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Biomedical subjects

P Cunningham

Publications and source records attributed to P Cunningham.

At least 91 records · Page 5Linked to original sources
PubMed1992

Long-term symptomless HIV-1 infection in recipients of blood products from a single donor.

There have been reported cases of long-term symptomless human immunodeficiency virus type 1 (HIV-1) infection, but it is not clear whether the benign course of infection was due to host, viral, or other unknown factors. During follow-up of subjects with transfusion-acquired HIV-1 infection in New South Wales, Australia, we identified a group of 6 subjects who had been infected through a single common donor. We were therefore able to study the contributions of various factors to the course of infection. Throughout follow-up (range 6.8-10.1 years after infection), 5 of the recipients and the donor (last follow-up 10.2 years after infection of the first recipient) remained clinically free of symptoms, with normal CD4 cell counts and no p24 antigenaemia. HIV-1 was isolated from only 1 recipient; the isolate did not induce syncytia in a SUPT1 co-culture assay and had a limited in-vitro host range. 1 infected recipient (who had received extensive immunosuppressive treatment for systemic lupus erythematosus) developed Pneumocystis carinii pneumonia and died 4.3 years after infection. The frequency of progression to AIDS or a CD4 cell count below 0.50 x 10(9)/l was significantly lower among the 6 subjects with a common donor (1/6) than among 101 other HIV-infected transfusion recipients for whom data from 7 years of follow-up were available (94/101; p less than 0.0001). These findings suggest that the subjects were infected by a less virulent strain of HIV-1. The identification of this group of subjects should stimulate a search for other similar groups, which will provide important information on the immunopathogenesis of HIV-1 disease.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Identification of HIV-1 in semen following primary HIV-1 infection.

OBJECTIVE: To determine whether HIV could be identified in semen samples during the first few weeks after infection. DESIGN: A series of three homosexual men with symptomatic primary HIV-1 infection. METHODS: Each subject provided a series of semen samples that was examined for HIV-1 by virus culture, polymerase chain reaction (PCR) and transmission electron micrography. RESULTS: The first samples obtained for each subject (17, 22 and 24 days following onset of primary HIV-1 infection) were all positive by PCR and negative by viral culture. Of 13 samples obtained during the first 80 days after onset of primary HIV-1 infection and analysed by PCR, 10 were positive. Only one of these samples was virus culture-positive. Four semen samples obtained from two subjects during treatment with zidovudine were PCR-positive. Eight samples were examined for presence of HIV-1 by electron microscopy and one was found to be positive. CONCLUSIONS: These results indicate that men with HIV-1 infection are potentially infectious through sexual transmission during the first few weeks after infection. The findings emphasize that individuals in all stages of HIV-1 infection should practise safer sex to reduce transmission of HIV-1.

Adult↗
PubMed1992

Vascular injuries in a rural state: a review of 978 patients from a state trauma registry.

The demographics, etiology, and outcome of 1148 vascular injuries suffered by 978 patients reported from eight trauma centers in a largely rural state to a trauma registry (NCTR) data base containing 26,617 patients entered over a 39-month time interval were analyzed. Vascular injury patients were more frequently transferred by helicopter (18%), referred from other hospitals (45%), transfused more blood (8 units mean/24 hours), had higher mean ISS values (14 vs. 9), had lower systolic blood pressures on admission (113 vs. 128 mm Hg), had higher emergency department mortality (3.3%), and required immediate surgery more often (79%) when compared with nonvascular injury NCTR patients (p = 0.0001). Vascular injury patients had significantly longer hospital stays (13 vs. 10 days), longer ICU stays (5 vs. 4 days), and greater hospital costs ($22,500 vs. $12,300) while incurring more serious AIS values for the regions of the chest, abdomen, and extremities. One hundred twenty-nine (13.1%) died, 97 after admission compared with a 6.2% mortality for NCTR nonvascular injury victims. Forty-seven percent of vascular injuries were extremity lesions; the amputation rate was 1.3%; and management was most often by simple repair (41.9%) or patching (22.2%). Rural vascular injury patients had a high incidence of blunt trauma (43.4%) and were older (average, 51 years); they were transported by helicopter more often (30.3%) and were frequently referred from another hospital (77.8%); they had longer ICU, ventilator, and hospital stays and greater hospital charges; and they had higher mortality (14.2%) compared with urban vascular trauma victims. The data suggest a need for the trauma care system to focus on earlier recognition, stabilization, and rapid transportation of this most seriously injured group of patients.

Age Factors↗
PubMed1992

The development of a posttransplant TLI treatment strategy that promotes organ allograft acceptance without chronic immunosuppression.

The effectiveness of fractionated TLI in promoting allograft tolerance without chronic drug therapy is well established experimentally. TLI has not been widely applied in clinical transplantation, largely due to logistic and medical limitations of pretransplant TLI conditioning. Potential use of posttransplant TLI (PT-TLI) has not been critically evaluated. In this study we investigated PT-TLI in combination with rabbit antithymocyte globulin (RATG) in the absence of chronic immunosuppressive drugs as a strategy for inducing long-term kidney allograft acceptance. Recipients were studied with and without infusion of DR-CD3- donor bone marrow cells (DBMC). Normal rhesus monkeys, which received no pretransplant treatment, underwent bilateral intrinsic nephrectomy and splenectomy at the time of transplantation. RATG was administered daily for 3-5 consecutive days beginning on day 0. A total dose of 500-625 cGy of fractionated TLI was given in 4-5 treatments at 125 cGy per day beginning on day +1. Whereas neither PT-TLI nor RATG monotherapy induced long-term graft acceptance in splenectomized recipients, the combination of these modalities was remarkable in promoting long-term allograft acceptance without immunosuppressive drug therapy. Of 4 recipients given RATG x 5, splenectomy and PT-TLI, all were free of acute rejection. Of these, 3/4 had graft survivals greater than 100 days, 2/4 were greater than 150 days and 1/4 greater than 365 days. Of 5 recipients given this treatment plus an infusion of DR-CD3-DBMC, 4/5 grafts survived greater than 150 days and 3/5 still have normal functioning grafts at greater than 365 days. PT-TLI accentuated and prolonged changes in PBL subpopulations that were initially affected by RATG. Depressed levels of CD3+ cells were present for 4-5 months, with large numbers of circulating CD4+CD3- and especially CD8+ CD3- cells. In addition, antibody responses to RATG and alloantigens were suppressed in PT-TLI-treated recipients. Overall, the combination of PT-TLI, splenectomy, and RATG was found to be effective in promoting long-term allograft acceptance without chronic immunosuppressive drug therapy. The infusion of DR-CD3- DBMC in recipients treated with PT-TLI, RATG and splenectomy appeared to further increase the incidence of stable long-term survivors. If infectious complications can be improved, this approach may provide a clinically applicable posttransplant treatment strategy for inducing functional allograft tolerance.

Animals↗
PubMed1992

Sequence similarity between HLA-DR1 and DR4 subtypes associated with rheumatoid arthritis and proteus/serratia membrane haemolysins.

Rheumatoid arthritis (RA) is found more often in subjects carrying the HLA-DR1 antigen and some subtypes of the HLA-DR4 antigen than in those without these antigens. Analysis of probes specific for HLA-DR4 has shown that amino acids encoding positions 69-74 (EQRRAA) of the beta chain indicates susceptibility to RA. A hexamer sequence of proteus haemolysin spanning residues 32-37 (ESRRAL) has been identified which resembles biochemically, and discriminates by charge, between HLA types associated with RA (DR1, Dw4, Dw14, Dw15), and those not linked with the disease (Dw10, Dw13).

Amino Acid Sequence↗
PubMed1992

Gonadotrophin surge-attenuating factor attenuates in-vitro LH secretion induced by gonadotrophin-releasing hormone from cultured ovine pituitary cells only during the breeding season.

Primary cultures of ovine pituitaries from adult ewes were used to investigate aspects of gonadotrophin surge-attenuating factor (GnSAF) bioactivity in human follicular fluid (hFF) from superovulated women. During the autumn and first half of the winter, LH secretion induced by gonadotrophin-releasing hormone (GnRH) was markedly reduced (43.5 +/- 5.2% of control GnRH-induced LH secretion) by incubation for 48 h with steroid-free hFF. For the rest of the year, treatment with the same batch of steroid-free hFF resulted in non-significant reduction or stimulation of GnRH-induced LH secretion (71.3 +/- 13.2 to 117.8 +/- 11.2% of control GnRH-induced LH secretion). Incubation of pituitary cells for 48 h with oestradiol (1 pmol/l to 1 mumol/l), progesterone (1 pmol/l to 1 mumol/l) or oestradiol and progesterone combined (1 pmol/l to 1 mumol/l) in a two-way titration for 48 h had no significant effect on GnRH-induced LH secretion (83.4 +/- 7.6 to 110.6 +/- 5.0% of control secretion). Separating hFF into fractions of different molecular mass by ultrafiltration demonstrated that GnSAF bioactivity was present in a form 10-30 kDa in size. Incubation for 48 h with these fractions had no significant effect on basal FSH secretion but significantly attenuated GnRH-induced LH secretion during the autumn. The same fractions had little effect on GnRH-induced LH secretion from pituitary cells collected during the summer. We conclude that ovine pituitaries display at least partial reduction in sensitivity to GnSAF outside the breeding season.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

The health care of poor persons living in wealthy areas.

This paper describes the problems inherent in targeting new health care initiatives to disadvantaged communities rather than to disadvantaged persons in the 100 wealthiest counties in the United States. The barriers to care experienced by such persons are generally comparable to those of other poor persons. Deprivations in access to care appear to be caused by poverty per se and not by the characteristics of the places in which the poor live. It is suggested that per capita income not be used as a criterion for the allocation of health care resources. The actual number of poor persons in a geographic area is a better criterion for determining the need for public health care programs.

Cost Allocation↗
PubMed1991

Transplantation of kidneys from pediatric cadaver donors to adult recipients.

Pediatric donors (less than 12 years old) are a potentially important source of kidneys for adult recipients. Previous reports of decreased graft survival and increased complication rates have made surgeons wary of using such kidneys. In 64 kidneys from younger donors transplanted to adult recipients the delayed graft function rate (41 versus 42%), and 2 and 3-year graft survival rates (67 versus 72% and 61 versus 65%, respectively) were similar to those seen with kidneys from adult donors. Kidneys from donors 24 months old or less experienced an 80% rate of graft loss at 1 year. When these kidneys are excluded the 1-year graft survival rate was similar to kidneys from older and younger donors (70 versus 77%). Mean serum creatinine at 1 year was similar in both groups (155 +/- 21 versus 151 +/- 10). Pediatric kidneys except those obtained from donors 2 years old or less are suitable for adult recipients. However, kidneys from very young donors may be more appropriate to pediatric recipients.

Adult↗
PubMed1991

The spectrum of abdominal injuries associated with the use of seat belts.

Several recent reports have described abdominal injuries occurring as a result of seat belt use, raising concerns about seat belts as an agent of injury in motor vehicle crashes. The purpose of this study was to characterize the distribution of abdominal injuries after motor vehicle crashes in belted and unbelted patients admitted to trauma centers. The mortality was higher in unbelted than belted patients (7% vs. 3.2%, respectively, p less than 0.0001). Unbelted patients also had significantly more frequent and more severe head injuries (50.0% vs. 32.9%, respectively, p less than 0.001). The incidence of abdominal injury was equal in both unbelted patients (13.9%), but the spectrum of organs injured was different in the two groups. Gastrointestinal tract injuries (stomach, small bowel, colon and rectum) were significantly more frequent in belted vs. unbelted patients (3.4% vs. 1.8%, respectively, p = 0.001). The frequency of liver and spleen injuries was the same in both groups. This study demonstrates that in patients admitted to trauma centers after motor vehicle crashes, belted and unbelted patients have an equal incidence of abdominal injury, but belted and unbelted patients have a different spectrum of injuries. Hollow viscus injuries are more common in belted crash victims. Seat belt use was associated with significantly fewer head injuries and deaths. Physicians evaluating trauma victims after motor vehicle crashes should be aware of the fact that the types of abdominal injuries may vary substantially depending on seat belt use.

Abdominal Injuries↗
PubMed1991

Standardizing nursing-home admission dates for short-term hospital stays.

In the Institutional Population Component of the 1987 National Medical Expenditure Survey, the definition of a nursing home admission was standardized to ignore the readmission of patients discharged for short-term hospital care. Approximately one out of six persons residing in nursing homes on the survey reference date (January 1, 1987) had been readmitted for this reason. The effect of the standardization was to increase the average length of stay of residents prior to the reference date by approximately 5 months. The percentage of long-stay residents, those living in the facility for more than three years, increased from 31% to 36%. The percentage admitted from the community during the previous year increased from 32% of those admitted in 1986 to 41%.

Aged↗
PubMed1991

Normalization of force generated by canine airway smooth muscles.

A variety of normalizations have been employed to compare maximal isometric force (Po) produced by smooth muscles at different locations and stages of maturation. Because these procedures have not always been based on rigorous principles, confusion has resulted. To obtain a less ambiguous index of force production, we measured in vitro Po from mongrel canine tracheal (TSM) and bronchial (BSM) smooth muscle with an electromagnetic lever and normalized it to force per unit cross-sectional area of whole tissue (tissue stress), to force per unit cross-sectional area of muscle in the cross section of total tissue (muscle stress), and to force per fractional unit of myosin in the tissue cross section (myosin stress). Proportion of myosin in cross-sectional area of tissue was deduced from data obtained by sodium dodecyl sulfate gel electrophoresis of crude muscle extracts. For TSM, tissue stress was 1.499 X 10(5) N/m2 +/- 0.1 (SE), whereas it was only 0.351 X 10(5) N/m2 +/- 0.05 (SE) for BSM, representing a 4.27-fold difference (P less than 0.01). There was a 1.60-fold difference (P less than 0.05) in muscle stress, which was correlated to the morphometric finding that 79 +/- 1.4% (SE) of the tracheal strip cross section was muscle, whereas only 30 +/- 1.0% (SE) of bronchial tissue was occupied by muscle. Average myosin content was the same in smooth muscle cells of TSM and BSM, indicating that total amount of myosin in tissue cross sections was essentially a function of proportional area of muscle cells in total tissue cross sections.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗