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Biomedical subjects

L Finn

Publications and source records attributed to L Finn.

At least 37 records · Page 2Linked to original sources

Minor surgery in general practice--setting the standards.

BACKGROUND: A self-assessment tool was trialled to set a baseline for control of infection in general practice and to assess the nature and adequacy of infection control precautions in primary care settings with particular reference to minor surgery. METHODS: A request for volunteers was included in a flier sent out periodically by the Communicable Disease Unit to all general practices in the county (n = 114). Eleven practices (9.6 per cent) volunteered to take part and an audit of infection control precautions was undertaken with the practice nurse and/or manager. RESULTS: Of the 11 general practices audited, nine did not have a written policy for control of infection, did not have a separate, dedicated room for minor surgery, did not use protective clothing appropriately, used terry towels for hand-drying and reprocessed single-use only items. Ten used inappropriate methods to decontaminate heat labile items, seven did not record sterilizer processing cycles and five did not comply with HTM 2010 with regard to sterilizer maintenance. Following the survey, minimum infection control requirements have been developed for future applications to provide extended minor surgery within general practice and these will be monitored at subsequent surgery inspection visits and through audit. CONCLUSIONS: Results suggest that there is little room for complacency with regard to standards of infection control in general practice. In view of the increasing shift towards primary care based minor surgery it would be helpful if minimum standards were to be agreed nationally.

England↗

Epstein-Barr virus infections in children after transplantation of the small intestine.

Epstein-Barr virus (EBV) infection in association with immunosuppressive drugs used for solid organ transplantation can produce a spectrum of illnesses. Forty-one children who ranged in age from 6 months to 18.5 years received small intestinal transplants alone or in combination with other organs while undergoing primary tacrolimus (FK506) immunosuppression between July 1990 and June 1995. We reviewed hematoxylin and eosin-stained sections from all biopsy, surgical, and autopsy material from these children to determine the incidence and morphology of EBV-associated disease. Nuclear staining with in situ hybridization for EBV early RNA transcript (EBER) using the EBER-1 probe confirmed the presence of EBV. The EBV lymphoproliferations were graded as 1 to 4 according to histopathology and EBV quantitation determined in the area of greatest positivity. Twenty-one patients (51%) had EBV documented histologically on one or more occasions; only 8 (38%) are alive; 5 of these had the highest grade of 2. Posttransplant lymphoproliferative disease (PTLD) developed in 13 patients. Three of 10 patients (30%) with grade 3 lesions (polymorphous PTLD) are alive with intermittent evidence of EBV infection; 6 died with PTLD. Monomorphic PTLD (grade 4) was the cause of death in the three additional patients. Thirteen of 20 patients (65%) with no histologic evidence of EBV are alive. The incidence of EBV infection in pediatric small intestinal transplant recipients is higher than reported for any other solid organ cohort. With the aid of frequent EBER staining we were able to diagnose EBV infections in 51% of 41 patients; PTLD (grade 3 or 4) developed in 32% of these children. Low-grade EBV infections often preceded the development of PTLD and were identified in gastrointestinal biopsy samples from patients with concurrent PTLD; however, results of gastrointestinal biopsy samples may be negative for EBV in some patients with PTLD and, thus, underestimate systemic EBV-associated lymphoproliferations. Rejection and EBV infection can occur simultaneously, therefore, attention to low-grade infection may be useful to patient management.

Adolescent↗

Nasal obstruction as a risk factor for sleep-disordered breathing. The University of Wisconsin Sleep and Respiratory Research Group.

Nasal obstruction frequently has been associated with sleep-disordered breathing as a potential etiologic factor. Nasal obstruction results in pathologic changes in airflow velocity and resistance. Experimentally produced nasal obstruction increases resistance and leads to sleep-disordered breathing events, including apnea, hypopnea, and snoring. Clinical research examining the correlation between nasal obstruction and sleep-disordered breathing is limited, especially in regard to patients with conditions that increase nasal resistance, such as rhinitis and sinusitis. To further identify risk factors for sleep-disordered breathing, the role of chronic and acute nasal congestion was investigated in a population-based sample. Data on nasal congestion history and sleep problems were obtained by questionnaire (n = 4927) and by objective inlaboratory measurement (n = 911). Participants who often or almost always experienced nighttime symptoms of rhinitis (5 or more nights a month) were significantly (p < 0.0001) more likely to report habitual snoring (3 to 7 nights a week), chronic excessive daytime sleepiness, or chronic nonrestorative sleep than were those who rarely or never had symptoms. Habitual snorers had significantly (p < 0.02) lower air flow than nonsnorers, although a linear relation between decreased airflow and sleep-disordered breathing severity did not exist. Participants who reported nasal congestion due to allergy were 1.8 times more likely to have moderate to severe sleep-disordered breathing than were those without nasal congestion due to allergy. Men and women with nasal obstruction, especially chronic nighttime symptoms of rhinitis, are significantly more likely to be habitual snorers, and a proportion also may have frequent episodes of apnea and hypopnea, indicative of severe sleep-disordered breathing. Because allergic rhinitis is a common cause of nasal obstruction and it is a modifiable risk factor, further study of this association is warranted.

Adult↗

Phase I-II study of gamma interferon and 5-fluorouracil for patients with metastatic renal cell carcinoma

We have completed a phase I/II trial to evaluate the toxicity and efficacy of the combination of gamma interferon and 5-fluorouracil in metastatic renal cell carcinoma. Gamma interferon was administered at a weekly dose of 100 micrograms. 5-fluorouracil was given as a 5 day continuous infusion days 1-5 of each 21 day cycle. In the phase I portion of the trial, the gamma interferon dose was held constant, while the 5-fluorouracil was escalated from 500 to 800 mg/m2/day. Serum neopterin and beta 2 microglobulin were measured prior to and 48 hours after each dose of gamma interferon for the first six weeks of treatment. Dose limiting toxicity was not encountered in the phase I part of the trial; therefore the phase II study was initiated at the 800 mg/m2/day dose of 5-fluorouracil. No responses were seen among 34 patients treated on the phase II trial. Forty-six percent of patients experienced disease stabilization and the remainder progressed through treatment. In the phase I trial, increments in neopterin and beta 2 microglobulin levels differed significantly between patients treated with lower and higher doses of 5-fluorouracil. We conclude that the addition of 5-fluorouracil to gamma interferon does not appear to enhance the cytokines clinical activity. Incremental increases in macrophage activation markers with escalating 5-fluorouracil doses suggests a role for 5-fluorouracil beyond its usual proposed cytotoxic activity and warrants further investigation into potential immunologic effects of this drug.

Journal Article↗

Sleep-disordered breathing and motor vehicle accidents in a population-based sample of employed adults.

Studies have consistently shown that sleep apnea patients have high accident rates, but the generalizability of the association beyond clinic populations has been questioned. The goal of this investigation was to determine if unrecognized sleep-disordered breathing in the general population, ranging from mild to severe, is associated with motor vehicle accidents. The sample comprised 913 employed adults enrolled in an ongoing study of the natural history of sleep-disordered breathing. Sleep-disordered breathing status was determined by overnight in-laboratory polysomnography and motor vehicle accident (MVA) history was obtained from a statewide data base of all traffic violations and accidents from 1988 to 1993. Men with five or more apneas and hypopneas per hour of sleep [apnea-plus-hypopnea index (AHI) > 5], compared to those without sleep-disordered breathing, were significantly more likely to have at least one accident in 5 years (adjusted odds ratio = 3.4 for habitual snorers, 4.2 for AHI 5-15, and 3.4 for AHI > 15). Men and women combined with AHI > 15 (vs. no sleep-disordered breathing) were significantly more likely to have multiple accidents in 5 years (odds ratio = 7.3). These results, free of clinic selection bias, indicate that unrecognized sleep-disordered breathing in the general population is linked to motor vehicle accident occurrence. If the association is causal, unrecognized sleep-disordered breathing may account for a significant proportion of motor vehicle accidents.

Accidents, Traffic↗

Estimation of the clinically diagnosed proportion of sleep apnea syndrome in middle-aged men and women.

The proportion of sleep apnea syndrome (SAS) in the general adult population that goes undiagnosed was estimated from a sample of 4,925 employed adults. Questionnaire data on doctor-diagnosed sleep apnea were followed up to ascertain the prevalence of diagnosed sleep apnea. In-laboratory polysomnography on a subset of 1,090 participants was used to estimate screen-detected sleep apnea. In this population, without obvious barriers to health care for sleep disorders, we estimate that 93% of women and 82% of men with moderate to severe SAS have not been clinically diagnosed. These findings provide a baseline for assessing health care resource needs for sleep apnea.

Adult↗

Ventilatory response to induced auditory arousals during NREM sleep.

Sleep state instability is a potential mechanism of central apnea/hypopnea during non-rapid eye movement (NREM) sleep. To investigate this postulate, we induced brief arousals by delivering transient (0.5 second) auditory stimuli during stable NREM sleep in eight normal subjects. Arousal was determined according to American Sleep Disorders Association (ASDA) criteria. A total of 96 trials were conducted; 59 resulted in cortical arousal and 37 did not result in arousal. In trials associated with arousal, minute ventilation (VE) increased from 5.1 +/- 1.24 minutes to 7.5 +/- 2.24 minutes on the first posttone breath (p = 0.001). However, no subsequent hypopnea or apnea occurred as VE decreased gradually to 4.8 +/- 1.5 l/minute (p > 0.05) on the fifth posttone breath. Trials without arousal did not result in hyperpnea on the first breath nor subsequent hypopnea. We conclude that 1) auditory stimulation resulted in transient hyperpnea only if associated with cortical arousal; 2) hypopnea or apnea did not occur following arousal-induced hyperpnea in normal subjects; 3) interaction with fluctuating chemical stimuli or upper airway resistance may be required for arousals to cause sleep-disordered breathing.

Acoustic Stimulation↗

Phase II trial of alternating weekly chemohormonal therapy for patients with androgen-independent prostate cancer.

Two distinct regimens of weekly chemotherapy for hormone-refractory prostate cancer were combined in an alternating schedule and tested in a Phase II trial to determine efficacy and toxic effects. Forty-six patients with hormone-refractory prostate cancer and rising prostate-specific antigen (PSA) levels entered the trial. Therapy consisted of doxorubicin (20 mg/m2/week) plus oral ketoconazole (400 mg three times a day) given at weeks 1, 3, and 5 and vinblastine (5 mg/m2/week) plus oral estramustine (140 mg three times a day) given at weeks 2, 4, and 6. No therapy was given at weeks 7 and 8. Replacement doses of hydrocortisone were administered throughout treatment to counteract potential adrenal insufficiency secondary to the ketoconazole. In 67% of patients (31 of 46), the PSA declined by 50% or greater for a minimum duration of 8 weeks (95% confidence interval, 52-80%). Among the 16 patients with measurable soft tissue disease, there were 12 responses (75%; 95% confidence interval, 47-92%). The median duration of response was 8. 4 months (1.8-14.9). The median survival for the entire group was 19 months. The median survival of PSA responders has not been reached, whereas that of nonresponders was 13 months (P = 0.010). Seventy-six percent of symptomatic patients noted improvement. Hematological toxicity was modest and was managed without growth factors. Peripheral edema (49%) and deep venous thrombosis (18%) were the most common nonhematological toxicities. The alternating weekly regimen of chemohormonal therapy is active for hormone-refractory prostate cancer, providing a high rate of symptom control, soft tissue response, and PSA decline.

Anti-Inflammatory Agents↗

The gender bias in sleep apnea diagnosis. Are women missed because they have different symptoms?

BACKGROUND: Population-based studies have shown that sleep apnea is underdiagnosed in women, relative to men. One hypothesis for this gender bias is that women with sleep apnea are missed because clinical guidelines for the evaluation and diagnosis of sleep apnea, established primarily on men, are not valid for women. In this investigation, data from the Wisconsin Sleep Cohort Study, a community-based study of the natural history of sleep apnea, were used to determine whether women with sleep apnea have unique symptoms or complaints. METHODS: The sample comprised 551 men and 388 women, none of whom had ever been given a diagnosis of sleep apnea. Data on typical sleep apnea symptoms and other factors were obtained by interview and survey. Sleep apnea status was determined from the frequency of apneic and hypopneic events during sleep as recorded by in-laboratory, whole-night polysomnography. The sensitivity and relative predictive power of each symptom or factor for sleep apnea at different severity levels were calculated and compared by gender. RESULTS: Regardless of severity level, women with sleep apnea did not report symptoms that differed significantly from those of men with the same level of sleep apnea. For men and women, snoring was the most sensitive and strongest predictor of sleep apnea. CONCLUSIONS: Current clinical indications for sleep apnea evaluation are as appropriate for women as they are for men. Other reasons for the gender disparity in sleep apnea diagnosis, including the possibility that health care providers disregard typical symptoms in women, should be pursued.

Diagnosis, Differential↗

An office system for organizing preventive services: a report by the American Cancer Society Advisory Group on Preventive Health Care Reminder Systems.

Despite increasing recognition of the importance of preventive services, such services are not provided in primary care practice as often as recommended. One of the most important reasons is the lack of a systematic, organized approach within practices. The American Cancer Society Ad Hoc Advisory Group on Preventive Health Care Reminder Systems reviewed evidence-based reports and expert opinion to summarize current knowledge about office systems for clinical preventive services. This article describes the process of developing an office system for preventive care, beginning with writing a practice policy, auditing charts for baseline performance, developing and implementing a plan for efficient delivery of preventive care, involving office staff, and monitoring progress. Strategies for dissemination of this approach to a wide range of primary care practices may involve professional medical organizations and managed care companies.

Ambulatory Care Information Systems↗

Optimal delivery of perioperative chemotherapy: preliminary results of a randomized, prospective, comparative trial of preoperative and postoperative chemotherapy for invasive bladder carcinoma.

PURPOSE: We performed a planned interim analysis of a randomized trial comparing initial to postoperative chemotherapy for bladder cancer. The purpose of our analysis was to detect early evidence of survival differences, tolerance to therapy influenced by the sequence of treatment, predictive value of clinical state and influence of methotrexate, vinblastine, doxorubucin and cisplatin (M-VAC) on bladder resectability. MATERIALS AND METHODS: A total of 100 consecutive patients were randomized to receive 2 M-VAC courses before and 3 courses after surgery (group 1) or 5 adjuvant M-VAC courses following cystectomy (group 2). Survival, clinical response, clinical and pathological stage, and toxicity were evaluated in this second timed interim analysis. RESULTS: Of all patients 70% received at least 4 M-VAC courses. Overall survival at 31.7 months (range 1.8 to 87.7) was similar in groups 1 (60%) and 2 (63%), and independent of clinical stage. Preoperative clinical staging accurately identified patients at high risk for recurrence, while 37 of the 48 group 2 patients (77%) were considered at high risk by pathological staging (P3b, P4a, node-positive and unresectable disease). Comparison of pathological stage revealed that 14 of the 51 group 1 patients (28%) achieved stage P0 while only 1 of the 48 group 2 patients (2%) had P0 disease at surgery (p= 0.00043). Disease was unresectable in 3 group 1 (6%) and 8 group 2 patients (17%, p= 0.09). Tolerance to treatment was not significantly different in the 2 study arms. CONCLUSIONS: No survival advantage was noted between neoadjuvant and adjuvant M-VAC in our interim analysis. However, results suggest that M-VAC chemotherapy may be effective in increasing the resectability of localized bladder cancer and may contribute to organ preservation. Clinical stage was a reliable predictor of pathological findings at surgery. Future studies can use clinical staging to determine therapy before surgery for the select stages that we treated. Identification of the subset likely to achieve complete pathological remission will permit the selection of patients for organ preservation strategies.

Adult↗

Snoring as part of a dose-response relationship between sleep-disordered breathing and blood pressure.

This report addresses the hypothesis that snoring without significant apneas and hypopneas (simple snoring) is associated with elevated blood pressure and cardiovascular disease (CVD). Data on blood pressure, previously diagnosed cardiovascular disease, and sleep-disordered breathing (SDB) status from a population-based sample of 580 adults was analyzed. Systolic and diastolic blood pressures, adjusted for age, sex, and body mass index, increased stepwise across categories of no SDB, simple snoring, mild, moderate, and more severe SDB (p < 0.05). A similar and significant trend was seen for CVD prevalence. The results provide evidence that simple snoring represents the beginning of the SDB severity spectrum and that simple snoring has a proportionately smaller but, nevertheless, significant, risk for elevated blood pressure and CVD.

Adult↗

A phase I trial of intermittent high-dose alpha-interferon and dexamethasone in metastatic renal cell carcinoma.

BACKGROUND: Evidence exists that the toxic of alpha-interferon can be ameliorated by co-administration of dexamethasone without compromise of therapeutic efficacy. We therefore conducted a phase I trial to determine the maximum tolerated dose of intermittent interferon when combined with oral dexamethasone. PATIENTS AND METHODS: Thirty patients with metastatic renal cell carcinoma were enrolled. The starting dose of interferon was 20 million IU/m2/day given as a subcutaneous injection days 1 to 4 of each 14 day cycle. Dose levels were escalated at increments of 5 million IU/m2. Dexamethasone 4 mg was administered orally every 6 hours during administration of high-dose interferon. Low-dose maintenance interferon, 3 million IU/m2/day, was administered without dose escalation on days 5 to 14 of each cycle. RESULTS: The maximum tolerated dose of intermittent high-dose interferon was 40 million IU/m2/day. The dose limiting toxicity was fatigue. EEG abnormalities developed in five patients and neuropsychiatric parameters deteriorated significantly in seventeen. CONCLUSIONS: We conclude that co-administration of dexamethasone improves the tolerance of intermittent high-dose interferon. The results of this trial may be useful in designing high-dose interferon regimens for renal cell carcinoma and other interferon-sensitive diseases.

Administration, Oral↗

Adaptation and verification of the relocatable Gill-Thomas-Cosman frame in stereotactic radiotherapy.

PURPOSE: Stereotactic radiotherapy (SRT) combines techniques of stereotactic radiosurgery (SRS) with radiation therapy fractionation schemes. Fractionation in SRT necessitates a relocatable immobilization system to precisely reproduce the patient's position at each treatment. The Gill-Thomas-Cosman (GTC) head frame is such an immobilization device compatible with the Brown-Roberts-Wells (BRW) stereotactic system. We describe this device, our modifications to the original design, the repeat position accuracy, and the daily verification procedure. METHODS AND MATERIALS: The original GTC frame was tested on volunteers. This testing led to an improved strapping system, the decision to construct the oral fixation appliance at our dental clinic, and the construction of a depth confirmation helmet to rapidly confirm the position of the frame on a daily basis. The GTC frame, at our institution, is not acceptable for children requiring anesthesia, and a new frame, the "Boston Childrens' Hospital" frame, was designed. This device uses the base ring of the GTC frame. Airway access is maintained through fixation on the nasal-glabellar region and the ear canal rather than the hard palate and upper gingiva. RESULTS: The modifications of the GTC frame and the verification protocol result in repeat positioning of the frame with respect to the patient anatomy, with a standard deviation of 0.4 mm for both the modified GTC frame and the Boston Childrens' Hospital frame. The relocatibility of the frames has been established in over 2,000 patient setups in over 60 patients to date. DISCUSSION: The GTC frame is a noninvasive and versatile fixation system that provides patient comfort, as well as accurate relocatibility for SRT. The frame is not appropriate for single fraction radiosurgery, as a large setup error (> 2 mm) for a single treatment cannot be excluded. The GTC frame is compatible with the BRW system, and treatment planning for SRT and SRS patients is identical. We currently treat 10-13 SRT patients per day with intracranial neoplasms on a dedicated stereotactic therapy unit. In addition, the Boston Childrens' Hospital frame allows the use of stereotactic therapy in the treatment of children under 6 years of age. This population will benefit especially from precise and highly focal cranial irradiation.

Brain Neoplasms↗