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Biomedical subjects

M Larson

Publications and source records attributed to M Larson.

At least 37 records · Page 2Linked to original sources
PubMed1997

Effect of amifostine on toxicities associated with sequential chemotherapy and radiation therapy for unresectable non-small-cell lung cancer: results of a phase II trial.

PURPOSE: To determine the effect of amifostine on the safety and efficacy of induction chemotherapy with high-dose cisplatin and vinblastine followed by large-field thoracic irradiation to 60 Gy in patients with stage IIIA or IIIB non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Twenty-six patients with unresectable stage IIIA or IIIB NSCLC were entered onto the study between May 1991 and November 1994. Patients received amifostine (740 or 910 mg/m2) followed by cisplatin (120 mg/m2) on days 1 and 29. Vinblastine (5 mg/m2) was given weekly for 5 weeks with no amifostine pretreatment. Following chemotherapy, patients received amifostine (340 mg/m2 4 days a week for 5 weeks, or 200 mg/m2 5 days a week for 6 weeks) 15 minutes before definitive thoracic radiation therapy to a total dose of 60 Gy in 6 weeks. RESULTS: Twenty-five patients were assessable for response and survival. The objective response rate was 60%. One-, 2-, and 3-year survival rates were 55%, 23%, and 23%. There was no grade 3 or greater renal toxicity during chemotherapy or grade 3 or greater esophagitis during radiation therapy. Neutropenia (secondary to vinblastine use) was the only grade 4 toxicity. There were no treatment-related deaths. CONCLUSION: Amifostine can be administered safely with high-dose cisplatin, vinblastine, and radiation therapy for NSCLC. The response rate and survival data provide no evidence that amifostine impairs response to treatment. Amifostine appears to reduce cisplatin-related nephrotoxicity and radiation-induced esophagitis.

Adult↗
PubMed1996

Factors associated with survival to 75 years of age in middle-aged men and women. The Framingham Study.

BACKGROUND: Whereas a variety of epidemiological studies have examined factors associated with overall and cause-specific morbidity and mortality, limited data exist about factors associated with longevity, particularly in middle-aged men and women. The present study examined factors associated with survival to 75 years of age in middle-aged men and women from the community-based Framingham Study. METHODS: After excluding persons with cancer, cardio-vascular disease, or diabetes, 747 men and 973 women from the Framingham Study, who were 50 years of age at the time of a routine clinical examination and who could potentially reach 75 years of age during follow-up, were studied. Logistic regression modeling was used to examine factors associated with survival to 75 years of age. RESULTS: Fewer cigarettes smoked per day, lower systolic blood pressure, and higher forced vital capacity were associated with longevity in both sexes. Lower heart rate in men and parental survival to 75 years of age in women were additionally associated with survival to 75 years of age. CONCLUSIONS: The results of this long-term prospective study suggest a number of lifestyle characteristics and one familial factor associated with increased life expectancy. These data lend further support to the positive impact on life expectancy of health promotional efforts directed at smoking cessation and control of hypertension in middle-aged men and women.

Age Factors↗
PubMed1996

Epidemiologic assessment of angina before and after myocardial infarction: The Framingham study.

Angina pectoris before and after MI was evaluated in a sample of 729 men and women from a general population in whom MI developed during a 36-year period of follow-up. Relations of AP to subsequent CHD events and mortality after initial MI were analyzed by proportional hazards regression models and were adjusted for covariates (age, sex, blood pressure, serum cholesterol, body mass index, glucose intolerance, cigarette smoking, and antihypertensive medications) obtained from routine biennial examinations preceding the initial MI. Comparisons of the influence of angina were made between pre-MI angina, post-MI angina, and absence of AP. The sample had 484 men and 245 women (mean ages, 63 and 69, respectively) who survived greater than / equal to 30 days after MI. The initial MI was clinically unrecognized in 165 (34%) men and 115 (47%) women. Data on covariates were complete for 622 subjects, among whom 30% had pre-Ml angina, 18% had post-MI angina, and 52% did not have AP. Angina was half as common in persons with unrecognized MIs as in those with clinically recognized MIs. During an average of 8.7 years of follow-up, 57% of subjects developed subsequent CHD events, including recognized and unrecognized MI, coronary insufficiency, and CHD death, and 74% died. Both pre-MI angina (hazard ratio, 1.49; 95% CI, 1.17 to 1.91) and post-MI angina (hazard ratio, 1.43; 95% CI, 1.06 to 1.94) adjusted for accompanying risk factors were associated with increased risk for subsequent CHD events compared with those without AP. Neither pre-MI nor post-MI angina was associated with excess overall mortality.

Age Factors↗
PubMed1996

Amifostine, cisplatin, and vinblastine in metastatic non-small-cell lung cancer: a report of high response rates and prolonged survival.

PURPOSE: Based on preclinical and clinical studies that suggested amifostine may potentiate the effects of cytotoxic drugs, we conducted a phase II trial of amifostine, cisplatin, and vinblastine (ACV) in patients with metastatic non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Twenty-five patients with metastatic NSCLC received amifostine (740 or 910 mg/m2) before 120 mg/m2 of cisplatin on day 1, plus weekly 5 mg/m2 of vinblastine without amifostine. Cycles were repeated every 4 weeks. Patients were required to have good performance status, no prior chemotherapy or biologic therapy, adequate organ function, and measurable disease. RESULTS: Sixteen of 25 assessable patients had an objective response documented by computed tomographic (CT) scan (64%; 95% confidence interval, 45% to 85%). With a median duration of follow-up of 19.2 months, the estimated median survival is 17 months and 1-year survival is 64% (+/- 10%). Toxicities included grades 3 and 4 neutropenia (8% and 92%, respectively) and nausea and vomiting (32% and 4%, respectively). Reversible grade 3 nephrotoxicity occurred in 12% of patients, although only one of 13 patients (7%) who received > or = four cycles of therapy had > or = 40% reduction in creatinine clearance. Grade 3 neuropathy was observed in seven patients at cumulative cisplatin doses that ranged from 324 to 660 mg/m2; grade 3 ototoxicity occurred in three patients at cumulative cisplatin doses that ranged from 390 to 450 mg/m2. Four patients (16%) required early stopping of an amifostine infusion due to hypotension. CONCLUSION: ACV appears to be a highly active regimen in metastatic NSCLC. Acute toxicities were generally reversible and the data suggest that amifostine may protect against long-term renal insufficiency from cumulative doses of cisplatin. Although the sample size of this trial is small, the results are significantly encouraging to warrant confirmation in randomized multiinstitutional trials.

Adult↗
PubMed1996

Eastern cooperative group trial of interferon gamma in metastatic melanoma: an innovative study design.

IFN-gamma is a potent immunomodulator, which has activity against melanoma in vitro and in murine models. However, preclinical data suggests that the optimal therapeutic and immunomodulatory dose may not be the maximally tolerated clinical dose. We conducted a Phase II/III trial in good prognosis patients with metastatic melanoma to determine whether a therapeutic and immunomodulatory dose-response curve of IFN-gamma could be identified, and whether the two could be correlated. Ninety-eight patients with metastatic melanoma were randomized to one of seven dose levels of IFN-gamma ranging from 0.01 to 0.90 mg/m2. All patients were required to have s.c., skin, soft tissue, or nodal disease, although visceral disease was also allowed, and no more than one prior chemotherapy regimen. Patients received IFN-gamma as a 1-h i.v. infusion three times per week for at least 8 weeks or until progressive disease. Ninety-five patients were eligible for toxicity evaluation; 81 were eligible for tumor response. Four patients responded to therapy (response rate, 5%) at three dose levels: two patients at 0.01 mg/m2 and one each at 0.5 and 0.9 mg/m2. The duration of response ranged from 5 to 58 weeks. Toxicities were typical of IFNs and included flu-like constitutional symptoms. No dose-response relationship was identified for efficacy. A dose-response relationship for toxicity was observed only for fever and chills (p = 0.035) and hepatic toxicity (p = 0.034). IFN-gamma has minimal activity in metastatic melanoma, and a therapeutic dose-response curve could not be identified. Although potent dose-dependent effects on immunomodulation were identified (J. M. Kirkwood, J. Bryant, J. H. Schiller, M. M. Oken, E. C. Borden, and T. L. Whiteside. Immunomodulatory function of interferon gamma in patients with metastatic melanoma: results of a phase IIB trial in subjects with metastatic melanoma: ECOG Study E4987, submitted for publication), this biological activity does not translate into therapeutic activity in the metastatic disease setting in this trial.

Adult↗
PubMed1995

Prognosis of left ventricular geometric patterns in the Framingham Heart Study.

OBJECTIVES: The goal of this study was to determine the incremental prognostic value of left ventricular geometric patterns beyond that provided by cardiovascular disease risk factors, including left ventricular mass. BACKGROUND: Left ventricular geometry may be classified into the following four mutually exclusive groups on the basis of left ventricular mass and relative wall thickness: concentric hypertrophy (increased mass and increased relative wall thickness), eccentric hypertrophy (increased mass and normal relative wall thickness), concentric remodeling (normal mass and increased relative wall thickness) and normal geometry (normal mass and normal relative wall thickness). The prognosis associated with these patterns in a population-based sample is not known. METHODS: Proportional hazards regression models were used to evaluate the prognostic importance of left ventricular geometry in 3,216 subjects in the Framingham Heart Study who were > or = 40 years old and free of clinically apparent cardiovascular disease, after adjustment for traditional cardiovascular risk factors and left ventricular mass. The follow-up period was 8 years. RESULTS: Subjects with concentric hypertrophy had the worst prognosis, followed by those with eccentric hypertrophy, concentric remodeling and normal geometry. Subjects with concentric hypertrophy also had the highest left ventricular mass. The association between type of geometry and prognosis was largely attenuated by adjustment for baseline differences in left ventricular mass. The odds ratio for incident cardiovascular disease in subjects with concentric hypertrophy compared with those who had normal geometry was 1.3 (95% confidence interval [CI] 0.8 to 2.1) in men and 1.2 (95% CI 0.6 to 2.3) in women after adjustment for other cardiovascular risk factors, including left ventricular mass. CONCLUSIONS: In a population-based sample of subjects without cardiovascular disease, knowledge of left ventricular geometry provided little prognostic information beyond that available from left ventricular mass and traditional cardiovascular risk factors.

Adult↗
PubMed1994

Short stature and risk for mortality and cardiovascular disease events. The Framingham Heart Study.

BACKGROUND: Several studies have observed an inverse association between height and risk for coronary disease, but it is unclear whether other traditional coronary disease risk factors may have confounded this association. We examined the original Framingham Heart Study cohort to determine whether short stature is associated with all-cause mortality, cardiovascular disease mortality, and myocardial infarction after adjusting for age and other traditional coronary heart disease risk factors. METHODS AND RESULTS: A total of 2019 men and 2585 women were followed up to 35.6 years. Subjects were stratified by sex and divided into quartiles according to height. Risk ratios were calculated from proportional hazards analyses comparing the first, second, and third quartiles of height to the tallest quartile before and after adjusting for age, hypertension, smoking, serum cholesterol, diabetes, relative weight, and alcohol intake. In both sexes, there were significant differences in the unadjusted event rates between the shortest and the tallest quartile for all-cause mortality, cardiovascular mortality, and myocardial infarction. Once the analyses were age adjusted, differences among height quartiles persisted only for risk of myocardial infarction in women. Further adjustment for other clinical variables had little additional impact on the results. CONCLUSIONS: After considering age and other coronary disease risk factors, short stature was not associated with increased risk for all-cause or cardiovascular mortality in either sex. It was associated with increased risk for myocardial infarction in women but not in men.

Adult↗
PubMed1994

Plasma homocysteine and thiol compound fractions after oral administration of N-acetylcysteine.

The total concentration of the atherogenic aminothiol acid homocysteine in plasma of healthy volunteers was decreased after oral administration of N-acetylcysteine (NAC), whereas the reduced and free (non-protein bound) fractions of homocysteine were increased. The decrease of the total fraction varied between 20 and 50% and was dose-related. Cysteinylglycine was also decreased after the administration of NAC, whereas cysteine did not change. Administration of high amounts of NAC probably displaces homocysteine and cysteinylglycine from their protein binding sites by disulfide interchange reactions. This leads to the formation of mixed low molecular-weight cysteine and NAC disulfides with high renal clearance and possibly also increased metabolic bio-availability, thereby eliminating homocysteine and cysteinylglycine from plasma. Since only a small amount of additional urinary homocysteine was recovered it is likely that this aminothiol acid is taken up by the tubular cells and further metabolized.

Acetylcysteine↗
PubMed1994

Seasonal variation in the function of blood monocytes obtained from healthy nonsmokers, asymptomatic smokers, and smokers with chronic bronchitis.

The present study focused on two questions: What effects do cigarette smoking and chronic bronchitis have on the function of the precursors of alveolar macrophages, the blood monocytes? Can seasonal variations affect the function of these cells? Phagocytic activity (the proportion of yeast-ingesting cells and the mean number of yeast particles per ingesting cell) and metabolism of arachidonic acid [secretion of prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) in zymosan-stimulated cultures] were studied as markers of monocyte function during three seasons: spring (May-June), autumn (November-December), and winter (February). Smokers with chronic bronchitis (SCBs) and asymptomatic smokers (ASs) had a lower proportion (p < 0.05) of ingesting monocytes than healthy nonsmokers (HNSs) during spring, but not during the other two seasons. The secretion of PGE2 was highest during autumn and lowest during spring in the monocytes of all three groups. In autumn, LTB4 secretion was increased in the monocytes of HNSs (p < 0.05) but not in those of ASs and SCBs. LTB4 secretion was similar in all groups during the other two seasons. Cigarette smoking and chronic bronchitis seem to impair the function of monocytes and may thereby affect the systemic host defense activity. Cells collected during autumn were generally more active than those sampled in spring, indicating marked seasonal variation in the function of monocytes from all three groups.

Arachidonic Acid↗
PubMed1993

Sex differences in cardiac adaptation to isolated systolic hypertension.

This study examines the association of isolated systolic hypertension with left ventricular (LV) mass and geometry in men and women. The subjects of this study were surviving members of the Framingham Heart Study and the Framingham Offspring Study who attended the index examination (between 1979 and 1983) and were aged > or = 50 years, free of clinically apparent cardiovascular disease, not taking antihypertensive medication and without diastolic hypertension (diastolic blood pressure < 90 mm Hg), and in whom LV mass could be determined by echocardiography. Examinations routinely included 12-lead resting electrocardiography, measurements of resting blood pressure, anthropometry, blood glucose levels, and M-mode echocardiography. M-mode echocardiograms adequate to assess LV hypertrophy were obtained for 1,282 normotensive subjects (538 men and 744 women) and 79 subjects with isolated systolic hypertension (26 men and 53 women). Adjusting for age, body mass index and diastolic blood pressure, the relative odds of LV hypertrophy associated with isolated systolic hypertension were 2.58 (95% confidence interval 0.97 to 6.86) in men and 5.94 (95% confidence interval 3.06 to 11.53) in women. Women with isolated systolic hypertension had increased LV wall thickness and mass without LV chamber enlargement, but men had LV dilation and increased LV mass without increased wall thickness. In conclusion, although isolated systolic hypertension was associated with increased LV mass in men and women, the geometric pattern of increased LV mass differed by sex; although women demonstrated a pattern of concentric hypertrophy, an eccentric pattern was observed in men.

Adaptation, Physiological↗
PubMed1993

A study of the safety and survival of the adoptive transfer of genetically marked syngeneic lymphocytes in HIV-infected identical twins.

This phase I/II pilot project will evaluate the survival, tolerance, safety, and efficacy of infusions of activated, gene marked, syngeneic T lymphocytes obtained from HIV seronegative identical twins on the functional immune status of HIV infected twin recipients. T cells from each seronegative twin will be obtained by periodic apheresis, separated into CD4 and CD8 enriched populations by monoclonal antibody affinity binding techniques, induced to polyclonal proliferation with anti-CD3 and rIL-2 stimulation, transduced with distinctive neoR retroviral vectors, and expanded 10-1,000 fold in numbers during approximately 2 weeks of culture. These marked T cell fractions will then be infused into the seropositive twins and the survival of the uniquely marked T cell populations will be monitored by vector-specific PCR, while the recipients' functional immune status is monitored by standard in vitro and in vivo testing protocols. A total of 3 cycles of treatment will be given at intervals of 6 weeks between infusions.

Adolescent↗
PubMed1993

Long-term epidemiologic prediction of coronary disease. The Framingham experience.

Atherosclerotic cardiovascular disease is a complex problem involving lipid deposition, pressure, rheologic forces, carbohydrate tolerance and thrombogenesis. The major contributors identified through epidemiologic research include atherogenic personal attributes, living habits which promote them, signs of a compromised coronary circulation and host susceptibility to these risk factors. Of the atherogenic risk attributes, such as blood lipids, blood pressure, glucose tolerance and fibrinogen, each independently contributes to risk, and the risk associated with any one is compounded by the presence of the others. The risk associated with hypertension, hyperlipidemia or diabetes varies widely depending on the level of associated risk factors. Also, at a given level of total cholesterol, risk is greatly affected by the total/HDL cholesterol ratio, which provides a practical means for assessing the two-way traffic of cholesterol. In addition, living habits, such as cigarette smoking or lack of exercise, can independently affect the risk associated with any of the atherogenic traits. These living habits, obesity and diet can also affect the level of atherogenic risk factors and must be taken into account in assessing risk and implementing preventive measures. Finally, preclinical indicators of silent myocardial ischemia greatly augment the risk associated with a poor cardiovascular risk profile. Hence, ECG left ventricular hypertrophy, blocked intraventricular conduction, repolarization abnormalities and abnormal response to exercise on monitoring must be taken into consideration. Optimal risk predictions require a quantitative synthesis of risk factors into a composite estimate. Handbooks, hand calculators and PC software have been devised for office use based on multiple logistic risk formulations. These have been shown to accurately predict disease risk in a variety of American population samples, in elderly as well as young coronary candidates. Preventive management as well as risk estimation should be multifactorial if optimal results are to be achieved. Preventive strategies should include public health measures to alter the ecology so as to shift the distribution of risk factors to a more favorable level, health education to enable people to protect their own health and preventive medicine for high-risk candidates. Greater skill must be developed to carry out such interventions. In selecting drugs to correct hypertension, diabetes and lipid disorders, it is important to choose agents which do not adversely affect the composite risk profile.

Causality↗
PubMed1993

Airway inflammation in smokers with nonobstructive and obstructive chronic bronchitis.

To assess the manifestation and location of airway inflammation in smokers with chronic bronchitis (CB) or chronic obstructive pulmonary disease (COPD), we lavaged the airways of 12 smokers with CB and 11 smokers with COPD and coexisting CB (OCB). For comparison, the airways of 5 asymptomatic smokers (AS) and 10 healthy nonsmokers (HNS) were lavaged. In all cases, the first lavage aliquot, labeled "bronchial lavage" (BL), was processed separately from the four subsequent aliquots, which were combined and labeled "bronchoalveolar lavage" (BAL). The composition of BL and BAL fluids indicate an ongoing inflammatory process in the airways of all three groups of smokers. CB patients with obstruction had significantly lower concentrations of inflammatory cells in the BL and BAL fluids compared with subjects with nonobstructed CB. Furthermore, airway obstruction, indicated by a reduced FEV1, was significantly correlated with the concentrations of glutathione (p < 0.001), myeloperoxidase (MPO; p < 0.01), and eosinophil cationic protein (ECP; p < 0.01) in BAL fluids. Taken together, these findings suggest that the manifestations of inflammation present in the airways of smokers with CB are different in those who have developed obstruction compared with those who have not.

Adult↗
PubMed1993

Morphologic effect of preoperative maxillofacial orthopedics (T-traction) on the maxilla in unilateral cleft lip and palate patients.

Sixty-eight children born with complete unilateral cleft lip and palate were studied using dental casts taken at ages 0-0.1; 0.2-0.4; and 0.5-0.6 years of age. They were all treated with preoperative maxillofacial orthopedics using an external device (T-traction). The treatment was started after the first model was taken. Dental casts were analyzed regarding the morphology of the cleft region and the maxillary segments before and after treatment. The measurements were compared with measurements on dental casts of nontreated cleft children of similar age. The results suggest that a more normal anatomy of the cleft region occurs during the first 6 months of life whether preoperative maxillofacial orthopedics (T-traction) is used or not. However, this normalized growth seems to occur faster with the T-traction.

Cleft Lip↗
PubMed1992

First time experiences in infancy: when they appear to be pleasant, do they activate the adrenocortical stress response?

The effect of a positive first-time experience on adrenocortical activity was examined in 48 6- to 13-month-old infants who took part in two sessions of a YMCA-like mother-infant swim class. Experience was manipulated by comparing Novice swimmers with infants who previously had taken a swim class, and by examining responses to first versus second class session. In addition, the effects of temperamental fear of novelty were examined by maternal report prior to the first session. Preswim and Postswim cortisol levels were compared to measures obtained at the same time of day in two comparison groups, one tested at home and one tested in a playroom at the University. The results yielded no evidence of an adrenocortical stress response (elevated cortisol) to the swim sessions for either the Novice or Experienced swimmers. Infant temperamental fearfulness predicted behavioral but not adrenocortical responses during swimming. Postswim cortisol levels were significantly lower than posttest levels in the two baseline comparison groups, and lower postswim cortisol levels were associated with less negative and more positive emotional behavior and engagement of the swimming experience. These results are consistent with the hypothesis that emotions serve as a major pathway influencing adrenocortical activity, and provide no support for the uncertainty hypothesis of adrenocortical activation.

Adaptation, Psychological↗
PubMed1991

Solvent exposure and the risk of slips, trips, and falls among painters.

This study evaluated risk factors for injurious and noninjurious slips, trips, and falls among painters and investigated the hypothesis that exposure to solvents influenced the risk of such accidents. The data were collected longitudinally over an 11 month period. Weekly self-administered questionnaires detailed paint solvent exposure; work-related slips, trips, and falls (STFs); and potentially hazardous job tasks and environmental conditions. An initial questionnaire ascertained personal data, such as age, solvent exposure history, and alcohol consumption. During the study, 2,088 person-weeks of data were collected. Some participants provided many weeks of data, while others responded sporadically. Exposure to potentially hazardous environmental conditions was significantly related to the occurrence of STFs during a week. Several measures of solvent exposure were evaluated for their effect on STFs. Low solvent exposure during a week significantly increased the occurrence of slips, trips, and falls compared to no exposure. Moderate and high weekly exposure were not associated with increased risk, however. Week-to-week variability in the amount of solvent exposure was a strong positive predictor of STFs. Further analysis showed that both increases and decreases in solvent exposure between the preceding 2 weeks and the week of the STF were positively related to the risk of such events. The strongest effect was observed for exposure increases over the preceding 2 weeks. Overall, the results suggest that solvent exposure variability may increase accident risk, and possible explanations are explored.

Accidental Falls↗
PubMed1991

Cortisol and behavioral responses to repeated stressors in the human newborn.

This manuscript reports on the effects of stressors repeated at a 24-hr interval on three samples of human newborns. In Study 1, newborns meeting criteria for obstetric and perinatal optimality experienced either 2 mock Discharge Exams, viewed as a type of handling stressor, or 2 Heelstick Blood Draws, viewed as a type of nocioceptive stressor. As in a previous study, newborns meeting optimality criteria showed habituation of the adrenocortical response to the repeated Discharge Exam. The adrenocortical response to the repeated Heelstick tended to increase or sensitize. In Studies 2 and 3, samples of newborns with more nonoptimal obstetric complication scale scores were examined. These newborns failed to show habituation of the adrenocortical response to the Discharge Exam, but responded like "Optimal" newborns to the repeated Heelstick. The applicability to these data of the Groves and Thompson (1970) Dual-Process Model of Habituation is discussed. The results also provided evidence of stability in behavioral distress independent of stability in adrenocortical activity. The implications of these data for studies using cortisol as an index of the physiological basis of early temperament are considered.

Adrenal Cortex↗