Ruptured retrocecal appendicitis in an adolescent presenting as portal-mesenteric thrombosis and pylephlebitis.
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Adolescent↗
Biomedical subjects
L Finn
Publications and source records attributed to L Finn.
Epidemiological insights into the public health burden of sleep disordered breathing: sex differences in survival among sleep clinic patients.
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Adult↗
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↗
Training and professional development in diabetes care.
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Delivery of Health Care↗
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↗
Alternative splicing of CD44 pre-mRNA in human colorectal tumors.
Expression of the CD44 molecule has been linked to tumor growth and metastases in both human and rodent cancers. Alternatively spliced variants expressed in rat and mouse tumors have been shown to confer metastatic potential to non-metastatic carcinoma cell lines, and human homologues of rat variant mRNA sequences are expressed in human tumors. In the present study matched sets of RNA from adenocarcinomas of the colon and distant normal mucosa were assayed for CD44 expression by quantitative RT-PCR. Retrospective analysis revealed that colonic tumor cells had both quantitative and qualitative differences in CD44 expression when compared to normal mucosa. These were: 1) an increase in levels of CD44 transcripts, 2) an increase in levels of alternatively spliced transcripts, 3) the presence of larger alternatively spliced transcripts with inserts > 400 bases and 4) the primary alternatively spliced CD44 isoform in colonic adenocarcinomas in all cases is CD44R. Interestingly, two patterns of CD44 isoform expression termed "variant dominant" or "balanced" patterns of expression, based on the ratio of variant to standard CD44 transcripts (R+V's/H), could be differentiated. An unfavorable prognosis was suggested for tumors expressing increased levels of CD44 variant exons previously associated with tumor metastasis. Specifically, patients with tumors expressing the "variant dominant" pattern of expression irregardless of Dukes classification and Dukes C and D staged tumors of both patterns exhibited a poorer prognosis.
Adenocarcinoma↗
Pattern of failure and survival of patients with metastatic urothelial tumors relapsing after cis-platinum-based chemotherapy.
Cis-platinum-based chemotherapy combinations have improved the outcome of patients with metastatic urothelial tumors, since two-thirds of these patients respond to treatment. Nevertheless, the majority of such patients have relapse within a median of 12 months. To define the pattern of failure and subsequent outcome, we retrospectively assessed 58 consecutive patients with relapse after prior response to cis-platinum-based combination chemotherapy. Of the patients who presented initially with local-regional metastases, 74% had relapse with involvement of a similar site, while only 26% of these patients had visceral metastases at relapse. The median survival after relapse was 9 months, and parameters associated with longer survival were local-regional relapse (10.7 months) and response to salvage chemotherapy (12.6 months). These data suggest that select patients with urothelial tumors and local-regional metastases may benefit from consolidation therapy with surgery or radiotherapy after maximum response to chemotherapy.
Adult↗