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Biomedical subjects

M Connor

Publications and source records attributed to M Connor.

At least 19 recordsLinked to original sources
PubMed2005

Restorative impact of rabeprazole on gastric mucus and mucin production impairment during naproxen administration: its potential clinical significance.

Rabeprazole augments gastric mucus and mucin production in humans. However, its potential restorative impact on gastric mucus and mucin production impairment, resulting from administration of naproxen, remained to be explored. Therefore, we measured the content of mucus and mucin in gastric juice (GJ) before and after administration of naproxen with rabeprazole or placebo. The study was approved by HSC at KUMC and conducted in 21 asymptomatic, H. pylori-negative volunteers in a double-blind, placebo-controlled, crossover design. The content of gastric mucus in GJ, after exhaustive dialysis and complete lyophilization, was assessed gravimetrically, whereas the content of mucin was measured after its purification with equilibrium density-gradient ultracentrifugation in CsC1. Gastric mucus secretion during administration of naproxen with placebo declined significantly both in basal (by 44%; P < 0.001) and in pentagastrin-stimulated (by 35%; P < 0.001) conditions. Coadministration of rabeprazole significantly restored the naproxen-induced impairment in mucus production in basal conditions (by 47%; P < 0.01) and by 22% during stimulation with pentagastrin. Gastric mucin secretion during naproxen/placebo administration also declined significantly in both basal (by 39%; P < 0.01) and stimulated (by 49%; P = 0.003) conditions. Rabeprazole also significantly restored the naproxen-induced decline of gastric mucin output during pentagastrin-stimulated conditions (by 67%; P = 0.003) and by 40% in basal conditions (P = 0.05). The restorative capacity of rabeprazole on the quantitative impairment of gastric mucus and mucin during administration of naproxen may translate into a clinical benefit of protection of the upper alimentary tract from NSAID-related mucosal injury.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2005

The South African stroke risk in general practice study.

BACKGROUND: Incidence of stroke is increasing in sub-Saharan Africa and stroke prevention is an essential component of successful stroke management. General practitioners (GPs) are well placed to manage stroke risk factors. To design appropriate strategies for risk factor reduction we need to know the risk factor prevalence in each of the population groups attending GPs. The aim of this study was to establish the prevalence of stroke risk factors in the South African general practice population. METHOD: We conducted a multicentre, observational study of patients attending general practice in South Africa. Two hundred general practices were randomly selected from lists provided by pharmaceutical representatives. Each GP approached 50 consecutive patients aged 30 years and older. Patients completed an information sheet and the GP documented the patient's risk factors. The resulting sample is relevant if not necessarily representative in a statistical sense. RESULTS: A total of 9 731 questionnaires were returned out of a possible 10,000. The mean age of particpants was 50.7 years. Seventy-six per cent had 1 or more risk factors and 40% had 2 or more risk factors. Hypertension was the commonest risk factor in all population groups (55%) but was highest in black patients (59%). Dyslipidaemia was commonest in whites (37%) and least common in blacks (5%). Diabetes was commonest in Asians (24%) but least common in whites (8%). Risk factors other than smoking increased with age. CONCLUSION: This study provides unique data on the prevalence of stroke risk factors in a South African general practice population. Risk factors are common in all population groups, but differ in distribution among the groups. There is considerable opportunity to reduce the burden of stroke in South Africa through GP screening for and treatment of risk factors.

Adult↗
PubMed2004

Vitrectomy and gas for inferior break retinal detachments: are the results comparable to vitrectomy, gas, and scleral buckle?

AIMS: To compare the success rates of vitrectomy and gas with vitrectomy, gas, and buckle in the treatment of inferior break retinal detachments. METHODS: A retrospective case note review of 86 patients who presented with inferior break retinal detachments was carried out. An inferior break was defined as a horseshoe tear present between 4 and 8 o'clock. Patients were analysed in two groups; group A consisted of 41 patients who underwent a vitrectomy and gas, group B consisted of 45 patients who underwent a vitrectomy, gas, and scleral buckle. The features of the retinal detachment, peroperative and postoperative complications, and outcomes of treatment were recorded for each patient. RESULTS: The primary anatomical success rate at 3 months was 89% in group A versus 73% in group B (p = 0.11). There was no statistical difference in the complication rate between the two groups (p = 0.819). The most common cause of treatment failure was proliferative vitreoretinopathy, 20% (n = 9) in group B compared with 5% (n = 2) in group A and this reached statistical significance (p = 0.0159). There was a higher rate of epiretinal membrane development in group B (p = 0.0004). The final attachment rate was not statistically different between the two groups, 95% (39) in group A and 93% (42) in group B (p = 1.0). CONCLUSION: Vitrectomy and gas without the application of a scleral buckle may be used to safely treat inferior break retinal detachments. It may be used as an alternative to vitrectomy, gas, and buckle which has an increased risk of choroidal haemorrhage, requires a longer operating time, and has all the associated complications of a scleral buckle.

Humans↗
PubMed2003

The life course prospective design: an example of benefits and problems associated with study longevity.

Although the life course prospective study design has many benefits, and information from such studies is in increasing demand for scientific and policy purposes, it has potential inherent design problems associated with its longevity. These are in particular the fixed sample structure and the data collected in early life, which are each determined by the scientific principles of another time and the risk over time of increased sample loss and distortion through loss. The example of a national birth cohort in Britain, studied from birth so far to age 53 years is used to address these questions. Although the response rate is high, avoidable loss, which was low in childhood, increased in adulthood, and was highest in those in adverse socio-economic circumstances and those with low scores on childhood cognitive measures. Recent permanent refusal rate rises may be the result of better tracing and/or a response to increased requests for biological measurement. Nevertheless, the responding sample continues in most respects to be representative of the national population of a similar age. Consistency of response over the study's 20 data collections has been high. The size of the sample responding in adulthood is adequate for the study of the major costly diseases, and for the study of functional ageing and its precursors. This study's continuation has depended not only on scientific value but also policy relevance. Although the problems inherent in the prospective design are unavoidable they are not, in the study described, a barrier to scientific and policy value. That seems also likely in Britain's two later born national birth cohort studies that have continued into adulthood.

Adolescent↗
PubMed2002

Safe and cost effective use of alteplase for the clearance of occluded central venous access devices.

PURPOSE: To determine whether cryopreserved solutions of the thrombolytic agent alteplase could be used as a safe, effective, and economically reasonable alternative to urokinase in patients presenting with occluded central venous access devices (CVADs). MATERIALS AND METHODS: Alteplase has been reported as an efficacious alternative to urokinase for treatment of occluded CVADs. However, the practicality of using alteplase as the thrombolytic of choice for this indication remained conjectural. To make this approach economically feasible, alteplase was diluted to 1 mg/mL and 2.5-mL aliquots were stored at -20 degrees C until use. A need to confirm that the cryopreserving and thawing of the reconstituted solution did not compromise the safety and efficacy reported from prior trials was recognized. A quality assessment initiative was undertaken to concurrently monitor the safety and efficacy of this approach. Patients presenting with occluded CVADs received a sufficient volume of the thawed alteplase solution to fill the occluded catheter(s). Data, including efficacy, adverse reactions, dwell time, and catheter type, were collected over a 5-month period. RESULTS: One hundred twenty-one patients accounting for 168 attempted clearances were assessable for safety and efficacy. One hundred thirty-six (81%) of the 168 catheter clearance attempts resulted in successful catheter clearance (95% confidence interval, 74% to 86%). No adverse events were reported. CONCLUSION: Cryopreserved 1-mg/mL aliquots of alteplase are safe and effective in the clearance of occluded CVADs when stored at -20 degrees C for 30 days. The ability to cryopreserve alteplase aliquots makes it an economically reasonable alternative to urokinase in the setting of CVAD occlusion.

Adolescent↗
PubMed2001

Nociceptin inhibits calcium channel currents in a subpopulation of small nociceptive trigeminal ganglion neurons in mouse.

1. The effects of nociceptin/orphanin FQ (N/OFQ) and opioid receptor agonists on voltage-activated calcium channel currents (I(Ca)) were examined in acutely isolated mouse trigeminal ganglion neurons using whole-cell patch-clamp recordings. These effects were correlated with responses of the neurons to capsaicin and binding of Bandeiraea simplicifolia isolectin B4 (IB4). 2. Trigeminal neurons were divided into two populations based on the presence (type 2) or absence (type 1) of a prominent T-type I(Ca). N/OFQ potently (EC(50) of 19 nM) inhibited high-voltage-activated (HVA) I(Ca) in most (82 %) small (capacitance < 12 pF) type 1 neurons, but few (9 %) larger (> 12 pF) type 1 neurons. N/OFQ inhibited I(Ca) in few (23 %) type 2 cells, and did not affect the T-type I(Ca) in any cell. 3. The mu-opioid agonists DAMGO and morphine inhibited I(Ca) in most type 1 neurons, more often (95 % versus 77 %) in the small cells. The inhibition of I(Ca) by DAMGO and morphine was more efficacious in small versus large type 1 neurons. mu-Opioids did not inhibit I(Ca) in type 2 neurons. 4. Most small type 1 neurons were sensitive to capsaicin (93 %) and bound IB4 (86 %). Fewer larger type 1 neurons responded to capsaicin (30 %) or bound IB4 (58 %). Type 2 neurons did not respond to capsaicin, although some bound IB4 (35 %). 5. Thus, N/OFQ preferentially inhibits HVA I(Ca) in a subpopulation of small nociceptive trigeminal ganglion neurons that is also highly sensitive to mu-opioid agonists.

Analgesics, Opioid↗
PubMed2001

Discovery and structure of a potent and highly specific blocker of insect calcium channels.

We have isolated a novel family of insect-selective neurotoxins that appear to be the most potent blockers of insect voltage-gated calcium channels reported to date. These toxins display exceptional phylogenetic specificity, with at least a 10,000-fold preference for insect versus vertebrate calcium channels. The structure of one of the toxins reveals a highly structured, disulfide-rich core and a structurally disordered C-terminal extension that is essential for channel blocking activity. Weak structural/functional homology with omega-agatoxin-IVA/B, the prototypic inhibitor of vertebrate P-type calcium channels, suggests that these two toxin families might share a similar mechanism of action despite their vastly different phylogenetic specificities.

Amino Acid Sequence↗
PubMed2001

Actions of nociceptin/orphanin FQ and other prepronociceptin products on rat rostral ventromedial medulla neurons in vitro.

1. Whole-cell patch clamp recordings were made from rat rostral ventromedial medulla (RVM) neurons in vitro to investigate the cellular actions of the opioid-like receptor ORL1 (NOP), ligand nociceptin/orphanin FQ and other putative prepronociceptin products. 2. Primary and secondary RVM neurons were identified as responding to the kappa-opioid receptor agonist U-69593 (300 nM to 1 microM) and the mu- and delta-opioid receptor agonist met-enkephalin (10 microM), respectively. Both primary and secondary RVM neurons responded to nociceptin (3 nM to 1 microM) with an outward current that reversed polarity at -115 mV in brain slices and with inhibition of Ca(2+) channel currents in acutely isolated cells. 3. The putative ORL1 antagonist J-113397 (1 microM) produced no change in membrane current and abolished the outward current produced by nociceptin (100 nM). In contrast, Phe(1)psi(CH(2)-NH)Gly(2)]-nociceptin-(1-13)NH(2) (300 nM to 1 microM) alone produced an outward current and partially reduced the outward current produced by nociceptin (300 nM) when co-applied. 4. In brain slices nociceptin (300 nM) reduced the amplitude of evoked GABA(A) receptor-mediated inhibitory postsynaptic currents (IPSCs) but not non-NMDA receptor-mediated excitatory postsynaptic currents (EPSCs). 5. Met-enkephalin (10 microM), but not nociceptin (300 nM), reduced the rate of spontaneous miniature IPSCs in normal external potassium solution (K(+) 2.5 mM). In high external potassium (K(+) 17.5 mM), nociceptin reduced the rate of miniature IPSCs in the presence (Ca(2+) 2.4 mM, Mg(2+) 1.2 mM) but not in the absence of external calcium (Ca(2+) 0 mM, Mg(2+) 10 mM, Cd(2+) 10 microM). Nociceptin and met-enkephalin had no effect on the amplitude of miniature IPSCs. 6. The putative nociceptin precursor products nocistatin (rat prepronociceptin(125-132)) and rat prepronociceptin(154-181) had no effect on membrane currents, evoked IPSCs and evoked EPSCs. 7. These results indicate that nociceptin acts via the ORL1 receptor to directly inhibit both primary and secondary RVM neurons by activating a potassium conductance and by inhibiting calcium conductances. In addition, nociceptin inhibits GABA release within the RVM via a presynaptic Ca(2+)-dependent mechanism. Thus, nociceptin has the potential to exert both disinhibitory and inhibitory effects on neuronal action potential firing within the RVM.

Animals↗
PubMed2001

The application of comparative genomic hybridization as an additional tool in the chromosome analysis of acute myeloid leukemia and myelodysplastic syndromes.

In acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) there are frequently complex karyotypes with multiple structurally altered chromosomes, many of which are marker chromosomes of unknown origin. The aim of this study was to apply comparative genomic hybridization (CGH) to cases of AML or MDS in transformation submitted for routine cytogenetic analysis to investigate whether this approach would yield any further information and, if possible, to predict which cases would benefit from CGH analysis. Nineteen cases with AML or MDS in transformation were analyzed. CGH revealed nine cases with gains or losses of chromosomal material. In six of these cases the chromosomal location of this material was not apparent from cytogenetic analysis especially when multiple markers were present. By using fluorescence in situ hybridization (FISH) with specific libraries for the chromosome regions that showed discordance between CGH and conventional cytogenetics, we were able to identify the chromosome location of material within the karyotype. In this group of six patients, four cases of an unbalanced translocation involving regions of chromosomes 5 and 17 were characterized. Three of these cases had additional abnormalities, including two cases with regions of amplification in which oncogenes are located (MYC, MLL) and one case with a dic(7;21)(p10;p10). In all six cases it was possible to characterize complex chromosomal aberrations such as derivative chromosomes, marker chromosomes, and ring chromosomes. This study demonstrates that CGH can detect true gain and loss of critical chromosome regions more accurately than conventional karyotyping in cases with very complex karyotypes, and can thus prove useful in predicting prognosis and pinpointing areas of the genome that require further study. Also, CGH can be a useful technique to identify the origin of marker chromosomes, and it can assist in choice of probes for confirmatory FISH, when there is no clue provided from the analysis of G-banded chromosomes.

Acute Disease↗
PubMed2001

Careless whispers.

Explore the source record for details and available documents.

Communication↗
PubMed2000

The spectrum of HIV-1 related cancers in South Africa.

Despite the high prevalence of infection by the Human Immunodeficiency Virus (HIV) in South Africa, information on its association with cancer is sparse. Our study was carried out to examine the relationship between HIV and a number of cancer types or sites that are common in South Africa. A total of 4,883 subjects, presenting with a cancer or cardiovascular disease at the 3 tertiary referral hospitals in Johannesburg, were interviewed and had blood tested for HIV. Odds ratios associated with HIV infection were calculated by using unconditional logistic regression models for 16 major cancer types where data was available for 50 or more patients. In the comparison group, the prevalence of HIV infection was 8.3% in males and 9.1% in females. Significant excess risks associated with HIV infection were found for Kaposi's sarcoma (OR=21.9, 95% CI=12.5-38.6), non-Hodgkin lymphoma (OR=5.0, 95%CI=2.7-9.5), vulval cancer (OR=4.8, 95%CI= 1.9-12.2) and cervical cancer (OR= 1.6, 95%CI= 1.1-2.3) but not for any of the other major cancer types examined, including Hodgkin disease, multiple myeloma and lung cancer. In Johannesburg, South Africa, HIV infection was associated with significantly increased risks of Kaposi's sarcoma, non-Hodgkin lymphoma and cancers of the cervix and the vulva. The relative risks for Kaposi's sarcoma and non-Hodgkin lymphoma associated with HIV infection were substantially lower than those found in the West.

Acquired Immunodeficiency Syndrome↗
PubMed2000

Isolation and pharmacological characterisation of delta-atracotoxin-Hv1b, a vertebrate-selective sodium channel toxin.

delta-Atracotoxins (delta-ACTXs) are peptide toxins isolated from the venom of Australian funnel-web spiders that slow sodium current inactivation in a similar manner to scorpion alpha-toxins. We have isolated and determined the amino acid sequence of a novel delta-ACTX, designated delta-ACTX-Hv1b, from the venom of the funnel-web spider Hadronyche versuta. This 42 residue toxin shows 67% sequence identity with delta-ACTX-Hv1a previously isolated from the same spider. Under whole-cell voltage-clamp conditions, the toxin had no effect on tetrodotoxin (TTX)-resistant sodium currents in rat dorsal root ganglion neurones but exerted a concentration-dependent reduction in peak TTX-sensitive sodium current amplitude accompanied by a slowing of sodium current inactivation similar to other delta-ACTXs. However, delta-ACTX-Hv1b is approximately 15-30-fold less potent than other delta-ACTXs and is remarkable for its complete lack of insecticidal activity. Thus, the sequence differences between delta-ACTX-Hv1a and -Hv1b provide key insights into the residues that are critical for targeting of these toxins to vertebrate and invertebrate sodium channels.

Amino Acid Sequence↗
PubMed2000

Isolation of a funnel-web spider polypeptide with homology to mamba intestinal toxin 1 and the embryonic head inducer Dickkopf-1.

We have isolated and determined the amino acid sequence of a novel peptide component from the venom of the Australian funnel-web spider Hadronyche versuta. This 68-residue toxin, ACTX-Hvf17, does not function like classical neurotoxins in modulating ion channel function as evidenced by its lack of insecticidal activity and its inability to affect vertebrate smooth or skeletal muscle contractility. The peptide shows significant sequence homology with mamba intestinal toxin 1 (MIT1) and to a lesser extent with a variety of colipases. The strong structural homology between MIT1 and porcine colipase leads us to propose that ACTX-Hvf17 also adopts the MIT1/colipase three-dimensional fold. However, we show that ACTX-Hvf17 has no colipase activity and does not stimulate muscle contractility like MITI. We also show that MIT1 and ACTX-Hvf17 display significant sequence homology with the C-terminal cysteine-rich domain of the Dickkopf-1 family of proteins that induce head formation in developing embryos, which leads us to propose that this domain of Dickkopf-1 also adopts the MIT1 colipase fold.

Amino Acid Sequence↗
PubMed2000

Discovery and characterization of a family of insecticidal neurotoxins with a rare vicinal disulfide bridge.

We have isolated a family of insect-selective neurotoxins from the venom of the Australian funnel-web spider that appear to be good candidates for biopesticide engineering. These peptides, which we have named the Janus-faced atracotoxins (J-ACTXs), each contain 36 or 37 residues, with four disulfide bridges, and they show no homology to any sequences in the protein/DNA databases. The three-dimensional structure of one of these toxins reveals an extremely rare vicinal disulfide bridge that we demonstrate to be critical for insecticidal activity. We propose that J-ACTX comprises an ancestral protein fold that we refer to as the disulfide-directed beta-hairpin.

Amino Acid Motifs↗
PubMed2000

Bisoprolol and nifedipine retard in elderly hypertensive patients: effect on quality of life.

Subjects over the age 60 with sustained sitting diastolic pressures of 95-115 mm Hg were randomised to a regime based on bisoprolol (n = 368) or nifedipine retard (n = 379) for 24 weeks. The goal diastolic pressure was < or =90 mm Hg and to achieve this, double-blind medication could be doubled (5/10 mg bisoprolol, 40/80 mg nifedipine retard) or hydrochlorothiazide 25 mg (unblinded) could be added to the higher dose. In an intention-to-treat analysis, 309 subjects in both the bisoprolol and nifedipine retard treated group provided at least a baseline and a second quality of life assessment (82%). An excess of symptoms was observed in the nifedipine group for oedema of the legs, nocturia, constipation, racing heart and heart thumping. Fewer patients reported wheeze in the nifedipine group. For quality of life, there were no statistically significant differences between the two groups after 8 weeks. However, when analysing the results of the last available assessment (usually at 24 weeks) there were significant (P < 0.05) improvements in tension/anxiety, anger/ hostility, vigour/activity, and confusion/bewilderment, assessed by the Profile of Mood States (POMS) in patients receiving bisoprolol in comparison to those receiving nifedipine retard. The Sickness Impact Profile and objective tests of cognitive function did not differ statistically between the two groups. Quality of life was maintained at a good level on both treatments with advantages for bisoprolol in certain areas. Journal of Human Hypertension (2000) 14, 205-212.

Adrenergic beta-Agonists↗