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Biomedical subjects

C Doherty

Publications and source records attributed to C Doherty.

At least 19 recordsLinked to original sources
PubMed2001

Neuronal hypertrophy in the neocortex of patients with temporal lobe epilepsy.

The underlying cause of neocortical involvement in temporal lobe epilepsy (TLE) remains a fundamental and unanswered question. Magnetic resonance imaging has shown a significant loss in temporal lobe volume, and it has been proposed that neocortical circuits are disturbed functionally because neurons are lost. The present study used design-based stereology to estimate the volume and cell number of Brodmann's area 38, a region commonly resected in anterior temporal lobectomy. Studies were conducted on the neocortex of patients with or without hippocampal sclerosis (HS). Results provide the surprising finding that TLE patients have significant atrophy of neocortical gray matter but no loss of neurons. Neurons are also significantly larger, dendritic trees appear sparser, and spine density is noticeably reduced in TLE specimens compared with controls. The increase in neuronal density we found in TLE patients is therefore attributable to large neurons occupying a much smaller volume than in normal brain. Neurons in the underlying white matter are also increased in size but, in contrast to other reports, are not significantly elevated in number or density. Neuronal hypertrophy affects HS and non-HS brains similarly. The reduction in neuropil and its associated elements therefore appears to be a primary feature of TLE, which is not secondary to cell loss. In both gray and white matter, neuronal hypertrophy means more perikaryal surface area is exposed for synaptic contacts and emerges as a hallmark of this disease.

Adolescent↗
PubMed2001

Vertical banded gastroplasty.

VBG and vertical Silastic ring gastroplasty are simple gastric restriction procedures that have defined technical standards. Two recent improvements in the operation have been the development of the six-row endolinear cutting-stapling instrument that divides the vertical partition without an increase in GI leakage and the application of minimally invasive laparoscopic techniques that have reduced the incidence of incisional hernia to less than 1%. VBG and vertical Silastic ring gastroplasty are procedures that can effectively help select patients to manage their morbid obesity. However, these procedures are critically dependent on patient compliance. It is not possible to know preoperatively whether a candidate will make the lifelong behavior modifications necessary for sustained weight loss. Experience has demonstrated that bariatric surgeons have limited control over a patient's level of motivation for compliance.

Contraindications↗
PubMed2000

Effects of size at birth, gestational age and early growth in preterm infants on glucose and insulin concentrations at 9-12 years.

AIMS/HYPOTHESIS: To test the hypothesis that small size for gestation and poor postnatal growth in preterm infants is associated with higher fasting and post-load plasma glucose and insulin concentrations at 9-12 years of age. METHODS: Prospective follow-up at 9-12 years of 385 preterm children with birth weight less than 1850 g, who had anthropometry recorded at birth, 18 months and 7 years. Fasting plasma glucose, insulin, proinsulin and 32.33 split proinsulin concentrations and glucose and insulin concentrations 30 min after a standard glucose load were measured. RESULTS: Post-load glucose concentrations were negatively related to birth weight, independently of gestation or subsequent growth. Fasting split proinsulin and 30-min insulin concentrations were highest in children who showed the greatest increase in weight centile between birth and current follow-up, regardless of gestation. When weight during childhood was included, birthweight centile was, however, no longer statistically significant: concentrations of fasting, split, proinsulin and 30-min insulin were highest in those children who had shown the greatest increase in weight centile between 18 months of age and current follow-up, with no evidence of a greater effect in those who were smallest at 18 months. CONCLUSION/INTERPRETATION: Our findings suggest that fetal growth influences plasma glucose 30 min after a glucose load in preterm children at 9-12 years. In contrast, childhood weight gain is the most important factor influencing insulin concentrations and this effect is the same regardless of early size.

Blood Glucose↗
PubMed2000

Shared governance--nurses making a difference.

AIM: This paper aims to describe how shared governance can be successfully integrated into existing management structures in a large medical directorate. It will show how the shared governance philosophy can lead to the creation of a culture where nurses feel important and valued and also consider its use as a foundation for the implementation of the nursing strategy. BACKGROUND: The hospital adopted shared governance in 1995 with the setting up of councils led by staff nurses. Shared governance advocates claim it broadens involvement of clinically-based nurses in the process of change through devolved decision-making thereby enhancing clinical practice and increasing staff moral and self-esteem. Key issues Shared governance is a cultural change that will develop the leadership and management skills of all grades of staff. Shared governance is not a quick fix for the profession; involvement of all staff needs time, persistence, determination and a strong commitment to training and development. CONCLUSION: The national nursing strategy puts nurses in a position to positively influence health care for the advantage of patients, however, for nurses to grasp this opportunity cultural change is required. This practical example of shared governance demonstrates how it can be used to create a proactive culture, focused on improving patient care. The nurturing and developing of clinically-based nurses provides them with the knowledge and skills to challenge the status quo and lead change. Thus, shared governance is an excellent foundation from which to develop the nursing strategy.

Decision Making, Organizational↗
PubMed2000

A randomized controlled evaluation of specialist nurse education following accident and emergency department attendance for acute asthma.

We investigated whether hospital-based specialist asthma nurses improved recognition and self-treatment of asthma episodes by patients followed up after attending accident and emergency departments (A&E) for asthma exacerbations. We carried out a randomized prospective controlled trial of adult asthma self-management, following a hospital outpatient nurse consultation in two outer-London District General Hospitals (secondary care centres). The study included 211 adults, over 18 years old (mean age 40 years) who attended for asthma in two accident and emergency departments over 13 months. One hundred and eight evaluable patients were randomized into the control group who continued with their usual medical treatment and were not offered any intervention during the study period. One hundred and three evaluable patients were randomized into the intervention group. They were offered three 6-weekly outpatient appointments with one of two specialist asthma nurses for a structured asthma consultation, after attendance at the accident and emergency department. Following assessment of their asthma treatment and control, the nurses advised patients, through the use of self-management-plans, how to recognize and manage uncontrolled asthma and when to seek medical assistance. Medication and inhaler device type were altered if necessary The primary outcome was patient reported self-management of asthma exacerbations for 6 months. Secondary outcomes were assessed at baseline, 3 months and 6 months. These included home peak flow and symptom diaries, structured telephone questionnaires and audit of general practitioner records to determine utilization of services (6 months before and after A&E). Data were analysed on an intention to treat basis by multiple and logistic regression. The intervention group increased their use of inhaled topical steroids in 31/61 (51%) vs. 15/70 (21%) attacks in controls (OR 3.91 CI 1.8-8.4, P<0.001) and their use of rescue medication in 54/61 (89%) severe attacks vs. 53/70 (76%) controls (OR 2.88 CI 1.1-7.9, P<0.05). Intervention patients had significantly higher (mean 20.1 l min(-1); CI 0.4-39.7; P<0.05) and less variable PEF and significantly lower and less variable symptom scores 6 months after entry. Thirty-four percent of intervention patients vs. 42% controls had severe attacks (61 and 70 respectively, OR 0.96 CI 0.7-1.4) during the 6 months. Intervention patients had fewer days off work than controls in the first 3 months (NS) but similar days off during the 6-month period. Intervention patients had fewer episodes away from work in the first (0.34 vs. 0.54, P = 0.08) and the second 3 months (0.25 vs. 0.30, NS) than the controls. Over 80% of the patients records were audited by their general practitioners; the active group had less routine consultations with the doctor (P = 0.03) and practice nurse (P = 0.03), less consultations for uncontrolled episodes (P = 0.06) and less hospital visits (NS) than the controls. Hospital-based specialist nurses reduced asthma morbidity by improving patient self-management behaviour in acute attacks leading to reduced symptoms, improved lung function, less time off work and fewer consultations with health professionals.

Acute Disease↗
PubMed1999

Characterisation of moisture uptake effects on the glass transitional behaviour of an amorphous drug using modulated temperature DSC.

The purpose of this study was to investigate the depression of the glass transition temperature, T(g), of the protease inhibitor saquinavir in the first heating scan as a function of the quantity of sorbed water by the application of modulated temperature differential scanning calorimetry (MTDSC). Samples of amorphous saquinavir were pretreated under various humidity conditions and the quantity of sorbed water measured by thermogravimetric analysis. MTDSC runs were performed using hermetically and non-hermetically sealed pans in order to determine the glass transition temperature. MTDSC allowed the separation of the glass transition from the enthalpic relaxation, thereby allowing clear visualisation of T(g) for amorphous saquinavir in the first heating scan. The plasticizing effects of water were assessed, with the depression in T(g) related to the mole fraction of water sorbed via the Gordon-Taylor relationship. An expression has been derived which allows estimation of the water content which lowers the T(g) to the storage temperature, thereby considerably increasing the risk of recrystallisation. It is argued that this model may aid prediction of the optimal storage conditions for amorphous drugs.

Algorithms↗
PubMed1999

An interval report on prospective investigation of adjustable silicone gastric banding devices for the treatment of severe obesity.

A review and updated report of an ongoing prospective investigation of two different adjustable silicone gastric banding devices is presented. One cohort of this study includes 40 subjects who have had a band placed by laparotomy. A second cohort includes 22 subjects who have had a newly designed adjustable silicone gastric band (ASGB) placed by laparoscopic or open technique. The goal of this investigation is to evaluate the achievement of sustained weight loss without the need for re-operation. Because of the frequent need for re-operation to correct life-threatening complications or ineffectiveness of ASGB devices, present clinical data indicate that improvements to the implantable system and the operative technique need to be made and verified by long-term study. At this point in development, ASGB remains an investigative procedure that has not fulfilled the scientific requirements of an accepted surgical treatment for severe obesity.

Cohort Studies↗
PubMed1998

Vertical gastroplasty: evolution of vertical banded gastroplasty.

The objective of this paper is to summarize the goals, technical requirements, advantages, and potential risks of gastroplasty for treatment of severe obesity. Gastroplasty is preferred to more complex operations, as it preserves normal digestion and absorption and avoids complications that are peculiar to exclusion operations. The medical literature and a 30-year experience at the University of Iowa Hospitals and Clinics (UIHC) provides an overview of vertical banded gastroplasty (VBG) evolution. Preliminary 10-year results with the VBG technique currently used at UIHC are included. At UIHC the VBG is preferred to other gastroplasties because it provides weight control that extends for at least 10 years and the required objective, intraoperative quality control required for a low rate of reoperation. It is recommended that modifications of the operative technique not be attempted until a surgeon has had experience with the standardized operation--and then only under a carefully designed protocol. Realistic goals for surgery and criteria of success influence the choice of operation and the optimum, lifelong risk/benefit ratio. In conclusion, VBG is a safe, long-term effective operation for severe obesity with advantages over complex operations and more restrictive simple operations.

Gastroplasty↗
PubMed1998

Prevalence of factor V Leiden mutation in young adults with cerebral ischaemia: a case-control study on 225 patients.

Cerebral ischaemia in young adults is a well-recognised disease, and approximately half of the cases remain aetiologically unclear despite extensive investigations. Thrombophilias are known to cause a subset of ischaemic strokes in this population. The factor V Leiden (FVL) mutation, causing resistance to activated protein C, has recently been recognised as the most important genetic thrombophilia in the Western population. Carriers of this gene mutation have a sevenfold increased risk of phlebothrombosis. We undertook this study to evaluate whether the FVL mutation constitutes a risk factor for juvenile cerebral ischaemias. A total of 225 patients aged < or = 45 years at onset of cerebral ischaemia and 200 age-matched healthy controls were investigated. The overall frequency of heterozygosity for the FVL mutation did not differ significantly between patients (8.4%) and controls [6.0%; odds ratio (OR) 1.4, 95% confidence interval (CI) 0.7-3.1]. In the subgroup of patients with cryptogenic cerebral ischaemia (n = 94), however, a significantly higher frequency of this gene defect (15.9%) was found compared with the controls (OR 3.0, CI 1.3-6.6). Further trends towards higher frequencies of the FVL mutation were found in patients with patent foramen ovale (OR 1.9), individual (OR 2.1) or family history of previous thrombembolisms (OR 2.0), and in those aged 25 years at onset of disease (OR 1.9, all not significant). In conclusion, the FVL mutation is not a risk factor for cerebral ischaemia of the young. However, our results suggest that this gene mutation plays an aetiological role in the subgroup of patients suffering from 'cryptogenic' ischaemic events.

Adolescent↗
PubMed1998

Characterisation of the glass transition of an amorphous drug using modulated DSC.

PURPOSE: The use of modulated differential scanning calorimetry (MDSC) as a novel means of characterising the glass transition of amorphous drugs has been investigated, using the protease inhibitor saquinavir as a model compound. In particular, the effects of measuring variables (temperature cycling, scanning period, heating mode) have been examined. METHODS: Saquinavir samples of known moisture content were examined using a TA Instruments 2920 MDSC at a heating rate of 2 degrees C/min and an amplitude of +/-0.159 degrees C with a period of 30 seconds. These conditions were used to examine the effects of cycling between - 50 degrees C and 150 degrees C. A range of periods between 20 and 50 seconds were then studied. Isothermal measurements were carried out between 85 degrees C and 120 degrees C using an amplitude of +/-0.159 degrees C with a period of 30 seconds. RESULTS: MDSC showed the glass transition of saquinavir (0.98 +/- 0.05%w/w moisture content) in isolation from the relaxation endotherm to give an apparent glass transition temperature of 107.0 degrees C +/- 0.4 degrees C. Subsequent temperature cycling gave reproducible glass transition temperatures of approximately 105 degrees C for both cooling and heating cycles. The enthalpic relaxation peak observed in the initial heating cycle had an additional contribution from a Tg "shift" effect brought about by the difference in response to the glass transition of the total and reversing heat flow signals. Isothermal studies yield a glass transition at 105.9 degrees C +/- 0.1 degrees C. CONCLUSIONS: MDSC has been shown to be capable of separating the glass transition of saquinavir from the relaxation endotherm, thereby facilitating measurement of this parameter without the need for temperature cycling. However, the Tg "shift" effect and the number of modulations through the transition should be taken into account to avoid drawing erroneous conclusions from the experimental data. MDSC has been shown to be an effective method of characterising the glass transition of an amorphous drug, allowing the separate characterisation of the Tg and endothermic relaxation in the first heating cycle.

Calorimetry, Differential Scanning↗
PubMed1998

Emergency medicine and the development of the Food and Drug Administration's final rule on informed consent and waiver of informed consent in emergency research circumstances.

This article reviews the federal regulations for emergency and acute resuscitation research in effect prior to October 1996, the historical issues that contributed to the development of these regulations, the controversies that arose surrounding the application of these regulations to emergency research circumstances, and the methods by which the regulations were changed. The new regulations introduced by the U.S. Food and Drug Administration (FDA) also are reviewed.

Disclosure↗
PubMed1998

Correlation of neuropsychological, morphological and functional (regional cerebral blood flow and glucose utilization) findings in cerebral microangiopathy.

UNLABELLED: Cerebral microangiopathy, indicated in MRI by lacunar infarctions (LIs) and deep white matter lesions (DWMLs), is said to be accompanied by vascular dementia, which is reportedly caused by LI and DWML. METHODS: To confirm this assumption, 57 patients with cerebral microangiopathy were assessed for changes in regional cerebral blood flow (rCBF) and glucose utilization (rMRGlu) in both white matter and cortex, and these findings were correlated to the results of extensive neuropsychological testing (cognitive, mnestic and attentiveness tests), as well as to MRI findings. A special head holder ensured reproducibility of positioning during measurement of rCBF (99mTc-HMPAO SPECT) and rMRGlu (18F-FDG PET) and MRI. White matter and cortex were quantified with regions of interest defined on MRI and superimposed to corresponding PET/SPECT slices. The rMRGlu was calculated according to Sokoloff, and rCBF was determined from normalization to the cerebellum. LI and DWML were graded by number and extent. Brain atrophy was classified as no to slight inner and/or outer atrophy (Group A) or moderate-to-severe inner and outer atrophy (Group B). RESULTS: Even in severe DWMLs and in multiple LIs, rCBFs and rMRGlu values were not reduced. Analysis of variance identified atrophy and neuropsychological deficits as the main determinants for reduced rCBF and rMRGlu values (p < 0.05). However, 60% of patients (19 of 31) with neuropsychological deficits in attentiveness tests and 61% of patients (23 of 38) with mnestic deficits belonged to Group A and revealed decreased rCBF and rMRGlu values. Neuropsychological deficits correlated well with decreased rCBF and rMRGlu, whereas MRI patterns, such as LI and DWML, did not. CONCLUSION: We conclude that LI and DWML are epiphenomena that morphologically characterize cerebral microangiopathy. Dementia or neuropsychological deficits, however, are exclusively reflected by functional criteria (rCBF and rMRGlu), as long as cerebral atrophy does not occur.

Aged↗
PubMed1997

Endoscopic sclerotherapy compared with percutaneous transjugular intrahepatic portosystemic shunt after initial sclerotherapy in patients with acute variceal hemorrhage. A randomized, controlled trial.

BACKGROUND: Hemorrhage from esophageal varices remains a substantial management problem. Endoscopic sclerotherapy was preferred for more than a decade, but fluoroscopically placed intrahepatic portosystemic stents have recently been used with increasing frequency. OBJECTIVE: To compare sclerotherapy with transjugular intrahepatic portosystemic shunt (TIPS) in patients with bleeding from esophageal varices. DESIGN: Randomized, controlled clinical trial. SETTING: Three teaching hospitals. PATIENTS: 49 adults hospitalized with acute variceal hemorrhage from November 1991 to December 1995: 25 assigned to sclerotherapy and 24 assigned to TIPS. INTERVENTION: Patients assigned to repeated sclerotherapy had the procedure weekly. In those assigned to TIPS, an expandable mesh stent was fluoroscopically placed between an intrahepatic portal vein and an adjacent hepatic vein. MEASUREMENTS: Pretreatment measures included demographic and laboratory data. Postrandomization data included index hospitalization survival, duration of follow-up, successful obliteration of varices, rebleeding from varices, number of variceal rebleeding events, total days of hospitalization for variceal bleeding, blood transfusion requirements after randomization, prevalence of encephalopathy, and total health care costs. RESULTS: Mean follow-up (+/-SE) was 567 +/- 104 days in the sclerotherapy group and 575 +/- 109 days in the TIPS group. Varices were obliterated more reliably by TIPS than by sclerotherapy (P < 0.001). Patients having TIPS were significantly less likely to rebleed from esophageal varices than patients receiving sclerotherapy (3 of 24 compared with 12 of 25; P = 0.012). No other follow-up measures differed significantly between groups. A trend toward improved survival, which was not statistically significant, was noted in the TIPS group (hazard ratio, 0.53 [95% CI, 0.18 to 1.5]). CONCLUSIONS: In obliterating varices and reducing rebleeding events from esophageal varies, TIPS was more effective than sclerotherapy. However, TIPS did not decrease morbidity after randomization or improve health care costs. It seemed to produce better survival, but the increase in survival was not statistically significant.

Adult↗
PubMed1997

Characterization of protein kinase A and protein kinase C phosphorylation of the N-methyl-D-aspartate receptor NR1 subunit using phosphorylation site-specific antibodies.

Modulation of N-methyl-D-aspartate receptors in the brain by protein phosphorylation may play a central role in the regulation of synaptic plasticity. To examine the phosphorylation of the NR1 subunit of N-methyl-D-aspartate receptors in situ, we have generated several polyclonal antibodies that recognize the NR1 subunit only when specific serine residues are phosphorylated. Using these antibodies, we demonstrate that protein kinase C (PKC) phosphorylates serine residues 890 and 896 and cAMP-dependent protein kinase (PKA) phosphorylates serine residue 897 of the NR1 subunit. Activation of PKC and PKA together lead to the simultaneous phosphorylation of neighboring serine residues 896 and 897. Phosphorylation of serine 890 by PKC results in the dispersion of surface-associated clusters of the NR1 subunit expressed in fibroblasts, while phosphorylation of serine 896 and 897 has no effect on the subcellular distribution of NR1. The PKC-induced redistribution of the NR1 subunit in cells occurs within minutes of serine 890 phosphorylation and reverses upon dephosphorylation. These results demonstrate that PKA and PKC phosphorylate distinct residues within a small region of the NR1 subunit and differentially affect the subcellular distribution of the NR1 subunit.

Amino Acid Sequence↗
PubMed1997

Two variants of quantitative reverse transcriptase PCR used to show differential expression of alpha-, beta- and gamma-fibrinogen genes in rat liver lobes.

Quantitative reverse transcriptase PCR (RT-PCR) is a sensitive method for the measurement of mRNA copy number. However, the methodology has gained a reputation for poor reproducibility, leading to concern over the validity of much of the data generated using this technique. We have developed two variants of quantitative competitive RT-PCR using a synthesized RNA as an internal standard to measure precisely the relative levels of alpha-, beta- and gamma-fibrinogen mRNAs in the four lobes of the rat liver. In the first of these variants we altered only the amount of total RNA in the RT-PCR reaction, keeping the amount of internal standard RNA and the number of PCR cycles constant. In the second variant only the number of PCR cycles was altered, and the amounts of total RNA and standard RNA were kept constant. Both variants of RT-PCR allowed calculation of the number of mRNA copies, which did not differ significantly between the two techniques. Of the two variants, the second gave better reproducibility, and the intra-assay coefficient of variation for this technique was 14% (n = 20). Using these two variants we have shown that there are different numbers of fibrinogen mRNAs in the four liver lobes for each of the three genes (alpha-fibrinogen F = 14.64, P = 0.0003; beta-fibrinogen F = 3.74, P = 0.04; gamma-fibrinogen F = 3.75, P = 0.04). In conclusion, by using two variants of quantitative competitive RT-PCR we have shown that this technique can be used to give reproducible results, and the low intra-assay coefficient of variation suggests that quantitative RT-PCR should be the technique of choice for accurate measurement of mRNA copy number.

Animals↗