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Biomedical subjects

E Jackson

Publications and source records attributed to E Jackson.

At least 37 records · Page 2Linked to original sources

Efficacy of postexposure prophylaxis after intravaginal exposure of pig-tailed macaques to a human-derived retrovirus (human immunodeficiency virus type 2).

Postexposure prophylaxis (PEP) after intravaginal exposure to human immunodeficiency virus (HIV) was investigated using the HIV type 2 (HIV-2)/pig-tailed macaque transmission model. PEP for 28 days with the reverse transcriptase inhibitor (R)-9-(2-phosphonylmethoxypropyl)adenine (PMPA; tenofovir) was initiated 12 to 72 h following HIV-2 exposure. Systemic infection was not evident in the 12- and 36-h groups, as defined by plasma viremia, cell-associated provirus, antibody responses, and lymph node virus. Breakthrough infection in the 72-h group was detected at week 16 post-virus exposure. These results demonstrate for the first time using a vaginal transmission model that early intervention after high-risk sexual exposures may prevent infection.

Acquired Immunodeficiency Syndrome↗

Abortion, autonomy and prenatal diagnosis.

The principle of patient self-determination has assumed central importance in British medical law in recent years. This article considers whether this increasingly strong commitment to patient autonomy has any resonance for abortion law. In particular, this article explores the possibility that the priority currently accorded to autonomous decision making may be in tension with the Abortion Act's requirement that a woman's reasons for seeking to terminate her pregnancy be judged acceptable by two medical practitioners. Moreover, interest in the moral legitimacy of a woman's reasons for wanting to terminate her pregnancy seems to be intensifying. Concerns arising from the increasing availability of precise prenatal tests have led to suggestions that access to abortion should be further restricted in order to prevent the cavalier use of abortion for reasons that might seem trivial or misguided. Using abortion following prenatal diagnosis as an example, this article considers whether it is anomalous for the common law's vigorous protection of an individual's freedom to make irrational or morally objectionable choices about his or her medical treatment to coexist with demands for further restriction of the acceptable grounds for abortion.

Abortion, Eugenic↗

Identification of a window period for susceptibility to dual infection with two distinct human immunodeficiency virus type 2 isolates in a Macaca nemestrina (pig-tailed macaque) model.

The potential to establish dual retroviral infections was investigated in this study. Groups of macaques infected with human immunodeficiency virus type 2 (HIV-2) isolate (either GB122 or CDC77618) were exposed to the other virus at 2, 4, 8, 12, 14, or 72 weeks after primary inoculation. Dual infections were established in macaques simultaneously exposed to both viruses. In other groups, secondary infections were observed only if challenge occurred at early intervals after primary infection but before a full seroconversion. Polymerase chain reaction and virus-isolation data demonstrated that challenges at 8, 12, 14, or 72 weeks after infection with the initial isolate failed to result in a dual infection. Anti-HIV-2 serologic titers, CD4 levels, virus burden, and the ability to superinfect peripheral blood mononuclear cells in vitro were not correlated with susceptibility to or protection from secondary challenges in this investigation. These findings demonstrate a window period for susceptibility to dual infection and indicate that protection from retroviral infection may be achievable.

Acquired Immunodeficiency Syndrome↗

"Pulse" nasal mupirocin maintenance regimen in patients undergoing continuous ambulatory peritoneal dialysis.

OBJECTIVE: To determine, among patients undergoing continuous ambulatory peritoneal dialysis (CAPD) who were Staphylococcus aureus nasal carriers, if periodic brief "pulses" of nasal mupirocin calcium ointment 2% after completion of a mupirocin eradication protocol would maintain these patients free of carriage. DESIGN: Noncomparative, nonblinded study with historical controls. SETTING: A county medical center. PATIENTS: Patients in a CAPD program during the period April 1996 to May 1998. METHODS: All patients in the CAPD program had monthly nasal cultures for S. aureus. After informed consent, S. aureus nasal carriers were administered mupirocin to the nares twice a day for 5 days followed by nasal mupirocin twice monthly. Peritonitis and exit-site infection rates were monitored independently by CAPD nursing staff. Patients were monitored monthly for adverse effects of mupirocin and compliance with the maintenance regimen. RESULTS: Twenty-four patients in the CAPD program were enrolled in the study and had a median duration of follow-up of 8.5 months. Fifteen (63%) of the 24 patients remained free of nasal carriage on follow-up cultures. Of the 9 patients with positive nasal cultures during the study, 8 had only one positive culture. There was no significant difference in the mean yearly peritonitis rate or S. aureus peritonitis rate (January 1995-May 1998). However, there was a significant decrease in the mean yearly exit-site infection rates both overall (from 8.8 episodes per 100 patients dialyzed per month in 1995 to 4.0 in 1998; P = .008) and due to S. aureus (from 5.6 in 1995 to 0.9 in 1998; P = .03). Adverse effects of nasal mupirocin were mild overall; 1 patient was removed from the study due to an allergic reaction to mupirocin. CONCLUSIONS: Among CAPD patients who were S. aureus nasal carriers, periodic brief treatment with nasal mupirocin after an initial eradication regimen kept them free of carriage, for the most part, with few adverse effects. The pulse mupirocin regimen offers simplicity and possibly better compliance, as well as minimizing exposure to this agent, thereby possibly reducing the risk of resistance. Further studies are warranted to compare this regimen to other commonly used mupirocin maintenance regimens in dialysis patients.

Administration, Intranasal↗

Import rate of the E1beta subunit of human branched chain alpha-ketoacid dehydrogenase is a limiting factor in the amount of complex formed in the mitochondria.

Components of the mitochondrial branched chain alpha-ketoacid dehydrogenase multienzyme complex are all encoded by nuclear genes. The functional complex is formed with a known stoichiometric relationship of subunits, but how they enter the mitochondria and form the complex is not defined. Although cytosolic precursors for several of the proteins have been identified, the requirements for import and processing have not been described. Here we demonstrate the similar requirements for in vitro import and processing of the three catalytic subunits unique the this complex. Import was not affected by the amount of endogenous BCKD within the mitochondria. No cooperativity or competition among the subunits for import was found when subunits were used in combination. The relative rates of entry are E1alpha>E2>/=E1beta, making E1beta the limiting component supporting previously reported observations.

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗

A case of giant cell myocarditis and malignant thymoma: a postmortem diagnosis by needle biopsy.

This paper reports a case of fulminant giant cell myocarditis arising in association with a malignant thymoma causing death in a 46-year-old woman. Although the diagnosis was suspected in life, postmortem examination was required for confirmation of giant cell myocarditis. Consent was obtained only for percutaneous needle biopsy of the heart. In order to respect the family's wishes and harvest sufficient diagnostic myocardium, a simple needle-based biopsy technique was devised. A bone marrow trephine needle was attached to a 20 ml syringe and, with suction, multiple passes were used to fill 15 tissue cassettes. The cores were placed immediately in formalin and B5 fixatives. High-quality tissue preservation was obtained without crush artefact. Immunohistochemical studies of the biopsy tissue confirmed that the giant cells were of macrophage derivation.

Biopsy, Needle↗

Low-dose theophylline increases urine output in diuretic-dependent critically ill children.

OBJECTIVE: Determine the effect of low-dose theophylline on urine output and the urinary adenosine: cAMP (cyclic adenosine monophosphate) excretion ratio (a measure of phosphodiesterase inhibition) in diuretic-dependent critically ill children. DESIGN: Observational clinical case series and animal laboratory experiment. SETTING: A university pediatric intensive care unit and a pharmacology research laboratory. PATIENTS: 10 consecutive oliguric patients treated with theophylline for diuresis. INTERVENTIONS: Urine output, fluid intake, diuretic dosages, and number of pressors (including dopamine) were monitored over the 24-h period prior to and the 24-h period immediately after theophylline was started. Hourly collections of urine were obtained at baseline and 1 and 3 h after theophylline was started and urinary excretion rates of adenosine and cAMP were measured and calculated. MEASUREMENTS AND RESULTS: Mean theophylline level in the children was 5.0 microg/ml. Urine output increased from 1.58 +/- 0.46 to 3.75 +/- 0.77 ml/kg per h (p = 0.008, paired t-test) after theophylline administration. There was no significant change in fluid intake, vasoactive agents, or dosages of other diuretics during the study periods. Intrarenal infusion of the IC50 concentration of isobutylmethylxanthine for phosphodiesterase activity resulted in a reduction of the adenosine: cAMP urinary excretion ratio in rats (p < 0.05). Low-dose theophylline had no effect on the adenosine: cAMP urinary excretion ratio in children. Concurrent therapy with dopamine was associated with an enhanced diuretic effect of theophylline (with dopamine, 1.30 +/- 0.30 to 5.07 +/- 0.77 ml/kg per h vs without dopamine, 1.77 +/- 0.76 to 2.86 +/- 1.08 ml/kg per h; p = 0.03, two-way ANOVA). There was no interaction between dopamine and low-dose theophylline on the urinary adenosine: cAMP excretion ratio (p = 0.56, two-way ANOVA). CONCLUSIONS: Theophylline increased urine output in diuretic-dependent critically ill children and the diuretic effect may have been potentiated by concurrent use of dopamine. Adenosine receptor antagonism may be a more likely mechanism for the diuretic effect of theophylline than phosphodiesterase inhibition.

Adenosine↗

Interstitial adenosine, inosine, and hypoxanthine are increased after experimental traumatic brain injury in the rat.

Adenosine is a putative neuroprotectant in ischemia, but its role after traumatic brain injury (TBI) is not clear. Metabolites of adenosine, particularly inosine and hypoxanthine, are markers of ischemia and energy failure. Adenosine triphosphate (ATP) breakdown early after injury and metabolism of cyclic adenosine monophosphate (cAMP) are potential sources of adenosine. Further delineation of the magnitude, location, time course, and source of production of adenosine after TBI is needed. We measured adenosine, inosine, and hypoxanthine in brain interstitial fluid after controlled cortical impact (CCI) in the rat. Rats (n = 15) were prepared for TBI induced by CCI. A microdialysis probe was placed in the cortex, and samples were collected every 10 min. After 3 h of equilibration, the catheter was removed, CCI was performed (4 m/sec, depth 2.5 mm), and the catheter was replaced. In the shams, the catheter was removed and replaced without CCI. The injury group included rats (n = 10) subjected to CCI. Within the injury group, the microdialysis probe was placed in the center of the eventual contusion (center, n = 5) or in the penumbral region (penumbra, n = 5). Purine metabolites were measured using ultraviolet-based high-pressure liquid chromatography. Adenosine, inosine, and hypoxanthine were dramatically increased after injury (61-fold, 37-fold, and 16-fold, respectively sham, all p < 0.05, two-way analysis of variance for repeated measures). No changes in cAMP were observed (p = 0.62 vs. sham). Adenosine peaked in the first 20 min and returned to near baseline 40 min, whereas inosine and hypoxanthine peaked at 30 min and remained increased for 40 min after CCI. Interstitial brain adenosine, inosine, and hypoxanthine were increased early after CCI in rats in the contusion and penumbra. ATP breakdown is a potential source of adenosine in this early period while metabolism of cAMP does not appear to play a role. Confirmation of these data in humans may suggest new strategies targeting this important metabolic pathway.

Adenosine↗

A comparison of the respiratory effects of sevoflurane and halothane in infants and young children.

BACKGROUND: This study compared the respiratory effects of sevoflurane with those of halothane in anesthetized infants and young children. METHODS: Infants were randomized to receive 1 minimum alveolar concentration (MAC) halothane or sevoflurane in a mixture of nitrous oxide and oxygen. Anesthetic management included the use of a laryngeal mask. Flow, airway pressure, and the end-tidal carbon dioxide pressure (PETCO2) were measured during spontaneous ventilation and airway occlusions. Respiratory inductive plethysmography was used to assess chest wall motion. RESULTS: Measurements were obtained in 30 infants and young children (mean (SD) age, 14.5 (5.9) months), 15 of whom received sevoflurane and 15 received halothane. Some respiratory depression, as indicated by a PETCO2 of 45 mmHg (6 kPa), was present in both groups. Minute ventilation and respiratory frequency were significantly lower during sevoflurane than halothane anesthesia (4.5 compared with 5.4 (1/ m2)/min, and 37.5 compared with 46.7 breaths/min, respectively, P < 0.05). There was no difference in respiratory drive, but the shape of the flow waveform differed according to anesthetic agent, with peak inspiratory flow reached later, and peak expiratory flow reached earlier, in the sevoflurane group. There was also significantly less thoracoabdominal asynchrony during sevoflurane anesthesia. CONCLUSIONS: Minute ventilation and respiratory frequency were lower in infants during 1 MAC sevoflurane in nitrous oxide than during halothane anesthesia. However, these differences may not be clinically relevant at these concentrations, given the modest increase in PETCO2. Differences in parameters of breath timing and shape between sevoflurane and halothane suggest different effects of these anesthetic agents on ventilatory control.

Anesthetics, Inhalation↗

Validation of respiratory inductive plethysmography using the Qualitative Diagnostic Calibration method in anaesthetized infants.

The aim of this study was to compare tidal volume (VT) derived from the Qualitative Diagnostic Calibration (QDC) method (VT,QDC) with measurements from pneumotachography (VT,PN,T) in anaesthetized infants. Measurements were made during spontaneous (SV) and intermittent positive pressure (IPPV) ventilation, sighs and airway occlusions. The VT,DIF was the difference between VT,QDC and VT,PNT (%VT). The contribution of the ribcage (rc) to VT,QDC (%rc) and the thoracoabdominal phase lag were also derived. Twenty-eight infants, mean (SD) age 14.0 (6.2) months were studied. VT,QDC represented VT,PNT most closely when > or = 20 breaths were analysed. There was close agreement during SV immediately after the calibration period (95% limits of agreement (LA; QDC - PNT) -23, 3.0%). The 95% LA increased to -9.6, 10.2% after 10 min. Accuracy diminished during IPPV (95% LA -38, 31%), and sighs. During airway occlusions, when VT,PNT was zero, the 95% LA were -63, 4.1 mL x kg(-1). Mean phase lag was 36 and 2%, respectively, during SV and IPPV (p<0.05). The %rc appeared to be overestimated, being in excess of 50% in infants under 12 months. The Qualitative Diagnostic Calibration method used to estimate tidal volume in anaesthetized infants was limited by the need to analyse > or = 20 breaths and by a loss of within-subject accuracy if measurement conditions or pattern of breathing changed.

Anesthesia, General↗

Epidemiology of IgA nephropathy in central and eastern Kentucky for the period 1975 through 1994. Central Kentucky Region of the Southeastern United States IgA Nephropathy DATABANK Project.

Population-based incidence data for IgA nephropathy (IgAN) are available for some countries but not for the United States. The purpose of this study was to determine the incidence of IgAN in central and eastern Kentucky for 5- and 10-yr periods between 1975 and 1994 and to examine differences among patient groups between those periods. The incidence of IgAN was 5.4 cases per one million population per year (MPPY) for period 1A (1975 through 1979), increasing to 12.4 cases per MPPY for period 2B (1990 through 1994) (P < 0.001). Males had a 2.7 times higher incidence than females for period 1 (1975 through 1984) and 2.2 times higher for period 2 (1985 through 1994). For period 1A, the incidence for Fayette County, which includes the city of Lexington, was lower than that of the rest of the study area (P=0.26), whereas for period 2 the incidence was higher for Fayette County (P=0.052). During period 1, the highest incidence of IgAN for any age and gender group was 24.3 cases per MPPY for males ages 30 through 39. For period 2, the incidence for males was similar for each decade between ages 20 and 59 (approximately 19 cases per MPPY). No African-American was diagnosed during period 1, but in period 2 incidences for blacks and whites were similar (10.7 and 10.2 cases per MPPY, respectively). For the last 5 yr of the study (1990 through 1994), the incidence of end-stage renal disease (ESRD) due to IgAN was 5.5 cases per MPPY: 8.4 for males and 2.7 for females. The incidence of IgAN in Kentucky for period 2B was still much lower than that in European studies, but the incidence of ESRD due to IgAN may be similar. Thus, IgAN may be as important a condition with respect to ESRD in Kentucky as it is in other regions of the world.

Adolescent↗

Using scalarane sesterterpenes to examine a sponge taxonomic anomaly.

A parallel study was conducted on two Indo-Pacific foliose sponges. The first specimen contains 3-hydroxy-20,22-dimethyl-20-deoxoscalarin (2), while the second contains 3-oxo-20,22-dimethyl-20-dioxoscalarin 8 (3). The physical properties as well as X-ray results confirming the structure and stereochemical features of these compounds are presented first. The difficulty we encountered in the taxonomic identification of these species is also discussed. One of our specimens is identical to material considered by different taxonomists as either Phyllospongia vermicularis or Dysidea vermicularis. The other is identified as Carteriospongia sp. We outline that the parallel chemistry of these two specimens suggests that they are closely related taxonomically.

Animals↗

3-Benzisothiazolylpiperazine derivatives as potential atypical antipsychotic agents.

A series of substituted phenethyl derivatives of 3-benzisothiazolylpiperazine incorporating potent D2 and 5-HT2A antagonist activity was investigated as an approach to a novel atypical antipsychotic agent. The in vitro profile of 8e from this series is a combination of D2 receptor affinity comparable to the typical antipsychotic agent haloperidol and a 5-HT2A/D2 ratio comparable to the atypical agent clozapine. In vivo 8e possesses activity consistent with an efficacious antipsychotic agent with less tendency to induce extrapyramidal side effects in man.

Amphetamine↗

A new microtransducer catheter for measuring esophageal pressure in infants.

Measurement of esophageal pressure, as a reflection of pleural pressure, is essential for assessment of dynamic lung mechanics in neonates and infants. Conventionally, an esophageal balloon or a fluid-filled catheter is used, but considerable skill is required to obtain accurate results. Both devices have problems, and failure to achieve valid occlusion tests have been reported, particularly in small infants with lung disease. Recently, a flexible #3 French gauge (FG) microtransducer catheter (MTC, Dräger Netherlands) has become available for medical monitoring. We have assessed the accuracy and feasibility of using this device for measuring lung mechanics in 51 spontaneously breathing infants and small children aged 1 day to 24 months (weight 1.35 to 12.0 kg), 9 of whom were healthy neonates, the remainder suffering from a variety of cardio-respiratory diseases, and in 18 sick ventilated infants (weight 0.6 to 4.0 kg). Positioning of the catheter was well tolerated by all infants. The ratio of esophageal to airway opening pressure changes (delta Pes:delta Pao) ranged from 0.94 to 1.09 [mean (SD) 1.013 (0.03)] for the spontaneously breathing infants and from 0.98 to 1.06 [mean (SD) 1.003 (0.02)] In the ventilated infants with no significant difference in this ratio between the two groups (p = 0.16). This new generation of catheter tip pressure transducers may provide a simpler and more reliable tool for assessing transpulmonary pressure changes in infants than has previously been available.

Catheterization↗

Studies on caprine responsiveness to nematodiasis: segregation of male goats into responders and non-responders.

Eighty-three 2-4-year-old intact male goats exposed to a combination of artificial and natural challenge were segregated into responders and non-responders by ranking of weekly faecal egg counts (FECs). Retrospective analysis of samples over a 15-week-period showed responders had a statistically lower mean FEC than non-responders. Estimates of repeatability between consecutive egg counts were significant in both groups. The 6 top responders and bottom non-responders were subsequently given an artificial trickle challenge with Teladorsagia circumcincta and Trichostrongylus vitrinus. Mean faecal egg output was significantly lower in responders than non-responders. Peripheral eosinophil numbers following challenge were significantly greater in responder than non-responder goats. Abomasal and intestinal worm burdens were considerably lower in responders, with evidence of retardation of worm development compared to non-responders. Both abomasal and jejunal tissue eosinophil numbers were significantly higher in responders, although there was no difference in mucosal mast cell or globule leucocyte numbers. These results suggest that under temperate climatic conditions, it is possible to segregate male goats into responders and non-responders on the basis of simple parasitological criteria.

Abomasum↗