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Biomedical subjects

J Thompson

Publications and source records attributed to J Thompson.

At least 847 records · Page 47Linked to original sources
PubMedDate not supplied

Association of emergence of HLA antibody and acute rejection in intestinal transplant recipients: a possible evidence of acute humoral sensitization.

Development of HLA antibody has been associated with chronic allograft failure in kidney recipients. We tested HLA antibody in posttransplant sera of intestinal recipients: 126 sera from 28 pediatric recipients were tested for HLA antibody by flow PRA (f-PRA). Median age was 1.1 years (0.44-17). Graft types included isolated intestine (n = 6), liver and intestine (n = 3), modified multivisceral (n = 3), and multivisceral grafts (n = 16). Greater than 10% of either class I (CI) or class II (CII) f-PRA was considered positive, and >30% strongly positive. Five of 28 patients had positive f-PRA in multiple samples; the remaining 23 had either no positive or only one positive sample. Three patients had strongly positive f-PRA. Patients with multiple positive samples were recipients of two modified multivisceral and three multivisceral grafts. Only one of these patients had a positive PRA pretransplant. Cytotoxic cross-match at transplant was negative for all. The three with strongly positive f-PRA showed significant episodes of rejection around the time of positive samples. One of them who persistently had f-PRA value >80% (from day 13-113) died of refractory rejection. The other two had f-PRA of 76% and 53% during the early postoperative course with associated episodes of rejection. F-PRA value decreased with rejection therapy. Only one of the 23 patients (4%) with negative f-PRA had an episode of rejection around the time of sample collection. Development of HLA antibody after intestinal transplantation seems to have significant association with acute rejection episodes.

Adolescent↗
PubMedDate not supplied

Inclusion of spleen in pediatric multivisceral transplantation.

Inclusion of the donor spleen may be beneficial for small children who receive multivisceral transplantation (MVT) because asplenia is associated with increased risk of bacterial sepsis. Beginning in 2003, the spleen was transplanted together with multivisceral transplantation in 17 children under daclizumab induction (spleen group). The results were compared to 23 children who received multivisceral transplantation without the spleen (control group) with the same immunosuppression regimen. Median age of 17 patients who received a spleen was 0.80 years (range 0.54-1.66). Platelet counts at 30 and 60 days posttransplant were significantly lower in the spleen group (average values: day 30: 399,000 vs 636,000, P = .015; day 60: 413,000 vs 622,000, P = .0056). WBC counts at 30 and 60 days posttransplant were also decreased in the spleen group but the difference was not statistically significant. Median rejection-free survival was 205 days in the spleen group and 101 days in the control group (P = NS). Median length of hospital stay was 39 days in the spleen group and 61 days in the control group. With a median follow-up of 398 days (spleen group) and 1232 days (control group), 3 of 17 (17%) in the spleen group developed graft versus host disease (GVHD), whereas 1 of 23 (4.5%) in control group did (P = NS). In one patient in each group, GVHD was fatal. No patient developed posttransplant lymphoproliferative disorder (PTLD) in the spleen group, whereas 4 of 23 (17%) in the control group developed PTLD. One-year patient survival was 84% in the spleen group and 86% in the control group. Recipients of the spleen as part of a multivisceral graft had significantly lower platelet counts. Rejection-free survival may be prolonged, but the risk of GVHD may be increased.

Antibodies, Monoclonal↗
PubMedDate not supplied

Expanded use of multivisceral transplantation for small children with concurrent liver and intestinal failure.

Fifty-five children with liver and intestinal failure have been transplanted at our center under daclizumab induction therapy since 1998. Of those, 19 received five multiviceral transplantation (MVT), 12 liver-intestine-pancreas transplants, and 2 noncomposite liver and intestine transplants (NCLIT) before 2001 (group 1). During this period, MVT was only used in children with gastric dysmotility. After 2001, we expanded the use of MVT. Therefore, 36 children in this period (group 2) received MVT except for two who received NCLIT. Median age was 1.08 in group 1 and 1.06 in group 2. Median recipient weight was 8.2 kg in group 1 and 7.5 kg in group 2. Six-month, 1-, and 2-year patient survivals were 54%, 37%, and 32% in group 1 and 94%, 91%, and 71% in group 2 (P = .00037). A statistically significant difference was observed in freedom from rejection between the two groups with group 2 being favorable (P = .0019). A statistically significant difference was observed in freedom from rejection between the two groups with group 2 being favorable (P = .0019) Four died of rejection in group 1 (21%); none died of rejection in group 2. There have been two esophago-gastrostomy strictures (one in each group) and a serious reflux of this anastomosis (group 2). Strictures were treated with balloon dilatation, and the reflux was surgically corrected. In 24 recent cases, gastro-gastric anastomosis was used in MVT with no complications to date. No pancreatic rejection was seen. Small children tolerated MVT with improved survival rates and reduced rates of rejection. Use of MVT may be considered as an alternative to liver-intestine-pancreas transplant.

Antibodies, Monoclonal↗
PubMedDate not supplied

Analysis of rejection episodes in over 100 pediatric intestinal transplant recipients.

Rejection after intestinal transplant is a significant source of morbidity and mortality. We analyzed number of rejections, severity, and duration of episodes in pediatric recipients of intestinal transplants. One hundred eighteen intestinal transplants were performed: intestine (n = 27), liver-intestine (n = 27), modified multivisceral (n = 7), and multivisceral (n = 57). A total of 186 rejections were classified: mild (n = 89), moderate (n = 70), severe (n = 27). Duration of episodes doubled for each increasing step in severity. Treatment of mild rejection was with steroids, moderate rejection was treated with OKT3, severe rejection required OKT3 and organ removal. Most rejections occurred during the first month posttransplant, with the incidence of all rejections declining after 6 months posttransplant. Intestine and liver-intestine recipients had significantly higher probability of developing severe rejections, as compared to MVT. In summary, recipients of MVT seemed to be protected from rejection as compared to intestine or liver-intestine recipients.

Adolescent↗
PubMedDate not supplied

Characterisation of the cardiovascular pharmacology of medetomidine in the horse and sheep.

Medetomidine was administered to sheep and horses at a dose rate of 5 microg kg(-1) (i.v.). Heart rate and blood pressure were recorded. Medetomidine induced bradycardia and a biphasic blood pressure response consisting of a transient hypertension followed by hypotension. Administration of prazosin (an alpha1 adrenoceptor antagonist; 100 microg kg(-1), i.v.) had no effect on the cardiovascular response to medetomidine (5 microg kg(-1), i.v.), but inhibited the cardiovascular response of methoxamine (an alpha1 adrenoceptor agonist; 75 microg kg(-1), i.v.). L-659,066 (an alpha2 adrenoceptor antagonist which does not cross the blood brain barrier; 264 microg kg(-1), i.v.) attenuated the medetomidine induced bradycardia, but had no effect on the cardiovascular response to methoxamine. L659,066 also reduced the medetomidine induced hypertension in sheep, but had less effect on the horse. It is concluded that both alpha1 and alpha2 adrenoceptors are important in the control of cardiovascular function in horses and sheep. Medetomidine appears to act on alpha2 adrenoceptors alone in the sheep. The cardiovascular effects of medetomidine in the horse are complex and may be influenced by central alpha2 adrenoceptor regulation or effects on other receptor subtypes as well as direct stimulation of peripheral alpha2 adrenoceptors.

Adrenergic alpha-Agonists↗
PubMedDate not supplied

Genetic construction and characterization of an anti-monkey CD3 single-chain immunotoxin with a truncated diphtheria toxin.

We have previously developed a chemically conjugated anti-rhesus monkey CD3 immunotoxin FN18-CRM9 that can deplete in vivo T cells and induce long term tolerance of mismatched renal allograft in rhesus monkeys. This immunotoxin is a monkey analogue of anti-human CD3 immunotoxin UCHT1-CRM9. In this study, we cloned the light and heavy chain variable regions of anti-monkey CD3 monoclonal antibody FN18 and constructed a single-chain Fv (sFv) by linking variable light and variable heavy regions with a (Gly4Ser)3 linker. The single-chain immunotoxin DT390-FN18sFv was constructed by ligating the sFv to the carboxyl terminus of DT390, a truncated form of diphtheria toxin. The DT390-FN18sFv fusion protein was expressed in Escherichia coli and purified with Ni-RTA affinity and anion exchange columns. Similar to the chemically conjugated immunotoxin FN18-CRM9, DT390-FN18sFv can also specifically inhibit protein synthesis in primary monkey T cells in a dose-dependent manner. DT390-FN18sFv at 10(-7) mol/L or FN18-CRM9 at 10(-8) mol/L is sufficient to reduce protein synthesis of monkey primary T cells to less than 5% of the control. The 50% inhibition dosage (IC50) of FN18-CRM9 is 1 x 10(-10) mol/L, while the IC50 of DT390-FN18sFv is 1 x 10(-8) mol/ L, reflecting the lowered affinity of monovalent Fab' FN18 to its parental divalent antibody. The availability of functional FN18sFv will provide the basis for the construction of divalent anti-CD3 immunotoxins for preclinical studies on the induction of tolerance in organ transplantation and experimental autoimmune diseases.

Adenosine Diphosphate Ribose↗
PubMedDate not supplied

Clinical studies of pneumococcal vaccines in infants. I. Reactogenicity and immunogenicity of two polyvalent polysaccharide vaccines.

Normal infants, selected at six months of age for participation in one of two separate studies of polyvalent pneumococcal vaccines, octavalent vaccine for Eli Lilly Laboratories (Indianapolis, Ind.) and 14-valent vaccine from Merck Sharp & Dohme (West Point, Pa.), were assigned randomly to groups to receive vaccine at six and/or 12 months of age or to control (unvaccinated) groups. Serum collected at ages six, seven, 12, 13, and 24 months provided pre- and postvaccination geometric mean titers (GMTs) as well as information about persistence of antibody titers. Clinical reactions were monitored by a home visit at 24 hr after each injection. The octavalent vaccine, when given at six months of age, stimulated significant antibody against Streptococcus pneumoniae type 3 and against types 3, 7, 18, and 23 when given at 12 months of age; GMTs were significantly higher than those of controls of the same ages (P less than or equal to 0.05). The 14-valent product, given at 12 months of age, was immunogenic against types 6, 7, 8, and 14 when GMTs were compared with those of controls (P less than or equal to 0.05). Vaccination at six months of age was followed by depressed GMTs on revaccination. Natural acquisition of antibody was indicated by rising GMTs in the unvaccinated controls, who had an increase of greater than or equal to 1.8-fold for all types during the interval between six and 13 months of age. By the age of 24 months, GMTs of all groups were similar. Clinical reactions were mild and brief (less than or equal to 36 hr). Results of these studies indicate that modification of the vaccines is needed for improvement of the immunogenicity in infants.

Antibodies, Bacterial↗
PubMedDate not supplied

Effect of systemic estrogen on seizure susceptibility in the immature animal.

Estrogens have previously been reported to be proconvulsants in adult animals. This study evaluated the effects of acute, high-dose estrogen administration on rate of kindling in immature rats. No significant differences in rate of kindling between the estrogen-treated rats and controls were noted. This study, using the kindling model, demonstrates that estradiol does not have a significant effect on the development of seizures in the immature animal.

Animals↗
PubMedDate not supplied

Failure of ACTH to alter transfer kindling in the immature brain.

For a study of the effects of ACTH on established seizures, 16-day-old rats that had been previously kindled in the amygdala were given a high daily dosage of ACTH gel for 15 days and then underwent transfer kindling in the contralateral amygdala. There were no significant differences in the rate of transfer kindling between the controls and ACTH-treated rats. This study indicates that in the immature animal ACTH does not alter the kindled state.

Adrenocorticotropic Hormone↗
PubMedDate not supplied

The utility of cerebrospinal fluid examination in patients with partial epilepsy.

The initial evaluation of patients with seizure disorders frequently includes cerebrospinal fluid (CSF) examination in order to identify an underlying cerebral lesion. With increasing use of computed tomography (CT) scanning to detect cerebral neoplasms, the value of CSF examination has become less certain. The significance of mild CSF abnormalities in patients with a normal CT scan remains unknown. We reviewed the records of 95 patients with adult onset partial epilepsy whose initial evaluation included CSF examination and CT scan. A CSF abnormality not temporally related to convulsive seizure was seen in 24 patients (25%). The CSF study confirmed a clinically suspect subarachnoid hemorrhage in 4 patients. Isolated mild (49-106 mg/dl) increases in CSF protein were seen in 19 patients. Of these 19 patients, 8 had a structural lesion on CT scan. Clinical follow-up of the other 11 patients (mean 5 years) has revealed no evidence of a focal lesion or increasing seizure frequency. This suggests that in an adult population with partial epilepsy routine CSF examination may not be necessary and should be reserved for situations in which there is particular clinical indication.

Brain↗
PubMedDate not supplied

Early sibling attachment.

A sample of 30 predominantly three- and four-year-old siblings were videotaped during their first meeting with a new sibling at the time of the mother's discharge from the hospital. The first five minutes of interaction were divided into 20, 15-second intervals, and each interval was coded for the presence or absence of 28 behaviors believed to be related to the early attachment process. The exploration behaviors of siblings showed considerable uniformity. The sibling's age, sex, or participation in sibling preparation classes produced no marked differences in behavior. Recommendations are made for further research.

Attention↗
PubMedDate not supplied

Health promotion and risk reduction in Malawi, Africa, village women.

OBJECTIVE: A train-the-trainer intervention was evaluated in which village leaders in Malawi, Africa, taught other villagers how to improve their health. DESIGN: Health knowledge and reported health practices were compared before and after the educational intervention in 15 villages in Chimutu, Malawi, Africa. SETTING: Surveys were completed by trained data gatherers in the village setting. PATIENTS/PARTICIPANTS: All men and women of childbearing age who were present in the village when data collection occurred were asked to participate. There were 187 participants in the preintervention survey and 175 participants in the postintervention survey. INTERVENTION: Seventy-six village women were trained, using low literacy techniques, to provide content on health promotion and risk reduction in pregnancy. Over 20,000 persons have received at least one health teaching session from the village trainers. RESULTS: The intervention resulted in reported changes in prenatal and postpartum care and in more births occurring in the hospital or clinic. Some positive nutritional changes were reported, although few changes in beliefs about use of herbal medicines or about the use of witchcraft were reported. CONCLUSIONS: A train-the-trainer approach is a sustainable intervention that appears to have positive benefits on the health of village women living in Malawi, Africa.

Adult↗
PubMedDate not supplied

Immunization against SIVmne in macaques using multigenic DNA vaccines.

All structural and regulatory genes of SIVmne were cloned into mammalian expression vectors to optimize expression in vitro and immunogenicity in mice. Macaca fascicularis were immunized four times with plasmid DNA (n = 4), or two DNA priming inoculations followed by two boosts of recombinant gp160 plus Gag-Pol particles (n = 4). Following intrarectal challenge with SIVmne, all macaques became infected. Three monkeys immunized with DNA alone maintained low plasma virus loads by 1 year post-challenge; the fourth exhibited high virus loads and significant CD4+ cell decline. Two of the DNA plus boost and three control macaques had high virus loads and associated CD4+ cell decline. Both vaccine protocols elicited antibodies and comparable helper T-cell proliferative responses to gp160. Cytokine mRNA levels in activated peripheral blood mononuclear cells (PBMC) taken at time of challenge suggested a dominant T helper (Th) 1 state in three DNA-immunized and one protein-boosted macaque, which correlated with low virus loads and high CD4+ cell counts post-challenge.

AIDS Vaccines↗