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Biomedical subjects

D Tomlinson

Publications and source records attributed to D Tomlinson.

At least 19 recordsLinked to original sources

Spatial learning ability of rats following differing levels of exposure to alcohol during early postnatal life.

Rats exposed to a relatively high dose (7.5 g/kg body weight) of alcohol on either the fifth or tenth postnatal day of age have been reported to have long-lasting deficits in spatial learning ability as tested on the Morris water maze task. The question arises concerning the level of alcohol required to achieve this effect. Wistar rats were exposed to either 2, 4 or 6 g/kg body weight of ethanol administered as a 10% solution. This ethanol was given over an 8-h period on the fifth postnatal day of age by means of an intragastric cannula. Gastrostomy controls received a 5% sucrose solution substituted isocalorically for the ethanol. Another set of pups raised by their mother were used as suckle controls. All surgical procedures were carried out under halothane vapour anaesthesia. After the artificial feeding regimes all pups were returned to lactating dams and weaned at 21 days of age. The spatial learning ability of these rats was tested in the Morris water maze when they were between 61-64 days of age. This task requires the rats to swim in a pool containing water made opaque and locate and climb onto a submerged platform. The time taken to accomplish this is known as the escape latency. Each rat was subjected to 24 trials over 3 days of the test period. Statistical analysis of the escape latency data revealed that the rats given 6 g/kg body weight of ethanol had significant deficits in their spatial learning ability compared with their control groups. However, there was no significant difference in spatial learning ability for the rats given either 2 or 4 g/kg body weight of ethanol compared with their respective gastrostomy or suckle control animals. We concluded that ethanol exposure greater than 4 g/kg over an 8-h period to 5-day-old rats is required for them to develop long-term deficits in spatial learning behaviour.

Animals

Male duct ectasia associated with HIV infection.

The incidence of male duct ectasia (periductal mastitis) is extremely rare, only eight cases having been reported. The underlying cause (as in females) is uncertain. Two cases in HIV positive males of recurrent unilateral nipple lesions are reported with histology consistent with duct ectasia. At presentation neither patient had an AIDS defining illness. An impaired immunity secondary to HIV infection may result in an increased susceptibility to repeated nipple infections, and the clinical as well as histological features of duct ectasia. The consideration of HIV infection in future cases of male duct ectasia may be warranted.

Adult

Randomised controlled trial comparing problem solving treatment with amitriptyline and placebo for major depression in primary care.

OBJECTIVE: To determine whether, in the treatment of major depression in primary care, a brief psychological treatment (problem solving) was (a) as effective as antidepressant drugs and more effective than placebo; (b) feasible in practice; and (c) acceptable to patients. DESIGN: Randomised controlled trial of problem solving treatment, amitriptyline plus standard clinical management, and drug placebo plus standard clinical management. Each treatment was delivered in six sessions over 12 weeks. SETTING: Primary care in Oxfordshire. SUBJECTS: 91 patients in primary care who had major depression. MAIN OUTCOME MEASURES: Observer and self reported measures of severity of depression, self reported measure of social outcome, and observer measure of psychological symptoms at six and 12 weeks; self reported measure of patient satisfaction at 12 weeks. Numbers of patients recovered at six and 12 weeks. RESULTS: At six and 12 weeks the difference in score on the Hamilton rating scale for depression between problem solving and placebo treatments was significant (5.3 (95% confidence interval 1.6 to 9.0) and 4.7 (0.4 to 9.0) respectively), but the difference between problem solving and amitriptyline was not significant (1.8 (-1.8 to 5.5) and 0.9 (-3.3 to 5.2) respectively). At 12 weeks 60% (18/30) of patients given problem solving treatment had recovered on the Hamilton scale compared with 52% (16/31) given amitriptyline and 27% (8/30) given placebo. Patients were satisfied with problem solving treatment; all patients who completed treatment (28/30) rated the treatment as helpful or very helpful. The six sessions of problem solving treatment totalled a mean therapy time of 3 1/2 hours. CONCLUSIONS: As a treatment for major depression in primary care, problem solving treatment is effective, feasible, and acceptable to patients.

Adolescent

Squamous cell carcinoma of the anus in patients with AIDS.

Squamous cell carcinoma of the anus accounts for 2%-3% of all malignancies of the lower gastrointestinal tract. There is an increased incidence in homosexual males who practise receptive and anal intercourse [1]. We report on three cases of squamous cell carcinoma of the anus in patients with the acquired immune deficiency syndrome (AIDS), all of whom were treated with conventional radiotherapy. Increased normal tissue damage with delayed healing was a severe problem in each patient. This led to prolonged delays in delivering an adequate dose of radiotherapy to the site of disease. Reasons for this are explored and suggestions made for the treatment of such patients in the future.

AIDS-Related Opportunistic Infections

Smoking habits of emergency department patients: an opportunity for disease prevention.

OBJECTIVE: To determine smoking habits, levels of addiction, readiness to quit, and access to primary care among ED patients. METHODS: A questionnaire was administered prospectively to all noncritical adult patients who presented to one university hospital ED during 23 randomly selected four-hour time blocks; 336 (89%) of 376 eligible patients responded. Self-reported smoking was validated by carbon monoxide breath testing in a pilot sample of 49 patients. RESULTS: The study patients were mostly young (mean age = 35 +/- 15 years), female (59%), white (62%), and high school-educated (73%). Of the 336 ED patients, 41% were current smokers (95% CI = 0.36-0.46); 42% of these were "moderately" to "very highly" dependent on nicotine (Fagerstrom Test for Nicotine Dependence > 4). Of those who smoked, 68% stated they wanted to quit, and 49% wanted to quit within the month. Fifty-six percent of all those who smoked stated that they had never been told to quit smoking by any physician. Thirty-five percent of the ED sample (118 patients) relied upon EDs for most or all of their routine, primary health care; 55% (95% CI = 0.46-0.64) of these patients were current smokers. CONCLUSIONS: The prevalence rates of smoking and nicotine addiction among ED patients are high. Almost half of ED smokers are ready to quit, but most state they have never been told by a physician to do so. Finally, a large proportion of ED smokers receive their primary care in EDs. Therefore, the ED may be an underused setting for smoking cessation intervention.

Adolescent

Smoking cessation counseling by emergency physicians: opinions, knowledge, and training needs.

OBJECTIVES: To determine: 1) the extent of emergency physicians' (EPs') training in smoking cessation counseling; 2) their understanding of counseling and pharmacologic treatment techniques; 3) their current practices in screening, counseling, and referring patients who smoke; and 4) perceived barriers to routine smoking cessation counseling in emergency medical practice. METHODS: A 26-item questionnaire addressing the above issues was mailed to all 256 members of the Colorado Chapter of the American College of Emergency Physicians. RESULTS: Completed questionnaires were returned by 196 physicians (77% response rate). The majority of respondents were men (80%), practiced in urban settings (87%), and were board-certified in emergency medicine (82%). Most EPs lacked formal smoking cessation training (55%) and felt poorly prepared to counsel patients about smoking cessation (65%). A minority (27%) of the physicians reported routinely asking patients to quit smoking. The physicians with formal smoking cessation training were more likely to counsel and refer patients routinely (34% vs 20%, p = 0.03). The physicians cited the following barriers to routine smoking cessation counseling: a lack of time; a perception that patients are not interested; a belief that the ED setting is inappropriate for counseling; and a sense that counseling is ineffective. Lack of reimbursement was cited by only 13% of the respondents. The physicians who had formal smoking cessation training perceived fewer barriers to ED-based counseling. CONCLUSIONS: Emergency physicians have received little training in smoking cessation and perceive many barriers to ED-based smoking cessation interventions. Not surprisingly, they infrequently take action to encourage or assist their patients to quit smoking.

Adult

Changes in dyspnea, health status, and lung function in chronic airway disease.

The purpose of this study was to examine longitudinal changes in clinical parameters in patients with chronic obstructive pulmonary disease (COPD). We postulated that progressive dyspnea and decline in lung function over time would influence or impact patient's health status. Clinical ratings of dyspnea, general health status, and physiologic lung function were measured every 6 mo over a 2-yr period in an original group of 110 male patients with stable but symptomatic COPD and no significant comorbidity. At enrollment, age was 67 +/- 8 yr (mean +/- SD), forced expiratory volume in one second (FEV1) was 1.28 +/- 0.59 I (44 +/- 17% of predicted), and forced vital capacity (FVC) was 2.84 +/- 0.84 I (68 +/- 18% of predicted). A total of 34 patients "dropped out" because of death (n = 20), relocation (n = 7), and other reasons (n = 7). Dyspnea was measured using the transition dyspnea index (TDI), which represented changes from the baseline state; general health status was measured using the Medical Outcomes Study (MOS) 20-item short-form survey; physiologic lung function was assessed by spirometry (FVC and FEV1) and inspiratory muscle strength (PImax). Statistical analyses were performed using all available data for each patient, including results until the time at which patients died or were lost to follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Liposomal-entrapped doxorubicin: an active agent in AIDS-related Kaposi's sarcoma.

PURPOSE: A phase II study was performed of single-agent liposomally entrapped doxorubicin ([LED] Doxil; Liposome Technology Inc, Menlo Park, CA) against locally advanced cutaneous/systemic AIDS-related Kaposi's sarcoma (KS). PATIENTS AND METHODS: Thirty-four patients with AIDS-related advanced cutaneous/systemic KS were treated with 20 mg/m2 of LED every 3 weeks on an outpatient basis. The median age was 39 years and the median Karnofsky score was 70. All patients had poor prognostic disease as judged by AIDS Clinical Trials Group (ACTG) criteria. Nineteen of 34 patients had received prior chemotherapy for KS, although no patient had received prior anthracyclines. RESULTS: An overall response rate of 73.5% (25 of 34) was observed. Partial responses (PRs) occurred in 67.7% (23 of 34) and complete responses (CRs) in 5.8% (two of 34). In patients who had received previous chemotherapy, the response rate was 68.4% (13 of 19), and all responses were PRs. The median time to response was 6 weeks. The median duration of response was 9 weeks. Toxicity according to World Health Organization (WHO) criteria was as follows: neutropenia (grade > or = 3), 34%; alopecia (grade 1 only), 9%; and nausea and vomiting (grade 1), 18%. One patient died of heart failure, which was not considered to be anthracycline-induced. CONCLUSION: LED appears to be highly active against AIDS-related KS. The major toxicity is neutropenia, which seems to be progressive in patients who receive several cycles of therapy. Comparative studies of LED versus conventional chemotherapy are needed.

Acquired Immunodeficiency Syndrome

Liposomal doxorubicin (Doxil): an effective new treatment for Kaposi's sarcoma in AIDS.

The objective of this study was to assess the efficacy and toxicity of a novel Stealth liposomal encapsulated formulation of doxorubicin (Doxil). A Phase I/II dose escalation study was carried out in a specialist HIV oncology unit in a teaching hospital (predominantly in an outpatient department). Fifteen patients with HIV related, biopsy confirmed, cutaneous Kaposi's sarcoma, with or without visceral involvement of sufficient severity to require systemic chemotherapy, were treated. Most patients had poor prognosis disease as assessed by the Tumour/Immune status/Systemic symptoms (TIS) system and Karnofsky indices; six patients had previously received combination chemotherapy. Primary treatment consisted of a dose of Doxil 10 mg/m2, repeated after 2 weeks. If the Kaposi's sarcoma (KS) responded and the treatment was tolerated, the patient began maintenance therapy at the same dose every 2 weeks. If there was no clinical response, the dose was increased to 20 mg/m2 for the further two cycles, before proceeding to maintenance therapy. Treatment continued until other intercurrent disease, lack of further response, patient preference, or toxicity precluded further treatment. Tumour response was assessed 2 weeks after completion of at least two cycles of chemotherapy. Toxicity was assessed for each cycle. Doxil was well tolerated, and toxicity was manageable, the principal toxicity being haematological. A partial response rate of 11/15 (73%) was achieved, with disease stabilization in the remaining patients. We conclude that Doxil is an effective palliative treatment for epidemic KS in a patient group with a poor predicted outcome.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome

The horizontal vestibulo-ocular reflex gain during active and passive high-frequency head movements.

Patients with bilateral peripheral vestibular loss complain of varying degrees of oscillopsia and balance difficulties. Some are able to engage in sporting activities while others are completely disabled. An assumption that other inputs are available to the vestibulo-ocular reflex (VOR) enabling it to achieve some degree of visual stability during high-frequency head movement is reasonable. In this study, the gain of the horizontal vestibulo-ocular reflex in 10 healthy subjects was examined during active high-frequency head-on-body rotation (head free), and compared to high-frequency passive whole-body rotation (head fixed). A statistical difference in the gain (P < .002) was noted for all frequencies between the two groups. In those individuals undergoing passive whole-body high-frequency movements, the gain was observed to rise (above unity) with increasing frequency of rotation, while the gain during active head-on-body rotation remained close to 1.

Adult

Ultrasound findings in hepatic mycobacterial infections in patients with acquired immune deficiency syndrome (AIDS).

Ultrasound findings in 12 AIDS patients with abdominal mycobacterial infections were reviewed and correlated with liver histology. Liver ultrasound abnormalities were common--present in 4/5 patients with Mycobacterium avium-intracellulare (MAI) and 7/7 patients with Mycobacterium tuberculosis (MTB) infection. The commonest ultrasound abnormality of the liver was a generally 'bright' liver, seen in 7/12 patients. Focal liver lesions were seen in 5/7 patients with MTB but were not seen in any patients with MAI infection. Both hyperechoic (two patients) and hypoechoic (three patients) lesions were seen. Lymphadenopathy as demonstrated on abdominal ultrasound was a relatively infrequent finding--only seen in three patients with MTB, all of whom also had focal liver lesions. On histology, 8/12 patients showed fatty infiltration and 8/12 showed granuloma. Abnormalities are commonly seen on ultrasound examination of the liver in AIDS patients with abdominal mycobacterial infections but are non-specific and ultrasound guided biopsy is indicated to confirm the diagnosis and exclude other disease.

Acquired Immunodeficiency Syndrome

Kaposi's sarcoma in HIV infection treated with vincristine and bleomycin.

OBJECTIVE: To evaluate the efficacy and toxicity of vincristine and bleomycin when used in combination to treat patients with progressive Kaposi's sarcoma. DESIGN: A retrospective case notes review. SETTING: The departments of Immunology and Genito-Urinary Medicine, St Mary's Hospital, London, UK. PATIENTS: All patients presenting with progressive Kaposi's sarcoma and requiring chemotherapy between January 1987 and January 1990, who had received no previous systemic chemotherapy. INTERVENTIONS: Treatment with vincristine (2 mg) and bleomycin (30 mg, 18 h infusion), or vinblastine (2.5-5.0 mg) if peripheral neuropathy developed. Treatment with zidovudine and prophylaxis of opportunistic infections where indicated. OUTCOME MEASURES: Response, toxicity and survival. RESULTS: Overall, patients had a poor prognosis: 33 out of 46 (72%) had had a previous opportunistic infection, had a mean CD4 count of 144 x 10(6) (20 out of 46 tested) and a mean Karnofsky index of 75.4. They received a median of five cycles of therapy: a partial response was achieved in twenty-six patients (57%), disease progression was halted in a further 16 (35%), while disease progression continued in four (9%) despite therapy; there were no complete responders. Mean duration of response was 2 months (s.d., 1.26 months), survival was 8 months (s.d., 6.7 months) from start of therapy and 17 months (s.d., 8.9. months) from first AIDS diagnosis. On multivariate analysis the best predictor of mortality was the presence of previous opportunistic infection (P = 0.00653). Side-effects were minimal in comparison with other studies. The most common side-effect, in 13 cases (28%), was peripheral neuropathy, which may in part represent the prevalence of HIV neuropathy or remain as background. Haematological toxicity was uncommon. CONCLUSIONS: Treatment for HIV-related Kaposi's sarcoma in advanced HIV disease is becoming more necessary as disease profiles change. Conventional chemotherapy regimens for malignancy are not well tolerated in these patients and may not be indicated. This regimen is effective and has low toxicity in AIDS patients. Non-responders should be considered for more intensive regimens.

Acquired Immunodeficiency Syndrome

Nocardia infection in AIDS: a clinical and microbiological challenge.

A case of Nocardia asteroides pneumonia was diagnosed after death in a patient with AIDS. Six sputum cultures and one bronchoalveolar lavage fluid contained no pathogens, and no growth was obtained from one pleural fluid aspirate. None of these specimens was incubated for more than two days. Extended incubation for mycobacteria also failed to help in the diagnosis. N asteroides was isolated from pus taken from the lung cavity during the post mortem examination. It is suggested that if nocardiosis enters the differential diagnosis all specimens should be cultured for at least two weeks and the use of selective media be considered. This case highlights the need for clinicians to maintain a high index of suspicion for this pathogen.

Acquired Immunodeficiency Syndrome

Rehabilitation therapy for patients with disequilibrium and balance disorders.

Vestibular rehabilitation is based on the use of adaptive and compensatory mechanisms already existing in the human brain. Research using animals provides a great deal of information on the neural mechanisms responsible for these functions and suggests strategies that should be helpful in rehabilitation of patients with disequilibrium and balance disorders. Research in animals and human beings suggests that rehabilitation should be specifically designed, depending on the patients' deficits. It also suggests that to be effective it needs to be started soon after impairment and that vestibulosuppressive medication may reduce recovery. Studies are now underway to evaluate the effectiveness of vestibular rehabilitation on several groups of patients and to answer some fundamental questions about the mechanisms and the effectiveness of these treatment methods. Current information suggests that vestibular rehabilitation is an effective method of therapy for many patients with disequilibrium and balance disorders and that for some patients it is the best therapy available.

Animals

Impact of dyspnea and physiologic function on general health status in patients with chronic obstructive pulmonary disease.

STUDY OBJECTIVE: To examine the relationship among clinical dyspnea ratings, physiologic pulmonary function, and general health status in symptomatic patients with chronic obstructive pulmonary disease (COPD). DESIGN: Observational data collected at a baseline state. SETTING: Outpatient pulmonary disease clinics at a university hospital and two VA medical centers. PATIENTS: One hundred ten male patients with COPD with no significant comorbidity were recruited. MEASUREMENTS AND RESULTS: Clinical ratings of dyspnea were measured by the multidimensional baseline dyspnea index (BDI). Pulmonary function tests included forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), and maximal inspiratory mouth pressure (PImax). General health status was assessed with the Medical Outcomes Study short-form survey, which consists of 20 questions that cover six health components. The mean age of the patients was 67 +/- 8 yr (+/- SD). The mean value for FVC was 2.84 +/- 0.84 L (68 +/- 18 percent of predicted), for FEV1 was 1.28 +/- 0.59 L (44 +/- 17 percent of predicted), and for PImax was 59.0 +/- 25.0 cm H2O. The BDI score and PImax were significantly correlated with five of the six components of general health status. Only three of the six components of general health were significantly correlated with FEV1 as percent predicted (rs value range, 0.30 to 0.44) and with FVC as percent predicted (rs value range, 0.25 to 0.33). Statistical comparisons showed that the BDI score had significantly higher correlations than FVC (percent predicted), FEV1 (percent predicted), and PImax values with physical functioning and role functioning. Multiple linear regression analysis showed that the BDI score was the only statistically significant predictor of role functioning, mental health, and health perceptions for general health status, whereas both the BDI score and FEV1 (percent predicted) were independent predictors of physical functioning and social functioning. CONCLUSION: Dyspnea ratings influence and predict general health status to a greater extent than do physiologic measurements in symptomatic patients with COPD. A shift in focus from the pathophysiology of disease to assessment and relief of symptoms may provide more meaningful benefits for the individual patient in terms of quality of life. This consideration requires that health-care providers use available measuring tools in clinical practice to quantify symptoms, as well as overall health status.

Adult