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Biomedical subjects

S J Kelly

Publications and source records attributed to S J Kelly.

At least 37 records · Page 2Linked to original sources

Comparison of social abilities of children with fetal alcohol syndrome to those of children with similar IQ scores and normal controls.

Children diagnosed with fetal alcohol syndrome (FAS) were assessed with items from the social skills domain of the Vineland Adaptive Behavior Scales (VABS) via interviews with their caregivers. Their scores were compared with scores from children in two control groups. The control groups included children matched for IQ to the FAS group (specifically on verbal IQ, henceforth, the VIQ group) and children with IQ scores in the average to above-average range (normal control group). Forty-five children (age range, 5 years 7 months to 12 years 11 months) were assessed (n/group = 15). All groups differed with regard to social ability, as measured by the VABS (NC > VIQ > FAS), even when the effects of socioeconomic status were held constant. The three subdomains of the VABS social scale (interpersonal relationship skills, use of play and leisure time, and coping skills) were assessed, and results showed that the children with FAS were most impaired on the subdomain that assessed interpersonal relationship skills. An additional measure was constructed by obtaining an age-equivalent score for the VABS social scale and calculating a difference score by subtracting the child's chronological age from his/her age-equivalent score. There was a significant correlation between chronological age and difference scores for children in the FAS group but not for children in the two control groups. Specifically, in older children with FAS, there was an increased discrepancy between their ages and their age-equivalent scores, a discrepancy that was not present in children in the control groups. These results suggest that social deficits in children with FAS are beyond what can be explained by low IQ scores and indicate that there may be arrested, and not simply delayed, development of social abilities in children with FAS.

Child↗

Development of heart inter-beat interval variability in preweanling rats: effects of exposure to alcohol and hypoxia.

The effect of alcohol exposure and hypoxia on the development of heart rate and heart inter-beat interval (IBI) variability was studied in preweanling rats. Rats were artificially reared from postnatal day (PD) 4 through 12 and either exposed to alcohol (5 g/kg/day) or hypoxia (2-15-min episodes/day) from PD 4 to 10. Control groups consisted of artificially reared and normally reared rats not exposed to alcohol or hypoxia. The heart rate and respiration was recorded for 20-min sessions every other day from PD 5 through 21. Inter-beat intervals and measures of their variability caused by respiratory sinus arrhythmia (RSA) were computed from the recordings. There was a steady decline in average IBI across this age range. There was little change in RSA from PD 5 to 15, followed by a large increase in RSA level from PD 15 to 21. The alcohol- and hypoxia-exposed rats showed significantly less increase in RSA level on PD 19 and 21. Large bradycardias occurred in all groups on PD 5, 9, and 17, and were more prevalent in rats exposed to alcohol or hypoxia. These data suggest that neural control of the chronotropic functions of the heart undergoes major changes in the late preweanling stage, and the changes in neural control are slowed by hypoxia or alcohol exposure during the early postnatal period.

Animals↗

Sustained remission of severe resistant autoimmune neutropenia with Campath-1H.

We report the course of a patient with severe autoimmune neutropenia in whom only transient responses occurred with corticosteroids, antilymphocyte globulin and granulocyte-colony stimulating factor, and who was resistant to treatment with azathioprine, cyclosporin and intravenous immunoglobulin. A 10 d course of intravenous Campath-1H monoclonal resulted in a sustained haematological response. The long-lasting effect of Campath-1H may be due to its remarkable ability to induce a profound and prolonged peripheral blood T lymphopenia.

Alemtuzumab↗

Mental calculation in an autistic savant: a case study.

We present a detailed investigation of mental calculation in RH, an autistic savant. In Experiment 1 RH performed faster and more accurately than control subjects in mentally solving multi-digit multiplication problems. However, we found no evidence that RH employed short-cut strategies to solve these problems. His response times were consistent with application of a left-to-right computational procedure employed by expert calculators. He also responded extremely quickly to 2-digit squares, suggesting that he may have memorized the answers. In Experiment 2 we taught RH a new computational algorithm for converting temperatures from Celsius to Fahrenheit. RH was able to learn the new algorithm, but required much assistance and made only slight gains with practice. RH did not recognize an easy solution strategy based on inverting steps in the conversion algorithm. We suggest that the inflexible nature of RH's performance may reflect his autistic tendencies coupled with limited intelligence.

Adult↗

Biocompatibility of silver-modified polyester for antimicrobial protection of prosthetic valves.

BACKGROUND AND AIMS OF THE STUDY: The biocompatibility of a silver-coated polyethylene terephthlate (PET, polyester) fabric for the inhibition of prosthetic valve endocarditis (PVE) associated with mechanical heart valves (MHVs) was assessed. The infrequency of PVE is outweighed by mortality rates commonly exceeding 50%. These high mortality rates have been attributed to the poor effect of antibiotic therapy on colonized valves and infected myocardial tissue. Silver has been used as an antimicrobial for centuries due to its general effectiveness and relative lack of toxicity. Our previous work has shown PET polyester fabric coated with metallic silver by an ion beam-assisted deposition (IBAD) process to: (i) be effective in vitro in the inhibition of microbial attachment and colonization; (ii) be tightly adherent and low leaching; and (iii) promote tissue ingrowth and the organization of tissue pannus in a short-duration (five weeks) sheep mitral mechanical heart valve model. METHODS: This paper addresses additional biocompatibility assessment consisting of a cell compatibility assay in which serum extracts of silver-coated fabric were exposed to fibroblasts for 48 hours, after which cell viability and function were measured. The amount of silver in the extract was measured using elemental analysis techniques. RESULTS: No signs of toxicity were seen in the cells until the extract concentration reached 1200 p.p.m. Ten-week duration mechanical valve replacement studies in sheep with uncoated or coated polyester sewing cuffs showed comparable tissue ingrowth and mature pannus with a suggestion of a thinner pannus on the silver-coated fabric. Additional antimicrobial testing confirmed the effectiveness of this coating in inhibiting colonization of polyester fabric. CONCLUSIONS: These current results, together with the earlier data, suggest that IBAD silver coating on polyester facilitates healing and may provide protection against PVE.

Animals↗

Alcohol exposure during development alters hypothalamic neurotransmitter concentrations.

The effect of exposure to alcohol during a period roughly equivalent to the human third trimester on neurotransmitter content in the rat hypothalamus was examined. The alcohol exposure was accomplished via an artificial rearing procedure. The alcohol group was exposed to 5 g/kg/day of ethanol from postnatal day (PD) 4 to 10. There was an artificially reared control group not exposed to alcohol and a normally reared control group. Noradrenaline, dopamine, homovanillic acid (HVA), 3,4-dihydroxyphenylacetic acid (DOPAC), serotonin, and 5-hydroxyindoleacetic acid (5-HIAA) concentrations were measured using high performance liquid chromatography with electrochemical detection in juvenile and adult rats. There were no effects in juvenile rats. In adult rats, alcohol exposure from PD 4 to 10 increased hypothalamic content of noradrenaline, dopamine, serotonin and 5-HIAA. While adult females had greater amounts of hypothalamic serotonin and 5-HIAA than adult males, there were no interactions of sex with alcohol exposure. These results suggest that hypothalamic function is seriously disrupted by alcohol exposure during development.

Aging↗

Early postnatal alcohol exposure in rats: maternal behavior and estradiol levels.

Long Evans male and female rats were exposed to alcohol or control conditions during the early postnatal period, and their maternal behavior was assessed between 25 and 29 days of age. Maternal behavior was induced by exposing experimental animals to pups, and behaviors included retrieval of pups and proximity to pups. After 5 days of continuous exposure to pups, experimental animals were decapitated, and trunk blood was measured for levels of estradiol and progesterone. Alcohol-exposed animals showed a deficit in maternal behavior as measured by a longer latency to retrieve pups than rats that were not treated with alcohol. In addition, alcohol-exposed animals had lower levels of circulating estradiol than controls. These effects may also be explained by undernutrition as a result of artificial rearing. No difference in progesterone levels was found. As estradiol is important for the onset of maternal behavior in adult rats, it may be that the alcohol-induced decrease in estradiol levels underlies the deficit in maternal behavior exhibited by alcohol-exposed rats.

Animals↗

Effects of alcohol exposure and artificial rearing during development on septal and hippocampal neurotransmitters in adult rats.

The effect of alcohol exposure during the early postnatal period in the rat on the hippocampus and septal region was investigated. The alcohol group was given 5 g/kg/day of ethanol from postnatal days 4 to 10 via an artificial rearing procedure. Control groups consisted of a gastrostomy control group that was treated in the same manner as the alcohol group, but not exposed to alcohol and a suckle control group that was reared normally by dams. Between 90 and 100 days of age, the hippocampus and septal region were assayed under nonstressed or stressed conditions using HPLC with electrochemical detection. Alcohol-exposed female rats exhibited increased hippocampal noradrenaline concentrations under stressed conditions, increased septal serotonin, and 5-hydroxyindoleacetic acid (5-HIAA) concentrations under nonstressed conditions, and decreased septal dopamine concentrations under stressed conditions. Artificially reared male rats (regardless of alcohol exposure) exhibited an increase in hippocampal noradrenaline concentrations under stressed conditions; a decrease in hippocampal 5-HIAA concentrations under nonstressed conditions; and a decrease in septal noradrenaline, serotonin, 5-HIAA, and dopamine concentrations under nonstressed conditions. The results suggest that female rats may be more susceptible to alcohol exposure during the postnatal period than male rats and that male rats may be more susceptible to the effects of artificial rearing than female rats.

Animals↗

Effects of colchicine on IgE-mediated early and late airway reactions.

BACKGROUND: The pathogenesis of bronchial asthma is thought to involve elements of both acute and chronic inflammation. Hence, there is growing interest in the potential of immunomodulatory drugs in asthma therapy. This study examines the effects of the anti-inflammatory compound colchicine on early and late allergen-induced, IgE-mediated airway reactions. METHODS: Nine mildly allergic asthmatic subjects were evaluated in a single-blind, two-way crossover study designed to examine the effects of colchicine and placebo on early and late airway reactions to ragweed allergen and related changes in nonspecific responsiveness to methacholine. RESULTS: Compared with placebo, colchicine provided 19% (p = 0.036) and 40% (p = 0.004) inhibition of early and late airway reactions to allergen, respectively. Allergen-induced increases in methacholine responsiveness were observed with both types of treatment, although there was a trend toward a smaller increase after administration of colchicine (p = 0.13). We also found that methacholine responsiveness per se was not directly altered by colchicine (n = 7). In 6 subjects, we found suppression of neutrophil leukotriene B4 generation after colchicine treatment, suggesting that the colchicine dose (0.6 mg twice daily) was sufficient to produce an anti-inflammatory effect. Further in vitro studies using purified human lung tissue mast cells failed to demonstrate inhibition of mediator release at concentrations corresponding to achievable tissue or blood levels during the in vivo trial. CONCLUSION: Colchicine partially inhibits IgE-mediated early and late airway reactions at conventional clinical doses. This inhibitory effect may be mediated via suppression of some cell species other than the lung tissue mast cell. Controlled studies to examine the benefits of colchicine in clinically evidenced asthma are warranted.

Adult↗

Acute myelomonocytic leukaemia following atypical congenital rubella.

The child of a woman immunised against rubella presented at 5 months with developmental delay and recurrent infection; she was shown to have congenital rubella. At 15 months she developed acute myelomonocytic leukaemia (AMML). Rubella is difficult to diagnose after immunisation. AMML has not been previously described in association with congenital rubella, as far as is known.

Bone Marrow↗

Recognizing acute health effects of substitute fungicides: are first-aid reports effective?

Recently, many British Columbia sawmills stopped using traditional chlorophenate anti-sapstain fungicides and substituted 2-(thiocyanomethylthio) benzothiazole (TCMTB) and copper-8-quinolinolate (Copper 8). We conducted a cross-sectional study with two aims: to ascertain which acute health effects, if any, were associated with the use of the substitute fungicides; and to determine the effectiveness of first-aid records as a means of detecting acute health outcomes. Workers in five coastal sawmills were asked to complete a self-administered questionnaire about symptoms considered potentially related and unrelated to fungicide exposure, and about injuries commonly reported in sawmills. In addition, we collected first-aid records from the mills, and asked senior workers to estimate the duration of exposure to fungicides for each job. Symptoms found to be consistently elevated in TCMTB mills included dry skin around the eyes, blood-stained mucus from the nose, nose bleed, peeling skin, burning or itching skin, and skin redness or rash. No symptoms were consistently elevated in the Copper 8 mills. Symptoms related to TCMTB exposure were recorded only 12 times in first-aid logs during the study period (versus 335 questionnaire self-reports). This low symptom-recording frequency may be a function of established patterns of first-aid use in which illness symptoms are reported less frequently than injuries.

Acute Disease↗

Molecular characterization of a novel 10.3 kb deletion causing beta-thalassaemia with unusually high Hb A2.

A family of Asian-Indian descent has a variant form of beta-thalassaemia characterized by unusually high levels of Hb A2 in the heterozygous state. The propositus who is homozygous for the mutation has thalassaemia intermedia. Restriction endonuclease mapping suggested the presence of a 10.3 kilobase (kb) deletion removing the whole of the beta-globin gene. Subsequently, molecular analysis was performed by directly sequencing a specifically amplified region of genomic DNA. A 10329 basepair deletion was precisely defined which results in the loss of the 5' beta promoter region and the entire beta-globin gene. The deletion extends from 3011 bp 5' to the mRNA cap site to an L1 repeat element downstream of the beta-globin gene and is very similar to the 12.6 kb deletion of Dutch beta zero-thalassaemia. In common with four other mutations, both these deletions remove the 5' promoter region of the beta gene and all are associated with unusually elevated levels of Hb A2 in the heterozygous state.

Adult↗

Indices of stress in rats: effects of sex, perinatal alcohol and artificial rearing.

Three groups of rats were normally reared by dams, artificially reared but not exposed to alcohol or artificially reared and exposed to 6.6 g/kg/day of ethanol condensed into 8 h of each 24-h period. Alcohol exposure was given from postnatal day 4 through 9 and artificial rearing was conducted from postnatal day 4 to 12. In adulthood, approximately half of the rats were fitted with a chronic jugular catheter and were exposed to swim stress for 1 min in 21 degrees C water. Alcohol exposure augmented the corticosteroid stress response to the swim stress in female rats but not in male rats. The other half of the animals were tested for acquisition and extinction of a conditioned emotional response (CER). While alcohol exposure had no effects on the CER, extinction of CER was greatly accelerated by artificial rearing alone in female rats but not in male rats. Taken together, these findings suggest that some aspects of the stress response in female rats are more vulnerable to insults during the early postnatal period than those in male rats and that the insult-induced alterations can affect hormonal and behavioral measures differentially.

Adrenal Cortex Hormones↗

Neonatal alcohol exposure alters suckling behavior in neonatal rat pups.

Prenatal alcohol exposure has been associated with a variety of suckling deficits in both humans and animals. In this study, the effect of neonatal alcohol exposure on suckling performance was examined in 15-day-old rat pups. Neonatal alcohol exposure has been used as a model to study the effects of alcohol exposure during a period equivalent to the human third trimester with respect to brain growth. Subjects were Long-Evans rats which had been artificially reared (AR) and fed through gastrostomy tubes from postnatal day (PN) 4-PN 12. The AR groups included two groups given ethanol doses of 6 g/kg/day or 4 g/kg/day and an isocaloric maltose-dextrin control group. A suckled control group raised by their natural mothers was also included to control for artificial rearing. Fifteen-day-old pups were individually placed with an anesthetized dam for a 1-h videotaped test session. Pups in the 6 g/kg alcohol group took longer to attach to the nipple and spent less time suckling than pups from all other treatment groups. Nipple-shifting behavior was disrupted in all artificially reared groups, but it was most severely affected in the 6 g/kg group. These findings suggest that neonatal alcohol exposure interferes with suckling performance and these altered behaviors may contribute to the postnatal growth deficits that have been reported following alcohol exposure in utero.

Animals↗

Nocardiosis in an immunocompromised patient--an unusual presentation.

A case of disseminated nocardiosis in a 39-year-old immunosuppressed patient is described. This presented clinically as a septicaemia with meningitis, and the true diagnosis was delayed following an apparent initial response to broad-spectrum antibiotics. The need for increased awareness of unusual infections in immunosuppressed patients who may have had repeated and sometimes invasive diagnostic techniques is discussed.

Adult↗

The development of the U.S. EPA health effects research laboratory frozen blood cell repository program.

We have suggested that proper blood-cell freezing and storage is necessary in longitudinal studies with reduced between tests error, for specimen sharing between laboratories and for convenient scheduling of assays. Our present purpose is to describe the design and use of a prototype computer program, Cryovial, for data-based management of frozen cell repositories. We are pleased to provide, free of charge upon request, a 5.25" (specify 0.36 or 1.2 MB) disk containing all files required to run Cryovial.

Blood Preservation↗