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Biomedical subjects

D Simpson

Publications and source records attributed to D Simpson.

At least 127 records · Page 7Linked to original sources
PubMed1998

Cerebellar degeneration associated with human immunodeficiency virus infection.

Cerebellar disorders associated with HIV infection are typically the result of discrete cerebellar lesions resulting from opportunistic infections such as toxoplasmosis and progressive multifocal leukoencephalopathy or primary CNS lymphoma. Clinical symptoms and pathologic abnormalities related to the cerebellum may also be observed with HIV dementia. A primary cerebellar degeneration with HIV has not previously been reported. Ten patients were identified over an 8-year period at five medical centers. All patients had clinical, laboratory, and radiologic evaluations, and three had neuropathologic examinations. Patients presented with progressively unsteady gait, slurred speech, and limb clumsiness. Examination revealed gait ataxia, impaired limb coordination, dysarthria, and abnormal eye movements. Cognition, strength, and sensory function remained normal. CD4 lymphocyte counts varied between 10 and 437 cells/mm3. Neuroimaging studies showed prominent cerebellar atrophy. Neuropathology showed focal degeneration of the cerebellar granular cell layer and unusual focal axonal swellings in the brainstem and spinal cord. Cultures, histopathology, and immunochemical studies showed no conclusive evidence of infection. We report a syndrome of unexplained degeneration of the cerebellum occurring in association with HIV infection.

Acquired Immunodeficiency Syndrome↗
PubMed1998

A phase I/II trial of nimodipine for HIV-related neurologic complications.

BACKGROUND: Few effective treatments are available for AIDS dementia complex (ADC) and HIV-associated neuropathy. However, recent in vitro studies indicate that nimodipine, a voltage-dependent calcium channel antagonist, can prevent HIV-related neuronal injury and may provide a novel form of treatment for these disorders. METHODS: To determine the safety and possible efficacy of this agent, 41 patients with mild to severe ADC, including 19 patients with neuropathy, were entered into the AIDS Clinical Trial Group multicenter, phase-I and phase-II study. Nimodipine at 60 mg p.o., five times daily; 30 mg p.o., three times daily; or placebo was administered for 16 weeks as adjuvant treatment to antiretroviral therapy. RESULTS: Neuropsychological performance at baseline, measured by the composite neuropsychological Z score (NPZ-8), correlated significantly with the ADC stage and with CSF levels of neopterin, a marker of immune activation. No significant differences in toxicity were observed among the three arms. Intent-to-treat analysis showed no significant change in the NPZ-8, although improvement was suggested in the high-dose arm. In addition, a trend toward stabilization in peripheral neuropathy was observed in both nimodipine arms compared with placebo. CONCLUSIONS: Nimodipine and other similar nonantiretroviral agents may provide a safe and promising avenue of treatment for neurologic disorders associated with HIV infection. The results of this study indicate that further clinical trials are warranted.

AIDS Dementia Complex↗
PubMed1998

A randomized trial of amitriptyline and mexiletine for painful neuropathy in HIV infection. AIDS Clinical Trial Group 242 Protocol Team.

BACKGROUND: Painful sensory neuropathy is a common complication of HIV infection. Based on prior uncontrolled observations, we hypothesized that amitriptyline or mexiletine would improve the pain symptoms. METHOD: A randomized, double-blind, 10-week trial of 145 patients assigned equally to amitriptyline, mexiletine, or matching placebo. The primary outcome measure was the change in pain intensity between baseline and the final visit. RESULTS: The improvement in amitriptyline group (0.31+/-0.31 units [mean+/-SD]) and mexiletine group (0.23+/-0.41) was not significantly different from placebo (0.20+/-0.30). Both interventions were generally well tolerated. CONCLUSIONS: Neither amitriptyline nor mexiletine provide significant pain relief in patients with HIV-associated painful sensory neuropathy.

Adrenergic Uptake Inhibitors↗
PubMed1997

Carbohydrate deficient transferrin in detecting relapse in alcohol dependence.

Patients reports together with findings at clinical examination and information from an informant such as a relative were used to categorise patients as relapsed or not relapsed during a 6 month period of out-patient treatment at an alcohol problems clinic. At each fortnightly visit, blood was taken for measurement of serum gamma-glutamyl transferase and carbohydrate deficient transferrin (Pharmacia method). A total of 53 patients attended for at least one follow-up visit. Mean CDT differentiated relapsers from non-relapsers at seven of the 11 visits (P < 0.05), but at no visit did mean GGT differentiate. CDT tended to become elevated after a relapse more quickly than GGT. However, whether using upper limit of normal (ULN), or defining a 'positive test' as > last test and either > 20% above lowest previous test or > ULN, specificity (averaged over the 11 visits) was greater for GGT than CDT. Some of the false positive results for CDT were in patients who, shortly after having a positive test, relapsed, suggesting that a rising CDT can herald a relapse admitted by the patient. This could not be shown for false positive GGT results. Inspection of individual trajectories of alcohol consumption and blood test results shows that for some patients GGT is the more effective marker of relapse, whilst for others CDT operates better.

Adult↗
PubMed1997

Pharmacokinetics of N-acetylcysteine are altered in patients with chronic liver disease.

BACKGROUND: The threshold plasma paracetamol concentration at which N-acetylcysteine (NAC) treatment is recommended to treat paracetamol poisoning in a patient with induced liver enzymes (for example, with chronic liver disease or taking anticonvulsant drugs) is 50% lower than in a patient without induced liver enzymes. More patients with chronic liver disease might therefore be expected to be exposed to NAC treatment than previously. In addition, there is increasing use of NAC in patients with chronic liver disease for multiorgan failure or hepatorenal syndrome. Little is known of NAC's pharmacokinetic properties in patients with cirrhosis. AIM: The aim was to determine if the pharmacokinetics of NAC are altered by chronic liver disease. SUBJECTS AND METHODS: NAC was given intravenously in a dose of 600 mg over 3 min to nine patients with biopsy-proven cirrhosis (Child's grade; 1 A, 4 B, 4 C: aetiology: 7 alcohol-related, 1 primary biliary cirrhosis, 1 secondary biliary stenosis) and six healthy matched controls. Venous blood was taken at 20, 40, 60 and 90 min then at 2, 3, 4, 6, 8 and 10 h after NAC administration. Serum NAC was estimated by HPLC. The data were normalized to a standard body weight of 70 kg. RESULTS: The area under the serum concentration-time curve was increased (152.34 mg/L.h +/- 50.38 s.d.) in cirrhotics compared with normal controls (93.86 mg/L.h +/- 9.60 s.d.) (P < 0.05). The clearance of NAC was reduced in patients with chronic liver disease (4.52 L/h +/- 1.87 s.d.) compared with controls (6.47 L/h +/- 0.78: P < 0.01). CONCLUSIONS: Increased vigilance for untoward anaphylactoid reactions is necessary in cirrhotics as they may have higher plasma NAC concentrations. Further studies to determine the optimum dosage regimen in such patients are required.

Acetylcysteine↗
PubMed1997

Genomic sequence analysis of a key residue (Arg183) in human G alpha q in invasive non-functional pituitary adenomas.

OBJECTIVE: With isolated exceptions the only oncogene significantly associated with pituitary tumours is a constitutively active Gs protein (G alpha s). The recent cloning of the cDNA of human G alpha q has facilitated the study of this activator of the phospholipase C beta/Ca2+/ protein kinase C pathway. Since, with isolated exceptions, non-functional tumours are responsive in vitro to TRH and GnRH which activate Gq, we have investigated the genomic sequence of G alpha q, in non-functional (NF) invasive pituitary adenomas, at a residue corresponding to the one most frequently mutated in G alpha s. PATIENTS AND MEASUREMENTS: We studied 27 invasive NF pituitary tumours by direct sequencing of DNA derived from archival slide extracted tumour cells. Primers were designed to encompass Arg183 (corresponding to Arg201 of G alpha s) which when mutated has been shown to have oncogenic potential when transfected into cultural rat fibroblasts. In a previous study we have described allelic loss at tumour suppressor gene loci (TSG) in 7 of these 27 tumours. RESULTS: We successfully amplified genomic DNA with primers designed from the cDNA sequence of G alpha q with specific exclusion of a processed pseudogene. No mutations were found at Arg183, in either the tumours showing allelic losses at specific TSG loci, or in the 20 remaining tumours in which we found no losses at the TSG loci investigated. CONCLUSIONS: Mutations at this key residue in G alpha q occur infrequently, if at all, in invasive non-functional pituitary tumours. However we cannot exclude the possibility of mutation(s) at the other key residue of G alpha q, Gin209, implicated in GTP hydrolysis, or in other components of this pathway.

Adenoma↗
PubMed1997

Strategies for efficient and effective teaching in the ambulatory care setting.

Medical education in the ambulatory care setting is characterized in part by the question of how to ensure educational effectiveness while simultaneously providing high-quality, cost-effective patient care. The constraints associated with managed care have only served to escalate the intensity of this dilemma. However, in spite of the difficulties faced by ambulatory care preceptors, there are educationally sound and time-efficient strategies clinical teachers may employ to improve ambulatory care education. Emphasizing the basic three-step process of planning, teaching, and reflection, the authors describe five such strategies: "wave" scheduling, orienting learners to patients, having learners do their case presentations in the examination room, employing the microskills of the "one-minute preceptor," and effectively reflecting on one's teaching in order to develop effective teaching scripts. Research in ambulatory care learning has indicated that learners must be given significant roles in patient care and that preceptors must observe trainees as they care for patients so that they can provide trainees with helpful feedback. Employing these strategies in the ambulatory care setting will help educators to accomplish these two objectives while minimizing disruption to cost-effective, high-quality clinical practice.

Ambulatory Care↗
PubMed1997

Defining and evaluating quality for ambulatory care educational programs.

As the training of medical students and residents increasingly moves to ambulatory care settings, clerkship and program directors must find a way to use their limited resources to guide the development and evaluation of the quality of these ambulatory-based learning experiences. To evaluate quality, directors must first define, in operational and measurable terms, what is meant by the term "quality" as it is applied to ambulatory-based education. Using educational theories and the definition of quality used by health care systems, the authors propose an operational definition of quality for guiding the planning, implementation, and evaluation of ambulatory care educational programs. They assert that quality is achieved through the interaction of an optimal learning environment, defined educational goals and positive outcomes, participant satisfaction, and cost-effectiveness. By describing the components of quality along with examples of measurable indicators, the authors provide a foundation for the evaluation and improvement of instructional innovations in ambulatory care education for the benefit of teachers, learners, and patients.

Ambulatory Care↗
PubMed1997

Paré as a neurosurgeon.

The Cowlishaw Collection gives a splendid representation of the works of a Ambroise Paré (1510-1590). His Complete Works, in the great French edition edited by J.F. Malgaigne, are essential in any study of Paré's achievement, but the 1649 English edition provides a good basis for consideration of Paré's practice in what would now be termed neurosurgery. Paré had a large clinical experience in head injury management. His patients included Henri II King of France, who died from a penetrating orbital wound, and be described a number of other craniofacial wounds sustained in war or in warlike sports. His surgical instruments and operative techniques do not appear very innovative, but were doubtless good in their day; his methods of trephination compare favourably with those of the English surgeon John Woodall, his younger contemporary. He operated on head injuries and cranial infection, but had no capacity to treat intradural conditions, such as cerebral abscesses and tumours: his technical limitations are obvious, and the physicians on whom he had to rely could give him no guidance in neurological diagnosis. He was keenly interested in developmental malformations, and described several conditions that would now be referred to a paediatric neurosurgeon. Paré is of great historical importance as an outstanding Renaissance surgeon, whose influence extended throughout the literate world, and as far as Japan. With him, France replaced Italy and Spain in leadership in European surgical progress, a position that France retained at least until the age of Hunter.

Craniotomy↗
PubMed1997

Atresia of the external acoustic meatus in a dog.

A 3 year old, female great Dane with atresia of the right external ear canal had recurrent episodes of ear pain. Radiography revealed absence of air in the right external acoustic meatus, thickened bone of the right tympanic bulla and increased radiodensity of the chamber of the bulla. Total ear canal ablation and lateral bulla osteotomy were performed. The superficial portion of the external ear canal was absent and the deeper segment of the vertical ear canal began as a blunt ended cartilage tube. A patent lumen in the existent portion of the external ear canal and the tympanic bulla contained wax, hair and exfoliated squames. The tympanic membrane was not intact. No bacteria were cultured from the contents of the external and middle ear. The dog responded well to surgery and was free of pain 11 months later. Failure to surgically correct atresia of the ear canal in young dogs may allow the accumulation of cellular and sebaceous debris with subsequent involvement of the middle ear in an inflammatory response.

Animals↗