PubMed Health⌕ Search

Biomedical subjects

B Higgins

Publications and source records attributed to B Higgins.

At least 37 records · Page 2Linked to original sources

Response of prostate cancer to anti-Her-2/neu antibody in androgen-dependent and -independent human xenograft models.

Antibody to the Her-2/neu gene product has been shown to inhibit the growth of breast cancer cells overexpressing Her-2/neu and to have clinical utility in treating breast cancer. We studied a recombinant, humanized anti-Her-2/neu antibody (Herceptin) in preclinical models of human prostate cancer. The androgen-dependent CWR22 and LNCaP human prostate cancer xenograft models and androgen-independent sublines of CWR22 were used. Her-2/neu staining of the parental, androgen-dependent, and androgen-independent CWR22 tumors and LNCaP tumors demonstrated variable Her-2/neu expression. Herceptin was administered i.p. at a dose of 20 mg/kg twice weekly after the xenograft had been established. No effect of Herceptin on tumor growth was observed in any of the androgen-independent tumors; however, significant growth inhibition was observed in both of the androgen-dependent xenograft models, CWR22 (68% growth inhibition at the completion of the experiment; P = 0.03 for trajectories of the average tumor volume of the groups) and LNCaP (89% growth inhibition; P = 0.002). There was a significant increase in prostate-specific antigen (PSA) index (ng PSA/ml serum/mm3 tumor) in Herceptin-treated androgen-dependent groups compared with control (CWR22, 18-fold relative to pretreatment value versus 1.0-fold, P = 0.0001; LNCaP, 2.35-fold relative to pretreatment value versus 0.6-fold, P = 0.001). When paclitaxel (6.25 mg/kg s.c., five times/week) was given to animals with androgen-dependent and -independent tumors, there was growth inhibition in each group. Paclitaxel and Herceptin cotreatment led to greater growth inhibition than was seen for the agents individually. Thus, in these prostate cancer model systems, Herceptin alone has clinical activity only in the androgen-dependent tumor and has at least an additive effect on growth, in combination with paclitaxel, in both androgen-dependent and androgen-independent tumors. Response to Herceptin did not correlate with the PSA levels, because the PSA index markedly increased in the Herceptin-treated group, whereas it remained constant in the control group. These results suggest the utility of Herceptin in the treatment of human prostate cancer.

Animals↗

Effect of pharmaceutical services on adherence to criteria-for-use guidelines in the operating room.

Guidelines for the use of neuromuscular blocking agents (NMBAs) and sedatives during two- to four-hour surgical procedures were developed, and the effect of pharmacy presence on adherence to the guidelines was determined. Differences in cost per dose of the NMBAs pancuronium bromide, cisatracurium besylate, and vecuronium bromide were determined. Pancuronium was designated as the first-line agent in the NMBA guidelines, cisatracurium as the second-line agent, and vecuronium as the third-line agent. In the sedative guidelines, lorazepam was the first-line agent, midazolam was the second-line agent, and propofol was the third-line agent. Pharmacy presence in the operating room was provided during January 1997. The pharmacist made a preliminary decision about the most appropriate agent and encouraged guideline adherence. Cost and adherence data were compared with data for November 1996 and March 1997. During January, the NMBA guidelines were followed 75% of the time and the sedative guidelines were followed 15% of the time; the corresponding rates for March were 40% and 12%. Compared with November 1996, a saving of $5.61 per case was observed in January in the NMBA category and a saving of $2.77 was observed in March; between January and March, there was an increase of $2.84 per case. Pharmacy presence in the OR was associated with better adherence to criteria-for-use guidelines for NMBAs and sedatives; NMBA cost savings associated with implementation of the guidelines were higher when a pharmacist was present.

Humans↗

Quality of life in advanced prostate cancer: results of a randomized therapeutic trial.

BACKGROUND: For patients with metastatic prostate cancer, treatment is primarily palliative, relying mainly on the suppression of systemic androgen hormone levels. To help document the achievement of palliation and to characterize positive and negative effects of treatment, we evaluated quality-of-life (QOL) parameters in patients with metastatic prostate cancer who were randomly assigned to two methods of androgen deprivation. METHODS: Patients (n = 739) with stage M1 (bone or soft tissue metastasis) prostate cancer were enrolled in a QOL protocol that was a companion to Southwest Oncology Group INT-0105, a randomized double-blind trial comparing treatment with bilateral orchiectomy (surgical castration) plus either flutamide or placebo. Patients completed a comprehensive battery of QOL questionnaires at random assignment to treatment and at 1, 3, and 6 months later. Data were collected on three treatment-specific symptoms (diarrhea, gas pain, and body image), on physical functioning, and on emotional functioning. All P values are two-sided. RESULTS: Questionnaire return rates for this study never dropped below 80%; only 2% of the patients did not submit baseline QOL assessments. Cross-sectional analyses (corrected for multiple testing) identified statistically significant differences that favored orchiectomy plus placebo for two of the five primary QOL parameters as follows: patients receiving flutamide reported more diarrhea at 3 months (P = .001) and worse emotional functioning at 3 and 6 months (both P<.003). Longitudinal analyses replicated these findings. Other analyzed QOL parameters favored the group receiving placebo but were not statistically significant after adjustment for multiple testing. CONCLUSIONS: We found a consistent pattern of better QOL outcomes at each follow-up assessment during the first 6 months of treatment for orchiectomized patients with metastatic prostate cancer who received placebo versus flutamide. Improvement over time was evident in both treatment groups but more so for patients receiving placebo.

Adult↗

Anorexia nervosa following gastric reduction surgery for morbid obesity.

Anorexia nervosa and morbid obesity are popularly considered to be opposite ends of the eating disorder spectrum. Research and clinical experience, however, suggest common psychological factors in a subgroup of obese people. This paper details case reports of two subjects who developed anorexia nervosa following gastric reduction surgery for morbid obesity. Clinical profiles, treatment, and outcome are reported. Psychological similarities between morbid obesity and anorexia nervosa in these subjects are explored. Implications for the selection of subjects for gastric reduction surgery and management after surgery are discussed.

Adult↗

Conservative treatment of anorectal tumors.

PURPOSE: To evaluate the results of interstitial radiotherapy of anorectal tumors. PATIENTS AND METHODS: From 1972 to 1993, one of the authors treated 45 patients by an interstitial implant for anorectal tumors. Of these, 33 patients suffered from primary tumors, 19 from squamous carcinoma, 2 from basaloid carcinoma of the anus and the other 12 from primary adenocarcinoma of the rectum. Of 12 patients treated for local recurrence, 10 had adenocarcinoma and 2 squamous cell carcinoma. Of the 33 patients with primary tumors, 27 received a course of external-beam radiotherapy before the implant. The median follow-up was 35 months. RESULTS: Local response depended on the tumor volume treated. All 21 anal tumors showed complete response, 5 patients developed local recurrence and 4 distant metastases: 3 died from their disease. Of 12 rectal adenocarcinomas, 9 responded completely, 4 patients developed local recurrence and 4 distant metastases; 6 died from active disease. In the last group of 12 patients who were treated for recurrent tumors, 7 responded completely. One patient developed local recurrence and 9 distant metastases, only 4 are alive. CONCLUSIONS: A combination of external-beam and interstitial radiotherapy is a relatively simple, non-mutilating, but well-tolerated and very effective method of treatment for early carcinoma of the lower rectum and anus.

Adenocarcinoma↗

Army and Air Force leadership in the Prostate Cancer Prevention Trial.

Prostate cancer is now the most common solid tumor in men in the United States. Although the current public health approach to this disease is early diagnosis and treatment, investigations are also focusing on the possibility of disease prevention. The Prostate Cancer Prevention Trial, begun in 1993, has completed recruitment of 18,000 men who will be randomized to receive either finasteride or placebo to determine if finasteride can prevent the development of this disease. Both Army and Air Force institutions are participating in this trial, with four Department of Defense institutions contributing over 10% of the patients randomized. The results of this study may have a major impact on active duty personnel for whom prevention of prostate cancer may become possible.

Enzyme Inhibitors↗

Trochanteric osteotomy in total hip arthroplasty: comparison of 2 techniques.

A study of 100 cemented total hip arthroplasties was performed in 2 different hospitals. Group 1 hips (50 hips in 42 patients; mean follow-up period, 5.4 years) had been operated on with the modified Liverpool technique involving an anterior osteotomy of the greater trochanter. These were compared with group 2 (50 hips in 41 patients; mean follow-up period, 6.2 years), in whom a Charnley transtrochanteric osteotomy approach was used. The 2 groups showed no significant difference with respect to hip abductor muscle power (MRC grading), trochanteric union, Trendelenberg gait, heterotopic ossification (Brooker grading), and patient satisfaction assessed with the help of a questionnaire. Group 2 had a larger number of trochanteric problems, whereas group 1 had a greater increase in mobility scores after surgery.

Adult↗

POSSUM and Portsmouth POSSUM for predicting mortality. Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity.

BACKGROUND: There is a need for an accurate measure of surgical outcomes so that hospitals and surgeons can be compared properly regardless of case mix. POSSUM (Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity) uses a physiological score and an operative severity score to calculate risks of mortality and morbidity. In a previous small study it was found that Portsmouth POSSUM (P-POSSUM; a modification of the POSSUM system) provided a more accurate prediction of mortality. METHODS: Some 10000 general surgical interventions (excluding paediatric and day cases) were studied prospectively between August 1993 and November 1995. The POSSUM mortality equation was applied to the full 10000 surgical episodes. The 10000 patients were arranged in chronological order and the first 2500 were used as a training set to produce the modified P-POSSUM predictor equation. This was then applied prospectively to the remaining 7500 patients arranged chronologically in five groups of 1500. RESULTS: The original POSSUM logistic regression equation for mortality overpredicts the overall risk of death by more than twofold and the risk of death for patients at lowest risk (5 per cent or less) by more than sevenfold. The P-POSSUM equation produced a very close fit with the observed in-hospital mortality. CONCLUSION: P-POSSUM provides an accurate method for comparative surgical audit.

England↗

Prolonged prostate-specific antigen response in flutamide withdrawal syndrome despite disease progression.

Flutamide withdrawal syndrome is characterized by a decrease in prostate-specific antigen (PSA) after flutamide withdrawal in a subset of patients with progressing metastatic carcinoma of the prostate. It is generally hypothesized to be due to a point mutation in the androgen receptor that allows the antiandrogen to function as an agonist, leading to a dramatic and rapid PSA response. We describe a patient with androgen-independent prostate cancer in whom PSA continued to decrease for a period of 15 months after flutamide withdrawal. With continuing fall in PSA, the patient had unequivocal progression of disease seen on bone scan. This case illustrates the potential decoupling of PSA response from disease status in flutamide withdrawal. It also illustrates the need for continued clinical evaluation of patients with metastatic prostate cancer, even in the face of PSA response.

Aged↗

Central nervous system complications after lung transplantation.

PURPOSE: This study describes the central nervous system (CNS) events after lung transplantation. METHODS: A chart review of all lung transplant recipients (LTR) to collect the clinical and neuroimaging data for CNS events defined as seizures, severe headaches, confusion, or stroke. RESULTS: Twenty-six patients of 100 LTRs from 1990 through 1995 had a CNS event; more than one event occurred in 5 patients for a total of 32 events. Severe headache was most common, occurring in 14 patients, followed by seizures in 10, stroke in 5, and confusion in 3. The CNS event was related to infection in three of the 26 patients. Of all evaluations performed, magnetic resonance imaging (MRI) identified the most abnormalities, the most common being white matter changes consistent with cyclosporine toxicity. Cyclosporine levels were elevated in slightly more than half of the patients. Hypomagnesemia was present in three of 10 patients with seizures. Prognosis for recovery from these complications was good, with only five patients having ongoing problems with headaches, one requiring long term anticonvulsant therapy, three having minor or no limitations from stroke and no long-term problems with confusion. One patient with seizures resulting from an aspergilloma died. CONCLUSION: CNS events occur commonly in LTRs, mostly related to cyclosporine toxicity or infection. MRI identifies more abnormalities than computed tomography. These events were not consistently associated with documented high cyclosporine levels and hypomagnesemia. In spite of significantly abnormal MRIs, the functional outcome is favorable.

Adolescent↗

An assessment of steroid hypersensitivity in asthma.

In dermatological practice, allergy to topical corticosteroids used to treat eczema is a recognized and common event. The typical presentation is of an eczema which fails to improve or deteriorates with treatment. Topical corticosteroids are also used to treat mucosal disease. This study assesses allergy to inhaled corticosteroids in asthmatics. In the patient group selected, there was no evidence of relevant corticosteroid allergy.

Administration, Inhalation↗

Differences between treatment seekers in an obese population: medical intervention vs. dietary restriction.

This study examined two groups of people who were pursuing treatment for obesity: either medical intervention (a hospital group; N = 20) or support for dietary restriction (a community group; N = 18). This study addressed four questions: (1) Were there differences between the two groups in terms of their psychological distress (as measured by the Symptom Checklist)? (2) Does binge eating moderate psychological distress? (3) Do feelings of ineffectiveness moderate psychological distress? and (4) Which variables best accounted for group membership (i.e., type of treatment sought)? Results suggested that the hospital group was significantly more distressed than the community group. However, there were no differences between the two groups with respect to binge eating or feelings of ineffectiveness. These findings suggest that it is the effects of morbid obesity that are most likely to moderate psychological distress.

Adult↗

The effects of smoking on labour after uncomplicated pregnancy: a comparison between the progress and outcome of labour in 400 smokers and 400 matched non-smokers.

A comparison was made between the progress of labour and its outcome after an uncomplicated pregnancy, in 400 smokers and 400 non-smokers. Strict selection criteria were applied to eliminate, as far as possible, the variables which might have influenced labour in both groups and to ensure that the two groups of women were matched. The duration of labour was longer in smokers, who also had a higher incidence of caesarean sections. Smokers had a higher incidence of retained placenta and postpartum haemorrhage. The neonates of smokers had a higher incidence of problems in the immediate post-delivery period.

Journal Article↗