PubMed Health⌕ Search

Biomedical subjects

M Scully

Publications and source records attributed to M Scully.

At least 19 recordsLinked to original sources
PubMed2005

Thrombotic thrombocytopaenic purpura in HIV-infected patients.

Thrombotic thrombocytopaenic purpura (TTP) results from deficiency of von Willebrand factor-cleaving protease (vWF-cp) activity. Eight HIV-infected patients presented with TTP, representing 12.5% of all TTP treated at this centre. In four patients presentation with TTP revealed underlying HIV infection, the other four patients were previously known to be HIV infected, with plasma exchange and highly active antiretroviral therapy (HAART) all recovered. Normalization of vWF-cp activity was associated with recovery. Relapse occurred in two patients who discontinued HAART against medical advice, suggesting that HIV has a causal role in this condition. Given the clear benefit from HAART in addition to plasma exchange, these data suggest that all patients presenting with TTP should undergo HIV testing.

Antiretroviral Therapy, Highly Active↗
PubMed2005

Contact tracing of tuberculosis in a school setting and the relevance of BCG in this population.

Tuberculosis (TB) remains a worldwide health problem. Treatment, contact tracing and screening of at-risk populations continue to be important issues even in countries with low rates of tuberculosis. In contact tracing, prior BCG vaccination can make interpretation of Mantoux positivity difficult. We had the opportunity to evaluate contacts of a student diagnosed with pulmonary tuberculosis. In the index case's class, 23 of 50 (46%) students screened had TB infection and a further 2 (4%) students had TB disease. Screening was offered to all students in the school (307 students) and 244 students (79%) attended. Students were stratified naturally into classes of ascending age, providing an opportunity to study disease transmission and Mantoux testing in a group who had received BCG at birth. Our findings illustrates that neonatal BCG vaccination has a minimal effect on Mantoux positivity at 12 years and older.

Adolescent↗
PubMed2001

Arg-Tyr-Asp (RYD) and Arg-Cys-Asp (RCD) motifs in dendroaspin promote selective inhibition of beta1 and beta3 integrins.

Arg-Gly-Asp (RGD) is a unique minimal integrin-binding sequence that is found within several glycoprotein ligands. This sequence has also been found in snake-venom anti-platelet proteins, including the disintegrins and dendroaspin, a natural variant of short-chain neurotoxins isolated from the venom of Dendroaspis jamesonii. In the present study, the motifs RYD and RCD were introduced into the dendroaspin scaffold to replace RGD. Both motifs in dendroaspin caused inhibition of ADP-induced platelet aggregation with IC(50) values of 200 and 300 nM respectively, similar to that of the wild-type RGD motif (170 nM). In comparison with wild-type dendroaspin, both RYD- and RCD-containing dendroaspins were more selective in the inhibition of the adhesion of K562 cells to laminin rather than to fibrinogen and fibronectin, even though they were 10-30-fold less potent at inhibiting K562 cell (containing alpha(5)beta(1) integrin) adhesion to laminin compared with wild-type. Interestingly, the RYD motif produced a similar IC(50) value to the RGD motif at inhibiting A375-SM cell (beta(3) integrin) adhesion to collagen, whereas the RCD motif was approx. 2-6-fold less potent compared with either RGD or RYD. These findings show that the selectivity of dendroaspin binding to beta(1) and beta(3) integrins can be modulated by the introduction of alternative cell recognition sequences.

Amino Acid Motifs↗
PubMed2001

Evaluation of the role of proline residues flanking the RGD motif of dendroaspin, an inhibitior of platelet aggregation and cell adhesion.

The effect of a panel of proline mutants of dendroaspin, an inhibitor of platelet aggregation and cell adhesion, including A(42)-dendroaspin, A(47)-dendroaspin, A(49)-dendroaspin, A(42,47)-dendroaspin and A(47,49)-dendroaspin, was investigated using platelet-aggregation and cell-adhesion assays. Here we show that a single alanine-for-proline substitution did not affect potency when measured as the ability either to inhibit platelet aggregation induced by ADP (IC(50) approximately 170 nM) or to block transfected A375-SM cell adhesion to fibrinogen in the presence of Mn(2+) as compared with wild-type dendroaspin. By comparison, double proline substitution with alanines significantly reduced the potency in both assays by approx. 5-8-fold. These observations, therefore, suggest that proline residues flanking the RGD motif in dendroaspin and other RGD-containing venom proteins, e.g. disintegrins, may contribute to maintaining a favourable conformation for the solvent-exposed RGD site for its recognition by integrin receptors.

Amino Acid Motifs↗
PubMed2001

Inhibition of cyclooxygenase-2 aggravates doxorubicin-mediated cardiac injury in vivo.

The clinical use of doxorubicin, an anthracycline chemotherapeutic agent, is limited by cardiotoxicity, particularly when combined with herceptin, an antibody that blocks the HER2 receptor. Doxorubicin induces cyclooxygenase-2 (COX-2) activity in rat neonatal cardiomyocytes. This expression of COX-2 limits doxorubicin-induced cardiac cell injury, raising the possibility that the administration of a prostaglandin may protect the heart during the in vivo administration of doxorubicin. Doxorubicin (15 mg/kg) administered to adult male Sprague Dawley rats induced COX-2 expression and activity in cardiac tissue. Prostacyclin generation measured as the excretion of 2,3-dinor-6-keto-PGF(1alpha) also increased, and this was blocked by a COX-2 inhibitor, SC236. In contrast, administration of a COX-1 inhibitor SC560 at a dose that reduced serum thromboxane B2 by more than 80% did not prevent the doxorubicin-induced increase in prostacyclin generation. Doxorubicin increased cardiac injury, detected as a rise in plasma cardiac troponin T, serum lactate dehydrogenase, and cardiomyocyte apoptosis; this was aggravated by coadministration of SC236 but not SC560. The degree of injury in animals treated with a combination of doxorubicin and SC236 was attenuated by prior administration of the prostacyclin analogue iloprost. These data raise the possibility of protecting the heart during the administration of doxorubicin by prior administration of prostacyclin.

6-Ketoprostaglandin F1 alpha↗
PubMed2000

Pharyngolaryngeal, neck, and jaw discomfort after anesthesia with the face mask and laryngeal mask airway at high and low cuff volumes in males and females.

BACKGROUND: There is controversy over (1) the relative incidence of sore throat between the face mask (FM) and laryngeal mask airway (LMA), (2) the efficacy of LMA intracuff pressure reduction as a mechanism for minimizing sore throat, and (3) the relative incidence of sore throat with the LMA between males and females. In a randomized double-blind study, the authors compared laryngopharyngeal, neck, and jaw discomfort with the FM and LMA at high and low cuff volumes in males and females. METHODS: Three hundred adult patients were randomly assigned to three equal-sized groups for airway management: (1) the FM, (2) the LMA with a fully inflated cuff (LMA-High), or (3) the LMA with a semi-inflated cuff (LMA-Low). Anesthesia was administered with propofol, nitrous oxide, oxygen, and isoflurane. In the FM group, a Guedel-type oropharyngeal airway and jaw thrust were used only if necessary. In the LMA groups, cuff inflation was achieved with either 15 or 30 ml for the size 4 (females) and 20 or 40 ml for the size 5 (males). The LMA was removed when the patient was awake. Patients were questioned 18-24 h postoperatively about surgical pain, sore throat, sore neck, sore jaw, dysphonia, and dysphagia, and about whether they were satisfied with their anesthetic. RESULTS: The incidence of sore throat was lower in the FM (8%) than the LMA-High (42%) and LMA-Low (20%) groups (both: P < or = 0.02). The incidence of sore neck was higher for the FM (14%) than the LMA-High group (6%; P = 0.05) but similar to the LMA-Low group (8%). The incidence of sore jaw was higher in the FM (11%) than the LMA-High (3%) and LMA-Low (3%) groups (both: P = 0. 02). There were no differences among groups for surgical pain or dysphonia. The incidence of dysphagia was lower in the FM (1%) than the LMA-High group (11%; P = 0.003), but similar to the LMA-Low group (1%). The incidence of sore throat and dysphagia was lower in the LMA-Low group than the LMA-High group for both males and females (all: P < or = 0.04). There were no differences in discomfort levels between males and females in any group. Two patients from the FM group and one from the LMA-High group were not satisfied with their anesthetic. These complaints were unrelated to postoperative morbidity. CONCLUSION: The LMA causes more sore throat and dysphagia but less jaw pain than the FM. Sore throat and dysphagia are more common with the LMA if the initial cuff volume is high. There are no differences in discomfort levels between males and females. However, these discomforts do not influence patient satisfaction after LMA or FM anesthesia.

Adult↗
PubMed1998

A prospective study comparing intravenous tenoxicam with rectal diclofenac for pain relief in day case surgery.

In a prospective, randomized, double-blind study, we compared intravenous tenoxicam with rectal diclofenac for post-operative pain relief after day case arthroscopy or laparoscopic sterilization. Intravenous tenoxicam (40 mg) was administered as a single bolus at induction, or rectal diclofenac (100 mg) was administered immediately after induction. Both groups were similar with respect to age, weight, sex of the patients, the operation performed and the operative time. There were no significant differences observed between the groups for pain scores at 30 min, 60 min and 24 h post-operatively. The time to first analgesic requirement, the dose of pethidine administered and total analgesic requirements in the first 24 h post-operatively were equivalent in both groups. In view of the similar efficacy of both of these drugs, patient preference and ease of administration, the use of tenoxicam is appropriate in many patients undergoing day case surgery.

Administration, Rectal↗
PubMed1995

Chrono-pharmacological study of once daily curative dose of a low molecular weight heparin (200 IU antiXa/kg of Dalteparin) in ten healthy volunteers.

Low molecular weight heparin (LMWH) is currently prescribed for the treatment of deep vein thrombosis at the dose of 100 IU antiXa/kg twice daily or at a dose of 175 IU antiXa/kg once daily with a similar efficacy. We decided to study the chrono-pharmacology of curative dose of LMWH once daily administrated according to the one previously described with unfractionated heparin (UFH). Ten healthy volunteers participated in an open three-period crossover study according to three 24 h cycles, separated by a wash-out interval lasting 7 days: one control cycle without injection, two cycles with subcutaneous injection of 200 IU antiXa/kg of Dalteparin (Fragmin) at 8 a.m. or at 8 p.m. Parameters of heparin activity were analysed as maximal values and area under the curve. Activated partial thromboplastin time (APTT), thrombin time (TT), prothrombin time (PT) and tissue factor pathway inhibitor (TFPI) were higher after 8 p.m. injection than after 8 a.m. injection (p < 0.05) while no chrono-pharmacological variation of anti factor Xa (AXa) activity was observed. Thus the biological anticoagulant effect of 200 IU antiXa/kg of Dalteparin seems to be higher after an evening injection than after a morning injection. A chrono-therapeutic approach with LMWH, as prescribed once daily, deserves further investigation since our results suggest that a preferential injection time may optimise the clinical efficacy of these LMWH.

Adult↗
PubMed1994

Prevalence of HIV and associated risk behaviour in attendees at a Dublin needle exchange.

The aim of this study was to measure the prevalence of HIV infection and assess the level of equipment-sharing and unsafe sexual activity among attendees at a Dublin needle exchange. Using an anonymous unlinked approach, attendees were asked to complete a brief questionnaire and provide a sample of saliva for HIV testing. Of the 144 attendees eligible for inclusion during the study period, 106 agreed to participate and complete a questionnaire, a response rate of 74%. Of the 81 respondents who submitted a usable saliva sample, 14.8% were HIV positive. Half of the respondents claimed that they had not shared equipment during the preceding 28 days, but a third had shared with multiple partners. Half of the respondents claimed that they had multiple sexual partners during the preceding year, but only a quarter said that they always used condoms. The prevalence of HIV infection is similar to that found in routine linked testing of drug users in Ireland. The high level of unsafe injecting and sexual activity makes clear the need for more effective health promotion among drug users in Dublin.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Mycobacterium haemophilum osteomyelitis in an AIDS patient.

Mycobacterium haemophilum is a fastidious species that has been isolated from skin and subcutaneous nodules. The authors describe a case of Mycobacterium haemophilum osteomyelitis and skin infection in an AIDS patient and successful treatment with minocycline.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Propranolol overdose--a dramatic response to calcium chloride.

OBJECTIVE: To present a case of severe propranolol overdose which responded dramatically to the administration of calcium chloride. CLINICAL FEATURES: A 22-year-old female Caucasian who was unemployed arrived by ambulance to a hospital emergency department after propranolol overdose. She was convulsing and in electromechanical dissociation. An electrocardiogram showed sinus rhythm with broad QRS complexes. She had no relevant medical history. INTERVENTION: Resuscitation with basic and then advanced life support and administration of oxygen, adrenaline, atropine, fluids and bicarbonate gave no response. Calcium chloride, however, repeatedly produced a dramatic restoration of blood pressure and a narrowing of the QRS complexes. She made a good recovery with no sequelae. CONCLUSION: Calcium chloride may have a role to play in propranolol overdose.

Adult↗
PubMed1983

The effect of divalent metal cations on the inhibition of human coagulation factor Xa by plasma proteinase inhibitors.

The inactivation of human coagulation factor Xa by the plasma proteinase inhibitors alpha 1-antitrypsin, antithrombin III and alpha 2-macroglobulin in purified systems was found to be accelerated by the divalent cations Ca2+, Mn2+ and Mg2+. The rate constant for the inhibition of factor Xa by antithrombin III rose from 2.62 X 10(4) M-1 X min-1 in the absence of divalent cations to a maximum of 6.40 X 10(4) M-1 X min-1 at 5 mM Ca2+, 8.10 X 10(4) M-1 X min-1 at 5 mM Mn2+, with a slight decrease in rate at higher cation concentrations. Mg2+ caused a gradual rise in rate constant to 5.65 X 10(4) M-1 X min-1 at 20 mM. The rate constant for the inhibition of factor Xa by alpha 1-antitrypsin in the absence of divalent cations was 5.80 X 10(3) M-1 X min-1. Ca2+ increased the rate to 1.50 X 10(4) M-1 X min-1 at 5 mM and Mn2+ to 2.40 X 10(4) M-1 X min-1 at 6 mM. The rate constant for these cations again decreased at higher concentrations. Mg2+ caused a gradual rise in rate constant to 1.08 X 10(4) M-1 X min-1 at 10 mM. The rate constant for the factor Xa-alpha 2-macroglobulin reaction was raised from 6.70 X 10(3) M-1 X min-1 in the absence of divalent cations to a maximum of 4.15 X 10(4) M-1 X min-1 at 4 mM Ca2+, with a decrease to 3.05 X 10(4) M-1 at 10 mM. These increases in reaction rate were correlated to the binding of divalent cations to factor Xa by studying changes in the intrinsic fluorescence and dimerization of factor Xa. The changes in fluorescence suggested a conformational change in factor Xa which may be responsible for the increased rate of reaction, whilst the decrease in rate constant at higher concentrations of Ca2+ and Mn2+ may be due to factor Xa dimerization.

Calcium↗
PubMed1982

Inhibition of human factor Xa by various plasma protease inhibitors.

The inhibitory effects of the plasma protease inhibitors antithrombin III, alpha 2-macroglobulin and alpha 1-antitrypsin on the activity of human factor Xa have been studied using purified proteins. The rate of inhibition was determined by measuring the residual factor Xa activity at timed intervals utilizing the synthetic peptide susbtrate Bz-Ile-Glu(piperidyl)-Gly-Arg-pNA. Kinetic analysis with varying molar concentrations of inhibitors demonstrated that the inhibition of factor Xa by antithromin III, alpha 2-macroglobulin and alpha 1-antitrypsin followed second-order kinetics. Calculated values of the rate constants for the inhibition of factor Xa by antithrombin III, alpha 2-macroglobulin and alpha 1-antitrypsin were 5.8 . 10(4), 4.00 . 10(4) and 1.36 . 10(4) M -1 . min -1, respectively. The plasma concentrations of the inhibitors can be used to assess their potential relative effectiveness against factor Xa. In plasma this was found as alpha 1-antitrypsin greater than antithrombin III greater than alpha 2-macroglobulin in the ratio 4.64: 2.08: 1.0. Cephalin was shown to inhibit the rate of reaction between factor Xa and antithrombin III.

Antithrombin III↗
PubMed1982

Modern management of anastomotic leak after esophagogastrectomy.

From 1970 to 1981, 167 patients, aged 35 to 84 years (mean 61), underwent resection of 94 adenocarcinomas and 73 squamous cell cancers. The operative mortality was 8.9 percent. Anastomotic leaks occurred in 19 patients (11.3 percent), including 18 of 72 (25 percent) after operations for palliation and 1 of 95 (1 percent) after procedures with curative potential (p less than 0.01). The leakage rate after esophagogastrostomy was 8.5 percent, compared with 43 percent after interposition operations. No leak is attributed to cancer in anastomotic margins. In contrast to previous reports of greater than 50 percent mortality from leaks, only 21 percent of our patients died in the past decade. Four of 19 contained leaks (sinus tract or upper gastrointestinal) were treated nonoperatively; esophagostomy was used only once. Factors responsible for improving results include early diagnosis with routine contrast studies on the fifth to seventh postoperative days, mandatory use of total parenteral nutrition, nonoperative management of contained leaks, accurate, aggressive use of adjuvant chest tubes, and selective esophagostomy for anastomotic disruption.

Adenocarcinoma↗