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Biomedical subjects

P McManus

Publications and source records attributed to P McManus.

17 recordsLinked to original sources

Population and family studies of HLA-DR4 by use of oligonucleotide typing.

Using PCR and DR4 group-specific primers and SSO's we have examined DRB1*04 nucleotide polymorphisms in a population of 123 DR4-positive individuals (86 NAC, 27 Hispanics and 10 African Americans) from New York carrying a total of 134 DR4 haplotypes. We found that the distribution of DRB1*04 alleles on DR4 haplotypes differs in these three ethnic groups. In this relatively small population, certain alleles such as DRB1*0406 and 0411 were encountered only in Hispanics, while others such as DRB1*0403, 0408 and 0409 were found only in NAC (North American Caucasians). Such differences may be important in studies of HLA-DR4 and disease associations. Evidence from MLC and PLT studies of an HLA-B/DR crossover family, which was informative for the segregation of HLA-DRB1*0406 and DRB1*0407, supports the concept that subtypes of HLA-DR4 and/or associated HLA-DP alleles elicit T-cell alloreactivity, and may thus play a role in transplantation.

Amino Acid Sequence

Polymorphism of HLA in the Romanian population.

We have investigated the HLA-class I and class II polymorphism in a population of 83 Romanians using conventional serology together with PCR amplification and oligonucleotide typing of HLA-class II genes. Romanians show a higher frequency of HLA-A11, B13, B18, B37, B39, B51 and DR2 than other European populations. HLA-DRB1*1501 and 1601 account for the high frequency of the serologic specificity DR2. In Romanians, HLA-DR2 is in linkage disequilibrium with HLA-B18 and HLA-Bw52 rather than with HLA-B7 as in the case in other Europeans. Unexpected HLA-DR2 haplotypes include HLA-DRB1*1502, DQA1*0102, DQB1*0601; HLA-DRB1*1602, DQA1*0102, DQB1*0502. Other unusual haplotypes include HLA-DRB1*0405, DQA1*03, DQB1*0302; HLA-DRB1*1305, DQA1*0103, DQB1*0603; and HLA-DRB1*1405, DQA1*0101, DQB1*05032. Analysis of the genetic distance between Romanians and other Europeans who have been studied serologically are consistent with the hypothesis that Romanians descend from Roman ancestors who colonized Dacia between the 1st century B.C. and 1st century A.D.

Base Sequence

RFLP analysis of HLA-DR5 haplotypes.

The analysis of HLA-DR5 haplotypes unravelled a new DRB3 polymorphism and permitted the identification of various associations between alleles of the DRB1 and DRB3 loci. This new polymorphism consists of a 10.5 kb Taq1 restriction fragment which was encountered in an African-American family (JS). In Caucasoids, the DRw11 allele has been previously observed only in association with the DRw52b allele. RFLP and oligonucleotide typing of HLA-DRw52 alleles associated with DRw11 showed, however, that 4 Caucasoid individuals from our panel carried the DRw52a allele and 1 the DRw52c allele. Similarly, DRw12, which is usually associated with DRw52b, was encountered with DRw52a in 1 Chinese and with DRw52c in an African-American and a Chinese panel member. The study of DRB3 alleles associated with DRw11 and DRw12 indicates that, similar to serology, RFLP studies become particularly informative when individuals of different races and ethnic origins are studied.

Alleles

Rubeosis capsulare.

Two patients with diabetes had extracapsular cataract extraction with intraocular lens (IOL) implantation. Both developed rubeosis iridis and neovascularization within the lens capsule supporting the IOL, a condition we have termed rubeosis capsular. Argon laser treatment was ineffective in both patients. One patient was successfully treated by virectomy with endophotocoagulation. The other patient had a vitrectomy which was followed by a fibrinoid reaction, continued inflammation, rubeosis, and phthisis bulbi.

Cryosurgery

Conservative treatment of uveal melanoma: local recurrence after proton beam therapy.

Twenty-three of 1006 (2.3%) uveal melanoma patients treated with proton beam therapy at the Harvard Cyclotron Laboratory between July 1975 and December 31, 1986 received additional treatment for documented (15 patients) or suspected (eight patients) tumor growth in the irradiated eye. Growth within the initially irradiated volume was documented at Massachusetts Eye and Ear Infirmary in 12 patients. Documented growth occurred in nine of 665 (1.4%) patients with small and intermediate size tumors, at times after treatment ranging from 6 to 48 months (median 16 months), and in three of 341 (.9%) patients with large tumors at 7, 11, and 12 months after treatment. Melanoma growing totally outside the treated volume was also documented in three additional patients at 7, 9, and 45 months; two of these were thought to be "ring melanomas". Eight patients had the treated eye removed elsewhere for suspected tumor growth. The additional treatment in these 23 patients was conservative in nine patients (repeat proton irradiation in five and laser photocoagulation in four). Thirteen underwent immediate enucleation and one had orbital exenteration. Ultimately, 17 of the 23 eyes (74%) were removed. Estimated probability of local control of the melanoma within the irradiated eye at 60 months was 96.3 +/- 1.5%. Dose distributions to the 12 patients with documented local failure within the irradiated volume were analyzed. Ten tumors recurred marginally in an area receiving less than the prescribed dose of 70 CGE (CGE = Cobalt Gray Equivalents = proton Gy X RBE 1.1), whereas only two recurred in the volume receiving full dose. Based on these data, it appears that a dose of 70 CGE in five fractions is associated with very high rates of local control in human uveal melanoma. It is reasonable to consider initiating studies using a lower total dose or a more protracted course, to determine if some of the observed complications are dose-related.

Adult

Fractionated proton radiation therapy of chordoma and low-grade chondrosarcoma of the base of the skull.

Sixty-eight patients with chordoma or low-grade chondrosarcoma at the base of the skull received fractionated high-dose postoperative radiation delivered with a 160-MeV proton beam. Protons have favorable physical characteristics which allow the delivery of high doses of radiation to these critically located tumors. The methods employed for these treatments are described. These patients have been followed for at least 17 months and for a median of 34 months. The median tumor dose was 69 CGE (cobalt Gy equivalent): CGE is the dose in proton Gy multiplied by 1.1, which is the relative biological effectiveness for protons compared to cobalt-60. The daily dose was 1.8 to 2.1 CGE. For this group the 5-year actuarial local control rate is 82% and disease-free survival rate is 76%. The incidence of treatment-related morbidity has been acceptable.

Adolescent

Distribution of indicator bacteria and Vibrio parahaemolyticus in sewage-polluted intertidal sediments.

The impact of a sewage point source on the bacterial densities in an intertidal mud flat in Boston Harbor, Mass., was investigated. The area, Savin Hill Cove, acts as a receiving basin for a combined storm and sewage outlet (CSO). Preliminary examination of sediments and overlying water at high tide demonstrated that fecal coliforms were present in sediments at abundances 2 to 4 orders of magnitude higher than in the overlying water column. The following bacterial counts were determined from sediments along a sampling transect extending 460 m from the CSO: total bacteria by epifluorescent microscopy, heterotrophic bacteria by plate counts on nutrient-rich and nutrient-poor media, fecal coliforms and enterococci by membrane filtration, and Vibrio parahaemolyticus by a most-probable-number technique with a resuscitation step. Median sediment grain size, average tidal exposure, carbon/nitrogen ratio, and total organic carbon were also measured. All bacterial indices, except for V. parahaemolyticus, declined significantly with distance from the outfall. Multiple regression analysis indicated that tidal exposure (low tides) may affect densities of total bacteria. Fecal coliforms and enterococci were still present in appreciable numbers in sediments as far as 460 m away from the CSO. In contrast, V. parahaemolyticus densities did not correlate with the other bacterial counts nor with any of the environmental parameters examined. These results indicate that intertidal sediments which adjoin point sources of pollution are severely contaminated and should be considered as potentially hazardous reservoirs of sewage-borne diseases.

Enterobacteriaceae

Trends in childhood disability.

This article summarizes and analyzes possible explanations for the near doubling, since 1960, of the proportion of children with limitations of activity due to chronic illness as reported in the National Health Interview Survey (NHIS). We examine several possible explanations for the upward trend in prevalence including: changes in survey design and procedures; changes in awareness of chronic illness on the part of parents and physicians; and changes in the institutionalized population of disabled children. Our analysis indicates that only a small part of the trend can be explained directly by these factors. Further examination of the NHIS data reveals that the types of limitations of activities now reported are less likely to cause frequent confinement in bed; whether this indicates lesser severity or principally different types of chronic conditions is as yet unclear.

Adolescent

Assessing the effectiveness of neonatal intensive care.

Although neonatal intensive care has been praised widely for individual successes, its effectiveness has not been established systematically or conclusively. The literature consists principally of reports from individual intensive care units with sample sizes too small for statistical validation or generalization. This study analyzes the results obtained by recalculating and pooling the isolated reports. In addition, the findings of the solitary clinical trial, some scattered epidemiologic data, and several analyses of regional birthweight-specific time series data are reviewed. Taken together, this constitutes a body of evidence that supports the conclusion that intensive neonatal medical care has played a significant role in bringing about the impressive reduction in infant mortality that has taken place in this country since 1965.

Birth Weight

Benzo(a)pyrene phenol production by perfused rat liver and its inhibition by ethanol.

A rapid and inexpensive method has been developed to estimate rates of benzo(a)pyrene phenol production by perfused rat liver. This method is based on the measurement of benzo(a)pyrene phenols utilizing a simple fluorometric procedure. Within 2 to 3 min after infusion of benzo(a)pyrene bound to serum albumin, phenols are excreted into the perfusate, primarily as glucuronide and sulfate conjugates. Maximal rates of phenol release were 8 to 10 nmol/g/hr in livers from control rats and 40 to 42 nmol/g/hr in livers from 3-methylcholanthrene-treated rats. Fasting of 3-methylcholanthrene-treated rats for 24 hr prior to perfusion experiments did not affect either the rate of phenol production or the extent of their conjugation. Ethanol (20 mM) inhibited rates of phenol formation by 50% in livers from fasted, 3-methylcholanthrene-treated rats but had no effect on benzo(a)pyrene hydroxylase activity in isolated hepatic microsomes. These data indicate that ethanol inhibits phenol formation from benzo(a)pyrene in intact liver, probably by diminishing the supply of the cofactor reduced nicotinamide adenine dinucleotide phosphate.

Animals

Federal health program reforms: implications for child health care.

The "Omnibus Budget Reconciliation Act of 1981" included a number of provisions designed to reduce federal spending for health care and to increase state authority over health programs. Evidence concerning the financial condition and health care needs of children served by federally-financed health programs, and recent trends in coverage and eligibility, make it possible to assess the likely impact of the new legislation. One conclusion seems clear: extensive federal funding reductions cannot be accommodated by eliminating excesses. While reforms of the Medicaid program may be advisable for a number of reasons, a simple reduction to funding will have serious, adverse consequences for poor children.

Aid to Families with Dependent Children

Pediatricians and family physicians: future competition for child patients?

The specialties of family practice and pediatrics, as well as the numbers of nonphysician child health practitioners, are growing much faster than is the population of children. Current figures suggest that the aggregate supply of practitioners is already adequate and will be in excess by 1990. These overall statements, however, mask the fact that physicians are unevenly dispersed and that substantial numbers of children have unmet medical care needs. If present trends in practice content and geographic preference continue, the outlook is for direct competition for patients between the specialties in many locations. Major factors that could influence the character of the competitive responses include differences in practice content amd location, public and private financing for time spent addressing psychosocial and behavioral problems, changes in Medicaid affecting participation by office-based physicians, and subspecialization trends within both specialties.

Adolescent