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Biomedical subjects

C Reid

Publications and source records attributed to C Reid.

At least 37 records · Page 2Linked to original sources

Pharmacokinetics and clinical efficacy of long-term epidural ropivacaine infusion in children.

The clinical efficacy and pharmacokinetics of long-term epidural ropivacaine infusion were investigated in 18 postoperative children aged between 0.3 and 7.3 yr. A lumbar or thoracic epidural catheter was inserted after the anaesthetic induction. Sixty minutes following a bolus dose of ropivacaine 1 mg kg-1, 0.2% ropivacaine was infused at a fixed rate of 0.4 mg kg-1 h-1 for a mean of 61.3 h (range 36-96 h). Clinical evaluation comprised hourly recording of pain, sedation, motor block, nausea/vomiting, pruritus-scores, SpO2, pulse and respiratory rates, and recording of non-invasive arterial pressure every 4 h. Total and free plasma concentrations were measured by high-performance liquid chromatography at 0, 1, 6, 12, 24, 36, 48, 72 and 96 h. Analgesia was of high quality and side effects were minor. No clinical signs of local anaesthetic toxicity were seen. Total (100-3189 micrograms litre-1) and free (10-56 micrograms litre-1) ropivacaine concentrations were within the range reported to be 'safe' in previous studies in adults. Mean (95% CI) volume of distribution was 3.1 litre kg-1 (2.1-4.2 litre kg-1), total clearance was 8.5 ml kg-1 min-1 (5.8-11.1 ml kg-1 min-1), free clearance was 220 ml kg-1 min-1 (170-270 ml kg-1 min-1) and elimination half-life was 4.9 h (3.0-6.7 h).

Amides↗

Communication skills training for emergency department senior house officers--a qualitative study.

OBJECTIVE: To identify common weaknesses in senior house officer-patient consultation skills, and evaluate direct observation with feedback and negotiation of educational contracts, as a teaching tool in an emergency department setting. METHOD: Common weaknesses were identified through review of feedback charts by three trained observers. Alteration in clinical and learning behaviour, as well as senior house officer and observer perceptions of the teaching were evaluated qualitatively by a combination of semistructured interviews and focus groups. RESULTS: Several common weaknesses were identified, notably the use of closed questions, and poor negotiation and explanation of treatment plan and follow up. The senior house officers perceived improvement in their clinical practice, welcomed feedback, and subsequently set, though did not complete educational contracts. While comfortable with this style of teaching, the observers felt that it did not make efficient use of teaching time. CONCLUSIONS: This study identifies common weaknesses in the consultation skills of emergency department senior house officers and confirms the need for training in this area. Direct observation is effective in changing behaviour to this end, though self directed learning is not necessarily stimulated. Video recorded consultations with group feedback may be a more effective teaching tool.

Communication↗

The European Donor Hospital Education Programme (EDHEP): enhancing communication skills with bereaved relatives.

Intensive care medical and nursing staff self-rate their communication skills as improved following attendance at the European Donor Hospital Education Programme (EDHEP) workshop. A prospective study was conducted to determine what impact EDHEP has on communication skills. Doctor-nurse pairs from 10 experimental and 10 control Intensive Care Units undertook two standardized simulated relative encounters (Breaking Bad News and Donation Request) at three measurement points (pre, post and follow-up). Nurses showed no change in communication skills. Experimental group doctors showed significant improvement in breaking bad news and requesting donation; most of these improvements were not maintained. Control group doctors showed some improvement in breaking bad news, indicating that participating in measurement by itself initiates some transient change in communication skills. Attendance at EDHEP does lead to significant improvement in some, but not all, communication skills essential in breaking bad news and requesting donation. Further research is necessary to determine what factors additional to EDHEP will contribute to enduring change in these particular skills.

Adult↗

Insulin resistance and substrate utilization in human endotoxemia.

Infection results in a state of insulin resistance, but the pathogenesis is poorly understood. Intravenous administration of bacterial lipopolysaccharide (LPS) has been used to mimic the febrile and systemic inflammatory responses to infection, but it is unclear whether LPS induces insulin resistance in man. To investigate the effects of LPS on insulin sensitivity and substrate utilization, we administered, in paired cross-over studies, either 20 U/kg Escherichia coli endotoxin or saline control to healthy volunteers (n = 6) 120 min after the start of a 10-h euglycemic hyperinsulinemic clamp (insulin infusion rate, 80 mU/m2 x min). LPS induced a fever, tachycardia, and mild arterial hypotension. Glucose utilization increased abruptly 120 min after LPS administration (+64.1+/-12.0%; P < 0.003), but then declined progressively, and insulin resistance was evident by 420 min (+1.9+/-3.5%; P < 0.05). The reduction in glucose utilization, like that observed in sepsis, was related to impaired nonoxidative glucose disposal and not abnormal glucose oxidation. The cortisol and GH responses to LPS were of sufficient duration and magnitude to explain the insulin resistance. LPS administration results in metabolic responses very similar to those observed in sepsis and could provide a useful model for the study of insulin resistance in human critical illness.

Adult↗

Diazepam-induced neuroprotection: dissociating the effects of hypothermia following global ischemia.

Global cerebral ischemia produces hippocampal CA1 neuronal loss which in turn leads to deficits in memory related tasks. Previous studies have shown that the benzodiazepine diazepam is effective at attenuating this cell death and the related behavioural impairments. However these studies have been confounded by diazepam-induced hypothermia. In this study we sought to determine the neuroprotective efficacy of diazepam in the absence of hypothermia. Diazepam (10 mg/kg) was administered to two groups of gerbils at 30 and 90 min following a 5-min ischemic insult. In one group the brain temperature was monitored for 24 h post-ischemically but not regulated. In the second group, post-ischemic brain temperature was maintained at 36.5 degrees C to counteract the hypothermia produced by diazepam. Both behaviour (open field performance) and CA1 cell counts from these groups were compared to those from sham/normal, no drug ischemic and vehicle ischemic groups at 10 days survival. In animals treated with diazepam without temperature regulation, there was significant histological and behavioural protection at 10 days compared to untreated ischemic animals. Preventing hypothermia in diazepam-treated animals resulted in a decrease in the number of cells surviving (from 41.2 to 31.6% of sham) and abolished behavioural protection. Diazepam appears to have limited ability to attenuate neuronal loss and its neuroprotective efficacy is augmented by the concurrent hypothermic actions of the drug itself.

Animals↗

Male breast carcinoma: a review of 229 patients who presented to the Princess Margaret Hospital during 40 years: 1955-1996.

BACKGROUND: A single-institution review of clinical presentation, treatment, and outcome of male breast carcinoma was conducted. METHODS: Data obtained by chart review of 229 cases were analyzed with respect to clinical presentation, treatment choice, significant prognostic factors, and survival. The patients were analyzed both as a single cohort and as four cohorts grouped according to decade of diagnosis. RESULTS: Presentation occurred at a median age of 63 years, most often with a self-detected lump. Pathology consisted of subtypes similar to those of female breast carcinoma. The majority of tumors were larger than 2 cm in greatest dimension. Lymph node status, hormone receptors, and histologic and nuclear grade were underreported. Primary, adjuvant, and advanced disease treatment practices were reviewed over time. The 5-year disease free survival (DFS), overall survival (OS), and local control were 47%, 53%, and 91%, respectively. No difference in outcome by decade of diagnosis was observed. Negative lymph nodes and adjuvant hormone treatment predicted for better DFS and OS. Younger age and Stage 0 also predicted for better OS. CONCLUSIONS: Compared with data from female breast carcinoma patients, 5-year OS for this series was low; however, when these patients were separated by lymph node status, survival was similar for those with axillary lymph node metastases. Despite a change in standard primary surgical treatment and an increased use of chemotherapy and hormone therapy over the study period, no difference in outcome was observed among these males. In the absence of prospective, randomized clinical trials, collection of comprehensive data on the presentation and management of male breast carcinoma may help to optimize clinical care.

Adult↗

Cystic kidney disease presenting in infancy.

AIM: The clinical, histological and imaging findings of 12 children with ultrasound features of severe renal cystic disease presenting in the first year of life were reviewed. METHODS AND RESULTS: Two children had cystic dysplasia and four had autosomal dominant polycystic disease. Two had a malformation syndrome, one a variant of Meckel syndrome and the other Bardet Biedl syndrome. One had autosomal recessive polycystic disease and in three there was no final diagnosis. Intravenous urography gave non-specific information. In six cases clinical findings combined with imaging established a diagnosis. Diagnosis was established by biopsy in two and gave supportive evidence in one. Outlook for renal function is variable. One child has had a transplant and one is on dialysis awaiting a transplant. Three have a degree of renal failure and one has died. Six have normal renal function. Renal cystic disease is the common pathway for a heterogeneous group of disorders as shown in these children. CONCLUSION: It is emphasized that a specific diagnosis could not be made from the renal sonographic appearances alone, nor could any prognostic implications for renal function be made. Contrast retention on intravenous urography was also insufficiently specific to be of value. Ultrasound of the parents was the most useful imaging procedure and should be done in all cases.

Adolescent↗

Prevention by a silymarin/phospholipid compound of ethanol-induced social learning deficits in rats.

We explored the possibility that silymarin (SY), a fraction from Silybum marianum, might protect against the effects of in utero exposure to ethanol upon subsequent social memory function. Three groups of 8 pregnant female Sprague-Dawley rats each were provided with a liquid diet containing 35% ethanol derived calories (EDC). One experimental group received a daily subcutaneous injection of 400 mg/kg SY, the second, a 400 mg/kg oral dose of SY, a third group was maintained on the 35% EDC diet. A fourth group served as the pair-fed control group. The liquid diet regimen was maintained throughout pregnancy. Rats pups were fostered by dams in a fifth group that had been maintained on rat chow. At 90 days the pups were tested for social memory. Social recognition scores recorded for the ethanol pups were significantly poorer than those observed in both SY/ethanol groups and the chow group.

Animals↗

Aortic rupture as a result of low velocity crush.

A case of aortic disruption in a 35 year old lorry driver is described. This occurred as a result of a low velocity crushing force. Clinicians should be aware that this mechanism of injury may result in aortic disruption as well as the more commonly mentioned severe deceleration force.

Abdominal Injuries↗

Renal chloride channel, CLCN5, mutations in Dent's disease.

Dent's disease is an X-linked renal tubular disorder characterized by low-molecular-weight proteinuria, hypercalciuria, nephrocalcinosis, nephrolithiasis, and renal failure. Patients with Dent's disease may also suffer from rickets and other features of the renal Fanconi Syndrome. Patients may have mutations in the X-linked renal chloride channel gene, CLCN5, which encodes a 746-amino-acid protein with 12-13 transmembrane domains. We have investigated the 11 coding exons of CLCN5 for mutations in eight unrelated patients with Dent's disease. Leukocyte DNA was used for the polymerase chain reaction amplification of CLCN5 and the products analyzed for single-stranded conformational polymorphisms (SSCPs). Abnormal SSCPs were sequenced and revealed eight mutations. These consisted of three nonsense mutations (Arg34Stop, Arg648Stop, Arg704Stop), four deletions involving codons 40, 86, 157, and 241, and one acceptor splice consensus sequence mutation tgcag --> tgaag. The mutations were confirmed either by restriction endonuclease or sequence-specific oligonucleotide hybridization analysis. In addition, an analysis of 110 alleles from 74 unrelated normal individuals demonstrated that the DNA sequence changes were not common polymorphisms. All of the mutations predict truncated chloride channels that are likely to result in a functional loss. Thus, our findings expand the spectrum of CLCN5 mutations associated with Dent's disease and the results will help to elucidate further the functional domains of this novel chloride channel.

Amino Acid Sequence↗

The synthesis of symmetrical and unsymmetrical P1/P1' cyclic ureas as HIV protease inhibitors.

Cyclic urea SD146, a potent HIV protease inhibitor bearing a flat resistance profile, possessed poor solubility and bioavailability, which precluded further development of the compound. In an effort to improve upon the pharmacokinetic profile of the compound, several analogs modified at the P1/P1' residues were prepared and evaluated. Several of those compounds displayed significant improvement of physical properties.

Binding Sites↗