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Biomedical subjects

T Smith

Publications and source records attributed to T Smith.

At least 361 records · Page 20Linked to original sources
PubMed1996

Plasmodium falciparum malaria in the first year of life in an area of intense and perennial transmission.

A longitudinal study of Plasmodium falciparum malaria in infants in Idete village, south-eastern Tanzania, was conducted over a period of 14 months in order to determine the incidence of P. falciparum infection and clinical malaria in the first year of life. Of 1356 blood slides from cross-sectional surveys, 52.1% were positive for asexual stages of P. falciparum. There were marked increases in P. falciparum prevalence, parasite densities, overall fever incidence and the incidence of malaria fevers with age for the first 6 months of life. The average attack rate, estimated from a reversible catalytic model, was 0.029 per day with a slight increase with age but there was no initial period of protection against infection in neonates. Estimated average duration of infections was 64 days, with infections in older infants lasting much longer than those contracted during the first 2 months of life. These results support the hypotheses that the main effect of passively transferred maternal immunity to malaria is in the control of asexual stage parasites, and that the level of clinical immunity depends upon the extent of recent exposure to parasites. Infants as young as 4 months of age are at high risk of clinical attacks. Intervention programmes against malaria in areas of the highest transmission should therefore be designed to include this group.

Cohort Studies↗
PubMed1996

Peritonitis, functional catheter loss and the sitting of the Dacron cuff in chronic peritoneal dialysis catheters in children.

Functional peritoneal dialysis catheter loss due to persistent or recurrent peritonitis is a common clinical problem in paediatric patients. To examine the effect of positioning of the cuff on infection and loss rate we compared catheters where the cuff was buried in the rectus sheath (deep cuffs) with those where the cuff was sutured to the external oblique muscle, just below the subcutaneous fascia (superficial cuffs). Of 62 catheters inserted into 35 patients (median age 7.76 yrs, range 0-17 yrs) 28 were lost through peritonitis of which 19 (68%) were due to Staph. aureus infection, usually associated with exit site colonisation or infection. 12 out of 20 catheters with superficial cuffs were lost through infection compared with 16 out of 42 with deep cuffs (relative risk reduction 37%, p = ns). Controlling for patient age and infecting organism made no difference to this statistic. 15 out of 21 catheters inserted into patients < 2yrs of age were lost through peritonitis compared to 13 out of 41 catheters inserted into patients over 2 yrs of age (p = 0.037). We conclude that although siting of the Dacron cuff in the rectus sheath is somewhat protective against penetrating infection this is still a major problem in the infant and young child where alternative strategies for the prevention of Staph. aureus infection need to be sought.

Adolescent↗
PubMed1996

Effect of modest vitamin E supplementation on blood glycated hemoglobin and triglyceride levels and red cell indices in type I diabetic patients.

OBJECTIVE: The glycation of proteins and elevated triglyceride (TG) levels are two of the major risk factors in the development of complications of diabetes. Previous studies have found some beneficial effects of supplementation of pharmacological doses (900-2000 IU/day) of vitamin E in Type II diabetic patients. This study examined whether supplementation with a modest dose of vitamin E (100 IU/day) had any effect on blood glucose, glycated hemoglobin (GHb), TG or red cell counts in Type I diabetic patients. METHODS: 35 diabetic patients were supplemented with either DL-alpha-tocopherol (vitamin E) capsules (orally, 100 IU/day) or a placebo for 3 months in a double-blind clinical trial. Fasting blood was collected from each diabetic patient before and after vitamin E or placebo supplementation. Data were analyzed using paired "t" tests and the Wilcoxon Signed Rank Test. RESULTS: Levels of GHb (mean +/- SEM) were 11.5 +/- 0.4 and 12.8 +/- 0.9% (p < 0.05); glucose, 8.8 +/- 1.2 and 11.6 +/- 1.3 mM; and TG, 2.2 +/- 0.2 and 2.9 +/- 0.3 mM (p < 0.03) after vitamin E supplementation versus before supplementation. There were no differences in these parameters after supplementation with the placebo. There was no effect on blood RBC, hematocrit, and hemoglobin levels after supplementation of vitamin E or the placebo. There were no differences in ages and duration of diabetes between placebo and vitamin E-supplemented groups. CONCLUSIONS: This study suggests that modest vitamin E supplementation (100 IU/day) can significantly lower blood GHb and TG levels and does not have any effect on red cell indices in Type I diabetic patients.

Blood Glucose↗
PubMed1996

Smaller children have greater bupivacaine plasma concentrations after ilioinguinal block.

We have measured plasma concentrations of bupivacaine after ilioinguinal block in children of different sizes. We studied 14 children with weights 10-15 kg and 17 children with weights 15-30 kg. Each child received 0.5% bupivacaine 0.25 ml kg-1 (1.25 mg kg-1) (Carbostesin, Astra, Germany). Venous blood was obtained before the block (control) and at 5, 10, 15, 20, 30 and 60 min after block. Mean maximal concentration in the 10-15-kg group (1.5 (SD 0.9) mg litre-1, range 0.43-4.0 mg litre-1, at 18 (5) min) was significantly higher (P < 0.05) than that in the 15-30-kg group (0.9 (0.3) mg litre-1 range 0.35-1.34 mg litre-1, at 16 (5) min). In the 10-15-kg group, unexpectedly high (up to 4 mg litre-1) bupivacaine concentrations were observed and often concentrations remained high (> 2 mg litre-1) at 60 min. We conclude that smaller children appear to differ in the pharmacokinetic handling of bupivacaine. The maximum safe plasma concentration of bupivacaine in small children, although not clearly established, is likely to be approximately 4 mg litre-1. We recommend, therefore, that a dose of bupivacaine 1.25 mg kg-1 should not be exceeded in the perioperative period when performing ilioinguinal block in children < 15 kg in weight.

Anesthesia, Inhalation↗
PubMed1996

Marked hemodilution increases neurologic injury after focal cerebral ischemia in rabbits.

Moderate hemodilution (hematocrit approximately 30%) reduces neurologic injury after focal cerebral ischemia. In contrast, both clinical and experimental studies suggest that marked hemodilution (hematocrit < 30%) may exacerbate neurologic injury. We compared the effect of marked versus minimal hemodilution on cerebral infarct volume after focal cerebral ischemia in rabbits. Anesthetized New Zealand White rabbits underwent hemodilution by exchange of arterial blood with 6% high molecular weight hydroxyethyl starch. In the marked hemodilution group (n = 15) the target hemoglobin concentration was 6 g/100 mL. In the minimal hemodilution group (n = 15) the target hemoglobin concentration was 11 g/100 mL. After hemodilution, middle cerebral artery occlusion was achieved by embolizing an autologous blood clot via the internal carotid artery. Four hours after embolization, the animals were killed and their brains removed. Brains were sectioned, stained with 2,3,5-triphenyltetrazolium chloride, and infarct volumes determined via quantitative image analysis. Systemic physiologic variables were similar between groups, except for arterial hemoglobin concentration. The percentage of hemispheric infarct was significantly larger in the marked hemodilution group as compared to the minimal hemodilution group, 70% +/- 19% vs 51% +/- 23%, respectively (mean +/- SD); P = 0.02. Similarly, the percentage of infarct was greater in the hemodilution group as compared to the minimal hemodilution group in both cortex (73% +/- 18% vs 54% +/- 23%, respectively; P = 0.02) and subcortex (62% +/- 25% vs 44% +/- 23%, respectively; P = 0.04). These findings indicate that marked hemodilution exacerbates neurologic injury resulting from permanent focal ischemia. Although some degree of hemodilution may improve neurologic outcome, the advantage is lost at an extreme level of therapy.

Acute Disease↗
PubMed1996

Rapid rewarming causes an increase in the cerebral metabolic rate for oxygen that is temporarily unmatched by cerebral blood flow. A study during cardiopulmonary bypass in rabbits.

BACKGROUND: Jugular venous hemoglobin desaturation during the rewarming phase of cardiopulmonary bypass is associated with adverse neuropsychologic outcome and may indicate a pathologic mismatch between cerebral blood flow (CBF) and cerebral metabolic rate for oxygen (CMRO2). In some studies, rapid rewarming from hypothermic cardiopulmonary bypass results in greater jugular venous hemoglobin desaturation. The authors wished to determine if rewarming rate influences the temperature dependence of CBF and CMRO2. METHODS: Anesthetized New Zealand white rabbits, cooled to 25 degrees C on cardiopulmonary bypass, were randomized to one of two rewarming groups. In the fast group (n = 9), aortic blood temperature was made normothermic within 4 min. In the slow group (n = 9), aortic blood temperature was made normothermic over 25 min. Cerebral blood flow (microspheres) and CMRO2 (Fick) were determined at baseline (25 degrees C), and at brain temperatures of 28 degrees, 31 degrees, 34 degrees, and 37 degrees C during rewarming. RESULTS: Systemic physiologic variables appeared similar between groups. At a brain temperature of 28 degrees C, CMRO2 was 47% greater in the fast rewarming group than in the slow group (2.2 +/- 0.5 vs. 1.5 +/- 0.2 ml O2.100 g-1. min-1, respectively; P = 0.01), whereas CBF did not differ (48 +/- 18 vs. 49 +/- 8 ml.100 g-1.min-1, respectively; P = 0.47). Throughout rewarming, CBF increased as a function of brain temperature but was indistinguishable between groups. Cerebral metabolic rate for oxygen differences between groups decreased as brain temperatures increased. CONCLUSIONS: Cerebral venous hemoglobin desaturation with rapid rewarming is caused by an increase in CMRO2 that is temporarily greater than the increase in CBF. This mismatch may indicate a transient abnormality in flow-metabolism coupling, or the effect of temperature gradients on oxygen transfer from hemoglobin to brain.

Animals↗
PubMed1996

Intestinal inflammation, ileal structure and function in HIV.

OBJECTIVES: This study examines small intestinal absorption-permeability, intestinal inflammation and ileal structure and function in HIV-positive male homosexuals. METHODS: Thirty HIV-seropositive male homosexuals at various stages of disease underwent intestinal absorption permeability and 111indium leukocyte studies (for quantification of intestinal inflammation). Twenty-six men with AIDS had a dual radioisotopic ileal function test (whole body retention of tauro 23-[75Se]-selena 25-homocholic acid and 58cobalt-labelled cyanocobalamine), and 17 underwent ileocolonoscopy with terminal ileal biopsy. RESULTS: Well, HIV-infected, subjects had normal intestinal absorption-permeability, but both functions were impaired upon the development of AIDS. The median faecal excretion of 111indium in well patients (0.66%) did not differ significantly (P > 0.5) from controls (0.46%), but subjects with AIDS who were well or who had diarrhoea had significant (P < 0.005) intestinal inflammation (1.33% and 2.18%, respectively). The median 7-day retention of tauro 23-[75Se]-selena 25-homocholic acid in well patients with AIDS (38.9%) did not differ significantly (P > 0.2) from controls (39.3%), whereas the absorption of 58cobalt-labelled cyanocobalamine was significantly (P < 0.05) lower than controls (32.1% and 59.4%). Patients with AIDS-diarrhoea had significant (P < 0.001) malabsorption of both the bile acid (7.7%) and vitamin B12 (8.9%) which was more severe than in Crohn's ileitis (14.2% and 30.3%, respectively). Morphometric analyses of ileal biopsies were unremarkable in AIDS. CONCLUSIONS: These studies demonstrate a low-grade enteropathy in patients with AIDS, severe ileal malabsorption in patients with AIDS diarrhoea and relatively minor ileal morphologic changes. Malabsorption of bile acids may play a pathogenic role in patients with AIDS and diarrhoea.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Relationship between the humidity and temperature of inspired gas and the function of the airway mucosa.

OBJECTIVE: To review the available literature on the relationship between the humidity and temperature of inspired gas and airway mucosal function. DATA SOURCES: International computerized databases and published indices, experts in the field, conference proceedings, bibliographies. STUDY SELECTION/DATA EXTRACTION: Two hundred articles/texts on respiratory tract physiology and humidification were reviewed. Seventeen articles were selected from 40 articles for inclusion in the published data verification of the model. Selection was by independent reviewers. Extraction was by consensus, and was based on finding sufficient data. DATA SYNTHESIS: A relationship exists between inspired gas humidity and temperature, exposure time to a given humidity level, and mucosal function. This relationship can be modeled and represented as an inspired humidity magnitude vs. exposure time map. The model is predictive of mucosal function and can be partially verified by the available literature. It predicts that if inspired humidity deviates from an optimal level, a progressive mucosal dysfunction begins. The greater the humidity deviation, the faster the mucosal dysfunction progresses. CONCLUSIONS: A model for the relationship between airway mucosal dysfunction and the combination of the humidity of inspired gas and the duration over which the airway mucosa is exposed to that humidity is proposed. This model suggests that there is an optimal temperature and humidity above which, and below which, there is impaired mucosal function. This optimal level of temperature and humidity is core temperature and 100% relative humidity. However, existing data are only sufficient to test this model for gas conditions below core temperature and 100% relative humidity. These data concur with the model in that region. No studies have yet looked at this relationship beyond 24 hrs. Longer exposure times to any given level of inspired humidity and inspired gas temperatures and humidities above core temperature and 100% relative humidity need to be studied to fully verify the proposed model.

Animals↗
PubMed1996

Vagus nerve stimulation activates central nervous system structures in epileptic patients during PET H2(15)O blood flow imaging.

OBJECTIVE: To determine the central areas of activation by vagal nerve stimulation (VNS) in epilepsy. VNS is a promising neurosurgical method for treating patients with partial and secondary generalized epilepsy. The anti-epileptic mechanism of action from VNS is not well understood. METHODS: We performed H2(15)O PET blood flow functional imaging on three patients with epilepsy in a vagal nerve stimulation study (E04 Protocol with Cyberonics). The three patients included two that had previous epilepsy surgery but continued to have frequent seizures. Seizure onset was frontal in two patients and bitemporal in the third patient. Twelve PET scans per subject were acquired every 10 minutes with a Siemens 953/A scanner. In 6 stimulus scans, VNS was activated for 60 seconds (2 mA, 30 Hz) commensurate with isotope injection. In 6 control scans no VNS was administered. No clinical seizures were present during any scan. Three way ANOVA with linear contrasts subject, task, repetition) of coregistered images identified significant treatment effects. RESULTS: The difference between PET with VNS and without revealed that left VNS activated right thalamus (P < 0.0006), right posterior temporal cortex (P < 0.0003), left putamen (P < 0.0002), and left inferior cerebellum (P < 0.0009). CONCLUSIONS: VNS causes activation of several central areas including contralateral thalamus. Localization to the thalamus suggests a possible mechanism to explain the therapeutic benefit, consistent with the role of the thalamus as a generator and modulator of cerebral activity.

Adult↗
PubMed1996

Evaluation of a novel PCR-based diagnostic assay for detection of Mycobacterium tuberculosis in sputum samples.

We report on a PCR-based assay we have developed for the detection of Mycobacterium tuberculosis in sputum samples. One hundred sputum specimens, which included 34 culture-positive and 66 culture-negative specimens, were evaluated with this system. Of the 34 culture-positive specimens, 31 were PCR positive, and 60 of the culture-negative specimens were PCR negative. An internal standard has been included in the assay system to monitor PCR inhibition and to confirm the reliability of the PCR assay.

Biological Assay↗
PubMed1996

Conditional human immunodeficiency virus type 1 protease mutants show no role for the viral protease early in virus replication.

The human immunodeficiency virus type 1 protease plays a critical role in the proteolytic processing of precursor polyproteins during virion maturation. Contradictory evidence has been obtained for a possible role for the protease early after infection, i.e., during DNA synthesis and/or integration. We have reexamined this question by using conditional mutants of the protease. In one set of experiments, protease mutants that confer a temperature-sensitive phenotype for processing were used to assess the need for protease activity early after infection. No significant difference from results with wild-type virus was seen when infections were carried out at either 35 or 40 degrees C. In a separate set of experiments, infections were carried out in the presence of a protease inhibitor. In this case, both wild-type virus and a drug-resistant variant were used, the latter as a control to ensure a specific effect of the inhibitor. Infection with either virus was not inhibited at drug concentrations that were up to 10-fold higher than those needed to inhibit intracellular processing by the viral protease. The results obtained by both of these experimental protocols provide evidence that the human immunodeficiency virus type 1 protease does not play a role early after infection.

Cell Line↗
PubMed1996

Assessing the site of increased intestinal permeability in coeliac and inflammatory bowel disease.

BACKGROUND: The precise site of intestinal permeability changes in patients with coeliac and inflammatory bowel disease is unknown. AIMS: To design a non-invasive technique for the localisation of altered gastrointestinal permeability to 51chromium labelled EDTA (51CrEDTA). The method depends on comparing and defining concentration/time profiles in serum of a series of simultaneously ingested indicators with a well defined absorption site (3-0-methyl-D-glucose (jejunal indicator), 57cobalt labelled vitamin B12 (ileal indicator), and sulphasalazine (caecal-colonic indicator)) in relation to simultaneously ingested 51CrEDTA. SUBJECTS: Five normal controls, six patients with untreated coeliac disease, five with Crohn's ileitis, and five with pan-ulcerative colitis underwent study, which entailed the simultaneous ingestion of the above four test substances followed, during the next 24 hours, by timed serial collection of urine and serum for marker analysis. RESULTS: Urinary excretion of 51CrEDTA was significantly increased in all patient groups. Analysis of serum appearances and profiles of the markers suggested that the increased intestinal permeation of 51CrEDTA took place in the diseased jejunum in patients with coeliac disease, predominantly in the ileum in Crohn's disease and in the colon in the patients with pan-ulcerative colitis. CONCLUSION: A new non-invasive technique has been assessed that permits the localisation of the site of permeability changes with the gastrointestinal tract.

Adult↗
PubMed1996

Functional STAT 1 and 3 signaling by the leptin receptor (OB-R); reduced expression of the rat fatty leptin receptor in transfected cells.

The leptin receptor (OB-R) bears homology to members of the class I cytokine receptor family. We demonstrate that leptin binding to OB-R stimulates formation of STAT-1 and STAT-3 complexes, thereby defining transcriptional motifs for genes that are under leptin control. Transfected fa OB-R bound leptin with equal affinity to that of wild type OB-R. fa OB-R abundance was about 7 fold reduced compared to control cells. Surprisingly, the low level of fa OB-R is fully capable of activating the STAT signal transduction pathway. We discuss plausible explanations for the obese phenotype in Zucker fatty rats.

Animals↗
PubMed1996

Effects of the Booroola gene (FecB(B)) on bodymass, testis development and hormone concentrations during fetal life.

In female fetuses the Booroola gene (FecB(B)) is known to affect germ cell development and consequently the pattern of ovarian follicular growth during fetal and post-natal life. However in males, the role of this gene during fetal development is unknown. The aims of the study reported here were to examine the effects of the FecB(B) gene on development of male fetuses with respect to body and organ mass for example, pituitary gland, adrenal and mesonephros), testes development, including numbers of germ cells, and also the plasma concentrations or tissue contents of the reproductive hormones (FSH, LH and testosterone) at days 40, 55, 75, 90 and 135 of gestation. The FecB(B) gene was found to influence litter size, bodymass, crown-rump length and testis mass at most stages of gestation. Some effects were also noted on the mesonephros at days 40 and 55 and on the pituitary and adrenal at days 90 or 135 of gestation. However, the FecB(B) gene was not observed to have an effect on the patterns of germ cell development, on pituitary content or plasma concentrations of immunoreactive or bioactive FSH or immunoreactive LH or testicular content of testosterone. When embryo transfer experiments were performed to eliminate the effects of litter size at days 40, 90 and 135 of gestation nearly all of the differences in bodymass, crown-rump length and organ mass disappeared. The only exception to this was at day 90 when bodymass continued to be lighter and crown-rump lengths smaller in the BB/B + fetuses compared with the +2 fetuses; the significance of this finding remains unknown. It is concluded that for Booroola male fetuses there are no direct effects of the FecB(B) gene on pituitary gonadotrophin function or testicular development after sexual differentiation. Moreover, although there may be temporal differences around day 90 of gestation, there are no long-term, direct effects of the FecB(B) gene on total body, adrenal, testis or pituitary mass. Collectively these findings for the male are similar to those for female fetuses except with regard to germ cell development.

Adrenal Glands↗
PubMed1996

Hsp47 and other ER-resident molecular chaperones form heterocomplexes with each other and with collagen type IV chains.

Collagen type IV is a genetically distinct secretory protein that constitutes a major component of the basement membranes. Despite the differences between collagen types I and IV, it appears that collagen IV alpha-chain translation/translocation through the ER should follow similar pathways to those established for procollagen I. Using a collagen IV-producing mouse teratocarcinoma cell line, we sought to determine if evolving nascent chains of collagen IV are associated with Hsp47 and other ER-resident molecular chaperones. We show that Hsp47, Grp78 and Grp94 appear to form heteromeric complexes associated with each other and with nascent chains of collagen IV. In addition, we investigated whether ATP depletion, a condition known to promote stable association of Grp78 and Grp94 proteins with their chaperone substrates, extended this response to include a chaperone independent of ATP, Hsp47. These studies reveal that ATP depletion increased the levels of newly synthesized collagen IV associated with Hsp47, Grp78, Grp94 and with each other. These results indicate that Hsp47, Grp78 and Grp94 exist as oligomers and form heterocomplexes during the maturation of newly synthesized collagen IV chains.

Adenosine Triphosphate↗
PubMed1996

Disseminated intravascular coagulation in adult acute lymphoblastic leukemia: frequent complications with fibrinogen levels less than 100 mg/dl.

In order to establish the frequency and clinical complications of DIC during remission induction of untreated adults with acute lymphoblastic leukemia, we retrospectively reviewed the records of 125 consecutive patients treated with vincristine, doxorubicin, and dexamethasone but without L-asparaginase. DIC, defined as hypofibrinogenemia in the presence of elevated fibrin-fibrinogen degradation products, was detected at presentation in 10% of 99 and during remission induction in 67% of 58 patients who were screened for DIC. Elevated levels of D-dimers (DD) were seen in all eight patients with DIC in whom they were measured. All cases of DIC were diagnosed by the ninth day of induction and were associated with infection in 15 of 39 patients. DIC did not cause any deaths but was temporally associated with two thromboses and four hemorrhages in six of the 16 patients with fibrinogen levels < 100 mg/dl but with only one hemorrhage among 23 patients (4%) with fibrinogen levels > 100 mg/dl (P < 0.01). Heparin was not administered to any patient, whereas platelets were administered to all to maintain platelet counts > 20 x 10(9)/l. Fresh frozen plasma (FFP) and/or cryoprecipitate were administered 26 patients resulting in a contemporaneous correction of the coagulopathy and in control of hemorrhages and thromboses. We conclude that DIC is rare at presentation but common during induction of adult ALL and is frequently associated with clinical complications when fibrinogen levels are < 100 mg/dl. We recommend daily testing of fibrinogen, PT, and DD during the first 10 days of induction, and for the patients with DIC platelet transfusions to maintain counts > 20 x 10(9)/l, and when fibrinogen levels fall below 100 mg/dl transfusions of FFP and/or cryoprecipitate. Additional studies are needed to determine the optimal management of the DIC during remission induction of adult acute lymphoblastic leukemia.

Adult↗