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Biomedical subjects

H Thomas

Publications and source records attributed to H Thomas.

At least 109 records · Page 6Linked to original sources

Functional organization of the auditory cortex in a native Chilean rodent (Octodon degus).

The tonotopic organization of primary auditory cortex (AI) and surrounding secondary regions has been studied in the Octodon degus using standard microelectrode mapping techniques. The results confirm and extend previous observations made in other species. The tonotopic organization of the largest field (AI) apparently covered the hearing range of O. degus. Low tonal frequencies were represented rostroventrally and high frequencies caudally, with isofrequency contours orientated dorsoventrally in a ventrocaudal slant. There were additional tonotopic representations adjacent to AI. Rostral to AI, a small field with a tonotopic gradient reversed with respect to that in AI (mirror image representation) was mapped and termed rostral auditory field (R). Best frequencies (BF's) in a range from 0.1-30.0 kHz were found in AI and R, with higher spatial resolution for the representation of lower BF's up to 10.0 kHz. Responses obtained in AI as well as in R were strong, with narrow tuning and short latencies. Caudal to AI, two small additional, tonotopically organized fields, the dorsoposterior field (DP) and the ventroposterior field (VP), could be distinguished. In fields VP and DP, high BF's were situated rostrally, adjacent to the high frequency representation in AI. Low frequency representations were found in caudal part of DP and VP fields. Responses to tone burst within DP and VP were mostly weak, with longer latencies and broader tuning compared to those found in AI and R.

Acoustic Stimulation↗

Collecting morbidity data in general practice: the Somerset morbidity project.

OBJECTIVE: To collect a valid, complete, continuous, and representative database of morbidity presenting to primary care and to use the data to help commission services on the basis of local need and effectiveness. SETTING: Computerised general practices in Somerset. METHODS: Participating general practices were selected to be representative of the district health authority population for general practice and population characteristics. All conditions presented at face to face consultations were assigned a Read code and episode type and the data were regularly validated. Data were sent by modem from the practices via a third party to the health authority each week. MAIN OUTCOME MEASURES: Proportion of consultations coded and accuracy of coding. RESULTS: 11 practices agreed to participate. Validations for completeness during April 1994 to March 1995 revealed that 96.4% of the records were coded; 94% of the 1090 records validated had appropriate episode types and 87% appropriate Read codes. The results have been used to help formulate the health authority's purchasing plans and have enabled a change in the local contracts for surgery for glue ear. CONCLUSIONS: The project has shown the feasibility of establishing a network of practices recording and reporting the morbidity seen in primary care. Early indications are that the data can be useful in evidence based purchasing.

Adolescent↗

Molecular cloning and disease association of hepatitis G virus: a transfusion-transmissible agent.

An RNA virus, designated hepatitis G virus (HGV), was identified from the plasma of a patient with chronic hepatitis. Extension from an immunoreactive complementary DNA clone yielded the entire genome (9392 nucleotides) encoding a polyprotein of 2873 amino acids. The virus is closely related to GB virus C (GBV-C) and distantly related to hepatitis C virus, GBV-A, and GBV-B. HGV was associated with acute and chronic hepatitis. Persistent viremia was detected for up to 9 years in patients with hepatitis. The virus is transfusion-transmissible. It has a global distribution and is present within the volunteer blood donor population in the United States.

Acute Disease↗

The mode of Roux-en-Y reconstruction affects motility in the efferent limb.

OBJECTIVES: To compare motility of a Roux-en-Y esophagojejunostomy after total gastrectomy with normal jejunal motility and to determine the effect on motility of the incorporation of a pouch in the reconstruction. DESIGN: Jejunal motility in normal subjects was compared with jejunal motility in the Roux-en-Y reconstruction with and without a Hunt-Lawrence pouch. SETTING: The case were collected during a 4-year period at a university hospital. The mean time from resection to study was 14 months (range, 4 to 49 months). PATIENTS: Seven control patients were compared with 10 patients with a Roux-en-Y reconstruction and 17 with a Roux-en-Y and Hunt-Lawrence pouch. OUTCOME MEASURE: The fasting-state motility of the jejunum used for reconstruction was measured by a water-perfused manometric system for 2 to 4 hours with the subject in the supine position. RESULTS: Compared with normal subjects, patients with a Roux-en-Y esophagojejunostomy without a pouch had an increased number of phases of the interdigestive motor complex per hour (P < .05). The phases were of shorter duration with a random sequence and increased total time spent in the quiescent phase 1 (P < .05). In patients with a pouch, no differences were detected between the motility in the pouch and the efferent limb. Compared with those without a pouch, there were significantly fewer orthograde interdigestive motor complex phase 3 fronts and more total time spent in phase 1 (P < .05). CONCLUSIONS: Construction of a gastric substitute from jejunum leads to substantial motility changes. The addition of a pouch decreases the overall activity, which may contribute to the storage function of the pouch.

Adult↗

Effects of recombinant human growth hormone and insulin-like growth factor-I, with or without 17 beta-estradiol, on bone and mineral homeostasis of aged ovariectomized rats.

This study aimed to evaluate whether recombinant human growth hormone (rhGH) or insulin-like growth factor-I (rhIGF-I) can reverse or prevent further bone loss in aged osteopenic ovariectomized (OVX) rats and to compare their effects with those of 17 beta-estradiol (E2). Twelve-month-old rats were OVX, remained untreated for 8 weeks, and subsequently received daily subcutaneous (SC) injections of rhGH (75 micrograms/day), rhIGF-I (250 micrograms/day), E2 (1.5 micrograms/day), and their respective combinations during 8 weeks, and were then compared with sham-operated, pretreatment OVX, and saline-treated OVX rats. A single sc injection of rhGH resulted in peak hGH concentrations after 90 minutes, with a half-life of 124 minutes; the highest plasma IGF-I concentrations were reached 45 minutes after rhIGF-I injection (+57% vs. baseline) with a gradual decline thereafter. Measurements included: biochemical parameters of bone remodeling (plasma osteocalcin and urinary pyridinolines); histomorphometry of proximal tibial metaphysis; DXA of femur; biomechanical analysis of femur and fifth lumbar vertebra (L5); plasma 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), and calbindin-D9K in duodenal mucosa. Whereas all E2-treated OVX rats had much suppressed bone remodeling, rhGH or rhIGF-I had no effect on any biochemical or histomorphometrical parameter of remodeling. The bone mineral density (BMD) at the distal femoral metaphysis as well as parameters of strength at L5 were maintained at pretreatment values in OVX rats treated with E2, GH, or IGF-I, but not in saline-treated OVX rats; their effects were not additive, however. Trabecular bone volume in the tibial metaphysis was also higher in rats treated with these agents than in saline-treated rats, but this was more apparent at the primary than at the secondary spongiosa, suggesting that their mechanism of action is on primary spongiosa formation or breakdown. E2 alone was ineffective to augment the BMD at the femoral diaphysis; however, the diaphyseal BMD was 12-14% higher (p < 0.01) after 8 weeks of GH treatment than in pretreatment or saline-treated OVX rats and sham-operated rats, while IGF-I was less effective than GH, GH or IGF-I treatment had no effect on plasma 1,25(OH)2D3 or duodenal calbindin-D9K concentrations, but the combination of GH or IGF-I with E2 potentiated the effect of E2 to stimulate calbindin-D9K concentrations and urinary calcium excretion, indicating "hyperabsorption hypercalciuria." In conclusion, the administration of rhGH and rhIGF-I, like that of E2, into aged OVX rats prevents further loss of bone mass and strength at sites containing trabecular bone. In addition, rhGH increases cortical bone mass above pretreatment values.

Absorptiometry, Photon↗

Decomposing Water-Level Responses: Field Effects as Separate Influences

A previous study on water-level task performance using binomial mixture analyses showed that subgroups of subjects could be identified which used different response rules. Some subjects used a bottom parallel rule, others used a random-like rule, and still others used the correct response rule. The present study relates the water-level task performance of these subgroups to field effect influences. Subjects were 604 children and adolescents aged 7 to 15 years who responded to eight water-level and eight rod-and-frame task items. The results show that the water-level response distribution is influenced by the frame of the vessel. These field effects are relatively small if subjects maintain a fixed response rule, and they are large if subjects use a nonfixed random rule. Both field effects and response rules contribute to the behavior of subjects responding to water-level task items.

Journal Article↗

[Modification of phagocytic microbicide function by antifungal agents--measuring luminol enhanced chemoluminescence in full blood].

Fungus infections are becoming more important in surgical intensive medicine, and various preparations are now available to treat them. The goal of our investigations was to determine the influence of the antimycotics in current use on the microbicide phagocytic function by measuring chemiluminescence. To this end the luminol-enhanced chemiluminescence in whole blood samples from a total of 29 healthy donors was measured with a LKB 1251 Luminometer after stimulation with zymosan or a Canadida albicans preparation. We tested the substances amphotericin B, flucytosin (Ancotil), fluconazol (Diflucan) and itraconazol (Sempera), each in three different concentrations within the recommended dose range and compared the results with those in an untreated sample. For the insertions of amphotericin B or intraconazol after zymosan stimulation no significant differences in the measurements were found (50.84 vs 47.99 mV and 46.10 vs 47.89 mV) compared with the blank test. Similar situations revealed by the tests with C. albicans administration (15.21 vs 12.35 mV and 11.16 vs 11.91 mV). However, the tests with flucytosin in the higher concentration range, after stimulation with either zymosan or C. albicans, evidenced a significant reduction in the measurements (34.70 vs 52.74 mV, P<0.005, and 10.98 vs 14.57 mV, P<0.01). The tests with fluconazol showed a decrease of the chemiluminescence exclusively for the highest concentration in the C. albicans group (14.36 vs 17.20 mV, P<0.005). Our results indicate a negative influence of the phagocytes on the oxidative metabolism especially with flucytosin in the higher concentrations. This emphatically confirms demands for exact indications and dosage of antimycotics and their correct administration.

Antifungal Agents↗

Bioequivalence assessment of etoposide phosphate and etoposide using pharmacodynamic and traditional pharmacokinetic parameters.

The bioequivalence of etoposide phosphate, a prodrug of etoposide, to etoposide was assessed in a randomized, crossover study in 29 patients with histologically established solid tumors that had failed conventional treatment. Cohorts of patients received one treatment course each of etoposide and etoposide phosphate which consisted of a 100 mg/m2 per day etoposide equivalent dose infused i.v. over 1 hr on a Day 1 to 5 schedule of treatment. The second course was administered 21 days later or on recovery of blood cell counts. Plasma and urine samples were collected over 24 hr on Day 1 of each course and assayed for etoposide content by a validated HPLC/UV method. Resulting data were subjected to noncompartmental pharmacokinetic analysis. Hematology profiles were obtained by collecting blood samples prior to the first course and twice a week after each course. The pharmacodynamics and pharmacokinetics of etoposide were virtually identical after the two treatments. The point estimates (90% confidence intervals) for nadir WBC, granulocytes, hemoglobin, and platelets expressed as % decrease from the baseline, and for the pharmacokinetic parameters, Cmax, and AUC0 infinity, after intravenous etoposide phosphate relative to etoposide were 100% (96%, 105%), 97% (91%, 103%), 95% (82%, 109%), 95% (84%, 106%), 107% (101%, 113%), and 113% (107%, 119%), respectively. Therefore, etoposide phosphate is bioequivalent to etoposide based on pharmacokinetic and pharmacodynamic assessments.

Adult↗

[Repeated addition of fentanyl to bupivacaine peridural analgesia in labor. Clinical action and fentanyl plasma level].

A combination of epidural opioids with local anaesthetics has been used to improve pain relief during labor and to reduce side effects, such as muscle weakness, usually seen when local anaesthetics are used alone. The addition of epidural fentanyl (F) produces highly effective analgesia, the only side effect being mild itching. Initial trials investigated the improvement in analgesia after a single administration of F during first- but not during second-stage labor. Even though pain perception during second-stage labor under epidural analgesia with local anaesthetics can be severe, the addition of opioids was avoided for fear of neonatal or maternal depression. A recent report found maternal and umbilical plasma concentrations following injection of 100 micrograms F to be safe and the investigators speculated that repeated addition of epidural/F to injection of local anaesthetic may prove beneficial for the parturient without exposing the mother or fetus to risk. We therefore studied maternal analgesia, maternal and umbilical plasma levels and associated side effects following repeated addition of 100 micrograms F to bupivacaine epidural analgesia during labor. METHODS. Following institutional and governmental approval 53 parturients were randomly assigned to receive either 8 ml bupivacaine 0.25% + 0.1 mg fentanyl (B + F group; n = 28) or 8 ml bupivacaine 0.25% + 2 ml saline (BUP group; n = 25) in an epidural catheter at L2/3. The same dose was reinjected upon the patients' request regardless of the degree of cervical dilatation. Blood pressure, heart rate, respiratory rate and the incidence of side effects were recorded before and following each epidural injection. Pain relief was determined at each injection and following cord clamping using the visual analogue pain scale (VAS; 0-100 mm). Maternal venous blood samples were collected to measure plasma F concentrations before and 20 and 40 min after each injection and at birth when umbilical venous and arterial blood was obtained. After centrifugation the samples were maintained at -20 degrees C and then analyzed by radioimmunoassay. At delivery, Apgar scores and umbilical venous and arterial blood gas values were determined. RESULTS. Both groups were comparable for age, weight, height, gestational age and parity. A total of 48 epidural injections were evaluated in the B + F group, 43 in the BUP group. No statistically significant group difference was found between the frequency of injections per delivery (B + F: 2.2; BUP: 1.8); regarding the time between the initial and the first top-up dose (B + F: 144 min; BUP: 140 min) or regarding the interval between the last injection and birth (B + F: 94 min; BUP; 90 min). However, the quality of pain relief during labor and particularly at birth was significantly improved by F (mean VAS in B + F group: 6 mm; mean VAS in BUP group: 42 mm). Mild itching was observed in 43% of patients receiving F, moderate shivering in 13% versus 40% in patients not receiving F. At control mean maternal F plasma levels were not zero but 0.25 ng/ml. After the initial injection and following the first and second top-up dose mean maximum maternal F plasma concentrations were 0.54 ng/ml (+/-0.32; +/-SD), 0.88 ng/ml (+/-0.62) and 1.06 ng/ml (+/-0.4) (range 0.18-2.76 ng/ml), respectively. The increase in maternal F concentrations with increasing injection frequency was statistically significant (P < 0.02). Mean umbilical venous and arterial F concentrations at birth were 0.72 ng/ml (+/-1.16) and 0.62 ng/ml (+/-0.52). No significant group differences were found regarding Apgar scores or umbilical blood gas analyses. In one newborn, radioimmunoassay resulted in unexplainably high umbilical F concentrations without any clinical signs of sedation, depressed vigilance and without any sequellae. DISCUSSION. Repeated addition of 100 micrograms F to epidural anaesthesia with bupivacaine significantly improves analgesia and provides pain relief not only during the fir

Adult↗

[Addition of fentanyl to bupivacaine--peridural analgesia in cesarean section].

UNLABELLED: Epidural anaesthesia for elective caesarean section can have advantages over general anaesthesia. The anaesthesiologist can avoid endotracheal intubation as well as fetal depression following placental transfer of systemic anaesthetics. However, despite reaching an effective blockade preoperatively, intraoperative discomfort and pain may occur during epidural anaesthesia with local anaesthetics alone, necessitating supplemental systemic analgesics or even conversion to general anaesthesia [21]. Addition of epidural fentanyl has been shown to improve onset and quality of perioperative analgesia without evident side effects for mother or newborn [24]. Nevertheless, administration of epidural opioids before cord clamping is still hotly debated, some fearing maternal and or neonatal depression [6, 26]. The aim of the present study was to investigate the quality of analgesia, associated side effects and the resulting maternal and neonatal plasma opiate concentrations after a single preoperative addition of 0.1 mg fentanyl to epidural bupivacaine analgesia in comparison to epidural bupivacaine analgesia alone. METHODS: Following governmental and ethics committee approval, 43 elective consenting patients for caesarean section were randomized to receive double-blind injections of either 8 ml 0.5% bupivacaine(+)0.1 mg fentanyl (B+F group, n = 22) or 8 ml 0.5% bupivacaine +2 ml saline (Bup group, n = 21) into an epidural catheter. In both groups additional injections of bupivacaine were given to achieve sensory blockade up to T4. Systolic blood pressure, heart and respiratory rates were measured regularly. Quality of intraoperative pain relief was assessed at delivery, uterine eventration, and during uterine and abdominal closure using a visual analogue scale (VAS). The duration of postoperative analgesia was compared between groups, as well as the incidence of nausea, itching or sedation. Similarly, Apgar scores and umbilical arterial and venous blood gas analyses were compared. Fentanyl concentrations were determined in maternal venous blood sampled before and 20 and 40 min after epidural injection and at birth, and in umbilical venous and arterial blood sampled after delivery. Radioimmunoassay analysis was performed from plasma specimens centrifuged and frozen at -20 degrees C [19]. The statistical level of significance was defined as P < 0.05. RESULTS: Groups were comparable regarding age, weight and time of gestation. Total bupivacaine doses and injection to delivery times were similar in both groups. Figure 1 shows that there were 40% more pain-free (VAS = 0) patients in the B+F group during uterine eventration and wound closure (P < 0.05). Mean postoperative duration of analgesia was significantly longer in the B+F group (382 vs 236 min). The rate of nausea and mild itching was significantly higher in the B+F group. Respiratory depression was never detected in patients or newborns. Small group differences in blood pressure or respiratory rate were inconstant and clinically irrelevant, as were differences in umbilical venous pCO2. One hundred and twenty-five blood samples were analysed for fentanyl concentrations. The mean fentanyl concentration before epidural injection was not zero, but 0.25 ng/mg (range 0.02-0.32). Maternal concentrations at 20 and 40 min after injection were 0.55 ng/ml (0.12-1.14) and 0.52 ng/ ml (0.26-1.04) (Fig. 3). At delivery, mean maternal fentanyl concentration was 0.58 ng/ml (0.14-1.18); mean umbilical arterial and venous concentrations were 0.51 ng/ml (0.04-1.8) and 0.41 ng/ml (0.18- 1.2), respectively. Rare results of fentanyl concentrations > 1.0 ng/ml correlated neither with sedation, maternal respiratory rate and side effects, nor with Apgar scores and umbilical blood gas values. No Apgar score at 5 min was below 9, and no umbilical pH was below 7.20. (ABSTRACT TRUNCATED)

Adjuvants, Anesthesia↗

Hypoxemia during diagnostic laparoscopy: a prospective study.

BACKGROUND: Laparoscopic liver biopsy can be safely performed using local anesthesia and intravenous sedation, but the frequency of hypoxemia is unknown. METHODS: We prospectively studied 68 patients undergoing diagnostic laparoscopy and liver biopsy managed by a standard protocol. RESULTS: The mean duration of laparoscopy was 27 +/- 5.53 minutes; the mean dose of diamorphine administered was 6.9 +/- 2.7 mg; diazepam, 7.05 +/- 3.52 mg. The baseline arterial oxygen saturation was 95.6% +/- 2.5% and trough was 85% +/- 5.1%. A fall of greater than 4% saturation from the baseline occurred in 64 out of 68 patients (94%). The mean decrease in saturation was 10.1% +/- 5.4%. An arterial oxygen saturation of less than 85% was seen in 32 patients (47%). There was no correlation between the fall in oxygen saturation and the dose of diamorphine or diazepam, the duration of procedure, body mass index, hemoglobin, or volume of pneumoperitoneum induced. One-way analysis of the variance failed to show a significant relationship between the degree of oxygen saturation and Child's class, etiology of liver disease, or smoking habit. CONCLUSIONS: In this study, we demonstrated that significant desaturation is common in diagnostic laparoscopy with liver biopsy and is likely due to a combination of different pharmacologic and physiologic effects. We recommend continuous monitoring of both arterial oxygen saturation and supplemental oxygen for all patients throughout laparoscopy.

Analysis of Variance↗

Ribavirin treatment for patients with chronic hepatitis C: results of a placebo-controlled study.

BACKGROUND/AIMS: Small, uncontrolled studies of ribavirin for patients with chronic hepatitis C have reported efficacy in chronic hepatitis C. We have evaluated the efficacy and safety of a 24-week course of oral ribavirin in patients with chronic hepatitis C, compared to placebo. METHODS: A total of 114 patients were randomised to ribavirin or placebo. Ribavirin was administered in doses of 1000 or 1200 mg/day for 24 weeks. Efficacy was determined in the intention-to-treat population: 76 received ribavirin and 38 placebo. RESULTS: Ribavirin was significantly more effective than placebo in reducing and normalising serum ALT levels: 42/76 (55%) of ribavirin-treated patients vs 2/38 (5%) placebo recipients had either normalisation of the ALT levels or a reduction from baseline of at least 50% (p < 0.001). ALT levels were normal in 22/76 (29%) of ribavirin-treated patients vs 0/38 placebo recipients (p < 0.001). Twenty-four weeks after stopping ribavirin, the majority of patients had abnormal ALT levels. There was no difference between the treatment groups in reduction or disappearance of HCV-RNA levels. HCV RNA disappeared during treatment in 3% of ribavirin-treated patients and 3% of placebo recipients. More ribavirin than placebo patients showed improvement in total Knodell score (45% vs 31%), but these differences were not statistically significant. Analysis of each component of a histology activity index revealed no statistically significant differences between treatment groups. Ribavirin patients had fewer lymphoid aggregates than did placebo recipients at the post-treatment assessment (p = 0.05). Ribavirin was associated with reversible haemolytic anaemia: a fall in haemoglobin occurred in 3% of placebo- and 32% (25/78) of ribavirin-treated patients, respectively (p < 0.001). CONCLUSIONS: These data indicate that ribavirin was no more effective than placebo in reducing or eliminating HCV-RNA levels, and was not significantly more effective than placebo in improving hepatic histology after 6 months of treatment. The role of a 6-month treatment of chronic hepatitis C with ribavirin alone, without a significant effect on HCV RNA, is therefore limited.

Administration, Oral↗

A community survey of adverse effects of cannabis use.

This survey estimates the frequency of various adverse effects of the use of the drug cannabis. A sample of 1000 New Zealanders aged 18-35 years were asked to complete a self-administered questionnaire on cannabis use and associated problems. The questionnaire was derived from criteria for the identification of cannabis abuse which are analagous to criteria commonly used to diagnose alcoholism. Of those who responded 38% admitted to having used cannabis. The most common physical or mental health problems, experienced by 22% of users were acute anxiety or panic attacks following cannabis use. Fifteen percent reported psychotic symptoms following use. Problems related to physical and mental health and control of level of intake were more common than social or relationship problems.

Adolescent↗

An inbred colony of oncogene transgenic mice: diversity of tumours and potential as a therapeutic model.

Transgenic mice carrying the activated rat c-neu oncogene under transcriptional control of the MMTV promoter were backcrossed to BALB/c mice, with the aim of developing a model for cancer therapy. A total of 86 of 268 transgene-positive mice in the first five generations developed 93 histologically diverse tumours (median age of onset 18 months). The cumulative incidence of breast tumours at 24 months was 18%, and overall tumour incidence 31%. As well as expected c-neu expressing breast cancers, lymphomas and Harderian gland carcinomas developed. Virgin mice had fewer mammary tumours than those with two litters. Breast carcinomas metastasised to the lungs, and lymphomas were widely disseminated. The tumours showed a range of architectural patterns, which resembled human breast cancers or lymphomas. This diversity was reflected in S-phase fraction and aneuploidy. Breast tumours transplanted to nude mice showed variable responses to interferon (IFN)-alpha and gamma. A tumour transplanted to BALB/c mice responded to interleukin (IL)-12. There was significant decline in transgene positivity with successive generations. The diversity, histological and biological resemblance to human cancer suggests that the model has potential for evaluating novel therapies. However, further genetic and environmental manipulations are required to increase tumour incidence and decrease age of onset.

Animals↗