Biomedical subjects

C K Chan

Publications and source records attributed to C K Chan.

At least 109 records · Page 6Linked to original sources

PubMed1999

Triple therapy for Helicobacter pylori eradication is more effective than long-term maintenance antisecretory treatment in the prevention of recurrence of duodenal ulcer: a prospective long-term follow-up study.

BACKGROUND: The effectiveness of Helicobacter pylori eradication treatment and long term acid suppression maintenance in the natural course of duodenal ulcer has not been directly compared. AIM: To compare in a prospective randomized study the effectiveness of H. pylori eradication on the prevention of recurrence of duodenal ulcer with long-term maintenance acid suppression therapy. METHODS: One hundred and fourteen duodenal ulcer patients were randomized to the treatment over a 12-month period. Fifty-seven of them received triple therapy consisting of 1 g sucralfate q.d.s. for 28 days, 300 mg metronidazole q.d.s. for 14 days and 250 mg clarithromycin q.d.s. for 14 days. Another 57 received 20 mg omeprazole q.d.s. for 12 months. An upper endoscopy was performed before treatment, at 6 weeks, and 2, 6 and 12 months after the first endoscopy. Side-effects were self-recorded and clinical follow-ups were arranged for up to 4.25 years. RESULTS: The ulcer healing rate was 90.2% (95% confidence interval (95% CI): 79-97%) in the omeprazole group at 6 weeks as compared to 83.3% (95% CI: 70-93%) in the triple therapy group (P = 0.38). There was a higher success rate of pain control in the omeprazole group. Side-effects were more frequently reported and compliance was poorer in the triple therapy group during the first 4 weeks. During follow-up, more relapses were seen in the omeprazole group (9.8%, 95% CI: 3-21%) than the triple therapy group (4.2%, 95% CI: 1-13%) at 1 year (P = 0.44). All relapses were due to the persistence of H. pylori infection. At the 1 year follow-up, none of the patients who were H. pylori negative had an endoscopic relapse compared to 7 out of 56 patients who remained H. pylori positive (12.5%, 95% CI: 5-24%, P = 0.018). After a mean follow-up of 4.07 years, none of those who remained H. pylori negative had an ulcer relapse while the 11 out of 41 who remained H. pylori positive had an ulcer relapse (26.8%, 95% CI 14-43, P = 0. 0005). CONCLUSIONS: Both regimens were highly effective in healing ulcers. The eradication of H. pylori infection was associated with more side-effects and poor compliance but was more effective than the maintenance therapy in reducing the recurrence of duodenal ulcers. For the prevention of ulcer recurrence, testing of H. pylori status after triple therapy is more important than maintenance therapy.

Adult↗

PubMed1999

Retroviral-mediated transfer and expression of the multidrug resistance protein 1 gene (MRP1) protect human hematopoietic cells from antineoplastic drugs.

Multidrug resistance protein (MRP1) is a member of the ATP-binding cassette (ABC) transmembrane transporter superfamily that confers multidrug resistance. The transfer and expression of the MRP1 gene in human hematopoietic stem cells may be a useful alternative to multidrug resistance (MDR1) gene transfer for protection from the myelosuppressive effects of chemotherapy in cancer patients. We constructed a gibbon ape leukemia virus packaging cell line (PG13) using the human MRP1 cDNA in a Moloney murine leukemia virus (MoMuLV) backbone containing a modified LTR. This PG13-based cell line, designated MRP1-PG13, produces retroviral vectors bearing the MRP1 gene at a titer of 1.7x10(5) viral particles/ml. Transduction of the human leukemic cell line K562 showed that viral MRP1-PG13 supernatants routinely transfer the MRP1 gene to approximately 35% of target K562 cells, of which at least one third are capable of proliferating in the presence of otherwise toxic concentrations of etoposide. Southern blot analyses indicated that most clones had only one proviral integration. Northern blot analysis of expanded K562 clones showed the presence of a major full-length approximately 8-kb MRP1 transcript as well as a minor approximately 6-kb transcript in all clones. Flow cytometric analysis of the producer cells and clones of transduced K562 cells demonstrated significantly increased MRP1 expression in these cells (approximately 30-fold increase). Human bone marrow mononuclear cells and CD34+ cells were also transduced with MRP1-PG13 supernatants on fibronectin-coated culture flasks in the presence of SCF, IL-3, and IL-6. PCR analysis of individual hematopoietic colonies in methylcellulose cultures demonstrated proviral DNA in approximately 10% of unselected human hematopoietic progenitor cells cultured from nonsorted mononuclear cell samples and in up to approximately 75% of progenitors when CD34-enriched cell populations were targeted. To assess functional MRP1 gene expression, normal human hematopoietic progenitors and K562 cells were cultured in methylcellulose assays containing vincristine or etoposide. All transduced samples gave rise to approximately 10% drug-resistant colonies, which were shown to be provirus-positive by PCR. Our studies document the development of an amphotropic MRP1 retroviral vector producer cell line and pave the way for large animal and preclinical studies of chemoprotection by MRP1 gene transfer.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1998

Relationship between imidazoline and alpha2-adrenoceptors involved in the sympatho-inhibitory actions of centrally acting antihypertensive agents.

Since the first suggestion of the existence of imidazoline receptors, there has been a continuing and yet unresolved debate as to their contribution to the antihypertensive actions of clonidine-like agents. In this review we bring together a number of studies from our laboratory which have examined the importance and interdependence of imidazoline receptors and alpha2-adrenoceptors in the mechanism of action of centrally acting antihypertensive drugs. Using conscious rabbits and a range of imidazoline and specific alpha2-adrenoceptor antagonists we have consistently found that second generation agents rilmenidine and moxonidine preferentially act via imidazoline receptors but that alpha2-adrenoceptors are important for the hypotension produced by clonidine and alpha-methyldopa. Despite this difference in receptor mechanism, the hypotension produced by all these drugs is dependent on central noradrenergic pathways. In other studies using anaesthetised rabbits and direct measures of sympathetic nerve activity we confirmed the generally held view that the major site of sympatho-inhibitory actions and sympathetic baroreflex effects of centrally acting antihypertensive agents is the rostral ventrolateral medulla (RVLM). We also found, using microinjection of specific antagonists, that alpha2-adrenoceptors in this nucleus appear to be activated as a consequence of imidazoline receptor activation. Thus, there appears to be a close relationship between imidazoline receptors and alpha2-adrenoceptors located in the RVLM in mediating the hypotension and inhibition of renal sympathetic nerve activity. Furthermore in recent studies using a noradrenergic neurotoxin microinjected into the RVLM we found that this treatment selectively blocked the actions of moxonidine but not clonidine, suggesting that I1-imidazoline receptors may be located on adrenergic terminals in situ. By contrast, clonidine acts predominantly via alpha2-adrenoceptors, perhaps located on cell bodies in the nucleus. We conclude that there is indeed a close nexus between 'presynaptic' imidazoline receptors on noradrenergic terminals and 'downstream' alpha2-adrenoceptors within the RVLM. Our hypothesis brings together opposing points of view that the mechanism for hypotension must involve either the imidazoline receptor or the alpha2-adrenoceptor. Clearly both are important.

Animals↗

PubMed1998

Signals mediating nuclear targeting and their regulation: application in drug delivery.

The recent progress with respect to understanding the signals mediating the transport of proteins in both directions through the NPC, and cellular proteins interacting with these signals to effect the transport process has made possible a number of advances in terms of the use of this information in a clinical setting. In particular, our knowledge of the mechanism of regulation of the process, and of how we may exploit the cellular transport machinery itself in a therapeutic situation, especially where there may be transport pathways specific to particular viruses, has advanced considerably. In this context, this review expounds current understanding of the signals conferring targeting to the nucleus, and their practical and potential use in delivering molecules of interest to the nucleus in a clinical context. It also deals with targeting signals conferring nuclear protein export/ shuttling between nuclear and cytoplasmic compartments as well as with those conferring nuclear or cytoplasmic retention, and with the specific mechanisms regulating the activity of these signals, and in particular those regulating signal-dependent nuclear protein import. Detailed understanding of the processes of signal-mediated nuclear protein import/export and its regulation enables the considered application and optimization of approaches to target molecules of interest, such as plasmid DNA or toxic molecules, efficiently to the nucleus according to need in a clinical or research context, and enhance the expression or efficiency of their action, respectively. The use of nuclear targeting signals in this context is reviewed, and future possibilities in terms of the application of our growing understanding of nuclear transport and its regulation are discussed.

Biological Transport↗

PubMed1998

Hematuria and clot retention after Burch colposuspension and Cystofix suprapubic catheterization: suprapubic cystotomy as an alternative suprapubic drainage method.

Suprapubic catheterization is a common procedure in continence surgery and hematuria is a common complication after suprapubic catheterization. The authors report an unusual case of acute clot retention after the removal of a Cystofix suprapubic catheter in a patient who had had a Burch colposuspension. Suprapubic cystotomy as an alternate suprapubic method is also discussed.

Adult↗

PubMed1998

Anionic glycoconjugates from differentiated and dedifferentiated cultures of bovine articular chondrocytes: modulation by TGF-beta.

Primary, high density bovine articular chondrocyte (BAC) cultures, stimulated with transforming growth factor-beta-1, elaborated a high molecular weight anionic glycoconjugate, kDa 540, which does not contain glycosaminoglycan chains (Chan and Anastassiades, 1996). The effect of exogenously added transforming growth factor-beta-1 on the elaboration of the high molecular weight glycoconjugate and of proteoglycans was studied during dedifferentiation of the chondrocytes, utilizing a serial subculture technique under anchorage-dependent conditions, up to four subcultures. The high molecular weight glycoconjugate was detected in the media of all growth-factor-stimulated chondrocyte subcultures, as well as stimulated primary cultures, but not in unstimulated primary cultures or subcultures. By contrast, a large proteoglycan, was only secreted by primary cultures and first subcultures, whether treated with transforming growth factor-beta-1 or untreated. This proteoglycan contained mostly chondroitin sulfate chains, whose hydrodynamic size was increased by the addition of transforming growth factor-beta-1. Further, the pattern of the proteoglycans appearing in the media of subcultures 2-4 was influenced by the addition of transforming growth factor-beta-1, so that while these control subcultures elaborated both the large and small chondroitin sulfate proteoglycans, the equivalent stimulated subcultures elaborated only intermediate sized chondroitin sulfate proteoglycan(s). These results suggest that while dedifferentiation of articular chondrocytes, achieved by subculturing, strongly modulates the effect of exogenously added transforming growth factor-beta-1 on the type of proteoglycan elaborated, the process of dedifferentiation does not influence the transforming-growth-factor-beta-dependent synthesis of the high molecular weight anionic glycoconjugate.

Animals↗

PubMed1998

Antiulcer drug prescribing in hospital successfully influenced by "immediate concurrent feedback".

OBJECTIVE: To determine whether immediate concurrent feedback (ICF) focused on inpatient omeprazole prescribing achieved more rational and cost-effective antiulcer drug prescribing and usage. METHODS: In a 1400-bed teaching hospital, an audit (by specially trained personnel) was conducted to monitor inpatient prescribing of omeprazole (1) in preference to H2-antagonists and other drugs according to agreed criteria (Helicobacter pylori eradication, severe reflux esophagitis, rapid ulcer healing deemed urgent because of severe symptoms or complications, high-dose steroid therapy of > or =30 mg/day prednisolone) and (2) appropriateness of intravenous dosing (oral route not feasible or contraindicated). After baseline monitoring for 1 month, followed by relevant antiulcer drug therapy education, ICF was instituted for 1 year. This entailed explanatory memoranda requesting a change in prescribing issued to the respective medical teams of patients whose omeprazole prescription did not "conform." The main outcomes of the study were omeprazole prescription numbers per month and the proportion conforming, defined daily doses of antiulcer drugs used and corresponding expenditures, and pertinent antiulcer drug utilization data from 9 other local hospitals. RESULTS: Baseline omeprazole prescribing conformed in 32 of 173 (18%) of the patients compared with 451 of 546 (83%) during institution of ICF (P < 0001; chi2 test). Correspondingly, average overall omeprazole and ranitidine usage (inpatient and outpatient) and expenditure decreased (44% and 45%, respectively); collectively, use of less expensive alternatives increased about 61%. Estimated savings averaged about HK$150,000 ($20,000) per month. No comparable changes in usage were noted in 9 other local hospitals. CONCLUSION: Regarding hospital antiulcer drugs, this ICF strategy was associated with more rational prescribing and usage, and an important saving of resources.

Administration, Oral↗

PubMed1998

Mutual exclusivity of DNA binding and nuclear localization signal recognition by the yeast transcription factor GAL4: implications for nonviral DNA delivery.

A novel approach to nonviral DNA delivery is the use of combinations of DNA-binding proteins such as the yeast transcriptional activator GAL4 and plasmid DNA containing the specific binding sequence of the DNA-binding protein inserted within it, in addition to the gene of interest to be transferred into target cells. The amino terminal 147 amino acids of GAL4 contain a DNA-binding domain that has been shown to bind specifically to a 17 bp nucleotide recognition sequence, while the amino terminal 74 amino acids have been shown to be sufficient to target large heterologous proteins to the nucleus. Although it has been previously exploited as a gene transfer vehicle, the exact relationship between GAL4's DNA binding and nuclear targeting activities has not been investigated. Using gel mobility shift assays and ELISA-based binding assays, this study examines this issue directly, establishing the mutual exclusivity of the DNA-binding and nuclear targeting activities of GAL4. We demonstrate that GAL4(1-147) can specifically enhance transfection of plasmids containing the 17 bp recognition sequence. Interestingly, we found that the nuclear localization signal (NLS) of GAL4 is distinct from conventional NLSs, such as those of the SV40 large tumor antigen and bipartite NLSs, in that it is recognized exclusively by the nuclear pore targeting beta-subunit of the NLS-receptor importin complex, rather than the alpha-subunit. Specific binding to DNA was blocked by beta-subunit binding, while the converse was also true, making the GAL4-NLS novel in being regulated by DNA binding; this may play an important role in effecting release of GAL4 from the beta-subunit following transport through the nuclear pore. This study encompasses the first direct analysis of NLS recognition/accessibility in vehicles for nonviral DNA transfer, with the results having relevance to the use of GAL4 and comparable DNA-binding proteins in such vehicles.

Animals↗

PubMed1998

Volatile anaesthetics have differential effects on recombinant m1 and m3 muscarinic acetylcholine receptor function.

Muscarinic acetylcholine signalling plays major roles in regulation of consciousness, cognitive functioning, pain perception and circulatory homeostasis. Halothane has been shown to inhibit m1 muscarinic signalling. However, no comparative data are available for desflurane, sevoflurane or isoflurane, nor have the anaesthetic effects on the m3 subtype (which is also prominent in the brain) been studied. Therefore, we have investigated the effects of these compounds on isolated m1 and m3 muscarinic receptor function. Defolliculated Xenopus oocytes expressing recombinant m1 or m3 muscarinic or (for comparison) AT1A angiotensin II receptors were voltage clamped, and Ca(2+)-activated Cl- currents (ICl(Ca)) induced by acetyl-beta-methylcholine (Mch) or angiotensin II were measured in the presence of clinically relevant concentrations of halothane, sevoflurane, desflurane or isoflurane. To determine the site of action of the volatile anaesthetics we compared anaesthetic effects on m1, m3 and AT1A receptor function and studied the effects of volatile anaesthetics on signalling induced by intracellular injection of the second messenger IP3. Desflurane had a biphasic effect on m1 signalling, enhancing at a concentration of 0.46 mmol litre-1 but depressing at 0.92 mmol litre-1. A similar, although not significant, trend was observed with m3 signalling. Isoflurane had no effect on m1 signalling, but profoundly inhibited m3 signalling. Sevoflurane depressed the function of m1 and m3 signalling in a dose-dependent manner. Halothane, similar to its known effect on m1 signalling, dose-dependently depressed m3 function. ICl(Ca) induced by intracellular injections of IP3 were unaffected by all four anaesthetics. Similarly, none of the anaesthetics tested affected AT1A signalling. Absence of interference with AT1A signalling and intracellular pathways suggest that the effects of anaesthetics on muscarinic signalling most likely result from interactions with the m1 or m3 receptor molecule. Multiple interaction sites with different affinities may explain the biphasic response to desflurane. Anaesthetic-specific effects on closely related receptor subtypes suggest defined sites of action for volatile anaesthetics on the receptor protein.

Anesthetics, Inhalation↗

PubMed1998

Influence of volatile anesthetics on thromboxane A2 signaling.

BACKGROUND: Thromboxane A2 (TXA2) is a member of the prostaglandin family; activation of its receptor induces several important effects, including platelet aggregation and smooth muscle contraction. Because volatile anesthetics interfere with aggregation and contraction, the authors investigated effects of halothane, isoflurane, and sevoflurane on TXA2 signaling in an isolated receptor model. METHODS: mRNA encoding TXA2 receptors was prepared in vitro and expressed in Xenopus oocytes. The effects of halothane, isoflurane, and sevoflurane on Ca2+-activated Cl- currents induced by the TXA2 agonist U-46619 and on those induced by intracellular injection of inositol 1-4-5 trisphosphate or guanosine 5'-O-(2-thiodiphosphate) were measured using the voltage-clamp technique. RESULTS: Expressed TXA2 receptors were functional (half maximal effect concentration [EC50], 3.2 x 10(-7) +/- 1.1 x 10(-7) M; Hill coefficient (h), 0.8 +/- 0.2). Halothane and isoflurane inhibition of TXA2 signaling was reversible and concentration dependent (halothane half maximal inhibitory concentration [IC50], 0.46 +/- 0.04 mM; h, 1.6 +/- 0.21; isoflurane IC50, 0.69 +/- 0.12 mM; h, 1.3 +/- 0.27). 0.56 mM halothane (1%) right-shifted the U-46619 concentration-response relationship by two orders of magnitude (EC50, 1 x 10[-5] M). That h and maximal effect (Emax) were unchanged indicates that halothane acts in a competitive manner. In contrast, isoflurane acted noncompetitively, decreasing Emax by 30% (h and EC50 were unchanged). Both halothane and isoflurane had no effect on intracellular signaling pathways. Sevoflurane (0-1.3 mM) did not affect TXA2 signaling. CONCLUSIONS: Both halothane and isoflurane inhibit TXA2 signaling at the membrane receptor, but by different mechanisms. This suggests that the effects of these anesthetics on TXA2 signaling are evoked at different locations of the receptor protein: halothane probably acts at the ligand binding site and isoflurane at an allosteric site.

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

PubMed1998

Use of guidelines in treating community-acquired pneumonia.

STUDY OBJECTIVES: Guidelines for empiric treatment of community-acquired pneumonia (CAP) have been developed to assist in prescribing appropriate antimicrobials. We studied utilization of guidelines developed by the American Thoracic, Canadian Infectious Diseases, and Canadian Thoracic Societies (ATS, CIDS, and CTS, respectively), physicians' familiarity with them, reasons that prompt deviation from them, and their effects on clinical outcomes. DESIGN: Two-part observational study, with prospective and retrospective groups. SETTING: A 1,100-bed, two-campus, tertiary-care teaching hospital. PATIENTS AND PARTICIPANTS: Patients admitted to the general medical ward who were being treated empirically for CAP and housestaff who provided their care. INTERVENTIONS: Medical residents reported on patients admitted to the hospital with CAP. The charts of all unreported patients admitted with CAP over the same period were reviewed. MEASUREMENTS AND RESULTS: One hundred twenty-two patients were prospectively described and another 130 patients were identified retrospectively. There was no difference in guidelines adherence between the prospective and retrospective groups (81% compared with 80%; p=0.94). Deviation occurred most commonly in suspected aspiration. When physicians believed that they were following guidelines, this was true in 88%. When physicians believed that they were deviating, they were actually adhering in 46%. Guidelines adherence did not alter in-hospital mortality (12% compared with 14%, p=0.92) or length of hospitalization (median, 6 days for both groups). CONCLUSIONS: ATS/CIDS/CTS guidelines for empiric treatment of CAP are widely used in our institution. Future amendments should address aspiration more explicitly. Residents' familiarity with them could be improved. Beneficial effects on outcomes remain unproven.

Aged↗

PubMed1998

Effects of long-term aerosol pentamidine for Pneumocystis carinii prophylaxis on pulmonary function.

OBJECTIVE: The purpose of the study was to evaluate the long-term effects of aerosolized pentamidine (AP) on the pulmonary function of HIV-positive individuals receiving AP for Pneumocystis carinii pneumonia (PCP) prophylaxis. DESIGN: A retrospective analysis of serial pulmonary function tests (PFTs) performed on a cohort of HIV-positive patients who had received AP for >2 years. METHODS: Of the 1,787 HIV-positive patients receiving AP prophylaxis in our database, 380 patients had been receiving AP for at least 24 months. Of these 380 patients, the PFTs at baseline and at 24 months after starting AP therapy were documented in 179. We compared the baseline PFTs of these 179 patients with results obtained 24 months later to evaluate if there was any change in pulmonary function parameters. RESULTS: Baseline and 24-month PFT parameters (total lung capacity [TLC], FVC, residual volume [RV], FEV1, FEV1/FVC, maximum midexpiratory flow rate at 50% of vital capacity [MEF50], diffusion of carbon monoxide [DLCO]) were all within the normal ranges. However, AP therapy over 24 months was associated with a modest decline in lung volume parameters (TLC, FVC, RV), a slight reduction in flow rates (FEV1, FEV1/FVC, and MEF50), but no change in DLCO. The mean treatment duration was 23.8 months (range, 21 to 27 months). CONCLUSIONS: Long-term AP therapy is associated with a mild combined restrictive and obstructive pulmonary defect. Since 24-month PFT parameters remained within the normal ranges, this level of decline is of unclear clinical significance. Overall, AP has good pulmonary tolerance when used up to 24 months for PCP prophylaxis in patients with normal baseline pulmonary function.

AIDS-Related Opportunistic Infections↗

PubMed1998

Penicillium marneffei infection and solitary pulmonary nodule.

We report on a patient infected with human immunodeficiency virus who presented with fever, a solitary pulmonary nodule, and cervical lymphadenopathy. The diagnosis of Penicillium marneffei infection was made from an excisional lymph node biopsy and a sputum culture. The microbiology, pathology, diagnosis, and treatment of the case are discussed. A high level of clinical suspicion is necessary for making an early diagnosis and improving the outcome of infection.

Journal Article↗

PubMed1998

Bilevel positive airway pressure nasal mask ventilation in patients with acute hypercapnic respiratory failure.

The efficacy and complications of bilevel positive airway pressure nasal mask ventilation for 22 patients with acute hypercapnic respiratory failure were reviewed retrospectively. The median patient age was 73 years (range, 57-92 years). The most common primary diagnosis (77%) was chronic obstructive pulmonary disease. The median duration of ventilation was 72.0 hours (range, 0.9 hours to 35 days). Within a median of 12 hours (range, 1-24 hours) after the initiation of therapy, there were significant improvements in the arterial oxygen and carbon dioxide tensions, oxygenation ratio, and arterial-alveolar ratio. Fourteen patients (64%) were treated successfully. Success with therapy was associated with a lower Acute Physiology and Chronic Health Evaluation score, a higher arterial oxygen tension, higher oxygenation and arterial-alveolar ratios, and lower respiratory and pulse rates. Complications were uncommon. We conclude that bilevel positive airway pressure nasal mask ventilation can be useful for patients with acute hypercapnic respiratory failure but who are otherwise clinically stable.

Journal Article↗

PubMed1998

Site and receptors involved in the sympathoinhibitory actions of rilmenidine.

INTRODUCTION: It is well accepted that centrally acting antihypertensive agents such as rilmenidine reduce blood pressure through inhibition of the sympathetic nervous system. The central receptor involved, be it a central imidazoline receptor or an alpha2-adrenoceptor and its location, is less certain. METHODS AND RESULTS: The present paper reviews studies from our laboratory examining these questions by using antagonists with differing affinity for imidazoline receptors and alpha2-adrenoceptors. In addition, we have used various routes of administration in conscious and anaesthetized normotensive rabbits. We found that rilmenidine was more potent in its hypotensive action when administered into the fourth ventricle than when given intravenously and considerably more potent when injected into the rostroventrolateral medulla (RVLM) compared to the nucleus of the solitary tract (NTS). By contrast, alpha-methylnoradrenaline, which acts solely through alpha2-adrenoceptors to produce hypotension, was similarly potent in both the NTS and RVLM. Injections of rilmenidine into the RVLM reduced renal sympathetic tone and produced a marked inhibition of renal sympathetic baroreflex responses. The pattern of renal sympathetic baroreflex effects of rilmenidine administered into the RVLM was similar to the effects of the fourth ventricular or intravenous administration. These studies together support the view that the RVLM is the major site of action. We have determined the relative importance of imidazoline receptors and alpha2-adrenoceptors in the inhibition of renal sympathetic nerve activity produced by rilmenidine administered into the RVLM, the fourth ventricle or intravenously. Initial studies in conscious rabbits showed that intravenous or fourth ventricular administration of rilmenidine induced renal sympatho-inhibition which was preferentially reversed by idazoxan or efaroxan (imidazoline/alpha2-adrenoceptor antagonist) compared to 2-methoxyidazoxan (alpha2-adrenoceptor antagonist). In anaesthetized rabbits, administration of idazoxan into the RVLM reversed the inhibition of the renal sympathetic activity induced by RVLM or intravenous administration of rilmenidine. In contrast, idazoxan had no effect on the responses produced by the alpha2-adrenoceptor agonist alpha-methylnoradrenaline. CONCLUSION: Our studies suggest that rilmenidine given systemically acts primarily on imidazoline receptors in the RVLM to reduce sympathetic tone and to modulate sympathetic baroreflexes.

Adrenergic alpha-Agonists↗

PubMed1998

Os supratrochlear dorsale of the elbow: a report of two cases.

The os supratrochlear dorsale, an accessory ossicle of the elbow, has rarely been described in the literature. Rather than being caused by trauma, it is subject to trauma by elbow extension with secondary chondrometaplasia, resulting symptomatology. The aim of this report is to remind readers that its presence is crucial for both diagnostic and therapeutic purposes. Arthroscopic removal may be required to relieve persistent pain, catching and limited range of motion.

Adolescent↗

PubMed1997

Quality of life in female lung transplant candidates and recipients.

OBJECTIVE: Quality of life (QOL) studies of lung transplant recipients indicate that there are improvements following transplantation. More recently, there has been some suggestion that certain QOL issues are different for men and women. The purpose of the present study was to examine changes in QOL, body satisfaction, and sexual functioning in women lung transplant recipients. STUDY POPULATION: Seven prelung transplant (PRE) and 34 postlung transplant (POST) women. MAIN OUTCOME MEASURES: The RAND-36 Health Survey, Body Cathexis Scale, Derogatis Sexual Functioning Inventory, Hospital Depression and Anxiety Scale, Rosenberg Self-Esteem Scale, and an open-ended questionnaire. RESULTS: Higher scores were found in the POST group with respect to general health and role limitations due to physical health. We were unable to detect significant differences between the groups with respect to emotional well-being, role limitations due to emotional health, and social functioning. There were significant differences between the PRE and the POST body satisfaction scores. Although there was no significant difference in overall sexual functioning, recipients in the PRE group reported higher sex drive. Eleven of the POST recipients (52%) scored below the 10th percentile in overall sexual functioning. CONCLUSIONS: Overall QOL improves following lung transplantation; however, the lack of differences in many domains of QOL raises the concern that women lung transplant recipients may continue to have significant impairments, including those regarding sexuality and body satisfaction.

Adult↗

PubMed1997

Inhibition of CD45 during neutrophil activation.

Tyrosine phosphorylation represents a balance between the activity of tyrosine kinases and phosphatases. We have demonstrated recently that reactive oxygen intermediates (ROI) produced by the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase enhance tyrosine phosphorylation in neutrophils. As tyrosine phosphatase activity can be regulated by oxidants, we sought to determine whether endogenously generated ROI inhibited the activity of the leukocyte tyrosine phosphatase CD45. Addition of guanosine 5'-O-(3-thiotriphosphate) (GTPgammaS) to electropermeabilized neutrophils, conditions known to activate the oxidase, inhibited CD45, as determined by immunoprecipitation and an in vitro phosphatase assay. That this inhibition was a consequence of activation of the oxidase was supported by three observations: 1) GTPgammaS-induced inhibition of CD45 was NADPH dependent; 2) pretreatment of cells with diphenylene iodonium, an oxidase inhibitor, partially prevented the inhibition; and 3) inhibition of CD45 was diminished markedly in neutrophils from chronic granulomatous disease (CGD) patients. The inhibition could be partially prevented by treatment of the cells with the antioxidants N-acetylcysteine or DTT, but direct antioxidant treatment of CD45 immunoprecipitates could not restore activity. Exposure to PMA, a direct activator of protein kinase C that also induces an oxidative burst, inhibited CD45 in both normal and CGD neutrophils. However, the magnitude of inhibition was less and the kinetics delayed in CGD cells when compared with normal cells. We conclude that ROI produced by the NADPH oxidase can contribute to inhibition of tyrosine phosphatases such as CD45 by oxidant-mediated effects, but that alternate regulatory mechanisms also exist.

Down-Regulation↗