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M A Moskowitz

Publications and source records attributed to M A Moskowitz.

At least 145 records · Page 8Linked to original sources

Patient, physician and presentational influences on clinical decision making for breast cancer: results from a factorial experiment.

This study examines the influence of six patient characteristics (age, race, socioeconomic status, comorbidities, mobility and presentational style) and two physician characteristics (medical specialty and years of clinical experience) on physicians' clinical decision making behaviour in the evaluation treatment of an unknown and known breast cancer. Physicians' variability and certainty associated with diagnostic and treatment behaviour were also examined. Separate analyses explored the influence of these non-medical factors on physicians' cognitive processes. Using a fractional factorial design, 128 practising physicians were shown two videotaped scenarios and asked about possible diagnoses and medical recommendations. Results showed that physicians displayed considerable variability in response to several patient-based factors. Physician characteristics also emerged as important predictors of clinical behaviour, thus confirming the complexity of the medical decision-making process.

Age Factors↗

Outcomes for older men and women with congestive heart failure.

OBJECTIVES: To describe and compare outcomes for men and women discharged alive following a hospitalization for congestive heart failure (CHF). DESIGN: Prospective cohort study. PARTICIPANTS: A total of 519 patients, aged > or = 65, who were discharged alive after a hospitalization for CHF (DRG = 127). MEASUREMENTS: Outcomes (Activities of Daily Living (ADLs), shortness of breath when walking, perceived health, living situation, rehospitalization, and mortality) were measured at 3 times (6 weeks, 6 months, and 1 year) post-discharge. RESULTS: The 205 men were, on average, younger (77 +/- 7 vs 80 +/- 8, P < .001), wealthier (46% vs 21% earned > or = $10,000, P < .001), and more often married (50% vs 19%, P < .001). Men were more likely than women to have a previous history of CHF (71% vs 63%, P = .052). Men also had higher 1-year mortality than women (48% vs 35%, P = .009), even after adjusting for age, comorbidity, physiological severity (APACHE II APS and RAND discharge instability), radiological evidence of CHF, prior ADLs, walking ability, living situation, and perceived health. Men and women survivors at 1-year had similar and substantial impairment for all non-fatal outcomes considered (all P values > or = .489). Their adjusted mean ADL scores were consistent with complete dependence on one essential activity (range 0-6 dependencies); 35% were short of breath walking less than 1 block; 62% had fair or poor perceived health; 32% received some formal care; and 46% were rehospitalized within 1 year of discharge. CONCLUSIONS: Men with CHF have a higher mortality than women with CHF. Men and women who survive have similar and substantial impairment for all non-fatal outcomes (ADLs, shortness of breath upon walking, perceived health, living situation, and rehospitalization).

Activities of Daily Living↗

5-Hydroxytryptamine1A and 5-hydroxytryptamine1B receptors stimulate [35S]guanosine-5'-O-(3-thio)triphosphate binding to rodent brain sections as visualized by in vitro autoradiography.

[35S]Guanosine-5'-O-(3-thio)triphosphate ([35S]GTPgammaS) binding to G proteins was measured by in vitro autoradiography in guinea pig and rat brain sections after activation by 5-hydroxytryptamine (5-HT) receptor agonists. 5-Carboxamidotryptamine stimulated binding strongly in hippocampus and lateral septum and weakly in substantia nigra. This effect was blocked in the substantia nigra by the 5-HT1B/1D receptor antagonist GR-127,935 and in the former two regions by the 5-HT1A antagonist NAN-190. 5-HT1B/1D receptor agonists stimulated binding in substantia nigra and in areas containing 5-HT1A receptors. In guinea pig substantia nigra, 5-(nonyloxy)-tryptamine maximally stimulated [35S]GTPgammaS binding by 54%, with an EC50 value of 62 nM; at 100 microM, this agonist increased binding by approximately 200% in hippocampus (with a 2-fold weaker EC50 value). The distribution of [3H]8-OH-DPAT binding sites was identical to that of the [35S]GTPgammaS labeling stimulated by the 5-HT1A agonist (R)-8-hydroxy-2-dipropylaminotetralin [(R)-8-OH-DPAT)]. (R)-8-OH-DPAT, (S)-8-OH-DPAT, and buspirone stimulated [35S]GTPgammaS binding in hippocampus by 340%, 140%, and 78%, with EC50 values of 71, 51, and 132 nM. Enhanced [35S]GTPgammaS binding was not detected in the presence of 5-HT1F, 5-HT2, 5-HT4, and 5-HT7 receptor agonists. Because activation of mu-opioid, muscarinic M2, histamine H3, and cannabinoid receptors was also visualized successfully, these data suggest that only receptors coupled to pertussis toxin-sensitive G proteins can be seen by [35S]GTPgammaS binding autoradiography. This study also shows that different 5-HT receptors coupled to these proteins can show a wide range of [35S]GTPgammaS binding stimulation. Although the functional significance of these variations is unclear, this technique offers advantages over receptor autoradiography because it does not require high affinity radioligands and provides a measure of agonist efficacies in various brain regions.

Animals↗

bFGF ameliorates focal ischemic injury by blood flow-independent mechanisms in eNOS mutant mice.

Genetically engineered mice deficient in the expression of type III nitric oxide synthase (NOS) [endothelial NOS (eNOS)] were used to decipher the importance of nitric oxide (NO)-dependent augmentation of regional cerebral blood flow (rCBF) to infarct volume reduction following basic fibroblast growth factor (bFGF) infusion during acute middle cerebral artery (MCA) occlusion. We have shown previously that intravenously administered bFGF reduces infarct volume following MCA occlusion in rats and that bFGF dilates cerebral pial arterioles by NO-dependent mechanisms. Halothane-anesthetized eNOS knockout and wild-type mice were subjected to permanent MCA occlusion by intraluminal filament for 24 h. bFGF (100 microg x kg(-1) x h(-1)) was infused intravenously for 2 h, beginning 15 min after the onset of occlusion. Infarct volume was reduced from 119 +/- 8 to 93 +/- 4 mm3 (22% reduction, P < 0.05) or from 102 +/- 9 to 77 +/- 6 mm3 (24% reduction, P < 0.05) in eNOS knockout or wild-type mice, respectively (means +/- SE; n = 10 per group), and neurological deficits were also significantly reduced. Although bFGF infusion caused a 27% increase in rCBF and a 17% reduction in vascular resistance in the infarct margin of wild-type animals as measured by laser Doppler flowmetry, bFGF did not enhance rCBF in the infarct margin of eNOS mutant mice. These data indicate that intravenous bFGF reduces infarct volume following focal ischemia by mechanisms that are largely blood flow independent.

Animals↗

Facilitation of postischemic reperfusion with alpha-PBN: assessment using NMR and Doppler flow techniques.

We examined the effects of the free radical spin trap N-tert-butyl-alpha-phenylnitrone (PBN) on focal cerebral ischemia/reperfusion injury in halothane-anesthetized rats. Ninety minutes after middle cerebral artery occlusion by an intraluminal filament, the artery was reperfused. Intravenous injections of 25 mg/kg PBN 5 min before and 30 min after insertion of the filament significantly attenuated the lesion volume measured 24 h after ischemia. During ischemia and during the first 30 min after reperfusion, cerebral blood volume and blood flow were measured by volume-sensitive and newly developed flow-sensitive magnetic resonance imaging (MRI) techniques and by laser-Doppler flowmetry. In all animals the area of decreased blood flow was larger than the area of decreased volume by a factor of 2.2. The area of the postreperfusion flow deficits matched the final lesion volumes at 24 h measured histologically much better than did the blood volume deficits in both saline and PBN-treated animals. Reperfusion led to a return of blood flow and volume to values close to the contralateral side in the PBN-treated animals, in contrast to the saline-treated control group. We conclude that in focal ischemia/reperfusion PBN provides protection of the vascular endothelium, leading to enhanced postischemic reperfusion. The implication of this is that the vascular endothelium may be a primary target for the damaging action of free radicals given the protection afforded by putative spin traps.

Animals↗

Primary afferent neurons innervating guinea pig dura.

We made recordings from filaments of guinea pig nasociliary nerve to study response properties of afferent axons innervating the anterior superior sagittal sinus and surrounding dura mater. We analyzed 38 units in 14 experiments. Units were initially located with the use of mechanical stimuli, and were then characterized by their conduction velocity and sensitivities to mechanical, thermal, and chemical stimuli. Single-unit recordings revealed innervation of dura and superior sagittal sinus by slowly conducting axons, mostly in the unmyelinated range. The receptive fields were 1-30 mm2, and typically had one to three punctate spots of highest sensitivity. All units tested responded to topical application of chemical agents. Ninety-seven percent of units responded to 10(-5) M capsaicin, 79% responded to a mixture of inflammatory mediators, and 37% responded to an acidic buffer (pH 5). These data underline the importance of chemical sensitivity in intracranial sensation. Heat and cold stimuli evoked responses in 56 and 41% of units tested, respectively. Although the response patterns during heating were typical of polymodal nociceptors innervating other tissues, the thresholds were lower than for other tissues (32.3-42 degrees C). Cooling led to a phasic discharge, with thresholds between 25 and 32 degrees C. Although units had different combinations of responses to mechanical, chemical, and thermal stimuli, when grouped by their sensitivities the groups did not differ regarding mechanical thresholds or presence of ongoing activity. This suggests that meningeal primary afferents are relatively homogeneous. Sensitivities of these units are in general consistent with nociceptors, although the thermal thresholds differ. These data provide the first detailed report of response properties of intracranial primary afferent units, likely to be involved in transmission of nociception and possibly mediation of intracranial pain.

Animals↗

Strain-related differences in susceptibility to transient forebrain ischemia in SV-129 and C57black/6 mice.

BACKGROUND AND PURPOSE: We explored susceptibility to injury after global ischemia in SV-129 and C57Black/6 mice, two commonly used-background strains in genetically engineered mice. METHODS: Mice (n = 84) were subjected to 15, 30, or 75 minutes of bilateral common carotid artery (BCCA) occlusion followed by reperfusion for 72 hours. BCCA occlusion was performed under halothane or chloral hydrate anesthesia, in one experiment, mean arterial blood pressure and regional cerebral blood flow (laser Doppler flowmetry) were matched by controlled exsanguination. Baseline absolute blood flow measurements were obtained in both strains using a tracer, N-isopropyl-[methyl 1,3-14C]-p-iodoamphetamine, indicator fractionation technique (n = 5 per group). Vascular anatomy of the circle of Willis was visualized by intravascular perfusion of carbon black ink (n = 10 per group). Cerebrovascular reactivity was assessed by measuring the diameter of pial vessels (intravital microscopy) to acetylcholine (ACh) superfusion (0.1 to 10 mmol/L) in a closed cranial window preparation (n = 29). RESULTS: Resting blood flow values did not differ between groups in striatum, cerebellum, and brain-stem regions. SV-129 mice were less susceptible than C57Black/6 mice to ischemic injury (0.0 +/- 0.0 versus 1.3 +/- 0.3 damage in hippocampal CA1 region after 30 minutes of ischemia in SV-129 and C57Black/6, respectively; P < .01). Cellular damage (grade 1 to 3 injury) comparable to 30-minute BCCA occlusion was achieved only after 75 minutes of ischemia in SV-129 mice (1.1 +/- 0.3). Ischemic damage was also significantly less in SV-129 mice after blood pressure and flow were matched during ischemia in halothane-anesthetized SV-129 mice (0.5 +/- 0.3 versus 1.4 +/- 0.2, P < .05), or after chloral hydrate anesthesia (0.4 +/- 0.2 versus 1.5 +/- 0.4, P < .05). Hypoplastic posterior communicating arteries were found in all 10 C57Black/6 mice and may explain the greater susceptibility of these mice to injury after BCCA occlusion. More robust vasodilation to ACh in C57Black/6 mice could also indicate genetic differences in responses to vasoactive substances. CONCLUSIONS: C57Black/6 mice exhibit enhanced susceptibility to global cerebral ischemic injury, an incompletely formed circle of Willis, and augmented pial vessel dilation to ACh compared with SV-129 mice. Our findings suggest that strain differences may confound results when genetically engineered mice generated from more than a single background strain are used.

Acetylcholine↗

Nonmedical influences on medical decision making: an experimental technique using videotapes, factorial design, and survey sampling.

OBJECTIVE: To study nonmedical influences on the doctor-patient interaction. A technique using simulated patients and "real" doctors is described. DATA SOURCES: A random sample of physicians, stratified on such characteristics as demographics, specialty, or experience, and selected from commercial and professional listings. STUDY DESIGN: A medical appointment is depicted on videotape by professional actors. The patient's presenting complaint (e.g., chest pain) allows a range of valid interpretation. Several alternative versions are taped, featuring the same script with patient-actors of different age, sex, race, or other characteristics. Fractional factorial design is used to select a balanced subset of patient characteristics, reducing costs without biasing the outcome. DATA COLLECTION: Each physician is shown one version of the videotape appointment and is asked to describe how he or she would diagnose or treat such a patient. PRINCIPAL FINDINGS: Two studies using this technique have been completed to date, one involving chest pain and dyspnea and the other involving breast cancer. The factorial design provided sufficient power, despite limited sample size, to demonstrate with statistical significance various influences of the experimental and stratification variables, including the patient's gender and age and the physician's experience. Persistent recruitment produced a high response rate, minimizing selection bias and enhancing validity. CONCLUSION: These techniques permit us to determine, with a degree of control unattainable in observational studies, whether medical decisions as described by actual physicians and drawn from a demographic or professional group of interest, are influenced by a prescribed set of nonmedical factors.

Age Factors↗

Black women receive less mammography even with similar use of primary care.

BACKGROUND: Black women with breast cancer have a decreased 5-year survival rate in comparison with white women, possibly because of less frequent use of mammography. Having a regular provider or source of health care is the most important determinant of mammography use. OBJECTIVE: To examine whether the difference in mammography use between elderly black women and elderly white women is related to the number of visits made to a primary care physician. DESIGN: Retrospective review of 1990 Health Care Financing Administration billing files (Medicare part B) from 10 states. SETTING: Outpatient mammography services in 10 states. PARTICIPANTS: Black women and white women, 65 years of age and older, residing in one of the 10 states. MEASUREMENTS: Any mammogram. Predictors included race, number of visits to a primary care physician (0, 1, 2, or 3 or more), median income of ZIP code of residence (a surrogate measure of income), and state. RESULTS: The following are findings from Georgia; similar results were found in each state studied. The mean age of the 335,680 women was 75 years; 20% were black. Sixty-eight percent of the black women and 69% of the white women made at least one visit to a primary care physician. Overall, 14% of the women had had mammography; black women had mammography less often than white women (9% compared with 15%). At each primary care visit level (1, 2, or 3 or more visits), black women had mammography less often than white women (1 visit, 7% compared with 15%; 2 visits, 12% compared with 21%; and 3 or more visits, 12% compared with 20%). Even among women who had made at least one visit to a primary care physician, a deficit for blacks occurred in each income quintile (lowest quintile, 13% compared with 20%; low, 10% compared with 18%; middle, 12% compared with 18%; high, 10% compared with 19%; and highest, 12% compared with 22%) and in each state (in Georgia, for example, the percentages were 14% compared with 21%). An age-, income-, and state-adjusted logistic model predicting mammography use for 2.9 million white women in all 10 states shows the powerful effect of primary care use on mammography (odds ratios for 1, 2, and 3 or more visits were, respectively, 2.73 [95% CI, 2.70 to 2.77]; 3.98 [CI, 3.93 to 4.03]; and 4.62 [CI, 4.58 to 4.67]). The same model fit to 250 000 black women shows a lesser effect (analogous odds ratios were 1.77 [CI, 1.67 to 1.87]; 2.49 [CI, 2.36 to 2.63]; and 3.15 [CI, 3.04 to 3.25]). CONCLUSION: Among older women, mammography is used less often for blacks than for whites. More frequent use of mammography is associated with more visits to a primary care physician in both groups, but the deficit for black women persists at each income level and in each state, even after primary care use is considered. Primary care visits are less likely to "boost" mammography use for black women than for white women.

Black or African American↗

Rating long-term care facilities on pressure ulcer development: importance of case-mix adjustment.

OBJECTIVE: To determine the importance of case-mix adjustment in interpreting differences in rates of pressure ulcer development in Department of Veterans Affairs long- term care facilities. DESIGN: A sample assembled from the Patient Assessment File, a Veterans Affairs administrative database, was used to derive predictors of pressure ulcer development; the resulting model was validated in a separate sample. Facility-level rates of pressure ulcer development, both unadjusted and adjusted for case mix using the predictive model, were compared. SETTING: Department of Veterans Affairs long-term care facilities. PATIENTS: The derivation sample consisted of 31 150 intermediate medicine and nursing home residents who were initially free of pressure ulcers and were institutionalized between October 1991 and April 1993. The validation sample consisted of 17 946 residents institutionalized from April 1993 to October 1993. MEASUREMENT: Development of a stage 2 or greater pressure ulcer. RESULTS: 11 factors predicted pressure ulcer development. Validated performance properties of the resulting model were good. Model-predicted rates of pressure ulcer development at individual long-term care facilities varied from 1.9% to 6.3%, and observed rates ranged from 0% to 10.9%. Case-mix-adjusted rates and ranks of facilities differed considerably from unadjusted ratings. For example, among five facilities that were identified as high outliers on the basis of unadjusted rates, two remained as outliers after adjustment for case mix. CONCLUSIONS: Long-term care facilities differ in case mix. Adjustments for case mix result in different judgments about facility performance and should be used when facility incidence rates are compared.

Aged↗

Continuous assessment of relative cerebral blood volume in transient ischemia using steady state susceptibility-contrast MRI.

The utility of a noninvasive steady state susceptibility-contrast MRI technique for continuous measurement of relative cerebral blood volume (rCBV) during global transient ischemia and subsequent hyperemia in a feline ischemia model is demonstrated. The measurements were obtained during a 10-min period of occlusion and 1-h period of reperfusion. Maximal hyperemic responses in gray matter, basal ganglia, and white matter (observed at 7,7, and 5 min, respectively) were 1.9 +/- 0.5, 1.8 +/- 0.3, and 1.7 +/- 0.6 times greater than baseline CBV (mean +/- SEM). Thirty to forty minutes after onset of reperfusion, CBV returned to normal. Thereafter, it decreased below baseline, nearing the control level by 1 h after onset of reperfusion. Steady state susceptibility-contrast MRI permits continuous, in vivo mapping of alterations in CBV.

Animals↗

Underdetection of clinical benign prostatic hyperplasia in a general medical practice.

OBJECTIVE: To measure detection of clinical benign prostatic hyperplasia (BPH) in a general medicine practice. DESIGN: Self-administered questionnaire and retrospective ambulatory medical record review. SETTING: Hospital-based general medicine practice. PATIENTS: Two hundred and four men aged 50 years and older. MEASUREMENTS AND MAIN RESULTS: Clinical information was obtained from a self-administered questionnaire containing the American Urological Association symptom index and the BPH Impact Index bother scale, and from retrospective review of ambulatory medical records for the previous 24 months. Thirty percent of patients had moderate to severe urinary tract symptoms, and 67% of these individuals were bothered by the symptoms. Only 52% with moderate to severe symptoms recalled any discussion with their primary care physician about their symptoms. There was medical record documentation of a review of urinary tract symptoms in only 18% and a prostate examination in only 64%. Patients with more symptoms and bother tended to recall a discussion of urinary tract symptoms with their physician. However, moderate to severe symptoms and bother were not associated with increased documentation of a history of urinary tract symptoms or prostate examination. CONCLUSIONS: Clinical BPH was underdetected in a general medicine practice. Because many men do not complain to their physicians about urinary tract symptoms and reduced quality of life, perhaps primary care physicians should pay more attention to recognizing this common condition of older men.

Family Practice↗

Variations in the management of acute myocardial infarction. Importance of clinical measures of disease severity.

OBJECTIVE: To determine the extent to which resource use for patients hospitalized with acute myocardial infarction varies with clinical status, and to see if an observed difference in resource use between two states can be explained by clinically detailed risk adjustment. DESIGN: Retrospective review of the clinical characteristics and resource use of 342 patients hospitalised in two states with acute myocardial infarction. DATA SOURCES: Merged data from three sources: a large, existing research database used in developing the Medicare Mortality Predictor Score, clinical data abstracted from medical charts specifically for this study, and Medicare Parts A and B claims records. PATIENTS: A probability sample of Medicare patients hospitalized in 1986 with a diagnosis of acute myocardial infarction and residing in either Wisconsin or Washington state; patients dying within 30 days are oversampled. MEASUREMENTS AND MAIN RESULTS: Although patients were clinically similar in the two states, there were systematic differences in resource use. Patients in Wisconsin spent more than one extra day in the intensive care unit (ICU) (2.8 vs 1.7) as well as more than one extra non-ICU day in the hospital (8.0 vs 6.5) than patients in Washington. Patients in Wisconsin were also more likely to receive an echocardiogram (35.6% vs 15.8%), nuclear ventriculogram (12.8% vs 4.1%), exercise tolerance test (21.5% vs 3.4), and Holter monitoring (5.4% vs 0%). (All p < .01.) Differences in utilization were greater for patients at lower risk of dying. The average cost of care was 20.8% higher in Wisconsin (p = .01); risk adjustment for clinical and other factors reduced this difference to 11.8%, but did not eliminate it (p = .04). CONCLUSIONS: Patients with acute myocardial infarction vary in resource use as a function of clinical factors present at admission and occurring during the hospital stay; comparisons that do not take account of these factors may not discriminate well between providers who care for sicker patients and those who are inefficient. The greater use of resources for patients in Wisconsin is at least partially explained by differences in clinical characteristics that are not presently captured in administrative data.

Aged↗

The exclusion of non-English-speaking persons from research.

OBJECTIVE: We sought to determine how often non-English-speaking (NES) persons are excluded from medical research. DESIGN. Self-administered survey. PARTICIPANTS: A Medline search identified all original investigations on provider-patient relations published in major U.S. journals from 1989 through 1991, whose methodologies involved direct interaction between researcher and subject (N = 216). Each study's corresponding author was surveyed; 81% responded. MEASUREMENTS AND MAIN RESULTS: Of the 172 respondents, 22% included NES persons; among these includers, 16% had not considered the issue during the study design process, and 32% thought including the NES had affected their study results. Among the 40% who excluded the NES (excluders), the most common reason was not having thought of the issue (51%), followed by translation issues and recruitment of bilingual staff. The remaining 35% (others) indicated that there were no NES persons in their study areas. CONCLUSIONS: NES persons are commonly excluded from provider-patient communication studies appearing in influential journals, potentially limiting the generalizability of study findings. Because they are often excluded through overnight, heightened awareness among researchers and granting institutions, along with the development of valid instruments in varied languages, may increase representation of non-English-speaking subjects in research.

Communication Barriers↗

Emerging treatments for stroke in humans.

Ischaemic stroke causes loss of brain function in millions of people worldwide each year. Despite the enormity of the problem, no currently approved therapy reduces stroke size or neurological disability. This contrasts with a number of recently developed agents, reviewed here by Walter Koroshetz and Michael Moskowitz, which limit infarct size in animal stroke models. Therapies that dissolve clot and restore blood flow, block excitatory neurotransmission, prevent the ischaemic inflammatory response or scavange free radicals have the potential to revolutionize stroke treatment if proven beneficial in ongoing, placebo-controlled clinical trials. Developments in the experimental arena continue to reinforce the need to characterize the pathophysiological stages leading to brain infarction and recovery.

Animals↗

Attenuated hippocampal damage after global cerebral ischemia in mice mutant in neuronal nitric oxide synthase.

To address the importance of nitric oxide or its reaction products as mediators of neurotoxicity in brain, tissue injury was assessed after transient global ischemia in mice rendered mutant in the gene for neuronal nitric oxide synthase. Halothane-anesthetized wild type and mutant mice were subjected to temporary occlusion of the basilar plus both carotid arteries for 5 or 10 min followed by three days of reperfusion. Hippocampal injury, assessed both by qualitative grading and by cell counting in the CA1 subregion, was significantly less in the mutant mice group after 5 or 10 min of ischemia. Mutant mice exhibited a lower mortality (P < 0.01), less weight loss, more normal grooming and spontaneous motor activity and better grasping in the 10 min group. There were no obvious differences in cerebrovascular anatomy or hemodynamics between wild type and mutant mice. The data suggest that a deficiency of neuronal nitric oxide synthase confers increased resistance to transient global cerebral ischemia, and support the suggestion that selective neuronal nitric oxide synthase inhibitors might reduce tissue injury associated with global cerebral ischemia.

Animals↗