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Biomedical subjects

B Lynch

Publications and source records attributed to B Lynch.

At least 19 recordsLinked to original sources

Safety evaluation of alpha-lipoic acid (ALA).

The safety of the antioxidant alpha-lipoic acid (racemic form) (ALA), also called thioctic acid (CAS RN 1077-28-7) was assessed in acute and subchronic toxicity studies as well as in in vitro and in vivo mutagenicity/genotoxicity studies. ALA was not acutely toxic to rats (LD(50)>2000mg/kg bw, OECD method 425). Administration of 31.6 or 61.9mg ALA/kg bw/day for 4 weeks to male/female Wistar rats did not show any adverse effects. Specifically, there was no significant difference between control and treated animals at 31.6 or 61.9mg ALA/kg bw with regard to body weight gain, feed consumption, animal behaviour, or haematological and clinical chemistry parameters. Only the high-dose of 121mg ALA/kg bw was associated with slight alterations in liver enzymes as well as histopathological effects on the liver and mammary gland. ALA did not possess any mutagenic activity in the Ames assays conducted with various bacterial strains of Salmonella typhimurium. Moreover, there was no evidence of genotoxic activity in a mouse micronucleus assay. The results of these studies support the safety of ALA. The no-observed-adverse-effect level (NOAEL) is considered to be 61.9mg/kg bw/day.

Animals↗

Long-term safety of alpha-lipoic acid (ALA) consumption: A 2-year study.

Alpha-lipoic acid (ALA) (CAS RN 1077-28-7), also referred to as thioctic acid, has been demonstrated to exhibit strong anti-oxidant properties. In order to test the long-term toxicity of ALA, groups of 40-50 male and female, 5-6-week-old, Sprague-Dawley rats were subjected to oral administration of 20, 60, or 180 mg/kg body weight (bw)/day ALA for 24 months. There was no significant difference between control animals and treated animals at 20 or 60 mg/kg bw/day with respect to body weight gain, food consumption, behavioural effects, haematological and clinical chemistry parameters, and gross and histopathological findings. In all treatment groups, mortality was slightly lower as compared to the control. The absolute weights of the heart (high-dose males), thymus (high-dose males), and left adrenal (mid-dose males), liver (high-dose females), and lungs (high-dose females) were decreased in comparison to controls. These changes were of no toxicological significance. The only notable finding in rats of both sexes dosed at 180 mg/kg bw/day was a reduction in food intake relative to the controls and a concomitant decrease in body weight. This decrease in body weight led to significant differences between the control and high-dose rats with respect to the absolute weights of certain organs. However, no gross or histopathological changes were associated with these findings. The no-observed-adverse-effect level (NOAEL) is considered to be 60 mg/kg bw/day.

Administration, Oral↗

Covariate analysis of late-onset Alzheimer disease refines the chromosome 12 locus.

Alzheimer disease (AD) is a progressive neurodegenerative disorder of later life with a complex etiology and a strong genetic component. Several genomic screens have suggested that a region between chromosome 12p13 and 12q22 contains at least one additional locus underlying the susceptibility of AD. However, localization of this locus has been difficult. We performed a 5 cM microsatellite marker screen across 74 cM on chromosome 12 with 15 markers in 585 multiplex families consisting of 994 affected sibpairs and 213 other affected relative pairs. Analyses across the entire data set did not reveal significant evidence of linkage. However, suggestive linkage was observed in several subsets. In the 91 families where no affected individuals carry an ApoE varepsilon4 allele, an HLOD score of 1.55 was generated at D12S1042. We further examined the linkage data considering the proposed linkages to chromosome 9 (D9S741) and chromosome 10 (alpha-catenin gene). There was a modest (P=0.20) increase in the LOD score for D12S368 (MLOD=1.70) when using the D9S741 LOD scores as a covariate and a highly significant (P<0.001) increase in the MLOD score (4.19) for D12S1701 in autopsy-confirmed families (n=228) when using alpha-catenin LOD scores as a covariate. In both cases, families with no evidence of linkage to D9S741 or alpha-catenin demonstrated most of the evidence of linkage to chromosome 12, suggesting locus heterogeneity. Taken together, our data suggest that the 16 cM region between D12S1042 and D12S368 should be the subject of further detailed genomic efforts for the disease.

Age of Onset↗

Vein of Galen aneurysm malformation (VGAM): closing the management loop.

We report a case where an antenatal scan showed a cerebral vessel dilatation consistent with a vein of Galen malformation (VGAM). After delivery the diagnosis was confirmed on MRI scan. The infant's condition was stable in relation to the two important clinical indicators, mainly not in congestive cardiac failure and no hydrocephalus. The vein of Galen assessment score as used in Hopital Bicetre was 20/21. The scoring system is based on a multiorgan assessment including the five parameters cardiac, cerebral, respiratory, hepatic and renal (Table 1). A score of < 8 indicates no treatment, 8-12 means immediate intervention while a score > 12 delays intervention to circa six months of age. At four months the head circumference accelerated with hydroceaphalus on scans and the infant became clinically symptomatic. Urgent embolisation was performed. The procedure uses N-butylcyanoacrylate (NBCA) glue as the embolisation agent, which in this case was inserted through the left posteriomedial choroidal artery. Complete obliteration was achieved. The infant subsequently required insertion of a ventriculoperitoneal shunt for the hydrocephalus component. The infant has had no recurrence. He remains well on objective examination he has mild developmental delay. In summary this case highlights the value of antenatal diagnosis,the VGAM assessment score to determine the optimal time of intervention and the effectiveness of embolisation.

Adhesives↗

Needs analysis for tele-neurophysiology in the Irish North-Western Health Board.

No clinical neurophysiology (CN) service is currently provided by the North-Western Health Board (NWHB) region in Ireland. Digital technology associated with CN is compatible with tele-neurophysiology service development and may increase the efficiency of patient care in remote areas. This study was conducted to assess the need for CN in the NWHB with a view to implementing a tele-neurophysiology service for the region. A retrospective audit of investigations performed at six CN departments in Dublin compared patient groups from regions with (Eastern Regional Health Authority--ERHA) and without (NWHB) local CN departments. 4954 records were audited. CN activity was lower than internationally expected (ERHA group 52% of expected, NWHB group 23% of expected). The 2 groups differ in the specialty of referring clinician (p < 0.0001). NWHB patients are more likely to be referred by clinicians outside their region (p < 0.0001) and wait longer for appointment (p < 0.0001). While there is an unmet demand for CN services in Ireland generally, the population of the NWHB is further disadvantaged. Tele-neurophysiology has the potential to provide fairer access to CN services across the country. The data from this study provide a baseline against which the outcome of investment in CN can be monitored and evaluated.

Chi-Square Distribution↗

Analysis of silica hydride and surface hydrosilation reactions by solid-state NMR in the preparation of p-chlorobenzamide bonded silica phase.

29Si and (13)C CP-MAS NMR spectroscopy was used to follow the conversion of native silica to a p-chlorobenzamide bonded silica material. The benzamide bonded phase was prepared via a hydrosilation reaction of a hydride silica intermediate with p-chloro- N-allylbenzamide. Solid-state NMR was used to show the disappearance of reactive surface hydride species (M(H)) and to identify newly formed bonded chemical species on the silica surface. DRIFT spectroscopy, elemental analysis, and specific surface-area determinations (BET) of the prepared phases are also reported.

Journal Article↗

Botulinum toxin treatment of spasticity in diplegic cerebral palsy: a randomized, double-blind, placebo-controlled, dose-ranging study.

This study evaluated the efficacy and safety of three doses of botulinum toxin A (BTX-A; Dysport) in 125 patients (mean age 5.2 years, SD 2; 54% male)with dynamic equinus spasticity during walking. Participants were randomized to receive Dysport (10, 20, or 30 units/kg) or placebo to the gastrocnemius muscle of both legs. Muscle length was calculated from electrogoniometric measurements and the change in the dynamic component of gastrocnemius shortening at four weeks was prospectively identified as the primary outcome measure. All treatment groups showed statistically significant decreases in dynamic component compared with placebo at 4 weeks. Mean improvement in dynamic component was most pronounced in the 20 units/kg group, being equivalent to an increase in dorsiflexion with the knee extended at 19 degrees, and was still present at 16 weeks. The safety profile of the toxin appears satisfactory.

Botulinum Toxins, Type A↗

Hereditary cerebral cavernous angiomas: presentation as idiopathic familial epilepsy.

In cavernous angiomas of the brain, abnormally dilated blood vessels are tightly clustered together with no intervening neural parenchyma. Commonly recognised as a sporadic finding, these lesions may also be inherited in an autosomal dominant fashion. This disorder was recognised as a common entity with the advent of MRI. As lesions were often not detected on CT imaging, symptomatic patients presenting with seizures were mistakenly diagnosed with an idiopathic seizure disorder. Seizures are the commonest presenting symptom followed by haemorrhage and focal neurologic deficit. We present another cause of familial epilepsy that also emphasises the importance of MRI as the modality of choice in investigating seizures in children.

Brain↗

Chronic survival of calves implanted with the DeBakey ventricular assist device.

The DeBakey ventricular assist device (VAD) is a miniaturized, electromagnetically driven axial flow pump capable of generating in excess of 10 L/min output. The VAD was evaluated in 19 calves during experiments designed to test iterative modifications in the system and to determine the safety of the DeBakey VAD for intermediate to long-term implant. Five of the animals died or were euthanized during the perioperative period (i.e., Days 1-5) due to complications associated with bleeding (n = 3), sudden cardiac arrest (n = 1), or pump occlusion due to a muscle remnant associated with coring (n = 1). The remaining 14 animals survived from 7-145 days. Ten of the 14 animals survived 30 or more days, and 2 animals survived 93 and 145 days before elective euthanasia. Pump function was evaluated in the 14 calves that survived beyond the perioperative period. Pump output at implantation averaged 3 L/min while output at 100 days (n = 2) averaged 4.22 L/min. The electrical current did not change across time during the study, indicating normal operation of the bearings. Pumps consumed less than 10.5 W of power for all support durations. Hemolysis did not occur; the average daily plasma free hemoglobin varied from 2.0 to 8.0 mg/dl. Evaluation of serum biochemical data showed that implantation of the DeBakey VAD in calves with normal hearts did not impair end organ function; BUN, creatinine, and total bilirubin varied minimally within the normal range. The white blood cell count of implanted animals remained within the normal range throughout the study.

Animals↗

Long-term outcome of prostatic stent treatment for benign prostatic hyperplasia.

OBJECTIVES: To evaluate the long-term result of prostatic stent treatment for patients with benign prostatic hyperplasia (BPH). METHODS: We reviewed our experience with prostatic stents in 24 patients with bladder outlet obstruction caused by BPH for whom up to 63 months of follow-up data were available. RESULTS: Prostatic stents were successfully placed in 24 of 25 patients enrolled in the study. All 9 patients treated for urinary retention voided spontaneously after stent placement. In 14 (93%) of 15 patients with nonretention, voiding symptoms decreased by 50% or more. The stent was removed in 9 patients for persistence of symptoms, symptom recurrence, or stent migration. Nine patients died of unrelated causes during the follow-up period. The stents functioned adequately in these patients until death. In the remaining 6 patients, the stent was still in place at the last follow-up visit (range 12 to 52 months, average 35) after placement, and their Madsen-Iversen symptom scores ranged from 3 to 10. Fourteen patients underwent cystoscopy 1 to 37 months after stent placement. Epithelium did not completely cover the stent in any of these patients; however, no stone formation was noted. CONCLUSIONS: Prostatic stents can be effective in relieving bladder outlet obstruction caused by BPH. They appear to be most useful in patients at high surgical risk and with a limited life expectancy. However, stent removal, which can be difficult, may be required in more than one-third of patients. We recommend prostatic stent placement primarily in patients who would otherwise be relegated to an indwelling catheter.

Aged↗

Randomized comparison of balloon dilation and transurethral incision for treatment of symptomatic benign prostatic hyperplasia.

The concept of relieving the symptoms of benign prostatic hyperplasia (BPH) by dilating the urethral has existed for centuries. Thirty patients with a clinically estimated prostate gland size of 25 g or less were randomized to either balloon dilation (BDP) or transurethral incision of the prostate (TUIP). The mean pretreatment Madsen-Iverson symptom scores in the two groups were 15.0 +/- 4.9 (SD) and 15.4 +/- 4.4, respectively. The early response rates were 87% fo BDP and 86% for TUIP, with the mean symptom scores declining to 3.4 +/- 2.8 after dilation and 4.2 +/- 6.6 after incision. Among the 14 patients who initially responded to BDP, 2 have been lost to follow-up, 1 died of unrelated causes at 17 months with no urinary symptoms, 2 remain in response at 32 and 38 months, and the other 9 (75% of those available for evaluation) have developed recurrences. Among the 12 patents who responded to TUIP, 2 have been lost to follow-up, 8 remain in response at 14 to 48 months, and 2 (20%) developed recurrences by 44 months of follow-up. In the short term, both BDP and TUIP are effective for treating bladder outlet obstruction in men with relatively small prostates. However, the effect of dilation appears to be less durable than that of incision.

Aged↗

Repeat consultations after antibiotic prescribing for respiratory infection: a study in one general practice.

BACKGROUND: Several new antibacterial drugs have been introduced in the last 10 years with the aim of improved treatment of respiratory tract infection. AIM: The study set out to use repeat consultations as a measure of the outcome of antibiotic treatment for respiratory tract infection, and to develop a simple model for discussion of the cost effectiveness of alternative antibiotic treatments. METHOD: All consultations to one practice during a single winter were reviewed by one general practitioner. RESULTS: A total of 1140 patients had acute symptoms suggestive of respiratory infection. Of these, 899 patients (79%) were prescribed antibiotics at the first consultation and 160 of the 899 patients (18%) returned for one or more repeat consultations; only nine repeat consultations were due to adverse effects of the antibiotics prescribed. Only two patients were admitted to hospital for respiratory symptoms following initial antibiotic therapy and both patients had additional reasons for their admission. Using the highest estimates, the cost of a repeat consultation was found to be 28.54 pounds. These data were used to calculate how much more might be spent on more effective antibiotics at the first consultation. It would be difficult to justify increasing the cost of antibiotic treatment by more than 5 pounds per patient, even if the new treatment were 100% effective and all repeat consultations were due to treatment failure (5 pounds is equal to 28.54 pounds x 0.18, which is the maximum cost of a repeat consultation multiplied by the proportion of patients prescribed antibiotics who make repeat consultations). CONCLUSION: From these results and a review of the literature it can be concluded that new antibacterial drugs will have to be carefully targeted if they are to prove cost effective in practice. Other methods for reducing repeat consultation merit investigation.

Adolescent↗

Quantitative dendritic and spine analyses of speech cortices: a case study.

The present case study documents an unprecedented opportunity for correlative investigation of brain structure and function by quantitatively investigating the basilar dendritic systems of supragranular pyramidal cells in several cortical areas from a subject who had undergone electrical stimulation mapping 2 years prior to death. Electrical stimulation mapping results provided valuable functional information about the cortical areas removed for postmortem histological analysis. Morphometric analyses distinguished between proximal (first, second, and third order) and ontogenetically later developing distal (fourth order and above) basilar dendritic branches. In general, perisylvian language association stimulation sites (classical Wernicke's and Broca's areas) were characterized by different dendritic patterns than motor strip sites. In primary motor strip tissue blocks, proximal segments were longer than distal segments. In "higher order" elaborative cortical zones, distal segments were longer than proximal segments. Proximal segments outnumbered distal segments in primary motor zones, but the numerical difference between proximal and distal segments was reduced in the association areas. Finally, fourth order segments had significantly more dendritic spines than third order segments in all sites. These dendritic findings suggest a somewhat later ontogenetic development in classical Broca's and Wernicke's areas than in primary motor cortex.

Adult↗

Cost-effectiveness of single dose cefotaxime plus metronidazole compared with three doses each of cefuroxime plus metronidazole for the prevention of wound infection after colorectal surgery.

The cost-effectiveness of prophylaxis for colonic surgery with single dose cefotaxime plus metronidazole has been compared with that of three doses each of cefuroxime plus metronidazole, by analysing data from a previously published study supplemented with additional data on the hospital and community costs of wound infection after colonic surgery. The original trial included 942 patients having elective colonic surgery in 14 hospitals. The data on costs of wound infection were collected from a further 124 patients undergoing elective colonic surgery at Ninewells Hospital. All these patients received a three dose regimen of cefuroxime plus metronidazole. The Dundee patients received three injections of 0.75 g cefuroxime at 8-hourly intervals whereas the trial patients received a single dose of 1.5 g followed by two further doses of 0.75 g at 8-hourly intervals. The cefuroxime prophylaxis regimen used in the trial cost 24.16 pounds per patient more than the cefotaxime regimen. The components of the excess cost were drugs (15.18 pounds), equipment (6.14 pounds) and staff time (2.84 pounds). The median cost to the hospital of a wound infection was 978.04 pounds (95% CI 482.04 pounds to 1521.22 pounds). The components of the hospital cost of wound infection were: hotel costs 858 pounds (88%), dressing costs 83.02 pounds (8%) and drug costs (excluding prophylaxis) 37.02 pounds (4%). Only five patients received additional antibiotic treatment in the community, and only one required home visits from the District Nurse. Applying the difference in costs of prophylaxis as 21 pounds (costs of drugs plus equipment) and the cost per wound infection as 1000 pounds to the observed wound infection rate of 7% in the cefuroxime group, the wound infection rate in the cefotaxime group would have to be 2.1% higher for the two regimens to be equally cost-effective. The probability that such a difference in efficacy exists is 0.088. A model was developed to calculate the probability of equal cost-effectiveness over a range of costs of wound infection.

Anti-Infective Agents↗

Intrarenal pancreatic cyst.

A case report of intrarenal true cyst of the pancreas is presented. The patient presented with flank pain. Her diabetes and hypertension were well-controlled. The cause of the pain was presumed to be a cystic renal mass, which proved to be of pancreatic origin only after the pathologic confirmation from the nephrectomy specimen.

Adult↗

Effect of colostral fat level on fat deposition and plasma metabolites in the newborn pig.

The effects of colostral fat level on fat deposition and plasma concentrations of glucose, insulin, and free fatty acids (FFA) were determined in 28 newborn pigs during the first postnatal day. Soon after birth, pigs were allotted to four treatments groups. Group 1 was killed at birth. The remaining pigs were fed intragastrically sow colostrum that contained high (10.2%; HFC), normal (4.8%; NFC) or low (1.0%; LFC) levels of total fat at the rate of 15 to 18 g/kg birth weight at 65- to 70-min intervals. A total of 21 feedings was provided and pigs were killed 1 h after the last feeding. Body fat deposition increased linearly (P less than .01) with the amount of ingested fat by .32 (+/- .04) g per 1-g increase in fat intake. Fatty acid composition of the pigs changed toward that of the colostrum with increased fat in colostrum. More liver glycogen was lost (P less than .01) in pigs given LFC. Plasma concentrations of glucose and insulin were similar in pigs fed HFC and NFC. After the 11th feeding (14 h postnatal), LFC resulted in lower plasma glucose concentrations (P less than .05) than HFC or NFC. Plasma insulin concentrations also were lower in pigs fed LFC. Plasma FFA concentrations remained unchanged in pigs fed LFC but increased with both fat content in colostrum (P less than .05) and time (P less than .05) in the other two groups. Colostral fat plays a major role in the supply of energy and in glucose homeostasis in the neonatal pig.

Adipose Tissue↗