Biomedical subjects

J Thomas

Publications and source records attributed to J Thomas.

At least 109 records · Page 6Linked to original sources

PubMed2001

Breast stimulation for cervical ripening and induction of labour.

BACKGROUND: Breast stimulation has been suggested as an effective means of inducing labour. It is both an inexpensive and non-medical intervention which allows women greater control over the induction process. It is not clear how breast stimulation increases uterine contractions, however it has been shown to be effective for contraction stress tests and for the augmentation of labour. This is one of a series of reviews of methods of cervical ripening and labour induction using a standardised methodology. OBJECTIVES: To determine the effectiveness of breast stimulation for third trimester cervical ripening or induction of labour in comparison with placebo/no intervention or other methods of induction of labour. SEARCH STRATEGY: The Cochrane Pregnancy and Childbirth Group trials register, the Cochrane Controlled Trials Register and bibliographies of relevant papers. Last searched: April 2001. SELECTION CRITERIA: (1) randomised controlled trials comparing breast stimulation used for third trimester cervical ripening or labour induction with no intervention or other methods listed above it on a predefined list of labour induction methods; (2) random allocation to the treatment or the control group; (3) adequate allocation concealment; (4) violations of allocated management not sufficient to materially affect conclusions; (5) clinically meaning outcome measures reported; (6) data available for analysis according to the random allocation; (7) missing data insufficient to materially affect the conclusions. DATA COLLECTION AND ANALYSIS: A generic strategy has been developed to deal with the large volume and complexity of trial data relating to labour induction. This involved a two-stage method of data extraction. The initial data extraction was done centrally. MAIN RESULTS: Six randomised controlled trials were included in the analysis involving 719 women. When trials comparing breast stimulation with no intervention were analysed there was a significant reduction in the number of women not in labour at 72 hours (62.7% versus 93.6%, relative risk (RR) 0.67, 95% confidence interval (CI) 0.60 - 0.74). However, this result did not remain significant in women with an unfavourable cervix. There were no instances of uterine hyperstimulation. A reduction in the rate of postpartum haemorrhage was reported (0.7% versus 6%, RR 0.16, 95% CI 0.03 - 0.87). No significant difference was detected in the caesarean section rate (9% versus 10%, relative risk RR 0.90, 95% CI 0.38 - 2.12) or rates of meconium staining. Three perinatal deaths were reported (1.8% versus 0%, RR 8.17, 95% CI 0.45 - 147.77). This finding should be interpreted with caution. The three deaths occurred in the breast stimulation arm of a three-armed trial (breast stimulation versus no intervention versus oxytocin) of questionable quality. The study was very small (n = 57), involved only high risk women, and the method of randomisation was not reported. When comparing breast stimulation with oxytocin alone the analysis found no difference in caesarean section rates (28% versus 47%, RR 0.60, 95% CI 0.31 - 1.18). No difference was detected in the number of women not in labour after 72 hours (58.8% versus 25%, RR 2.35, 95% CI 1.00 - 5.54). There was no significant difference in the rates of meconium staining. There were four perinatal deaths. Three in the breast stimulation arm, and one in the oxytocin arm of the three-armed trial noted above (17.6% versus 5%, RR 3.53, 95% CI 0.40-30.88). REVIEWER'S CONCLUSIONS: Breast stimulation cannot be fully evaluated on efficacy and safety grounds from the included studies. Whilst it would appear beneficial in terms of a reduction in the number of women not in labour after 72 hours, and a reduction in postpartum haemorrhage, until safety issues have been fully evaluated it should not be considered for use in a high risk population.

Breast↗

PubMed2001

Oestrogens alone or with amniotomy for cervical ripening or induction of labour.

BACKGROUND: Studies in sheep showed that there is a pre-labour rise in oestrogen and a decrease in progesterone, both of these changes stimulate prostaglandin production and may help initiate labour. Though oestrogen has been suggested as an effective cervical ripening or induction agent, research in humans have failed to demonstrate a similar physiological mechanism. The use of oestrogen as an induction agent is not currently common practice, as such this systematic review should be regarded as an historical review. This is one of a series of reviews of methods of cervical ripening and labour induction using a standardised methodology. OBJECTIVES: To determine, from the best available evidence, the effectiveness and safety of oestrogens alone or with amniotomy for third trimester cervical ripening and induction of labour in comparison with other methods of induction of labour. SEARCH STRATEGY: The Cochrane Pregnancy and Childbirth Group trials register, the Cochrane Controlled Trials Register and bibliographies of relevant papers. Last searched: April 2001. SELECTION CRITERIA: (1) randomised controlled trials comparing oestrogens alone used for third trimester cervical ripening or labour induction with placebo/no treatment or other methods listed above it on a predefined list of labour induction methods; (2) random allocation to the treatment or control group; (3) adequate allocation concealment; (4) violations of allocated management not sufficient to materially affect conclusions; (5) clinically meaningful outcome measures reported; (6) data available for analysis according to the random allocation; (7) missing data insufficient to materially affect the conclusions. DATA COLLECTION AND ANALYSIS: A generic strategy has been developed to deal with the large volume and complexity of trial data relating to labour induction. This involved a two-stage method of data extraction. The initial data extraction was done centrally. MAIN RESULTS: When comparing oestrogen with placebo there was no difference between the rate of caesarean section (7.1% versus 10.3%, relative risk (RR) 0.70, 95% confidence interval (CI) 0.30,1.62). There were no differences between rates of uterine hyperstimulation with or without fetal heart rate changes or instrumental vaginal delivery. None of the studies reported the rates of either vaginal delivery not achieved in 24 hours, or cervix unfavourable/unchanged after 12-24 hours. There were insufficient data to make any meaningful conclusions when comparing oestrogen with vaginal PGE2, intracervical PGE2, oxytocin alone or extra amniotic PGF2a, as to whether oestrogen is effective in inducing labour. REVIEWER'S CONCLUSIONS: There were insufficient data to draw any conclusions regarding the efficacy of oestrogen as an induction agent.

Amnion↗

PubMed2001

Transcutaneous electrical nerve stimulation does not augment epidural labor analgesia.

STUDY OBJECTIVE: To evaluate whether transcutaneous electrical nerve stimulation (TENS) can increase the quality and duration of an initiation dose of bupivacaine used for the establishment of epidural labor analgesia. DESIGN: Randomized, double-blind study. SETTING: Tertiary-care academic medical center. PATIENTS: 40 ASA physical status I and II parturients in early, active spontaneous labor with a singleton, vertex term fetus, and requesting analgesia. INTERVENTIONS: A standardized epidural technique with either an active or inactive TENS unit was performed. Before epidural placement, TENS intensity thresholds were determined with electrodes placed over the paraspinus muscles at T(10)-L(1), and S(2)-S(4); TENS settings for mode, cycle, and pulse width were standardized. MEASUREMENTS: Data were collected at timed intervals on pain as measured by visual analog scale (VAS), sensory level (pinprick), motor blockade (Bromage score), cervical dilation, and duration of analgesia. MAIN RESULTS: The duration of analgesia produced by the initial dose of epidural bupivacaine did not differ between groups (TENS turned off 82.3 +/- 26 [mean +/- SD] vs. TENS activated 80.7 +/- 40 min, p = 0.88). Kaplan-Meier survival analysis and Mantel-Cox log rank analysis showed no difference between the two treatments (p = 0.75). No difference in the quality of analgesia was observed between the two groups. CONCLUSIONS: In healthy laboring parturients, the application of a TENS unit did not alter the quality or duration of an initiation dose of bupivacaine utilized for the establishment of epidural labor analgesia.

Adult↗

PubMed2001

Overcoming turf battles: developing a pragmatic, collaborative model to improve glycemic control in patients with diabetes.

BACKGROUND: Collaboration between primary care physicians (PCPs) and endocrinologists should be the first step in improving care of patients with diabetes. However, the coordination of care between specialists and PCPs often does not work well. At Vanderbilt University Medical Center, a collaborative model between PCPs and endocrinology was used in an effort to improve glycemic control for patients with diabetes. METHODS: In 1998 a project team was formed; the team members attempted to find ways to improve the care of patients with diabetes, specifically patients with poor glycemic control. The team proceeded through ten iterations of the model before reaching one accepted by all-one with clear responsibilities and referral criteria. RESULTS: Survey results indicated a high level of satisfaction with the collaborative model among patients and PCPs. Appropriate referrals to the diabetes improvement program--a 12-week outpatient program consisting of instruction and support in diabetes self-management coupled with adjustment of insulin and oral hypoglycemic medications-increased during the team effort, and a control chart indicated a change in the process that was significant and sustained. The patients enrolled in the program experienced a reduction of mean glycated hemoglobin levels from 9.2% at entry to 7.5% after 3 months (p < 0.05). DISCUSSION: An initial first step to improving care is to create an environment of trust and collaboration between the PCPs and specialists who assist in that care. After this collaboration has been established, many of the improvements identified in other studies can more easily be implemented.

Adult↗

PubMed2001

Plasma concentrations of ropivacaine following a single-shot caudal block of 1, 2 or 3 mg/kg in children.

BACKGROUND: For documenting the properties of ropivacaine used for regional anaesthesia in children, the relationship between dose and resulting systemic exposure is essential. The aim of this pharmacokinetic part of a randomised, multicentre, double-blind study was to determine the free and total plasma levels of ropivacaine in children aged between 4 and 12 years following a single-shot caudal dose of 1, 2 or 3 mg/kg of ropivacaine for postoperative pain management. METHOD: Following induction of a standardised general anaesthetic (halothane; nitrous oxide: oxygen 60:40), a caudal block using 1 ml/kg ropivacaine in concentrations of 1, 2 or 3 mg/ml was performed in 43 ASA I children (body weight 12-25 kg) scheduled for elective inguinal surgery. Blood samples were collected prior to and 15, 30, 45, 60 and 240 min after placement of the caudal block for determination of total and free ropivacaine plasma concentrations. RESULTS: The peak plasma concentration of total ropivacaine, reached within 15-241 min after the block, increased in proportion to dose, with mean values at 0.27, 0.64 and 0.90 mg/l following 1, 2 and 3 mg/kg respectively. The peak plasma level of free ropivacaine also increased in a dose-proportional manner, with mean levels at 0.014, 0.030 and 0.042 mg/l. The highest individual peak plasma level of free ropivacaine was 0.070 mg/l, well below the threshold levels of CNS toxicity described in adults. No clinical signs of systemic toxicity were observed. CONCLUSION: Following single-shot caudal doses of 1-3 mg/kg in children up to 25 kg and aged between 4 and 12 years, plasma levels of free ropivacaine increase in proportion to dose and all were shown to be within safe limits.

Amides↗

PubMed2001

Subantimicrobial dose doxycycline as an adjunct to scaling and root planing: post-treatment effects.

BACKGROUND/OBJECTIVE: Subantimicrobial dose doxycycline (SDD 20 mg bid) plus scaling and root planing (SRP) significantly improved clinical attachment level (CAL) and reduced probing depth (PD) compared with placebo plus SRP in a double-blind, placebo-controlled, multicenter study of patients with adult periodontitis (AP). In a study conducted as a follow-up, the post-treatment effects of SDD were assessed in patients who completed the SRP study. METHODS: The SRP study was a 9-month, active-treatment study and the follow-up was a 3-month, no-treatment study. In the SRP study, tooth sites in qualifying quadrants were scaled and root planed and patients were randomized to receive twice daily SDD 20 mg or placebo. In the follow-up, patients received no study drug; investigators and patients remained blinded to the previous treatment group assignments. Efficacy measures included the change in CAL and PD from baseline values determined at the start of the SRP study in tooth sites stratified by baseline PD (i.e., 0-3 mm, 4-6 mm, > or =7 mm). Safety was evaluated using adverse event data and the results of clinical laboratory tests, oral pathology examinations, and microbiological assessments. RESULTS: Within each disease stratum, the incremental improvements in PD and CAL demonstrated in the SDD group over 9 months of active treatment were maintained through 3 additional months of no treatment. Treatment cessation did not result in an accelerated regression of periodontal health. No differences in the incidence of adverse events (including those related to infection) or laboratory or microbiological parameters were noted between the SDD group and the placebo group. CONCLUSIONS: The administration of SDD 20 mg bid for a period of up to 9 months is not associated with rebound effects or delayed or negative after-effects for a 3-month period after cessation of therapy.

Adult↗

PubMed2001

Domestic violence: a comparative survey of levels of detection, knowledge, and attitudes in healthcare workers.

The objective of this study was to compare the knowledge, attitudes, responses and levels of detection of domestic violence among a variety of healthcare workers in different specialities.Self-administered questionnaires were sent to community and hospital based healthcare workers in Oxfordshire working in primary care, obstetrics and gynaecology, mental health and accident and emergency. These comprised all principal general practitioners and general practitioner registrars, 50% of practice/district nurses and health visitors in each practice, and all healthcare workers in obstetrics and gynaecology, community mental health teams and accident and emergency in one trust. The amount of domestic violence detected in different healthcare settings was far less than indicated by anonymous surveys and crime figures. Knowledge about many of the issues surrounding domestic violence was inconsistent and there were fundamental deficiencies. The attitudes of healthcare workers to domestic violence were generally sympathetic and supportive. Women, nurses and community mental health workers reported significantly better knowledge and more positive attitudes than other respondents. Gender, role and speciality were independently associated with more positive attitudes and the latter two were independently associated with good knowledge. The response that healthcare workers make when they uncover domestic violence is confused and often inappropriate. In conclusion, most healthcare workers accept that domestic violence is a healthcare issue but lack fundamental knowledge about the issues surrounding domestic violence itself and appropriate agencies that can offer help. They also lack skills in identifying and discussing this issue with patients/clients. A large, unfulfilled training need has been identified.

Attitude of Health Personnel↗

PubMed2001

Can positron emission tomography with [(18)F]-fluorodeoxyglucose after first-line treatment distinguish Hodgkin's disease patients who need additional therapy from others in whom additional therapy would mean avoidable toxicity?

To assess the ability of restaging positron emission tomography (PET) scanning to predict clinical outcome after first-line treatment in patients with Hodgkin's disease, we included 60 patients with histologically proven HD, who underwent whole-body [(18)F]-fluorodeoxygenase ([(18)F]-FDG)-PET studies after first-line treatment and with a follow-up of at least 1 year. Persistence or absence of residual disease on PET was related to progression-free survival (PFS) using Kaplan-Meier survival analysis. After treatment, 55 patients showed a normal [(18)F]-FDG-PET scan; 50 of 55 remained in complete remission (CR), with a median follow-up of 955 d. Only five patients relapsed (median PFS, 296 d). During follow-up in all five patients, [(18)F]-FDG-PET was the first tool that became positive for relapse. Persistent abnormal [(18)F]-FDG uptake was seen in only five patients; all of them relapsed (median PFS, 296 d). In four of five patients, only PET predicted persistent disease. All relapses were proven histologically. Two-year actuarial PFS rate for negative patients was 91% compared with 0% for positive patients. We concluded that [(18)F]-FDG-PET has an important prognostic role in the post-treatment evaluation of HD patients.

Adolescent↗

PubMed2001

Body composition and quality of life in adults with growth hormone deficiency; effects of low-dose growth hormone replacement.

OBJECTIVE: Adult growth hormone deficiency (AGHD) is characterized by abnormalities in body composition and a poor perceived quality of life (QoL). Weight-based high-dose growth hormone replacement (GHR) results in improvements in body composition and QoL in AGHD. However, a high patient percentage reported side-effects on high-dose GHR resulting in a high rate of patient withdrawal from growth hormone (GH) treatment. High-dose GH therapy also leads to supraphysiological serum insulin-like growth factor-I (IGF-I) concentrations that have been associated with breast and prostate cancer, raising major concerns over the use of such high-dose GH regimen in AGHD. The aim of this study was to assess the effects of low-dose growth hormone replacement (GHR) on body composition and QoL as early as 1 and 3 months. STUDY DESIGN: A prospective, open treatment design study to determine the early effects of low-dose GH administration on body composition and QoL. GH was initiated at a daily dose of 0.4-0.5 IU, and titrated up to achieve and maintain IGF-I standard deviation score (IGF-I SDS) between the median and upper end of the age-related reference range. PATIENTS: Forty-six, post-pituitary surgery, severe AGHD patients (22 women), defined as peak GH response < 9 mU/l to provocative testing. The mean age was 50.4 years (range 26-72). Forty-three patients required additional pituitary replacement hormones following pituitary surgery and were on optimal doses at recruitment. MEASUREMENTS: Body composition and QoL were assessed prior to GHR and subsequently at 1 and 3 months after initiating GHR. Body mass index (BMI) and waist hip ratio (WHR) were calculated from measurements of height, weight, and waist and hip circumference, respectively. Bioelectrical impedance analysis (BIA) was used to determine body fat and lean body mass. QoL was assessed using the disease-specific 'QoL-assessment of growth hormone deficiency in adults (QoL-AGHDA)' questionnaire. Serum IGF-I was measured at each visit to assess the adequacy of GHR. RESULTS: IGF-I and IGF-I SDS increased significantly at 1 and 3 months (P < 0.001) after commencing GHR. The increase in IGF-I (P < 0.05) and IGF-I SDS (P < 0.01) was significant between 1 and 3 months in the absence of any significant increase in GH dose (P = ns) during this period. Eighty-five per cent of patients achieved IGF-I SDS levels between median and upper end of the age-related reference range after 3 months of GHR, and no side-effects were reported during this period. There was a significant reduction in body fat percentage (BFP) from 36.1 +/- 9.1% at baseline to 34.9 +/- 9.3% (P < 0.01) at 1 month and 34.1 +/- 9.2% (P < 0.001) at 3 months. Body fat mass (BFM) reduced from 32.8 +/- 13.6 kg at baseline to 31.9 +/- 13.9 kg at 1 month (P < 0.05) and 31.1 +/- 13.6 kg at 3 months (P < 0.001). These changes in BFP and BFM occurred in the absence of any significant change in BMI and WHR (P = ns). Lean body mass (LBM) was 55.9 +/- 11.1 kg at baseline and increased to 57.1 +/- 11.3 kg after 1 month (P < 0.01) and to 57.6 +/- 11.5 kg (P < 0.001) after 3 months of GHR. Significant improvement was observed in the perceived QoL with the AGHD assessment scores reducing from 13.3 +/- 6.4 to 11.5 +/- 6.6 within 1 month (P < 0.01) and 10.0 +/- 6.6 at 3 months (P < 0.001). There was no significant correlation between improvement in QoL and changes in body fat percentage (r = 0.01 at 1 month and r = 0.12 at 3 months, P = ns) or IGF-I levels (r = 0.04 and r = 0.003, P = ns at 1 and 3 months, respectively). The improvement in body composition and QoL was significant between 1 and 3 months. CONCLUSIONS: Low-dose GHR improves body composition and QoL as early as 1 month after commencement and the beneficial effects continue at 3 months. Most importantly, these changes occur in the absence of side-effects. We therefore suggest the use of low-dose GH therapy, maintaining IGF-I between the median and upper end of the age-related reference range, for the treatment of AGHD.

Adult↗

PubMed2001

Identification and characterization of DAlk: a novel Drosophila melanogaster RTK which drives ERK activation in vivo.

BACKGROUND: The mammalian receptor protein tyrosine kinase (RTK), Anaplastic Lymphoma Kinase (ALK), was first described as the product of the t(2;5) chromosomal translocation found in non-Hodgkin's lymphoma. While the mechanism of ALK activation in non-Hodgkin's lymphoma has been examined, to date, no in vivo role for this orphan insulin receptor family RTK has been described. RESULTS: We describe here a novel Drosophila melanogaster RTK, DAlk, which we have mapped to band 53 on the right arm of the second chromosome. Full-length DAlk cDNA encodes a phosphoprotein of 200 kDa, which shares homology not only with mammalian ALK but also with the orphan RTK LTK. Analysis of both mammalian and Drosophila ALK reveals that the ALK family of RTKs contains a newly identified MAM domain within their extracellular domains. Like its mammalian counterpart, DAlk appears to be expressed in the developing CNS by in situ analysis. However, in addition to expression of DAlk in the Drosophila brain, careful analysis reveals an additional early role for DAlk in the developing visceral mesoderm where its expression is coincident with activated ERK. CONCLUSION: In this paper we describe a Drosophila melanogaster Alk RTK which is expressed in the developing embryonic mesoderm and CNS. Our data provide evidence for the existence of a DAlk RTK pathway in Drosophila. We show that ERK participates in this pathway, and that it is activated by DAlk in vivo. Expression patterns of dALK, together with activated ERK, suggest that DAlk fulfils the criteria of the missing RTK pathway, leading to ERK activation in the developing visceral mesoderm.

Amino Acid Sequence↗

PubMed2001

Follicular adenoma with papillary architecture: a lesion mimicking papillary thyroid carcinoma.

AIMS: The purpose of this study was to investigate the significance of 'benign' encapsulated follicular thyroid nodules with papillary structures. METHODS AND RESULTS: Twenty-one cases of encapsulated neoplastic thyroid nodules with papillary structures and nuclear features not diagnostic of papillary thyroid carcinoma (PTC) were obtained. All cases were reviewed with particular attention to nuclear features (fine chromatin pattern, optical clearing, grooves and inclusions). Representative sections were submitted for measurement of the maximum diameter of 200 round or nearly round nuclei and for immunostaining for MIB1, CK19, HBME and Ret oncogene protein. Nine cases displayed scattered optically clear nuclei or nuclear grooves in less than 30% of total neoplastic cells. They were grouped in the category of thyroid nodules with limited nuclear features of papillary thyroid carcinoma (PTC), but not diagnostic of PTC. The other 12 cases had fine or coarse chromatin, but lacked other features of nuclei in PTC. The diameter of the nuclei ranged from 5.6 to 7.2 microm and were smaller than those of PTC (6.3-10.0 microm). Immunostaining revealed positive reactivity for MIB1 in the papillary structures. Immunostaining for CK19 and HBME varied from negative or focally weak to diffusely moderate reactivity. Ret oncogene protein immunostaining showed focal and weak reactivity in one case and was negative in other cases of the study. Clinical follow-up from 6 months to 15 years revealed no evidence of metastasis. CONCLUSIONS: The papillary structures in the study cases are unlikely to represent degenerative changes due to their proliferative activity. In view of (i) the encapsulation and the uniformity of the constituent cells, (ii) the varying degrees of immunoreactivity for CK19 and HBME and negative immunoreactivity for Ret oncogene protein, and (iii) the absence or insufficiency of nuclear criteria for the diagnosis of PTC and the absence of lymph node metastasis in all study cases, we believe that these lesions represent the papillary variant of follicular adenoma. Recognition of this pathological entity is important to avoid an over-diagnosis of PTC.

Adenoma↗

PubMed2001

Substrate complexes and domain organization of the Salmonella flagellar export chaperones FlgN and FliT.

The flagellar proteins FlgN and FliT have been proposed to act as substrate-specific export chaperones, facilitating incorporation of the enterobacterial hook-associated axial proteins (HAPs) FlgK/FlgL and FliD into the growing flagellum. In Salmonella typhimurium flgN and fliT mutants, the export of target HAPs was reduced, concomitant with loss of unincorporated flagellin into the surrounding medium. Gel filtration chromatography of wild-type S. typhimurium cell extracts identified stable pools of FlgN and FliT homodimers in the cytosol, but no chaperone-substrate complexes were evident. Nevertheless, stable unique complexes were assembled efficiently in vitro by co-incubation of FlgN and FliT with target HAPs purified from recombinant Escherichia coli. The sizes of the chaperone-substrate complexes indicated that, in each case, a chaperone homodimer binds to a substrate monomer. FlgN prevented in vitro aggregation of FlgK monomers, generating a soluble form of the HAP. Recombinant polypeptides spanning the potentially amphipathic C-terminal regions of FlgN or FliT could not complement in trans the chaperone deficiency of the respective flgN and fliT mutants, but efficient flagellar assembly was restored by homodimeric translational fusions of these domains to glutathione S-transferase, which bound FlgK and FlgL like the wild-type FlgN. These data provide further evidence for the substrate-specific chaperone function of FlgN and FliT and indicate that these chaperones comprise common N- and C-terminal domains mediating homodimerization and HAP substrate binding respectively. In support of this view, the flgN mutation was specifically complemented by a hybrid chaperone comprising the N-terminal half of FliT and the C-terminal half of FlgN.

Bacterial Proteins↗

PubMed2001

Do gap junctions couple interstitial cells of Cajal pacing and neurotransmission to gastrointestinal smooth muscle?

Interstitial cells of Cajal (ICC) pace gastrointestinal phasic activity and transmit nerve activity. Gap junctions may couple these cells to smooth muscle, but no functional evidence exists. The objective of this study was to use uncouplers of gap junctions, 18 alpha-glycyrrhetenic acid and its water-soluble analogue carbenoxolone, to evaluate if gap junctions function in pacing and neurotransmission. After inhibition of nerve function with tetrodotoxin (TTX) and N(G)-nitro-L-arginine (L-NOARG), ionomycin- or carbachol-initiated regular phasic activities of circular muscle strips from canine colon and ileum. In some cases, the primary ICC network responsible for pacing was removed. The effects of inhibitors of gap junction conductance (10(-5)-10(-4) mol L(-1)) on frequencies and amplitudes of contraction were compared to appropriate time controls. Lower oesophageal sphincter (LOS) relaxations to nerve stimulation were studied before and after inhibition of gap junction functions. No major changes in LOS relaxations or frequencies of colonic or ileal contractions occurred, but amplitudes of contractions decreased from these agents. Similar results were obtained when the myenteric plexus-ICC network of ileum was removed. Regular phasic activity was not obtained after removal of the colon submuscular plexus ICC. These findings suggest that mechanisms other than gap junctions couple gut pacemaking activity and nerve transmission.

Animals↗

PubMed2001

Cell surface heparan sulfate proteoglycans control the response of renal interstitial fibroblasts to fibroblast growth factor-2.

BACKGROUND: While the progression of renal disease to end stage is strongly correlated with tubulointerstitial changes, the control of the fibrotic process within the interstitium is poorly understood. Basic fibroblast growth factor (FGF-2) has been implicated as a major growth factor involved in fibroblast activation and extracellular matrix synthesis. Furthermore, in many cells, the activity of FGF-2 is controlled by a low-affinity but high-capacity interaction with heparan sulfate (HS) proteoglycans (PGs), such as members of the syndecan family. These molecules are likely to be central to the control of interstitial fibrosis, but as yet, there has been no characterization of their synthesis by interstitial cells. METHODS: The expression of HSPG on the surface of NRK 49F fibroblasts was demonstrated by immunohistochemistry and by metabolic labeling with [(35)S]-sulfate. HSs were characterized by specific enzymatic digestion, size exclusion chromatography, and anion exchange chromatography. The mRNA for syndecan 1 through syndecan 4 in the fibroblasts was detected by semiquantitative reverse transcription-polymerase chain reaction. Fibroblast proliferation was measured by the MTT assay. RESULTS: Immunohistochemistry and [(35)S]-sulfate-labeling demonstrated that renal fibroblasts expressed HSPGs on their surface. Furthermore, enzymatic removal of these HS (but not chondroitin sulfate) glycosaminoglycan (GAG) chains, or inhibition of GAG sulfation, abolished the proliferative response of both NRK cells and primary human cortical fibroblasts to FGF-2 but not to platelet-derived growth factor. The addition of conditioned medium, containing HS-GAG fragments, restored the proliferative response to FGF-2, confirming the specificity of the interaction. Finally, the mRNA for all four syndecans was detected in the fibroblasts, and that for syndecan 1 in particular was up-regulated by FGF-2. CONCLUSIONS: The present study demonstrates that the expression of cell surface HSPG was essential for the proliferation of renal fibroblasts in response to FGF-2, and therefore may play a major role in the development and persistence of a proliferating phenotype during interstitial nephritis.

Animals↗

PubMed2001

Contractile hyporesponsiveness of hepatic arteries in humans with cirrhosis: evidence for a receptor-specific mechanism.

Splanchnic vasodilatation and vascular hyporesponsiveness to vasopressors are characteristic features of patients with cirrhosis. Although the vascular response to different vasopressors has been shown to be attenuated in cirrhosis, alterations on the receptor level are discussed controversially. Thus, impaired postreceptor signaling has been postulated. However, so far this has not been studied in human splanchnic vessels. Therefore, we assessed the vascular response of human hepatic arteries after activating the G-protein-dependent signal transduction pathway by stimulation with angiotensin II, the thromboxane A(2) analog U46619, or by G-protein activation with NaF/AlCl(3). After endothelium denudation, cumulative isometric concentration contraction curves were obtained for hepatic arteries from 32 cirrhotic patients undergoing liver transplantation and from 40 organ donors after stimulation with either angiotensin II (10(-11)-10(-5) mol/L), U46619 (10(-10)-10(-6) mol/L) or AlCl(3) (30 micromol/L)/NaF (10(-4)-3 x 10(-2) mol/L). Hepatic arteries from cirrhotic patients were markedly less responsive to angiotensin II (P <.0001) than those from organ donors. Both stimulation of the G-protein phospholipase C pathway via the thromboxane A(2) receptor and receptor-independent G-protein stimulation with AlCl(3)/NaF, induced an intact contractile response. In conclusion, the G-protein-dependent signal transduction system itself is unaltered in cirrhosis. Hence, the cause of the hyporesponsiveness to some vasoconstrictors in cirrhosis appears to be a receptor-specific phenomenon localized upstream from the G-protein level.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

PubMed2001

[Increased demand for psychosomatic consultation service (C-service) in a department of cardiology/pneumology due to psychometric screening].

The aim of the study was to test whether the routine use of the Hospital Anxiety and Depression Scale HADS changes the frequency and the duration of calling the psychosomatic C-service. 70% of all patients of the department of cardiology/pneumology were registered by the HADS. Psychometric screening raised the number of patients checked by the C-service (15.3 vs. 2.7% of all patients of the department; p < 0.01) and reduced the duration of the call for the C-service (2.7 vs. 6.4 days; p < 0.01) compared to conventional C-service. Elevated scores in HADS were found in 26% of the patients (21% depression, 12% anxiety).

Aged↗

PubMed2001

A tripartite anoikis-like mechanism causes early isolated islet apoptosis.

BACKGROUND: This study examines the mechanisms of early isolated islet apoptosis (II-APO) and loss of functional islet mass. METHODS: Rhesus islets were isolated for transplantation, and an aliquot was used for in vitro molecular studies of II-APO. These studies used Western blotting to examine caspase activation and perinuclear envelope protein cleavage that are associated with II-APO and used immunofluorescence analysis of Annexin V and mitochondrial permeability index to examine spontaneous and tripartite anoikis-like (TRAIL) mechanism--induced II-APO. RESULTS: Caspase 6 was prominently activated in association with spontaneous II-APO, which occurred after overnight culture. In contrast, caspase 7, 8, and 9 were not activated. Cleavage of focal adhesion kinase and Lamin, substrates of caspase 6, was also evident in spontaneous II-APO. II-APO was exaggerated by the addition of the TRAIL mechanism. The TRAIL mechanism--induced II-APO was blocked by the caspase 6 inhibitor, VEID, and by the soluble fusion proteins, DR4 or DR5, which act as decoy receptors. In vivo studies in diabetic severe combined immunodeficiency disease mice showed that rhesus islets were cytoprotected by either ex vivo gene transfer of Bcl-2 or treatment of the isolated islet with VEID. CONCLUSIONS: These studies suggest 3 major mechanisms involved in II-APO: caspase 6 activation, a TRAIL-induced apoptosis pathway, and the mitochondrial-associated apoptosis pathway. Inhibition of these II-APO pathways may improve isolated islet survival and reduce functional islet mass loss, which compromises the stable reversal of diabetes.

Animals↗

PubMed2001

Risk behaviours of Hong Kong male residents travelling to mainland China: a potential bridge population for HIV infection.

The objective was to assess levels of high-risk sexual behaviour, condom use, sexually transmitted disease (STD) history and AIDS-related perceptions among Hong Kong men returning from China by land; 1,254 systematically sampled subjects were interviewed. Of respondents, 32.5% had sexual intercourse with a commercial sex worker (CSW) in China in the past six months; 11.2% have done so on this trip. A third of those who reported having sex with CSWs did so without a condom. A fifth had a history of STDs: seventy per cent of respondents who did not use a condom with a CSW would not use a condom with their regular sexual partner. Less educated respondents, 31-40-year-olds and non-business and frequent travellers were more likely to have sex with a CSW. Those who practice high-risk sex fear AIDS more, are aware that their own risk of HIV infection is not negligible, but think that chances of HIV infection from CSWs in China are small. Although Hong Kong's estimated HIV prevalence among adults is low (0.06%), the huge volume of cross-border travel between Hong Kong and China and the common practice of high-risk sex by Hong Kong male travellers provide a bridge for emerging epidemics to spread.

Acquired Immunodeficiency Syndrome↗