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Biomedical subjects

J Hanrahan

Publications and source records attributed to J Hanrahan.

18 recordsLinked to original sources
PubMed2001

Forced expiratory flow in uninfected infants and children born to HIV-infected mothers.

The Pediatric Pulmonary and Cardiovascular Complications of Vertically Transmitted HIV (P(2)C(2) HIV) Study is a multicenter study examining pulmonary and cardiac outcomes in offspring of HIV-infected mothers. This portion of the P(2)C(2) study tests the hypothesis that infants exposed to, but uninfected by, maternal HIV have normal maximal expiratory flow at functional residual capacity (V'max,(FRC)). We obtained 500 measurements of V'max,(FRC) by rapid thoracic compression in 285 children ages 6-30 mo in five U.S. centers. The data were compared with those from a healthy cohort of children described elsewhere. V'max,(FRC) rose with height in a linear relationship. The slope of the regression line in the exposed infants did not differ statistically from the slope in the comparison group, but the intercept was about 20% lower (p < 0.001). Height and weight were comparable in the two cohorts, and the differences between intercepts persisted after adjusting for birth weight and gestational age. However, maternal HIV infection cannot be assumed to be the cause as the cohorts may have differed in other variables, such as socioeconomic status and frequency of maternal smoking and drug use. Also, measurements varied substantially within and between our five centers, probably in part because of different racial and ethnic distributions. In summary, maternal HIV infection probably has only a modest effect, if any, on maximal expiratory flow at functional residual capacity in uninfected infants.

Age Factors↗
PubMed2000

Geographic distribution of a large mobile element that transfers ampicillin and vancomycin resistance between Enterococcus faecium strains.

In several clonally unrelated VanB-type vancomycin-resistant Enterococcus faecium strains, we demonstrated a common physical relationship between pbp5 and Tn5382 as well as common mutations within pbp5. The majority of these strains transferred vancomycin and ampicillin resistance to E. faecium in vitro, suggesting the dissemination of similar transferable pbp5-vanB-containing mobile elements throughout the United States.

Ampicillin Resistance↗
PubMed2000

A genetic investigation of E2A function in lymphocyte development.

Lymphocytes are derived from hematopoietic stem cells (HSC) following a series of regulated differentiation events. Multipotent HSCs become committed to the B cell lineage in bone marrow and the T cell lineage in the thymus after receiving appropriate signals from the corresponding microenvironment. These committed lymphoid cells must then undergo V(D)J recombination at the immunoglobulin gene or T cell receptor gene locus resulting in clonal production of functional B or T lymphocytes, respectively. Lymphocyte commitment and differentiation are accompanied by programmed gene expression or repression events which are driven by lineage and stage specific transcription factors. The basic-helix-loop-helix (bHLH) transcription factors encoded by the E2A gene are involved in several differentiation events during B and T cell development, including lineage commitment, initiation of V(D)J recombination, and antigen receptor mediated proliferation and differentiation. Several recent reviews have provided a comprehensive discussion of biochemical, cellular, and genetic research on E2A function in lymphocyte development (1,2). Here, we only discuss some of the genetic approaches our laboratory (except where it is noted) has undertaken to investigate the molecular pathways mediated by E2A transcription factors in lymphocyte development.

Animals↗
PubMed1990

Symptomatic abdominal aortic aneurysms in long-term survivors of cardiac transplantation.

Herein we report the only two long-term survivors of cardiac transplantation who underwent successful repair of symptomatic abdominal aortic aneurysms since the advent of cyclosporine therapy in 1983. Review of the world's literature indicates that the only two recorded cases of repair of symptomatic abdominal aortic aneurysms after cardiac transplantation occurred before the use of cyclosporine. The presentation and clinical course of our patients recently treated are presented, and perioperative care and immunosuppressive management are outlined. As the number of long-term survivors after cardiac transplantation increases, the incidence of other atherosclerotic complications including abdominal aortic aneurysm is likely to become more common, requiring extended cardiovascular follow-up.

Aorta, Abdominal↗
PubMed1989

Measles immunisation non-acceptance: validation of computer-held records and raising the vaccine uptake at early school age; the Maidstone experience.

The parents of all 977 resident children born in 1981 and 1982 recorded as not having received measles vaccine were contacted by letter. They were strongly advised to seek immunisation for their children and asked to complete and return a reply-paid questionnaire. Details of their children's immunisation status, reasons for non-immunisation and history of measles infection were sought, and whether they then intended to have their children immunised. The response rate was 53.3%. Of responders, 27% claimed to have written evidence that their children had already been immunised, the majority of them having been done outside the District. There was a high degree of mobility, mainly into the District, emphasising the need to record immunisation status when registering newly arrived children. The main reasons for non-immunisation were: a history of measles infection, personal or family history of fits or allergy, and mistrust of the vaccine. Many parents had been inappropriately advised by health professionals. 78 children from these cohorts are now known to have been vaccinated in the three months following the mailing and these together with the validation exercise have raised vaccination cover for 1981-born children from 74.7% to 78.9% and for 1982-born children from 77.0% to 81.4%.

Attitude to Health↗
PubMed1985

A prospective randomized trial of pretransfusion/azathioprine/prednisone versus cyclosporine/prednisone immunosuppression in cardiac transplant recipients: preliminary results.

Cyclosporine has gained acceptance as the immunosuppressive agent of choice in cardiac transplantation, but the validity of this assumption has yet to be established. Since January 1983, 25 patients have been randomly assigned to receive either conventional immunosuppression (azathioprine/antithymocyte globulin/prednisone) and pretransplant transfusion (PAAP, n = 11) or cyclosporine immunosuppression (cyclosporine and prednisone [CyA], n = 14). There was no difference in the age distribution (41 +/- 9 vs 38 +/- 11 years), indications for transplantation, preoperative serum creatinine level (1.2 +/- 0.2 vs 1.4 +/- 0.3 mg/dl), or postoperative follow-up time (13.5 +/- 5.4 vs 13.5 +/- 5.2 months). Mortality was not different (PAAP = 2, CyA = 3) and there was no difference in rejection episodes per patient (PAAP = 1.8, CyA = 1.9). Patients in the PAAP group had more serious infections (PAAP = 8, CyA = 3; P less than .02), but those in the CyA group developed a greater incidence of systemic hypertension (PAAP = 1, CyA = 10; p less than .02), pericardial effusion (PAAP = 0, CyA = 6; p = .05), and impaired renal function (creatinine 1.5 mg/dl, PAAP = 2, CyA = 11; p less than .02). Thus it appears that in this small series, cyclosporine is not associated with a significant increase in early survival. It does appear that patients on PAAP immunosuppression develop a greater number of serious infections, but the incidence of rejection episodes appears to be the same. Renal dysfunction and hypertension in patients receiving cyclosporine continue to be long-term concerns and may add to the morbidity and mortality of patients treated with this immunosuppressive regimen.

Adult↗
PubMed1983

Mechanism and control of salt absorption in locust rectum.

The rectum is the main reabsorptive site in the excretory system of locusts. The primary urine entering this organ from the Malpighian tubules is rich in K+ (140 mM) and Cl- (90 mM), and most of this fluid is normally reabsorbed. Fluid and active Cl- reabsorption in the rectum are regulated by neuropeptide hormones from the corpus cardiacum. We have studied the mechanism of KCl reabsorption using voltage clamp, tracers, double-barreled ion-sensitive microelectrodes, and ion substitutions. Locust Cl- absorption differs from vertebrate systems in that it is not dependent on Na+ or HCO-3/CO2, and it is insensitive to normal inhibitors of Cl- transport. Entry of Cl- into rectal cells is active, electrogenic, and stimulated by luminal K+. This cation substantially increases the electrochemical gradient across the apical membrane against which Cl- is pumped; therefore K+ does not act solely and indirectly by electrical coupling. Kinetic studies also suggest that K+ activates the Cl- pump. Consequently at least two levels of control are exerted during cAMP stimulation; K+ permeability of the epithelium and the transepithelial potential generated by active Cl- transport both increase. The enhanced net K+ absorption from the lumen side after stimulation is largely passive, being electrically coupled to Cl- transport. However, this general increase in KCl absorption is "fine tuned" by K+ itself, through its direct effect on the Cl- pump.

Animals↗
PubMedDate not supplied

The inhibition of acetylcholinesterase by irinotecan and related camptothecins: key structural properties and experimental variables.

Irinotecan (CPT-11), a water-soluble and semi-synthetic topoisomerase I poison of the camptothecin family, has activity against both adult and paediatric malignancies. Recently, we demonstrated that CPT-11 (lactone) is also a potent inhibitor of human acetylcholinesterase (AChE) at clinically relevant concentrations. Attachment of heterocyclic and branched amino groups onto the camptothecin back-bone continues to be a strategy for the synthesis of water-soluble analogues, but this may lead to undesirable inhibition of AChE. In this study, we screened a range of camptothecin analogues, degradation products and metabolites for their ability to inhibit AChE. Those compounds possessing N-substitutions at C-10 were all found to inhibit AChE in a similar kinetic manner to CPT-11, but with a broad range of potencies. It is recognized that the charge-state is important for ligands that bind to the peripheral anionic site and we postulated that the protonated distal piperidine of CPT-11 would be important. To address this question, an N-methyl piperidinium iodide analogue was synthesized and tested. This derivative inhibited electric eel AChE with an inhibition constant (Ki) of 1 nM. Kinetic and deacylation experiments demonstrated that it acted relatively less as an inhibitor of deacylation than CPT-11. Overall, our experiments reveal that nitrogenous substitutions at the permissive C-10 of the camptothecin backbone may lead to AchE inhibition, particularly if they involve a quaternary nitrogen.

Acetylcholinesterase↗
PubMedDate not supplied

Sexual function after heart transplantation.

To define sexual interest, ability, and activity before and after heart transplantation, we surveyed all discharged, male heart transplant recipients from our institution. Of the 115 potential subjects, 71 (62%) responded. Respondents were predominantly (89%) white, had a mean age of 47.9 years (24 to 64 years), and most (74%) were living with their spouses. Pretransplant libido was strong and remained unchanged after heart transplantation. Transplant recipients reported their partner's libido to be strong, and even stronger after transplantation than before (p = 0.033). In contrast, erectile rigidity and orgasmic ability were impaired before, and declined further after, the transplant procedure. Respondents perceived this gap between libido and sexual ability to be a problem, and interest in evaluation and treatment was high.

Attitude to Health↗
PubMedDate not supplied

Clinical significance of pericardial effusion after heart transplantation.

Fifty-two consecutive patients who underwent orthotopic heart transplantation at our institution were evaluated by two-dimensional (2D) echocardiography at frequent intervals for 12 weeks after transplantation and at three monthly intervals for 1 year. Thirty-eight of 52 patients had adequate 2D echocardiograms and comprised the retrospective study group. Pericardial effusion was documented in 15 of 38 patients (40%). Pericardial effusion was moderate in two (5%) and small in seven patients (18%). Large pericardial effusion was demonstrated in six of 38 patients (16%). Three of 38 patients (8%) developed cardiac tamponade manifested by hypotension in the presence of a large pericardial effusion. The diagnosis of cardiac tamponade was aided by 2D echocardiography leading to prompt pericardiocentesis. The presence of pericardial effusion in patients after their transplantation did not demonstrate independent correlation with chest tube output after operation, cyclosporine therapy, acute rejection, level of blood urea nitrogen (BUN), infection or preoperative diagnosis of idiopathic dilated cardiomyopathy. The presence of cyclosporine therapy, acute rejection, and a preoperative diagnosis of idiopathic dilated cardiomyopathy, however, yielded an 86% probability of having pericardial effusion. Follow-up 2D echocardiograms obtained 301 +/- 106 days after transplantation were available in 25 patients. Fifteen patients (60%) had no pericardial effusion present on either the initial or follow-up 2D echocardiogram. The majority of cases of the pericardial effusion present on initial or follow-up echocardiograms were resolving on the follow-up study.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMedDate not supplied

Comparison of immunosuppression therapy following heart transplantation: pretransfusion/azathioprine/ATG/prednisone versus cyclosporine/prednisone.

Since the introduction of cyclosporine in heart transplantation, the search for the ideal combination of immunosuppressive agents continues. Between January 1983 and February 1985, 32 patients have been randomized prospectively to either one of two immunosuppressive regimens: one includes pretransplant transfusion, prednisone, azathioprine and rabbit anti-thymocyte globulin [Group I, n = 14], the other includes cyclosporine and prednisone [Group II, n = 18]. There were no differences between Group I and II in relation to age distribution, indications for transplantation, preoperative serum creatinine, length of follow-up, mortality or number of rejection episodes per patient. However, there was a statistically significant increase in the incidence of serious infections in Group I compared to Group II patients, and also in Group II of the incidence of systemic hypertension (p less than 0.001), of symptomatic pericardial effusion (p less than 0.05) and impaired renal function (p less than 0.02). Adding cyclosporine to azathioprine immunosuppression is effective in treating ongoing rejection in patients not previously treated with cyclosporine. In conclusion, patients treated with azathioprine and prednisone (Group I) develop a greater number of serious infections, but both groups had a similar incidence of rejection. The development of renal dysfunction and hypertension in patients treated with cyclosporine continues to be of concern and may preclude its use as an effective long-term immunosuppressive agent in heart transplant recipients.

Adult↗