. This suggests that the problems shared by device patients such as being anticoagulated, having a difficult reoperation at the time of transplantation, and having increased inflammation and decreased immunity clearly place these patients in a very different risk group than other potential recipients. Second, these results lead us to believe that some high-risk device patients may not be suitable for transplantation and might be better if treated with devices as alternatives to transplantation.

Academic Medical Centers↗

Strong Amerind/white sex bias and a possible Sephardic contribution among the founders of a population in northwest Colombia.

Historical and genetic evidences suggest that the recently founded population of Antioquia (Colombia) is potentially useful for the genetic mapping of complex traits. This population was established in the 16th-17th centuries through the admixture of Amerinds, Europeans, and Africans and grew in relative isolation until the late 19th century. To examine the origin of the founders of Antioquia, we typed 11 markers on the nonrecombining portion of the Y chromosome and four markers on mtDNA in a sample of individuals with confirmed Antioquian ancestry. The polymorphisms on the Y chromosome (five biallelic markers and six microsatellites) allow an approximation to the origin of founder men, and those on mtDNA identify the four major founder Native American lineages. These data indicate that approximately 94% of the Y chromosomes are European, 5% are African, and 1% are Amerind. Y-chromosome data are consistent with an origin of founders predominantly in southern Spain but also suggest that a fraction came from northern Iberia and that some possibly had a Sephardic origin. In stark contrast with the Y-chromosome, approximately 90% of the mtDNA gene pool of Antioquia is Amerind, with the frequency of the four Amerind founder lineages being closest to Native Americans currently living in the area. These results indicate a highly asymmetric pattern of mating in early Antioquia, involving mostly immigrant men and local native women. The discordance of our data with blood-group estimates of admixture suggests that the number of founder men was larger than that of women.

Africa, Northern↗

An association study of bipolar mood disorder (type I) with the 5-HTTLPR serotonin transporter polymorphism in a human population isolate from Colombia.

The short variant of a functional length polymorphism in the promoter region of the serotonin transporter has been associated with several behavioural and psychiatric traits, including bipolar mood disorder. The same short allele has also been implicated as a modifier of the bipolar phenotype. Here we evaluate the etiologic/modifier role of this polymorphism in a case (N=103) / control (N=112) sample for bipolar mood disorder (type I) collected from an isolated South American population. We did not detect an association between bipolar disorder and the 5-HTT promoter polymorphism in this sample. However, an excess of the short allele was seen in younger cases and in cases with psychotic symptoms. When combined with data from the literature, the increased frequency of the short allele in patients with psychotic symptoms was statistically significant.

Age of Onset↗