Clinical multimorbidity and physical function in older adults: a record and health status linkage study in general practice

BACKGROUND: Multiple chronic conditions occurring in the same individual are associated with adverse health outcomes. In family practice, individuals are seen who, over time, may experience many different symptoms, illnesses and chronic diseases. Measures for defining multimorbidity, which incorporate the diverse range of health problems seen in population-based family practice, remain to be developed. We have investigated whether routinely collected consultation data could be used as the basis for a simple classification of multimorbidity that reflects an individual's overall health status. METHODS: Morbidity consultation data for 9,439 English patients aged 50 years and over in an 18-month time period were linked to their self-reported physical health status measured by Short-Form 12 at the end point. Associations between physical function and all-cause multimorbidity counts were estimated relative to single morbidity only, and between physical function and morbidity severity (185 morbidities categorized on four ordinal scales of severity) relative to persons who had not consulted about any of the 185. RESULTS: In the 18-month period, 19% had consulted for a single morbidity and 23% for six or more (a high multimorbidity count). An estimated 24% of poor physical function in the family practice consulting population may be attributable to high multimorbidity. There was an increasing strength of association between poor physical function and increasing severity of multimorbidity on all four severity scales. Estimated associations (adjusted odds ratios) of the most severe morbidity categories with poor physical function were, for each of the four scales, respectively, 5.6 for chronicity [95% confidence interval (CI) 4.4-7.1], 7.0 for time course (4.5-10.6) and 3.6 for health care use (2.0-6.6) and for patient impact (6.7; 5.2-8.8). CONCLUSIONS: Multimorbidity defined by using routinely collected family practice consultation data and classified by count and by severity was associated with poorer physical function. This approach offers the potential for systematic use of routine records to classify multimorbidity and to identify groups with high likelihood of poor physical status for needs assessment and targeted intervention.     

Regional patterns of brain metabolites in AIDS dementia complex

The relationship of the cellular changes in the HIV-infected brain to the onset and progression of AIDS dementia complex (ADC) remains uncertain. We undertook an in vivo proton magnetic resonance spectroscopy (MRS) study and used factor analysis to identify specific cellular and regional brain changes that may serve as metabolic markers of ADC. The ratio of N-acetyl aspartate (NAA), choline (Cho), and myoinositol (MI) over creatine (Cr), markers of neuronal and glial cell metabolism, were measured in the basal ganglia, centrum semiovale, and parietal cortex from 100 subjects with and without ADC. Three metabolic patterns were identified, which we termed "inflammatory" (mainly MI/Cr elevations in all three regions plus Cho/Cr increases in the centrum semiovale and parietal cortex), "basal ganglia" (mostly NAA/Cr and Cho/Cr elevations in the basal ganglia), and "neuronal" (primarily NAA/Cr reductions in the centrum semiovale and the parietal cortex). Logistic regression analysis revealed that, adjusted for age, basal ganglia and neuronal pattern scores were strongly associated with ADC but inflammatory levels were not. We conclude that by using factor analysis, we are able to combine multiple metabolites across brain regions in a biologically plausible manner and construct a predictive model of ADC adjusting for relevant factors such as age.     

Virtual colonoscopy with magnetic resonance imaging: In vitro evaluation of a new concept

BACKGROUND & AIMS: Screening for colonic polyps is desirable. A new concept based on cross-sectional and endoscopic analysis of a magnetic resonance (MR) data set is presented. METHODS: Ex vivo autopsy colonic specimens, containing artificially placed polyps, were obtained and filled with a gadolinium-containing solution. Forty-four thin-section MR images were obtained in a 1.5-T MR scanner in 28 seconds. A three- dimensional endoscopic fly-through of these images was rendered. Fly- throughs and two-dimensional cross-sectional images were analyzed by two observers for the presence of polyps. RESULTS: The average sensitivity and specificity for the detection of polyps based on three- dimensional endoscopic MR colon imaging were 87% and 96%, respectively. Analysis of cross-sectional images showed an overall sensitivity and specificity of merely 57% and 84%, respectively. The difference in the interpretation of three-dimensional MR colonoscopy and two-dimensional cross-sections was statistically significant (P < 0.001). With three- dimensional MR colonoscopy, overall sensitivity for detection of polyps measuring < or =5 mm in length and diameter was 70%; for larger polyps, it increased to 95% (P < 0.01). CONCLUSIONS: The feasibility of an MR- based endoluminal assessment of the colon is shown. Minimal invasiveness, lack of radiation exposure, and high in vitro diagnostic accuracy warrant further investigation of this novel concept. (Gastroenterology 1997 Jun;112(6):1863-70)     

Genetic basis for systems of skeletal quantitative traits: principal component analysis of the canid skeleton

Evolution of mammalian skeletal structure can be rapid and the changes profound, as illustrated by the morphological diversity of the domestic dog. Here we use principal component analysis of skeletal variation in a population of Portuguese Water Dogs to reveal systems of traits defining skeletal structures. This analysis classifies phenotypic variation into independent components that can be used to dissect genetic networks regulating complex biological systems. We show that unlinked quantitative trait loci associated with these principal components individually promote both correlations within structures (e.g., within the skull or among the limb bones) and inverse correlations between structures (e.g., skull vs. limb bones). These quantitative trait loci are consistent with regulatory genes that inhibit growth of some bones while enhancing growth of others. These systems of traits could explain the skeletal differences between divergent breeds such as Greyhounds and Pit Bulls, and even some of the skeletal transformations that characterize the evolution of hominids.     

Treatment of progressive Hodgkin's disease with intensive chemoradiotherapy and autologous bone marrow transplantation

Twenty-six patients with progressive Hodgkin's disease after conventional chemotherapy received intensive chemoradiotherapy and autologous bone marrow transplantation (ABMT); 19 also received additional involved-field radiotherapy. Twenty-one patients [81%, 95% confidence intervals (CI) 61% to 94%] attained complete (n = 18) or partial responses. Ten patients (38%, 95% CI 20% to 59%) are disease- free a median of 4.5 years later (range 3.5 to 7.0 years), including seven patients with continuous complete responses. The likelihood of overall response was not significantly influenced by any clinical or treatment variable examined. However, there was a trend favoring patients with higher Karnofsky scores, and higher scores were associated with attainment of complete responses (P = .06 and P = .02, respectively, Mann-Whitney U test). Both higher Karnofsky scores and shorter durations of disease before transplantation were associated with improved survival in a stepwise Cox multivariate analysis. The chief cause of failure was progression at sites previously involved with Hodgkin's disease. No patient relapsed in the marrow, and two of three patients with a history of marrow involvement with Hodgkin's disease achieved durable complete responses after transplantation. These data suggest that inadequate pretransplant conditioning, and not the reinoculation of occult tumor cells in the autologous marrow, caused most relapses. Fatal treatment-related toxicity occurred in six patients. Three patients died of idiopathic interstitial pneumonitis; each had previously received local mediastinal irradiation before intensive chemoradiotherapy. Intensive chemoradiotherapy and ABMT produces durable responses in some patients with Hodgkin's disease incurable with conventional therapy. Use of such therapies at the first sign of failure with conventional chemotherapy and development of more effective conditioning regimens should further improve results.     

Cytogenetic studies in patients with secondary leukemia/dysmyelopoietic syndrome after different treatment modalities

Cytogenetic studies of 68 patients who developed secondary leukemia (SL)/dysmyelopoietic syndrome (DMS) after extensive chemotherapy and/or radiation therapy as well as patients who developed SL/DMS without such treatment showed that those patients who received radiation alone or with chemotherapy had more extensive numerical and structural abnormalities than those who received only chemotherapy. In terms of the specific chromosomal abnormalities, there are no differences between the various treatment groups. Hypodiploidy is the most common form of aneuploidy in these patients, with the most common numerical abnormality being the loss of chromosome 7. The most common structural abnormalities involved chromosomes 3 and 5. When compared with patients with de novo leukemia and DMS, the chromosomal abnormalities in these patients are more complex and extensive. Serial studies revealed that cytogenetic abnormalities do not precede the development of hematologic changes by significant time periods.     

High-dose cytosine arabinoside and daunorubicin as consolidation therapy for acute nonlymphocytic leukemia in first remission: a pilot study

High-dose (HD) cytosine arabinoside (ARA-C) is more effective treatment than conventional-dose ARA-C regimens for patients with relapsed acute nonlymphocytic leukemia (ANLL). We report here that HD ARA-C given during the first remission of ANLL has resulted in long remission durations and a high proportion of patients who survive more than three years free of disease. From August 1979 to September 1983, 36 adult patients with ANLL in first remission received one to three courses of HD ARA-C (3 g/m2 by one-hour infusion every 12 hours for 12 doses on days 1 through 6) alone or with daunorubicin (30 mg/m2 for two or three doses on days 7 through 9). Three patients died of sepsis or hemorrhage during consolidation, and 14 patients have relapsed from five to 48 months after diagnosis. The remaining 19 patients are in continued complete remission (CCR) from 11 to 62 months. Denoting all deaths in remission as relapse, the actuarial probability of CCR is 42% at 62 months, with an apparent plateau in the survival curve. Of the first 22 patients treated, ten remain in CCR from 37 to 62 months with no therapy for at least three years. Due to its heightened anti-leukemic activity, HD ARA-C allows brief but effective consolidation of ANLL in first remission, with long-term disease-free survival comparable to other approaches.     

HPLC柱切换法对炔诺酮α,β-聚(3-羟丙基)-DL-天冬酰胺在兔体内释放炔诺酮的测定

以柱切换HPLC(CSHPLC)技术,对炔诺酮α,β-聚(3-羟丙基)-DL-天冬酰胺在家兔体内释放液中炔诺酮的血药浓度进行了测定,以自制ODS预柱,水为流动相联机净化、富集样品;以Shim-packCLC-ODS为分析柱,甲醇-水(7:3)为流动相。结果表明CSHPLC对炔诺酮血药浓度有良好的选择性,回收率为82.6%(n=5),日内和日间精密度(RSD)分别小于4%和6%。在血清0.22～1.10μg/m1范围内炔诺酮色谱峰面积与浓度有较好的线性关系(n=5,r=0.998).