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Biomedical subjects

R Grossman

Publications and source records attributed to R Grossman.

At least 37 records · Page 2Linked to original sources

Weight gain following unilateral pallidotomy in Parkinson's disease.

OBJECTIVE: To determine the clinical correlates and infer pathogenesis of weight gain following pallidotomy in patients with Parkinson's disease (PD). BACKGROUND: Surgical ablation of the globus pallidus internus (GPi) improves levodopa induced dyskinesias, moderately improves most other "cardinal" manifestations of PD, and has been noted to result in increased weight. METHODS: We incorporated Unified Parkinson's Disease Rating Scales (UPDRS) subscales, the Beck depression inventory and feeding questionnaire data into a linear regression model in order to determine which post-surgical change(s) may lead to weight gain over the first year following pallidotomy, n = 60. RESULTS: The mean weight gain 1 year after pallidotomy was 4.0 +/- 4.1 kg. Improvement in "off" motor scores (P < 0.005), especially gait subscores (P<0.0001), and to a lesser extent improvement in "on" motor scores (P<0.05) predicted weight gain. Changes in dyskinesia ratings, mood, food intake, dysphagia, levodopa dose, weight loss in the year prior to pallidotomy, age, and duration of PD did not correlate with subsequent weight gain. CONCLUSION: The high correlation between post-pallidotomy weight gain and "off" motor scores, suggests that this phenomenon is related to some change in underlying homeostasis associated with changes in the cardinal manifestations of PD itself, rather than secondary changes resultant from the surgery.

Dyskinesia, Drug-Induced↗

Introduction: the role of bacterial infection in chronic bronchitis.

Acute exacerbations of chronic bronchitis reflect increased airway inflammation and are characterised by one or more symptoms of increased sputum production, sputum purulence, and breathlessness. The causes are multifactorial, and bacterial infection is involved in about half of cases. A proportion of patients also have chronic colonization of the bronchial tree between exacerbations, and this may act as a stimulant of airway inflammation. Colonization represents a balance in which compromised host defences limit bacterial numbers but do not eradicate them. The balance is upset during an exacerbation, often due to extraneous factors such as a viral infection or air pollution, leading to increased bacterial numbers and consequently more inflammation. In patients with severe airway damage, infective exacerbations are more likely to occur, and serious consequences may result if baseline lung function is impaired or there are comorbid conditions. In these circumstances, the exacerbation is less likely to resolve spontaneously. Antibiotic treatment benefits patients by achieving bacterial eradication and resolution of the inflammatory response. However, since superficial mucosal infections may resolve spontaneously, there are serious concerns about widespread antibiotic use in patients with more trivial illness. Future studies should include better definition of the type of patients enrolled, improved techniques to determine bacteriological response, and better outcome measures.

Anti-Bacterial Agents↗

Holistic dying?

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Aging↗

Anti-CD4 monoclonal antibody treatment of moderate to severe psoriasis vulgaris: results of a pilot, multicenter, multiple-dose, placebo-controlled study.

BACKGROUND: OKTcdr4a (IMUCLONE) is a humanized anti-CD4 IgG4 monoclonal antibody that retains the binding and in vitro immunosuppressive properties of the parent murine antibody. Psoriasis is a chronic disease for which treatment with multiple doses of monoclonal antibodies is likely to be required for adequate control. OBJECTIVE: This study was performed to test the efficacy and safety of OKTcdr4a, given in sequential courses over a period of several weeks, in the treatment of moderate to severe psoriasis vulgaris. METHODS: Twenty-eight patients (45.6 +/- 10.1 years of age) were studied, with a mean pretreatment Psoriasis Area and Severity Index (PASI) score of 18.3. In the first double-blind phase of the study, patients were randomized to receive OKTcdr4a as a 225 mg/course (low dose), 750 mg/course (high dose), or placebo divided into 3 identical infusions over a 5-day period. After 42 days, patients who met the criteria for re-treatment with OKTcdr4a were re-treated with the 750 mg/course in an open phase of the study. RESULTS: After the double-blind course of treatment, the mean PASI decreased by 11% in the placebo group, by 4% in the low-dose group, and by 17% in the high-dose group at 15 days. Twenty patients met the criteria for re-treatment (ie, did not experience a decrease in PASI score of 50% at 42 days). They were re-treated with OKTcdr4a at 43 days with the 750 mg/course in the open phase of the study. By day 99, the mean PASI score decreased from 19.9 at baseline to 17 in those patients who had received either placebo or low-dose OKTcdr4a followed by high-dose OKTcdr4a. In contrast, the mean PASI score decreased from 17.4 at baseline to only 7.7 in those patients who had received high-dose OKTcdr4a for both courses. Sustained CD4 saturation was not necessary for sustained clinical response. No patients had significant changes in circulating CD4(+) T-cell counts. The infusions were well tolerated. CONCLUSION: Targeting CD4 using sequential treatments with a humanized monoclonal antibody (OKTcdr4a) may offer another therapeutic option for the treatment of moderate to severe psoriasis.

Adult↗

Postural control in Parkinson's disease after unilateral posteroventral pallidotomy.

Postural control changes were studied in 27 patients with Parkinson's disease after unilateral posteroventral pallidotomy (PVP). Patients were evaluated before PVP and at 3, 6 and 12 months post-PVP, both 'off' and 'on' parkinsonian medications, with selected evaluation tools representing functional performance, functional balance and posturographic components of balance. The majority of variables in the 'off' state were significantly improved at 3 months post-PVP. Improvement was maintained at 6 months but had declined for some variables by the 12 month follow-up. Standing up from a chair (P = 0.009), the balance and gait sections of the Performance-Oriented Assessment (P < or = 0.0004), and the limits of stability (LOS) posturography variables (P < 0.0005) of the average time to reach a target, the number of targets missed and the initial excursion distance to the target (P = 0.029) retained significant improvement at the 12 month follow-up. When the patients were in the 'on' state, LOS posturography variables of average time to target, average path length deviation, and the number of targets missed were the only variables significantly improved at 3 months post-PVP (P = -0.013) and this improvement was maintained at 12 months post-PVP (P = 0.012-0.041). Unilateral PVP improves axial symptoms of Parkinson's disease involved in functional performance such as gait disturbance as well as improving postural stability in the 'off' state. Generally, the maximum improvement is seen at 3 months post-PVP with many variables remaining significantly improved at 12 months post-PVP. Axial dyskinesias in the 'on' state are also significantly reduced with the improvement maintained at 12 months post-PVP. These findings suggest that unilateral pallidotomy is not only effective in abolishing levodopa-induced dyskinesias, but that it also improves the axial signs of Parkinson's disease.

Aged↗

A comparative evaluation of tretinoin gel microsphere, 0.1%, versus tretinoin cream, 0.025%, in reducing facial shine.

Tretinoin gel microsphere, 0.1%, is a highly effective anti-acne medication formulated with sponge-like microspheres encapsulating the active ingredient, tretinoin. In addition to minimizing cutaneous irritation, this system may also reduce facial shine. This single-center, double-blind, half-face study evaluated the potential of tretinoin gel microsphere, 0.1%, to reduce the appearance of facial shine compared to tretinoin cream, 0.025%. Thirty-five subjects (ages 12 to 24 years) with moderate acne vulgaris and moderate facial oiliness, were evaluated after 4 consecutive days of product use. On sides treated with tretinoin gel microsphere, 0.1%, investigators found significantly reduced facial shine at 3 and 6 hours posttreatment. Subjects' self-evaluations revealed a significant reduction in facial shine at 3 hours posttreatment. Photographic analyses showed reductions in facial shine for both treatments, but decreases were greater on tretinoin gel microsphere, 0.1%-treated sides. Both therapies were well tolerated, and no adverse events occurred. Tretinoin gel microsphere, 0.1%, has the added benefit of reducing the appearance of facial shine, which is a frequent concern in acne patients.

Acne Vulgaris↗

Levodopa-induced dyskinesias treated by pallidotomy.

Pallidotomy has been reported to improve parkinsonian symptoms, but its effects on levodopa-induced dyskinesia (LID) have not been thoroughly examined. We describe here the results of stereotactic, unilateral, posteroventral pallidotomy on LID in 42 patients (22 women), who were followed for up to 9 months. Their mean age was 60. 6+/-9.3 (range: 40-74), age at onset was 46.1+/-9.1 (range: 24-46), and duration of symptoms was 14.5+/-5.3 (range: 4-25) years. Three months following pallidotomy, the percent time with dyskinesia decreased from 37.0 to 17.3 (P<0.0001) and the percent time the patients were 'on' with dyskinesias decreased even more, from 71.0 to 22.9 (P<0.0001). Furthermore, the number of patients with troublesome (moderate to violent) dyskinesia had decreased from 36 (86%) prior to surgery to only 5 (12%) after surgery. The mean unified Parkinson disease rating scale (UPDRS) scores for LID-related disability and pain decreased from 1.95 to 0.74 (P<0. 0001) and from 1.02 to 0.17 (P<0.0001), respectively. Since the pre- and post-pallidotomy daily levodopa dosage remained essentially the same, the improvement in LID could not be attributed to a reduction in levodopa. Surgery-related complications occurred in eight (19%) patients, but none of them had persistent disability as a result of these complications. We conclude that pallidotomy is an effective and safe procedure in the treatment of medically intractable LID.

Adult↗

Movement and reaction times and fine coordination tasks following pallidotomy.

The effect of a unilateral, microelectrode-guided lesion in the globus pallidum internum (GPi) was evaluated in 41 patients (21 women) with moderately advanced Parkinson's disease (PD). The mean age was 60.3+/-9.0 years (range, 40-74) and the mean symptom duration was 14.7+/-5.3 years (range, 4-25). In addition to clinical ratings, movement time (MT) and reaction time (RT) tests were performed at baseline and 3 months after surgery during the "practically defined off" state (more than 12 hours after the last dose of levodopa). Improvement occurred bilaterally with more robust and statistically significant improvement on the contralateral side in all RT tests. Simple reaction time (SRT) improved by 14.5% (p<0.001) and the choice reaction time (CRT) by 12.2% (p<0.001) when the arm contralateral to the pallidotomy side was tested. There was a trend toward improvement in the ipsilateral arm. The MT, determined by repetitive movement between two adjacent targets, improved by 24% contralaterally (p<0.0001) and by 12% ipsilaterally (p<0.005). In addition, the Purdue Pegboard (PP) test scores, used to evaluate hand dexterity, improved on the contralateral side by 35.5% (p<0.0002) but there was no statistically significant ipsilateral improvement. To the extent that MT and RT are quantitative measures of bradykinesia, our study provides evidence that this parkinsonian feature improves after pallidotomy.

Adult↗

Economic evaluation of ciprofloxacin compared with usual antibacterial care for the treatment of acute exacerbations of chronic bronchitis in patients followed for 1 year.

OBJECTIVE: To undertake a 1-year prospective economic evaluation of ciprofloxacin compared with usual antibacterial care (any antibacterial other than a quinolone) for the treatment of acute exacerbations of chronic bronchitis (AECB) in adults presenting with a type I or type II AECB. DESIGN: Patients entered the study with an initial AECB and were randomised to the ciprofloxacin group or the usual care group. The following measurements were taken at the end of each AECB and every 3 months: resource utilisation, St. George's Respiratory Questionnaire, Nottingham Health Profile and Health Utilities Index (HUI). The following additional measurements were taken after each AECB: AECB-symptom days and willingness to pay to avoid the AECB. Economic evaluations were performed from the societal viewpoint and the viewpoint of a major third-party payer. Cost-effectiveness analysis was based on cost per AECB-symptom day averted; cost-utility analysis (CUA) was based on cost per quality-adjusted life-year (QALY) gained using the HUI as the basis for calculating QALYs. Cost-benefit analysis was based on the willingness-to-pay (WTP) data. SETTING: This was a study of outpatients enrolled from 46 family physicians and 2 respirologists in Ontario (29 sites) and Québec (19 sites), Canada, between November 1993 and June 1994. PATIENTS AND PARTICIPANTS: 240 adult male and female patients aged > or = 18 years with chronic bronchitis. MAIN OUTCOME MEASURES AND RESULTS: WTP data did not pass scope tests for reasonableness. Ciprofloxacin was more costly and provided better outcomes compared with usual antibacterial care. The base-case results are as follows (1994/1995 values): the incremental annual cost was 578 Canadian dollars ($Can) from the societal viewpoint and $Can840 for the third-party payer; the cost-effectiveness ratio per AECB-symptom day averted was $Can209 from the societal viewpoint and $Can304 for the third-party payer; the cost-utility ratio per QALY gained was $Can18,600 from the societal viewpoint and $Can27,000 for the third-party payer. According to Laupacis criteria, these CUA results are strong evidence in favour of adoption from the societal viewpoint and moderate evidence in favour from the viewpoint of the third-party payer. A subgroup analysis suggests that ciprofloxacin may be particularly cost effective, even 'win-win', in patients with more severe disease. CONCLUSIONS: The sensitivity analyses indicate that the results are relatively robust. Nevertheless, the statistical uncertainty in the results is sufficient that the findings cannot be accepted unequivocally. A further study with a larger sample size would be useful to confirm (or deny) the findings of this study.

Adult↗

Treatment of recalcitrant plaque psoriasis with a humanized non-depleting antibody to CD4.

The presence of activated CD4(+) T lymphocytes in psoriatic skin plaques suggests an immune-mediated pathogenesis for the disease. Six patients with recalcitrant plaque psoriasis (PASI>12) received a humanized non-depleting monoclonal antibody to CD4 (ORTHOCLONE OKT(R)cdr4a). The antibody was well tolerated. Four weeks from treatment, the mean decrease in PASI score was 46%. In three patients disease remission was prolonged for up to 6 months and, in one case, up to 1 year post-treatment. In all patients, circulating CD4+ T-cell counts remained normal and peripheral OKTcdr4a-coated CD4+ lymphocytes were detected up to 10 days after antibody infusion. These results point to the relevance of CD4+ lymphocytes in psoriasis. They also emphasize that depletion of CD4+ cells is not mandatory to achieve therapeutic effectiveness.

Adult↗

Malignant meningioma: an indication for initial aggressive surgery and adjuvant radiotherapy.

Malignant meningiomas constitute a rare subset of meningiomas and display a marked propensity for postsurgical recurrence. This retrospective study evaluates the various parameters which alter the recurrence rate. The records of all malignant meningioma patients treated from 1984 through 1992 were reviewed, and the time to recurrence or current patient status was determined, and the influence of various patient and disease parameters were analyzed. Thirty-eight patients were treated with 48 malignant meningioma resections performed (28 total and 20 subtotal), 25 at initial presentation and 23 for recurrent disease; 19 patients received postoperative radiotherapy. Subtypes included 32 anaplastic meningioma, 11 hemangiopericytoma, 2 meningiosarcoma, and 3 papillary meningioma. Followup ranged from 3 to 144 months, with five patients excluded from analysis. Actuarial disease free/progression free survival (DFS) at 5 years was 39% following total resection versus 0% after subtotal resection (p=0.001). For all totally excised lesions, the 5-yr DFS was improved from 28% for surgery alone to 57% with adjuvant radiotherapy (p=NS). Adjuvant irradiation following initial resection increased the 5-yr DFS rates from 15% to 80% (p=0.002). When administered for recurrent lesions, adjuvant radiotherapy improved the 2-yr DFS from 50% to 89% (p=0.015), but had no impact on 5-yr DFS. Multivariate analysis indicates extent of resection, adjuvant radiotherapy, and recurrence status are independent prognostic factors. Malignant meningiomas display a tendency for post surgical recurrence, with recurrence significantly increased for multicentric and recurrent disease. Complete surgical resection and the administration of adjuvant irradiation following initial resection are crucial to long-term control.

Adolescent↗

Short-term single-blind fluvoxamine treatment of pathological gambling.

OBJECTIVE: The authors' goal was to assess the efficacy and tolerability of the selective serotonin reuptake inhibitor fluvoxamine in the treatment of pathological gambling. METHOD: Sixteen patients with pathological gambling entered an 8-week placebo lead-in phase, and 10 of these patients completed an 8-week single-blind fluvoxamine trial. RESULTS: Seven of the 10 patients who completed the fluvoxamine trial were judged treatment responders at the end of the study: 1) they had greater than 25% decreases in their gambling behavior scores on the pathological gambling modification of the Yale-Brown Obsessive Compulsive Scale, and 2) their clinician-rated Clinical Global Impression scores for gambling severity were very much improved or much improved. Fluvoxamine treatment resulted in gambling abstinence in seven of the 10 patients. CONCLUSIONS: Findings from this preliminary study suggest that fluvoxamine may be effective in reducing the urge to gamble. Randomized placebo-controlled and maintenance trials are required to confirm these findings and to determine whether improvement persists.

Adult↗

A 1-year community-based health economic study of ciprofloxacin vs usual antibiotic treatment in acute exacerbations of chronic bronchitis: the Canadian Ciprofloxacin Health Economic Study Group.

OBJECTIVE: To evaluate the costs, consequences, effectiveness, and safety of ciprofloxacin vs standard antibiotic care in patients with an initial acute exacerbation of chronic bronchitis (AECB) as well as recurrent AECBs over a 1-year period. DESIGN: Randomized, multicenter, parallel-group, open-label study. SETTING: Outpatient general practice. PATIENTS: A total of 240 patients, 18 years or older with chronic bronchitis, with a history of frequent exacerbations (three or more in the past year) presenting with a type 1 or 2 AECB (two or more of increased dyspnea, increased sputum volume, or sputum purulence). MAIN OUTCOME MEASURES: The assessment included AECB symptoms, antibiotics prescribed, concomitant medications, adverse events, hospitalizations, emergency department visits, outpatient resources such as diagnostic tests, procedures, and patient and caregiver out-of-pocket expenses. Patients completed the Nottingham Health Profile, St. George's Respiratory Questionnaire, and the Health Utilities Index. The parameters were recorded with each AECB and at regular quarterly intervals for 1 year. These variables were compared between the ciprofloxacin-treated group and the usual-care-treated group. RESULTS: Patients receiving ciprofloxacin experienced a median of two AECBs per patient compared to a median of three AECBs per patient receiving usual care. The mean annualized total number of AECB-symptom days was 42.9+/-2.8 in the ciprofloxacin arm compared to 45.6+/-3.0 days in the usual-care arm (p=0.50). The overall duration of the average AECB was 15.2+/-0.6 days for the ciprofloxacin arm compared to 16.3+/-0.6 days for the usual-care arm. Treatment with ciprofloxacin tended to accelerate the resolution of all AECBs compared to usual care (relative risk=1.20; 95% confidence interval [CI], 0.91 to 1.58; p=0.19). Treatment assignment did not affect the interexacerbation period but a history of severe bronchitis, prolonged chronic bronchitis, and an increased number of AECBs in the past year were associated with shorter exacerbations-free periods. There was a slight, but not statistically significant, improvement in all quality of life measures with ciprofloxacin over usual care. The only factors predictive of hospitalization were duration of chronic bronchitis (odds ratio=4.6; 95% CI, 1.6, 13.0) and severity of chronic bronchitis (odds ratio=4.3; 95% CI, 0.8, 24.6). The incremental cost difference of $578 Canadian in favor of usual care was not significant (95% CI, -$778, $1,932). The cost for the ciprofloxacin arm over the usual care arm was $18,588 Canadian per quality-adjusted life year gained. When the simple base case analysis was expanded to examine the effect of risk stratification, the presence of moderate or severe bronchitis and at least four AECBs in the previous year changed the economic and clinical analysis to one favorable to ciprofloxacin with the ciprofloxacin-treated group having a better clinical outcome at lower cost ("win-win" scenario). CONCLUSIONS: Treatment with ciprofloxacin tended to accelerate the resolution of all AECBs compared to usual care; however, the difference was not statistically significant. Further, usual care was found to be more reflective of best available care rather than usual first-line agents such as amoxicillin, tetracycline, or trimethoprim-sulfamethoxazole as originally expected. Despite the similar antimicrobial activities and broad-spectrum coverage of both ciprofloxacin and usual care, the trends in clinical outcomes and all quality of life measurements favor ciprofloxacin. In patients suffering from an AECB with a history of moderate to severe chronic bronchitis and at least four AECBs in the previous year, ciprofloxacin treatment offered substantial clinical and economic benefits. In these patients, ciprofloxacin may be the preferred first antimicrobial choice.

Adolescent↗

Large airway disease associated with inflammatory bowel disease.

Lung disease is a rare complication of inflammatory bowel disease (IBD). Herein is a series of seven IBD patients who developed new, persistent and unexplained symptoms of respiratory disease, particularly chronic productive cough. Using a CT scan of the chest, a diagnosis of bronchiectasis was made in five patients, while the diagnosis of chronic bronchitis was made in two patients. Factors, other than IBD, that could account for pulmonary disease in these patients were absent. Several important clinical patterns for IBD-associated large airway disease were uncovered and are reviewed in light of earlier case reports in the medical literature. A discussion regarding the possible pathogenesis of IBD-associated airway disease follows.

Adult↗