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M Connolly

Publications and source records attributed to M Connolly.

At least 37 records · Page 2Linked to original sources
PubMed2002

Comparison of low ionic diluents for use with the Diamed antiglobulin gel test.

Microtube column systems, although widely used in transfusion serology for the detection of red cell antibodies, may not detect weak Fy(a), Jk(a), S and K antibodies. A number of low ionic diluents are used to shorten the incubation time required for red cell antibody detection in the antiglobulin test. However, there are no published reports to show whether these low ionic diluents vary in their ability to detect red cell antibodies using microcolumn detection systems. Three low ionic diluents, Diamed ID-CellStab, Diamed ID-Diluent2 and an in-house produced low ionic strength solution (LISS), were assessed using the Diamed-ID LISS/Coombs microtube column system (in accordance with the manufacturer's instructions), to ascertain whether the choice of diluent influences red cell antibody detection. Two hundred and seventy patient samples were screened for red cell antibodies. The reaction strength was increased in 50% of the samples with detectable red cell antibodies using LISS as the diluent compared with ID-CellStab. Of the 51 red cell antibodies directed against Rhesus, Duffy, Kidd or Kell antigens, 21% reacted more strongly in LISS compared with Diamed ID-CellStab with a difference in grading of > or =1. Minimal disparity was found between ID-Diluent2 and LISS. Biochemical analysis of pH, osmolality, sodium, potassium and phosphate were comparable for ID-CellStab, ID-Diluent2 and LISS. Measurement of conductivity in each low ionic diluent was performed as a measure of ionic strength in the final reactant mix, as the same amount of low ionic diluent was used for each test. The conductivity was 3 x 5 mS cm for LISS and ID-Diluent2, and 5 x 8 mS cm for ID-CellStab; the acceptable range being 3 x 7 +/- 0 x 3 mS cm as cited in the Guidelines for the Blood Transfusion Services in the United Kingdom. This evaluation suggests that ID-CellStab is a suboptimal low ionic diluent for red cell antibody detection using Diamed-ID LISS/Coombs gel cards. The poorer performance of ID-CellStab compared with LISS may be explained by its higher ionic strength.

Antibodies↗
PubMed2001

Cryotherapy of viral warts: a sustained 10-s freeze is more effective than the traditional method.

BACKGROUND: Cryotherapy is a standard treatment for viral warts. Although textbooks recommend treating until there is a halo of ice around the wart (traditional freeze), many authors advocate more aggressive cryotherapy. There are no previously published studies assessing the efficacy of longer freezing times. OBJECTIVES: To compare the efficacy of the traditional freeze and a sustained 10-s freeze in the treatment of common viral warts with liquid nitrogen. METHODS: Patients attending a dedicated wart clinic were randomized to receive either a traditional freeze or a 10-s sustained freeze with liquid nitrogen delivered by a spray gun. Two hundred patients were recruited, 100 in each group. RESULTS: After five treatments, 49 patients in the 10-s freeze group were clear of warts (64% of non-defaulters) as compared with 31 (39%) of those in the traditional freeze group (chi2 = 6.7; P = 0.009). Seventy-four patients in the 10-s freeze group as compared with 59 in the traditional freeze group had either improved or cleared after five treatments (chi2 = 5.0; P = 0.02). Morbidity was significantly greater in the 10-s freeze group. Sixty-four patients suffered pain or blistering as compared with 44 in the traditional freeze group (chi2 = 10.8; P = 0.0045). Five patients were withdrawn from the 10-s freeze group because of pain as compared with one patient in the traditional freeze group. CONCLUSIONS: A 10-s sustained freeze is more effective in the cryotherapy of viral warts but carries a significantly greater morbidity in terms of pain and blistering.

Adolescent↗
PubMed2001

Surgical resection for intractable epilepsy in "double cortex" syndrome yields inadequate results.

PURPOSE: To analyze the results of surgical treatment of intractable epilepsy in patients with subcortical band heterotopia, or double cortex syndrome, a diffuse neuronal migration disorder. METHODS: We studied eight patients (five women) with double cortex syndrome and intractable epilepsy. All had a comprehensive presurgical evaluation including prolonged video-EEG recordings and magnetic resonance imaging (MRI). RESULTS: All patients had partial seizures, with secondary generalization in six of them. Neurologic examination was normal in all. Three were of normal intelligence, and five were mildly retarded. Six patients underwent invasive EEG recordings, three of them with subdural grids and three with stereotactic implanted depth electrodes (SEEG). Although EEG recordings showed multilobar epileptic abnormalities in most patients, regional or focal seizure onset was recorded in all. MRI showed bilateral subcortical band heterotopia, asymmetric in thickness in three. An additional area of cortical thickening in the left frontal lobe was found in one patient. Surgical procedures included multiple subpial transections in two patients, frontal lesionectomy in one, temporal lobectomy with amygdalohippocampectomy in five, and an additional anterior callosotomy in one. Five patients had no significant improvement, two had some improvement, and one was greatly improved. CONCLUSION: Our results do not support focal surgical removal of epileptogenic tissue in patients with double cortex syndrome, even in the presence of a relatively localized epileptogenic area.

Adolescent↗
PubMed2001

Temporal lobectomy in early childhood: the need for long-term follow-up.

We retrospectively identified 15 children ages 12 years and under with anticonvulsant resistant epilepsy who underwent a temporal lobectomy at Children's Hospital, Boston, between 1978 and 1993. Our aim was to study the long-term seizure outcome. Data pertaining to preoperative evaluation, electroencephalography (EEG), neuroimaging, surgery, seizure outcome, and postoperative complications were reviewed. Only patients followed for more than 12 months were included. The average duration of follow-up was 57 months. At the last visit, 47% (7 of 15) of the children were seizure free or only had auras: another 33% (5 of 15) had > 90% reduction in seizure frequency. Three patients had < 90% seizure reduction. Four cases were initially seizure free but had subsequent recurrence between 11 and 28 months after the epilepsy surgery. Factors associated with a good outcome include exclusively focal EEG discharges or an imaging suggestive of a low-grade tumor; factors associated with a poor outcome include generalized EEG discharges and a normal magnetic resonance image. Temporal lobectomy is useful in the treatment of early childhood drug-resistant partial epilepsy, but long-term follow-up is necessary as late seizure recurrence may occur up to 28 months after surgery.

Child↗
PubMed2001

The concerns of patients under palliative care and a heart failure clinic are not being met.

Patients with a terminal illness, identified by palliative care teams working in Manchester, and patients attending a heart failure clinic, were asked to participate in a prospective survey to determine their main concerns. Data were collected from 213 palliative care (PC) patients (mostly with cancer) and 66 patients with heart failure (HF). The median ages of the two patient groups were similar, but the HF patients were more likely to be male and living with a partner; 13% of PC and 7% of HF patients reported that they had no carer. The PC patients had more district nurse, hospice, social work and physiotherapy input. The most frequently reported troublesome problems for PC patients were pain (49%), loss of independence (30%) and difficulty walking (27%). HF patients reported dyspnoea (55%), angina (32%) and tiredness (27%) as the most troublesome problems. From a checklist of symptoms, the frequency of tiredness (PC = 77%, HF = 82%) and difficulty getting about (PC = 71%, HF = 65%) were high in each group. Psychological problems were reported by 61% of PC and 41% of HF patients. Cardiac patients reported more breathlessness and cough than PC patients (83% vs 49% and 44% vs 26%, respectively). Reduced libido was more common in cardiac patients (42% vs 21%). Patient disclosure of troublesome problems to professional carers was high (>87% in both PC and HF patients). Documented action was greater for physical than social or psychological problems. For PC patients, documented action was recorded for 83% physical, 43% social/functional and 52% psychological problems. For HF patients documented action was recorded for 74% cardiac, 60% physical - non-cardiac, 30% social/functional and 28% psychological problems. Clearly many patients' troublesome problems were not being addressed. As a result of this study, specific action by health care professionals was taken in 50% of PC patients and 71% of HF patients. We plan to target specific educational events on the treatment of physical problems, psychological assessment and social service provision.

Activities of Daily Living↗
PubMed2000

Pharmacokinetics of levamisole in cancer patients treated with 5-fluorouracil.

PURPOSE: To investigate the pharmacokinetics of levamisole and a metabolite, p-hydroxylevamisole in patients with colorectal cancer treated with 5-fluorouracil (5-FU). METHODS: Following an intravenous bolus dose of 5-FU, 20 patients with colorectal cancer received oral doses of 50 mg levamisole every 8 h for 3 days. Immediately after the last dose, blood and urine samples were collected over at least an 8-h period. Samples were assayed for levamisole and p-hydroxylevamisole by GC/MS. The levamisole plasma and urine data were subjected to pharmacokinetic analysis using NONMEM software. RESULTS: Substantial interpatient variability was observed in the levamisole plasma concentration-time curves. Patients with cardiovascular or gastrointestinal complications demonstrated altered absorption of levamisole. Pharmacokinetic parameter values for levamisole were similar to those obtained previously in healthy subjects and other cancer patients. CONCLUSIONS: There is no evidence that the pharmacokinetics of levamisole are altered by 5-FU administered immediately prior to levamisole administration. The relationship between the substantial intersubject variability in levamisole plasma concentration-time curves and clinical outcome following 5-FU/levamisole adjuvant chemotherapy should be examined.

Adjuvants, Immunologic↗
PubMed2000

Pediatric peri-insular hemispherotomy.

A number of surgical procedures are available for patients with epilepsy associated with diffuse hemispheric disorders. In this report, 16 pediatric patients had hemispherectomy: 5 underwent hemidecortication and 11 had peri-insular hemispherotomy. The clinical records were retrospectively reviewed, and the results and complications of the procedures were documented. The procedure was feasible in very young children and in the absence of ventriculomegaly.

Adolescent↗
PubMed2000

Health-related quality of life for adults with cystic fibrosis: a regression approach to assessing the impact of recombinant human DNase.

STUDY OBJECTIVES: To examine the general health-related quality of life (HRQOL) of adults with cystic fibrosis (CF) using available generic instruments, and to determine important predictors of change in HRQOL, including therapy with recombinant human Dnase (rhDNase). DESIGN: Prospective, observational study. PATIENTS: Fifty-nine adults with CE. INTERVENTION: The Medical Outcomes Study Short-Form 36 (SF-36) and the EuroQol (EQ-5D) were mailed to patients; follow-up surveys were mailed 1 year later. MEASUREMENTS AND MAIN RESULTS: Multivariate regression analyses assessed the relationships between clinical and demographic variables and change in health status. The 39 respondents reported lower HRQOL scores compared with general population norms for generic instruments. Regression analyses indicated that age (p=0.010), percentage predicted forced expiratory volume in 1 second (p=0.005), hospital admission (p=0.023), and rhDNase therapy (p=0.026) were positively associated 1998 EQ-5D index scores, whereas body mass index was negatively associated (p=0.025) with 1998 EQ-5D index scores after controlling for baseline 1997 scores. The size of the regression coefficients indicated that only 1997 scores and hospital admission in the year were quantitatively importantly associated with 1998 scores. Baseline HRQOL assessments showed that adults with CF reported important decrements in health status and functioning. An interesting relationship between functional status and total household income was observed. CONCLUSION: Although a statistically significant association between rhDNase and 1-year change in HRQOL was found on multivariate regression analysis, the magnitude of this relationship may not be clinically important.

Adult↗
PubMed2000

Cortical visual impairment in children with infantile spasms.

BACKGROUND: Infantile spasms are often associated with cortical visual impairment. METHOD: We report a series of 10 patients with infantile spasms, hypsarrhythmic electroencephalograms, and developmental delay, (ie, West syndrome), who presented with severe visual inattention despite a normal ocular examination. RESULTS: At follow-up (14 months to 6 years), 5 patients (50%) had no improvement in their visual behaviour. Although some degree of improvement was observed in the others, their visual function remained abnormal. All patients had moderate or severe mental retardation. CONCLUSIONS: The clinical features of West syndrome are reviewed, and the cause of the associated cortical visual impairment is discussed. Cortical visual impairment with infantile spasms is an important association, which pediatric ophthalmologists should recognize.

Diagnosis, Differential↗
PubMed2000

Assessment of patient sociodemographic variables in clinical trials--can patient characteristics make a difference?

INTRODUCTION: The recruitment of patients into clinical trials is often thought to be a selective process whereby non-biological variables such as education, occupation, family/social support, and socioeconomic status are often found to be predictive of patient volunteers. This paper considers whether the susceptibility of trials to recruit non-representative patient populations may impair the extrapolation of results to diverse sociodemographic patient groups and/or hinder operational trial efficiency. METHOD: A review of the Embase and Medline databases was conducted using Subject Headings (clinical trial or randomised-controlled trial) combined with Keywords (sociodemographic, education, occupation or socioeconomic). References presenting patient sociodemographic characteristics in relation to trial recruitment or impact on measured trial data points were reviewed. RESULTS: Both quantitative and qualitative reports suggest clinical trials are prone to recruit biased sociodemographic cohorts. This review suggests three trial cohort analyses that may enhance the interpretation of trial results and provide insight into the operational efficiency of clinical trials. Assessments include: (1) comparing recruited trial cohort with source population; (2) assessing trial data points across sociodemographic groupings irrespective of treatment; (3) assessment of patient dropouts based on sociodemographic characteristics. CONCLUSION: In view of the known sociodemographic disparities found in trial recruitment, a methodology is suggested which may provide valuable information regarding the external validity of trial results and/or assessing operational trial efficiency. The challenge to those undertaking clinical trials should be to firstly determine whether recruitment biases may exist, and secondly whether trial integrity may be compromised by the presence of such biases.

Clinical Trials as Topic↗
PubMed1999

Comment

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Journal Article↗
PubMed1999

Analogues of 1-(3,10-dibromo-8-chloro-6,11-dihydro-5H-benzo-[5,6]-cyclohepta [1,2-b]pyridin-11-yl)piperidine as inhibitors of farnesyl protein transferase.

The synthesis of several 4-pyridylacetyl N-oxide derivatives of 4-(3-bromo-6,11-dihydro-5H-benzo[5,6]-cyclohepta[1,2-b]-pyridin-11-yl)pi perazine/piperidine 3 is described. This study was aimed at identifying fomesyl protein transferase (FPT) inhibitors in these two series of tricycles containing different phenyl ring substituents. The in vitro activity profile of the initial group of compounds 7a-7g led to the synthesis of the 8-methyl-10-methoxy and 8-methyl-10-bromo analogues 7i, 13i, and 13j. The 11R(-) enantiomers of these compounds were found to exhibit potent in vitro FPT inhibition activity.

Alkyl and Aryl Transferases↗
PubMed1999

Is group C meningococcal disease increasing in Europe? A report of surveillance of meningococcal infection in Europe 1993-6. European Meningitis Surveillance Group.

A surveillance system to assess the impact and changing epidemiology of invasive meningococcal disease in Europe was set up in 1987. Since about 1991, contributors from national reference laboratories, national communicable disease surveillance centres and institutes of public health in 35 European countries provided information on all reported cases of meningococcal disease in their country. We describe some trends observed over the period 1993-6. The main findings were: the overall incidence of meningococcal disease was 1.1 per 100000 population but there was some evidence of a slow increase over time and with northern European countries tending to have a higher incidence (Kendall correlation 0.5772, P < 0.001), an increasing predominance of serogroup C, and a shift in the age distribution towards teenagers and away from younger children (chi2 test for trend 44.56, P < 0.0001), although about half of the cases were under 5 years of age. The overall case fatality rate was 8.3% and the most common serosubtypes were B:15:P1.7,16 and C:2a:P1.2,5.

Adolescent↗
PubMed1999

Teaching a research-based approach to the management of breathlessness in patients with lung cancer.

Breathlessness is a common but complex symptom experienced by patients with lung cancer. Corner and colleagues have developed a therapeutic nursing intervention for the management of breathlessness. The Macmillan Practice Development Unit (MPDU) have recently undertaken a multi-centre evaluation of the intervention. The authors were involved in this multi-centre study as clinical practitioners offering the intervention in a randomised control trial. There is strong evidence to suggest that much research fails to influence clinical practice. A commitment to practice development led us to explore the reasons for this research-practice gap. This paper considers the factors that facilitate implementation of research and, in particular, how this applies to the breathlessness intervention. Practitioners need to feel competent in the skills described in the intervention to implement the research findings into their practice. Therefore, we developed a course to teach the breathlessness intervention. A description of the course is presented, together with the theoretical basis for the course design and the tools used to evaluate it.

Clinical Competence↗
PubMed1998

(+)-4-[2-[4-(8-Chloro-3,10-dibromo-6,11-dihydro-5H-benzo[5, 6]cyclohepta[1,2-b]- pyridin-11(R)-yl)-1-piperidinyl]-2-oxo-ethyl]-1-piperidinecarboxamid e (SCH-66336): a very potent farnesyl protein transferase inhibitor as a novel antitumor agent.

We have previously shown that appropriate modification of the benzocycloheptapyridine tricyclic ring system can provide potent farnesyl protein transferase (FPT) inhibitors with good cellular activity. Our laboratories have also established that incorporation of either pyridinylacetyl N-oxide or 4-N-carboxamidopiperidinylacetyl moieties results in pharmacokinetically stable inhibitors that are orally efficacious in nude mice. We now demonstrate that further elaboration of the tricyclic ring system by introducing a bromine atom at the 7- or the 10-position of the 3-bromo-8-chlorotricyclic ring system provides compounds that have superior potency and selectivity in FPT inhibition. These compounds have good serum levels and half-lives when given orally to rodents and primates. In vitro and in vivo evaluation of a panel of these inhibitors has led to identification of 15 (SCH 66336) as a highly potent (IC50 = 1.9 nM) antitumor agent that is currently undergoing human clinical trials.

Alkyl and Aryl Transferases↗
PubMed1998

Inhibitors of farnesyl protein transferase. Synthesis and biological activity of amide and cyanoguanidine derivatives containing a 5,11-dihydro[1]benzthiepin, benzoxepin, and benzazepin [4,3-b]pyridine ring system.

Bioisosteric replacement of the C-6 carbon atom in piperidine I and piperazine II with S, O, and N heteroatoms is described. Amide and cyanoguanidine derivatives of these compounds were evaluated in vitro and found to be good inhibitors of farnesyl-protein transferase. An improved method of preparing the 5,11-dihydro-[1]-benzthiepin nucleus 6 was accomplished in high yield and with excellent regioselectivity using an AlCl3 melt protocol.

Alkyl and Aryl Transferases↗
PubMed1998

Novel H3 receptor antagonists. Sulfonamide homologs of histamine.

Sulfonamides derived from 4(5)-(omega-aminoalkyl)-1H-imidazoles containing chain lengths of three- to five-carbons were synthesized. Good to moderate H3 receptor binding affinities were observed for several butyl and pentyl homologs, whereas binding affinities were considerably weaker in the propyl series. Separation of the imidazole ring and the sulfonamide unit by a four- or five-carbon tether afforded potent H3 receptor antagonists.

Animals↗