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Biomedical subjects

P C O'Brien

Publications and source records attributed to P C O'Brien.

At least 145 records · Page 8Linked to original sources

Tropicamide eyedrops cannot be used for reliable diagnosis of Alzheimer's disease.

OBJECTIVE: To evaluate the mydriatic effect of tropicamide eyedrops as a diagnostic test for Alzheimer's disease. MATERIAL AND METHODS: In a double-blind, placebo-controlled study, we assessed pupillary responses in 22 normal control subjects, 23 patients with probable Alzheimer's disease, 4 patients with isolated memory difficulty, and 6 patients with non-Alzheimer's dementia. Three separate studies were performed, the second and third on a subset of the original group. With use of infrared binocular pupillography, after 5 minutes of dark adaptation, we averaged pupil size during a 1-minute interval for baseline determinations. We then instilled 0.01% tropicamide into one eye. In the first two studies, we averaged pupil size for a 1-minute period at 5-minute intervals for 30 minutes, followed by a pupil light reflex test. In the third study, we measured pupil size every 5 minutes for 45 minutes and omitted the light reflex test. RESULTS: No significant difference was noted in pupil dilatation between normal subjects and patients with Alzheimer's disease and between patients with non-Alzheimer's dementias and the Alzheimer's disease group in all three studies. Furthermore, on reperformance of the test in the same patients, more than 50% changed from a group above or below 13% pupil dilatation (a cutoff reported to distinguish Alzheimer's disease from normal control subjects) to the opposite group. CONCLUSION: Results of this study indicate that pupil measurement after instillation of tropicamide cannot be used as a reliable diagnostic test for Alzheimer's disease. Moreover, test-retest reliability with use of dilute tropicamide eyedrops is questionable.

Aged↗

Preliminary results of combined chemotherapy and radiotherapy for non-AIDS primary central nervous system lymphoma. Trans-Tasman Radiation Oncology Group (TROG).

OBJECTIVES: To assess the results and toxicity of a regimen of combined chemotherapy and radiotherapy for patients with non-AIDS-related primary central nervous system lymphoma. DESIGN: Prospective assessment of patients treated with intravenous methotrexate followed by cranial irradiation between 1 January 1991 and 31 July 1995. PATIENTS AND SETTING: Patients attending nine Australian and New Zealand centres who were eligible and gave informed consent. MAIN OUTCOME MEASURES: Probability of survival at two years, and acute toxicity. RESULTS: Twenty-four patients were treated. Their probability of survival at two years was 70% (95% confidence interval [CI], 45%-95%). The acute toxicity of the regimen was minimal in most cases, but one patient died of treatment-related neutropenia and subsequent sepsis. Two patients showed progression of pre-existing short term memory disturbance, without evidence of recurrent lymphoma. CONCLUSIONS: Combined-modality therapy improves survival in patients with non-AIDS-related primary central nervous system lymphoma, at least in the short term, relative to radiotherapy alone. The combined regimen resulted in only moderate treatment-related morbidity. Longer follow-up is required for a more accurate estimate of late effects and long-term survival prospects.

Antimetabolites, Antineoplastic↗

Tumour recurrence or treatment sequelae following radiotherapy for larynx cancer.

Differentiating between recurrent carcinoma and significant sequelae of radiotherapy after treatment of laryngeal carcinoma is an uncommon but difficult clinical problem. Head and neck surgeons can be faced with deciding on the necessity for salvage laryngectomy without prior histological confirmation of recurrence. This paper reviews the literature pertaining to this topic to provide a better overall estimate of the risk of recurrence in these cases. Approximately 50% of patients with severe oedema or necrosis following radiotherapy for larynx cancer will have recurrence. Less than 10% of all larynges removed will be histologically negative when persistent or recurrent tumour is suspected clinically or indicated by biopsy following radiotherapy.

Edema↗

A standard test of heat-pain responses using CASE IV.

Heat-pain threshold and stimulus response characteristics can be evaluated with graduated heating pulses from a radiant heat source or a contact thermode. Results may be used to: (1) evaluate differences in sensation among anatomical sites, sides of the body, and with development and aging; and (2) provide an end-point for the study of the efficacy of drugs; or to follow the course of sensory alteration in disease (medical practice, epidemiologic studies, and controlled clinical trials). Because there is great variability in how tests of this kind are performed and scored, comparisons of results among medical centers are difficult. To meet this need, we have developed, and here describe, a standardized and validated test of heat-pain. We use both pyramidal and trapezoid-shaped stimuli. The range of stimulus magnitudes we recommend is sufficient to test heat-pain at a sensitive region (the face) of young people and an insensitive region (the foot) of healthy old people. From tests on healthy subjects and patients, we find that neither our previously published forced-choice or 4, 2, and 1 stepping algorithms are suitable for testing heat-pain sensation. We, therefore, introduce the Non-Repeating Ascending with Null Stimuli (NRA-NS) algorithm which performs satisfactorily. The graphed data points of responses to increasingly stronger heat pulses were made up of two components-the no pain (0) response line and the heat-pain response line (> or = 1 numerical scaling of the pain responses graded from 1 [least] to 10 [greatest]). For the pain responses, we found that usually a curve could be fit using a quadratic equation. Using this equation, or interpolation where necessary, it is possible to compute the heat-pain detection threshold (HPDT or HP:0.5), an intermediate heat-pain response (HP:5.0), and the difference between the two (HP:5.0-0.5). Our studies show that a certain time is needed between successive stimuli and tests to minimize changing basal skin temperature or threshold. We also demonstrated that low or high baseline skin temperatures can affect heat-pain responses, therefore, we advocate specific testing conditions. Based on a study of 25 healthy subjects, the reproducibility of the test falls within +/-1 stimulus steps 88% of the time for HP:5.0 and 76% of the time for HP:0.5. The precise approaches employed to make the test standard and reproducible are described. We illustrate that the algorithm and testing system is able to document altered pain threshold with skin abrasion, with intradermal injection of nerve growth factor, and with diabetic polyneuropathy.

Adult↗

Impact of referral bias on clinical and epidemiological studies of Alzheimer's disease.

We used the resources of the Rochester Epidemiology Project to compare sociodemographic and clinical characteristics in three groups of Alzheimer's disease patients. The first group included incidence cases occurring among residents of Rochester, Minnesota (population-based series; n = 241). The second group was a sample of patients referred to the Mayo Clinic form the remainder of Minnesota and the four surrounding states (n = 58); the third was a sample referred from the remainder of the United States (n = 94). Patients from Rochester were more frequently women, less highly educated, less commonly white collar workers, more frequently institutionalized, less frequently married, and more often lived along than those in the two referral groups. Patients from Rochester also had a more advanced age of onset of dementia. For occupation, education, and living arrangement, the differences across groups increased with increasing distance of referral. Clinical and epidemiological studies based on patients referred form primary to secondary or tertiary care centers may suffer from severe selection bias.

Adult↗

Cause of death in Alzheimer's disease.

Cause of death among 917 of the 959 subjects in a population-based incidence cohort with Alzheimer's disease (AD) during the years 1960 to 1984 was compared to that of an age- and gender-matched control group (n = 703). In general, a summary of the diagnostic codes entered anywhere on a death certificate suggests that control subjects had more cardiovascular disease and neoplasms than did patients, while patients more often had a diagnostic code of bronchitis/pneumonia (P < 0.01). By logistic regression, this difference remained statistically significant after adjusting for age and gender.

Alzheimer Disease↗

Mucosal regeneration during radiotherapy. Trans Tasman Radiation Oncology Group (TROG).

BACKGROUND AND PURPOSE: Regeneration of the aerodigestive mucosa is known to occur during conventionally fractionated radiotherapy. The circumstances surrounding its time of onset and magnitude are not well understood, however. MATERIAL AND METHODS: Mucosal reactions were observed in 100 patients undergoing conventionally fractionated treatment at 2 Gy/day over 7 weeks and 88 receiving accelerated treatment at 1.8 Gy twice daily over 3 1/2 weeks on the Trans Tasman Radiation Oncology Group head and neck cancer trials. Similar observations in 61 patients treated palliatively at dose rates between 0.8 and 240 Gy/h using ten 3.0-4.2 Gy fractions over 2 weeks are compared. RESULTS: Several findings emerged from these studies: 1. Reactions evolved more quickly at oropharyngeal sites than in the hypopharynx. 2. Reactions at both sites evolved more rapidly at greater rates of dose accumulation. 3. The timing of reactions suggested the presence of a strong regenerative mucosal response that started before the manifestation of "patchy' (grade II) mucosal reactions. 4. The regenerative response was strong enough to "make good' damage accumulated at a rate of 2 Gy/day in over a third of cases. 5. The linear quadratic model without time correction failed to provide an adequate prediction of the frequency or intensity of mucosal reactions produced by any of the regimes. A simple model of the regenerative response is presented. CONCLUSIONS: This study suggests that the timing and magnitude of the regenerative response vary between sites and individuals but are linked to the amount of epithelial cellular depletion occurring during treatment.

Head and Neck Neoplasms↗

Population-based study of seizure disorders after cerebral infarction.

We performed the first population-based study that determined the magnitude of the risk and identified the factors predictive of developing seizure disorders after cerebral infarction. Five hundred thirty-five consecutive persons without prior unprovoked seizures were followed from their first cerebral infarctions until death or migration out of Rochester, Minnesota. Thirty-three patients (6%) developed early seizures (within 1 week), 78% of which occurred within the first 24 hours after infarction. Using multivariate analysis, the only factor predictive of early seizure occurrence was anterior hemisphere location of infarct (odds ratio 4.0; 95% CI 1.2 to 13.7). Twenty-seven patients developed an initial late seizure (past 1 week), whereas 18 developed epilepsy (recurrent late seizures). Compared with the population in the community, the risk during the first year was 23 times higher for initial late seizures and 17 times higher for epilepsy. The cumulative probability of developing initial late seizures was 3.0% by 1 year, 4.7% by 2 years, 7.4% by 5 years, and 8.9% by 10 years. Independent predictive factors on multivariate analysis for initial late seizures were early seizure occurrence (hazard ratio of 7.8 [95% CI 2.8 to 21.7]) and stroke recurrence (3.1 [1.2 to 8.3]). Both early seizure occurrence (16.4 [5.5 to 49.2]) and stroke recurrence (3.5 [1.2 to 10.5]) independently predicted the development of epilepsy as well. We also found that early seizure occurrence predisposed those with initial late seizures to develop epilepsy.

Adolescent↗

Epidemiology of dementia in Rochester, Minnesota.

OBJECTIVE: To present the results of several retrospective epidemiologic studies of dementia in Rochester, Minnesota. MATERIAL AND METHODS: These studies were done by using the medical records-linkage resources of the Rochester Epidemiology Project. RESULTS: The incidence and prevalence of dementia increase sharply with advancing age. No difference is noted in overall age-adjusted incidence rates by gender. Rochester studies provide the only 25-year time trend analyses of the incidence of dementia in the United States. Time trends over three prevalence dates indicate an increase in prevalence in this community. Survival is decreased among patients with dementing illness. Case-control studies of Alzheimer's disease (AD) show that general medical conditions, previous head injury, thyroid disease, exposure to therapeutic radiation, anesthesia, and blood transfusion are generally not risk factors for AD. Patients with depression may have an increased risk for the development of AD. Sociodemographic factors such as education, occupation, marital status, and type of dwelling were not significantly different among patients with AD and their age-and gender-matched control subjects. CONCLUSION: The Rochester Epidemiology Project has proved to be an excellent resource for the study of the incidence, prevalence, and risk factors for dementia.

Adult↗

Breast cancer following treatment for Hodgkin's disease: the need for screening in a young population. Australasian Radiation Oncology Lymphoma Group (AROLG)

Several recent publications have highlighted the issue of an increased risk of breast cancer in women treated with radiotherapy, chemotherapy, or combined modality therapy for Hodgkin's disease. The risk is greatest in women 30 years or younger at the time of treatment. In the Australasian Radiation Oncology Lymphoma Group database, 60% of women fell into this age category. This article reviews the available data pertaining to induction of breast cancer by radiotherapy for Hodgkin's disease. Breast examination should now be an integral part of the long term follow up for these women. There is also a case for the use of screening mammography. Any breast mass developing subsequent to treatment for Hodgkin's disease should be regarded with a high index of clinical suspicion and, accordingly, biopsies should be performed in the majority of cases, even when mammography is negative.

Adult↗

The prevalence of dementia is changing over time in Rochester, Minnesota.

Resources of the Rochester Epidemiology Project were used to estimate prevalence rates for dementia on January 1, 1975, 1980, and 1985, and to evaluate trends over time. Prevalence rates increased with age for both men and women. There was no difference in the prevalence rates for January 1, 1975, and January 1, 1980, but there was a significant increase between January 1, 1980, and January 1, 1985. Similar results were found for Alzheimer's disease. Age was an important factor in the trend data. The apparent increase in prevalence over time is probably multifactorial.

Age Factors↗

Optic neuritis: a population-based study in Olmsted County, Minnesota.

We reviewed the records of all patients with optic neuritis (ON) in Olmsted County, Minnesota, identified through the comprehensive records-linkage system at the Mayo Clinic, and identified 156 ON patients from 1935 to 1991 who had onset of the disease while residing in Olmsted County (incidence cases). Poisson regression analysis revealed that age, gender, and calendar year were associated with incidence. The annual age- and sex-adjusted incidence rate was 5.1 per 100,000 person-years from 1985 to 1991. On December 1, 1991, 128 patients with a documented history of ON resided in Olmsted County (prevalence cohort). The age- and sex-adjusted prevalence rate per 100,000 was 115. The average length of follow-up for the incidence cohort was 13.2 years. Life table analysis showed that 39% of the 95 patients with isolated ON in the incidence cohort had progressed to clinically definite multiple sclerosis (MS) by 10 years of follow-up, that 49% had by 20 years, 54% by 30 years, and 60% by 40 years. There was no difference in the risk of developing MS between men and women. The presence of venous sheathing (p = 0.044) and evidence for recurrent ON (p < 0.0001) were associated with an increased likelihood of developing MS. The estimated 25-year survival rate was 88.3% +/- 5.8% for the incidence cohort with isolated ON, compared with 83.9% for the general US population of similar age and sex.

Adolescent↗

Variables influencing neuropathic endpoints: the Rochester Diabetic Neuropathy Study of Healthy Subjects.

We determined the normal limits for various neuropathic tests in healthy subjects. The study, the Rochester Diabetic Neuropathy Study (RDNS), is noteworthy because of its size (more than 400 subjects), random selection of subjects, and selection of at least 15 men and 15 women without neuropathy, neurologic disease, or diseases predisposing to neuropathy from each hemidecade between 18 and 74 years of age from the population of a defined region (Rochester, MN). Subjects were classified into those with (nonhealthy subjects, RDNS-NS) and without (healthy subjects, RDNS-HS) neuropathy, neurologic or psychiatric disease, or diseases known to predispose to neuropathy. The study provides normal limits for tests used in the RDNS but it has broader uses as well. We found that (1) less than 10% of subjects in the third decade, approximately 20% in the fourth decade, and approximately 30% in the fifth or older decades were placed into the RDNS-NS category; (2) healthy subjects (RDNS-HS) retain their ability to walk on toes and heels regardless of age, excessive weight, or lack of physical fitness, but not their ability to arise from a kneeled position--lost in more than 5% of persons 60 years and older; (3) the frequency of decreased or absent ankle reflexes exceeds 5% in healthy subjects older than 50 years--limiting their value as a sign of diabetic polyneuropathy and necessitating a grading change with age in the neuropathy impairment score.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Guamanian neurodegenerative disease: investigation of the calcium metabolism/heavy metal hypothesis.

OBJECTIVE: There is a high prevalence of neurodegenerative disease (parkinsonism, dementia, and motor neuron disease) on the western Pacific island of Guam. We sought evidence in support of the hypothesis that these conditions are triggered by nutritional deficiencies of calcium and magnesium leading to secondary hyperparathyroidism that then facilitates the entry of calcium and toxic heavy metals into the brain. METHODS: We analyzed indices of calcium metabolism plus blood-serum, urine, nail, and hair heavy metal concentrations in 12 patients with Guamanian neurodegenerative disease and 12 Chamorro control subjects. RESULTS: All 12 patients with Guamanian neurodegenerative disease had normal values for serum total and ionized calcium, 25-hydroxyvitamin D, and 24-hour urine collections for calcium. Eleven of 12 patients had normal serum parathyroid hormone values and alkaline phosphatase levels. No patient had reduced serum phosphorus or magnesium values although a minority of patients and controls had low urinary magnesium concentrations. Median blood-serum and 24-hour urine collections for heavy metals (aluminum, arsenic, cadmium, copper, iron, lead, manganese, mercury, and zinc) were statistically similar in the patient and control groups except for a slight elevation of blood, but not urine, lead in the patient group. Concentrations of heavy metals in hair and nails were similar in the two groups. CONCLUSIONS: We could find no evidence in support of abnormalities of calcium metabolism or heavy metal absorption as a major causative factor in the development of neurodegenerative disease on the island of Guam.

Aged↗

Bilaterally symmetric hippocampi and surgical outcome.

This study investigates the relationship between hippocampal volume and seizure control following temporal lobectomy in patients with volumetrically symmetric hippocampi. Forty-six patients who underwent temporal lobectomy for nonlesional temporal-lobe-onset seizures, and in whom the volumes of the two hippocampi were roughly equal (ie, the difference of the right minus the left hippocampal volume fell between -0.1 and 0.3 cm3), were included. We graded postoperative seizure control on a four-point scale according to criteria defined by Engel. We found no relationship between the hippocampal sum (sum of the right plus left hippocampal volumes normalized for cranial size) and operative outcome. A satisfactory operative outcome is possible in patients with bilaterally symmetric mesial temporal sclerosis by MRI criteria.

Adult↗