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Biomedical subjects

A McLean

Publications and source records attributed to A McLean.

At least 55 records · Page 3Linked to original sources

HIV-1 dynamics after transient antiretroviral therapy: implications for pathogenesis and clinical management.

Simple models of CD4 lymphocyte interactions with human immunodeficiency virus (HIV) lead to the hypothesis that progression of HIV infection involves an increase in viral replicative capacity, due either to changes in the virus or in the host environment, or both. In order to consider how changes in plasma virus load after transient, potent antiretroviral therapy can be used to test the above hypothesis--a simple mathematical model that encompasses the processes of (1) arrival of new CD4 lymphocytes, (2) death/removal of these cells by HIV-independent mechanisms, (3) infection of susceptible CD4 lymphocytes by HIV, and (4) death/removal of infected cells was investigated. This showed that the in vivo rate of increase in plasma virus load immediately after transient therapy provides a measure of the viral replicative capacity. Thus, the hypothesis that progression of HIV infection involves an increase in viral replicative capacity can be tested by measuring this viral growth rate in patients with high CD4 counts and in patients with low CD4 counts. Studies should thus investigate dynamics of changes in virus levels after stopping antiretroviral therapy and, in particular, measure rates of increase in virus in patients at high and low CD4 counts. In practice, such data may assist in therapeutic management of patients with HIV infection.

Anti-HIV Agents↗

Prognostic factors in intraoperative facial nerve monitoring for acoustic neuroma.

OBJECTIVES: To determine the predictive value of intraoperative threshold stimulus for facial nerve outcome and the prevalence and prognostic value of persistent trains of activity and frequent spontaneous or mechanically induced contractions during acoustic neuroma surgery. STUDY DESIGN: Prospective recording and subsequent review of facial nerve activity. SETTING: Tertiary referral centre. PATIENTS AND METHODS: Consecutive patients undergoing acoustic neuroma surgery. Intraoperative facial nerve activity was digitised and stored on a personal computer for future analysis. Operative events were flagged. Recordings were available in 27 patients. MAIN OUTCOME MEASURES: Frequent mechanically induced contractions (< 20), prolonged trains of facial nerve activity (total time > 199 seconds), and facial nerve brainstem stimulus threshold were correlated with facial nerve outcome. RESULTS: A brainstem stimulus threshold > 0.1 mA was significantly associated with intermediate or poor facial nerve function (House-Brackmann grade > 2) on the sixth postoperative day, at 1 month and 6 months. Patients with normal or near-normal facial function on the first day and a threshold of > 0.1 mA were significantly more likely to develop a delayed facial nerve palsy. Frequent contractions were noted in 74% of patients and persistent train activity in 59%. Neither was predictive of facial nerve outcome. CONCLUSIONS: An elevated brainstem threshold is helpful in predicting delayed facial nerve palsy and suboptimal facial nerve outcome. Persistent train activity and frequent contractions, do not have major prognostic significance.

Adult↗

A locus for bipolar affective disorder on chromosome 4p.

The main clinical feature of bipolar affective disorder is a change of mood to depression or elation. Unipolar disorder, also termed major depressive disorder, describes the occurrence of depression alone without episodes of elevated mood. Little is understood about the underlying causes of these common and severe illnesses which have estimated lifetime prevalences in the region of 0.8% for bipolar and 6% for unipolar disorder. Strong support for a genetic aetiology is found in the familial nature of the condition, the increased concordance of monozygotic over dizygotic twins and adoption studies showing increased rates of illness in children of affected parents. However, linkage studies have met with mixed success. An initial report of linkage on the short arm of chromosome 11 (ref. 4) was revised and remains unreplicated. Reports proposing cosegregation of genes found on the X chromosome with bipolar illness have not been supported by others. More recently bipolar disorder has been reported to be linked with markers on chromosomes 18, 21, 16 and a region on the X chromosome different from those previously suggested. We have carried out a linkage study in twelve bipolar families. In a single family a genome search employing 193 markers indicated linkage on chromosome 4p where the marker D4S394 generated a two-point lod score of 4.1 under a dominant model of inheritance. Three point analyses with neighbouring markers gave a maximum lod score of 4.8. Eleven other bipolar families were typed using D4S394 and in all families combined there was evidence of linkage with heterogeneity with a maximum two-point lod score of 4.1 (theta = 0, alpha = 0.35).

Bipolar Disorder↗

Empowerment and the psychiatric consumer/ex-patient movement in the United States: contradictions, crisis and change.

A political movement in the United States by consumers and ex-patients of psychiatry has challenged the assumptions and negative consequences of traditional mental health practice and its control by professionals. In recent years, the movement has succeeded in gaining support to produce alternative programs based on a philosophy of 'consumer empowerment' and run entirely by consumers and ex-patients. In this article, I present results from an ethnographic study of one such alternative and I attempt to explain the discrepancy between the center's philosophy of empowerment and its actual practices. Utilizing this data, the consumer literature, and interviews with consumer leaders nationwide, I explain this situation in terms of conceptual problems with the terms 'empowerment' and 'consumer empowerment', local structural conditions under which the center operated, and the larger situation of the psychiatric consumer/ex-patient movement in the United States today. The case study represents a crisis in the consumer movement today, in which rapid growth of alternatives has been accompanied by a social amnesia of the emancipatory vision that originally spawned the movement.

Adult↗

Post-operative serial prostate-specific antigen and transrectal ultrasound for staging incidental carcinoma of the prostate.

OBJECTIVES: To examine the value of post-operative serum prostate-specific antigen (PSA), PSA density, incremental change in serial serum PSA (PSA slope) and transrectal ultrasound (TRUS) in the assessment of residual malignancy after the diagnosis of clinically unsuspected prostatic adenocarcinoma at transurethral resection of the prostate (TURP). PATIENTS AND METHODS: Forty-eight untreated patients with incidental carcinoma of the prostate, demonstrated at TURP for a clinically benign gland, were evaluated post-operatively with serum PSA and TRUS with multiple systematic prostatic biopsies. Prostatic volume was determined from TRUS measurements and PSA density was defined as serum PSA divided by gland volume. Those patients who did not undergo further treatment were monitored with serial PSA levels, and PSA slope was calculated as the overall annual percentage increase in serum PSA. RESULTS: Among 36 patients staged T1A (A1), 11 (31%) had histologically proven residual carcinoma, and five of the 12 patients (42%) with T1B (A2) disease had no residual disease on biopsy. Serum PSA levels following TURP were greater in those patients with residual disease than those without (P = 0.001), but at a cut-off of 4.0 ng/mL--providing a sensitivity of 89%--the specificity of PSA alone was 57%. PSA density had an 83% sensitivity and a 67% specificity with a cut-off of 0.15 ng/mL/cm3. TRUS had a sensitivity of 63% and a specificity of 52%. An incremental rise in PSA exceeding 20% per year in untreated patients gave a sensitivity of 90% and specificity of 79% for biopsy proven residual malignancy. CONCLUSION: This study demonstrates the inaccuracy of staging incidental prostatic malignancy by TURP. Although the performance of PSA density is better than that of PSA alone, the reliability of both are limited by the lack of specificity, and TRUS imaging lacks both sensitivity and specificity. The PSA slope has sufficient sensitivity and specificity to distinguish reliably most patients with biopsy proven residual malignancy. Although ultrasound-guided systematic biopsies provide a means for confirming residual malignancy, they may not be indicated in all patients with incidental carcinoma: for such patients, PSA progression may provide a rational basis for subsequent treatment.

Aged↗

Peak inspiratory flow through Turbuhaler in acute asthma.

Efficient use of dry powder inhalers, such as Turbuhaler, is dependent on the generation of adequate inspiratory flow. It is not clear whether patients with acute asthma are able to generate adequate flow. Peak inspiratory flow (PIF) was measured through an empty Turbuhaler, and without this device, in 99 adults presenting to hospital with acute exacerbations of asthma. Where possible, patients were studied prior to nebulized bronchodilator therapy. Mean (SD) forced expiratory volume in one second (FEV1) was 1.2 (0.7) L, forced vital capacity (FVC) 2.1(1.0) L and peak expiratory flow (PEF) 199 (92) L.min-1. PIF without Turbuhaler was 152 (77) L.min-1 and correlated with PEF (r = 0.69). PIF through Turbuhaler was 60 (20) L.min-1 and weakly correlated with PEF (r = 0.35), and with PIF without Turbuhaler (r = 0.43). Two patients failed to generate the minimum inspiratory flow (30 L.min) required for efficient use of Turbuhaler; both recorded 26 L.min-1. Acute asthma is associated with considerable inspiratory, as well as expiratory airflow limitation. The relationship between inspiratory and expiratory airflow is not strong enough to predict whether patients with severe acute asthma will have difficulty using dry powder inhalers efficiently. Despite this, 98% of patients in this study generated inspiratory flow through Turbuhaler which would allow a therapeutically active amount of bronchodilator drug to be delivered to the airways.

Acute Disease↗

Screening in general practice.

Screening for prostate cancer in a general practice setting seems to be technically feasible and generally acceptable. In our study, 14 cancers were diagnosed among the 568 men screened, giving an overall detection rate of 2%; five of these were either locally advanced or associated with metastatic disease. Although these results may reflect our somewhat conservative biopsy rate, there is a considerable false positive rate in the PSA range of 4-10 ng/ml, particularly among men with clinical evidence of benign prostatic hyperplasia. A large scale prospective controlled study will be necessary to establish the true benefit of screening.

Aged↗

Clinical audit of a specialist symptomatic breast clinic.

The efficient delivery of health care requires vigilant quality assurance. We describe the audit of our symptomatic breast clinic, which includes the option of a one-stop diagnostic service. A total of 134 new and 386 follow-up patients attended over four consecutive clinics. The majority of new referrals (68%) were seen by a consultant surgeon. Urgent referrals were seen significantly sooner than routine referrals (P < 0.001, chi 2-test), and the mean wait from designated appointment to seeing the surgeon was 37.6 (range-68 to 171) min. One-stop investigations were offered to 50 patients; of these, 36 women (72%) had a total wait of less than 2 h. For those not investigated at the same clinic, the mean time until investigations was 6.1 (range 0-36) days and mean recall was 2.7 (range 1-8) weeks. Patients undergoing definitive surgery for cancer (n = 5) were operated on average 14.2 (range 7-27) days after the decision was made in outpatients, while the mean waiting time for non-cancer operations was 49.7 (range 15-98) days. Objective audit on outpatient services is possible and can lead to improvement of services.

Adult↗

One-stop diagnosis for symptomatic breast disease.

A consultant-led one-stop diagnostic service has been available at a busy symptomatic breast clinic each week at St Bartholomew's Hospital for 18 months. Women can be investigated appropriately using mammography, ultrasonography and cytology with immediate reporting. The aim is to achieve a diagnosis and management plan for each patient at the initial outpatient visit. A prospective audit of four consecutive clinics was undertaken to assess the impact of this service on clinical practice. Fifty patients out of 134 new and 386 follow-up clinic attenders had one-stop investigations. As a result of immediate reporting, 48 (96%) patients had a management decision made at the first outpatient visit, 9 (18%) were offered surgery, and 18 (36%) were discharged with a benign diagnosis and no dominant mass. Four symptomatic cancers were detected and evaluated on a one-stop basis, constituting 8% of the workload of this clinic. The mean wait from designated appointment until surgical consultation was 37.7 min (range -68-171 min) and that for investigation until subsequent clinical review was 56.9 min (range -4-191 min). Thirty-six (72%) one-stop patients had a total wait of less than 2 h and 95% were seen in under 3 h. It is felt that the one-stop clinic allows optimum patient management, minimises anxiety associated with symptomatic breast disease, and maximises utilisation of hospital outpatient resources.

Adult↗

Tuberculous pancreatitis: a diagnostic problem. Case report and review of literature.

A 22-year-old Pakistani man presented with a 1-year history of recurrent attacks of pancreatitis of unknown etiology that had required hospitalization and extensive investigation in Pakistan. He was admitted with abdominal pain, fever, and weight loss. An ultrasound and computed tomographic scan of the abdomen revealed abdominal lymphadenopathy, bulky and inhomogeneous pancreas, and a large fluid collection anterior to the right lobe of the liver. The collection was aspirated but Gram-stain, Ziehl-Neelsen stain for acid-fast bacilli, and DNA analysis by a highly specific polymerase chain reaction-based assay were negative. Because of a strong clinical suspicion of tuberculosis, the patient was started on antituberculous chemotherapy; 4 weeks later the aspirate grew Mycobacterium tuberculosis (hominis). The patient improved rapidly and has remained well after 18 months follow-up. A high index of clinical suspicion and appropriate microbiological investigation is required for the diagnosis of this rare, but potentially curable cause of pancreatitis.

Adult↗