Impact of managed care on obstetrician-gynecologists' practice: the providers' perspective.

The American College of Obstetricians and Gynecologists' 1998 Socioeconomic Survey of Fellows included questions, developed in collaboration with the Jacobs Institute of Women's Health, to assess the impact of managed care on respondents' practices and patients. Participation in managed care is extensive among obstetricians and gynecologists (ob/gyns), especially in commercial managed care plans. The greatest areas of dissatisfaction for physicians were administrative workload, external review of clinical decisions, and promptness of payment. More research is needed to determine the impact of administrative burdens, restrictions on access to ob/gyns, and denial of coverage on women's receipt of timely and appropriate services.

Surface states in nearly modulated systems.

A Landau model is used to study the phase behavior of the surface layer for magnetic and cholesteric liquid-crystal systems that are at or near a Lifshitz point marking the boundary between modulated and homogeneous bulk phases. The model incorporates surface and bulk fields and includes a term in the free energy proportional to the square of the second derivative of the order parameter in addition to the usual term involving the square of the first derivative. In the limit of vanishing bulk field, three distinct types of surface ordering are possible: a wetting layer, a nonwet layer having a small deviation from bulk order, and a different nonwet layer with a large deviation from bulk order that decays nonmonotonically as the distance from the wall increases. In particular, the large deviation nonwet layer is a feature of systems at the Lifshitz point and also those systems having only homogeneous bulk phases.

Which chronic conditions are associated with better or poorer quality of life?

The objective of the present study is to compare the QL of a wide range of chronic disease patients. Secondary analysis of eight existing data sets, including over 15,000 patients, was performed. The studies were conducted between 1993 and 1996 and included population-based samples, referred samples, consecutive samples, and/or consecutive samples. The SF-36 or SF-24 were employed as generic QL instruments. Patients who were older, female, had a low level of education, were not living with a partner, and had at least one comorbid condition, in general, reported the poorest level of QL. On the basis of rank ordering across the QL dimensions, three broad categories could be distinguished. Urogenital conditions, hearing impairments, psychiatric disorders, and dermatologic conditions were found to result in relatively favorable functioning. A group of disease clusters assuming an intermediate position encompassed cardiovascular conditions, cancer, endocrinologic conditions, visual impairments, and chronic respiratory diseases. Gastrointestinal conditions, cerebrovascular/neurologic conditions, renal diseases, and musculoskeletal conditions led to the most adverse sequelae. This categorization reflects the combined result of the diseases and comorbid conditions. If these results are replicated and validated in future studies, they can be considered in addition to information on the prevalence of the diseases, potential benefits of care, and current disease-specific expenditures. This combined information will help to better plan and allocate resources for research, training, and health care.

Expression of different isoenzymes of adenylate deaminase in cultured human muscle cells. Relation to myoadenylate deaminase deficiency.

Adenylate deaminase activity was determined in cultured muscle cells of different maturation grades and muscle biopsies from normal subjects and four patients with a primary myoadenylate deaminase (MAD) deficiency. Adenylate deaminase activity was much lower in cultured human muscle cells than in normal muscle. The activity increased with maturation. The ratio of activities measured at 5 and 2 mM AMP decreased in the order: immature muscle cells greater than more mature muscle cells greater than muscle. Adenylate deaminase activity was detectable in muscle cell cultures of MAD-deficient patients. However, both at 2 and 5 mM AMP this activity was significantly lower than in cultured cells with the same high maturation grade obtained from control subjects, whereas the ratio between the activities at 5 and 2 mM AMP was higher. The observations indicate that transition from a fetal to an adult muscle isoenzyme of adenylate deaminase takes place in human cultured muscle cells during maturation. In cultures obtained from MAD-deficient patients this transition does not occur and only the fetal isoenzyme is present.

Effects of growth medium, electrical stimulation and paralysis on various enzyme activities in cultured rat muscle cells. Comparison with activities in rat muscles in vivo.

1. Replacement of fetal calf serum and chicken embryo extract by Ultroser G and rat brain extract during the proliferation phase resulted in a higher maturation grade of cultured rat muscle cells after 7 days of differentiation, on base of the percentage of the muscle specific isoenzyme of creatine kinase (CK-MM). 2. Furthermore, the activities of creatine kinase, citrate synthase, cytochrome c oxidase and hexokinase were significantly higher. 3. Compared to the enzyme activities in m. quadriceps of 10 day-old rat and m. quadriceps, m. soleus and m. extensor digitorum longus of young adult rats, the metabolic capacity of cultured myotubes most closely resembles that of the first muscle. 4. Paralysis with tetrodotoxin caused a slight decrease of the creatine kinase activity and the percentage of CK-MM of cultured myotubes and an increase of the activities of hexokinase, phosphorylase and AMP deaminase. 5. Electrical stimulation performed at different frequencies and time periods had no effect on the enzyme activities of cultured rat muscle cells. 6. Only the AMP deaminase activity was decreased after intense electrical stimulation.

Effect of various agents on the cytoplasmic calcium concentration in cultured human muscle cells.

1. We determined the cytoplasmic Ca2+ concentration ([Ca2+]i) in cultured human muscle cells using the fluorescent indicator Quin-2. 2. The [Ca2+]i was dependent on the external Ca2+ concentration. Acetylcholine in the presence of external Ca2+ caused a transient increase in [Ca2+]i. Inhibition by nifedipine indicated that this response was mediated through activated voltage-operated channels. In nominally Ca2(+)-free buffer acetylcholine did not markedly increase [Ca2+]i. Therefore, the increase in [Ca2+]i as a response to depolarization is mainly due to influx of external Ca2+. 3. Various concentrations of caffeine did not influence the [Ca2+]i. Dantrolene decreased [Ca2+]i, both in the presence and absence of external Ca2+. The reduction probably resulted from an action of dantrolene on the intracellular Ca2+ stores, since dantrolene did not influence 45Ca2+ influx or efflux and caffeine partially counteracted the reduction.

The calcium homeostasis and the membrane potential of cultured muscle cells from patients with myotonic dystrophy.

Using the fluorescence indicator, quin2, we compared the cytoplasmic Ca2+ concentration ([Ca2+]i) of cultured myotubes obtained from control subjects and myotonic dystrophy (MyD) patients. In Ca2(+)-free buffer the [Ca2+]i of the cultured MyD muscle cells was not significantly different from that of the control cells. In the presence of 1 mM external Ca2+ the cultured MyD muscle cells showed a significantly higher [Ca2+]i, which was due to the influx of Ca2+ through voltage-operated nifedipine-sensitive Ca2+ channels. In the presence of external Ca2+, MyD myotubes did not respond to acetylcholine, whereas control myotubes showed a transient increase in [Ca2+]i after addition of acetylcholine. This increase was inhibited by the addition of nifedipine. The differences in Ca2(+)-homeostasis between cultured MyD muscle cells and control cells were not due to differences in the resting membrane potential or the inability of the MyD cells to depolarize as a response to acetylcholine. Therefore, cultured MyD muscle cells exhibit altered nifedipine-sensitive voltage-operated channels which are active under conditions in which they are normally present in the inactive state, and which are unable to respond to depolarization caused by acetylcholine.

2-Deoxy-D-glucose uptake in cultured human muscle cells.

Hexose uptake was studied with cultured human muscle cells using 2-deoxy-D-[1-3H]glucose. At a concentration of 0.25 and 4 mM, phosphorylation rather than transport was the rate-limiting step in the uptake of 2-deoxy-D-glucose. This was not due to inhibition of the hexokinase activity by either ATP depletion or 2-deoxyglucose 6-phosphate accumulation. In cellular homogenates, hexokinase showed a lower Km value for glucose as compared to 2-deoxyglucose. Intact cells preferentially phosphorylated glucose instead of 2-deoxyglucose. Therefore, transport instead of phosphorylation may be rate limiting in the uptake of glucose by cultured human muscle cells. These data suggest caution in using 2-deoxyglucose for measuring glucose transport.

Purine and pyrimidine metabolism in human muscle and cultured muscle cells.

Using radiochemical methods, we determined the activities of various enzymes of purine and pyrimidine metabolism in homogenates of human skeletal muscle and of cultured human muscle cells. Results show a large discrepancy between the enzyme activities in muscle and cultured cells. With regard to purine metabolism, adenylate (AMP) deaminase activity was only 1-3% in cultured cells compared to that in muscle, whereas the activity of adenosine deaminase, purine-nucleoside phosphorylase, adenosine kinase, adenine phosphoribosyltransferase and hypoxanthine phosphoribosyltransferase was 7-15-fold higher in the cultured cells. The enzymes of pyrimidine metabolism, orotate phosphoribosyltransferase, orotidine 5'-monophosphate decarboxylase and uridine kinase showed activity of 100-200-fold higher in cultured cells than in adult muscle. The differences in enzyme activity are probably related to the low differentiation stage and the absence of contractile activity in the cultured muscle cells. Care must be taken when using these cells as a model for studying purine and pyrimidine metabolism of adult myofibers.

Myoadenylate deaminase deficiency: a clinical, genetic, and biochemical study in nine families.

The clinical significance of myoadenylate deaminase (MAD) deficiency and its mode of inheritance is still questioned. There were 36 relatives of 9 unrelated MAD deficient patients who were examined with the aid of a standardized ischemic forearm test: 8 new cases of MAD deficiency were detected, 5 of which were confirmed histochemically and biochemically. Obligate heterozygotes showed a normal ammonia production and MAD staining, but the mean activity of the enzyme was significantly less than in a group of controls. The results obtained from the family study strongly suggest an autosomal recessive mode of inheritance. However, only 2 of the 8 newly found MAD deficient individuals complained of exertional myalgia, whereas the remaining 6 were without any symptoms or complaints. This finding casts doubt on the clinical significance of MAD deficiency and the relationship of the deficiency state with exertional myalgia.

Palmitate oxidation and some enzymes of energy metabolism in human muscles and cultured muscle cells.

1. Palmitate oxidation rates and activities of creatine kinase, cytochrome c oxidase and citrate synthase were determined in homogenates of three different human muscles and their derived muscle cell cultures. Palmitate oxidation was also assayed in intact cultured cells (myotubes). 2. Biopsies obtained from m. rectus abdominis exhibited a lower palmitate oxidation rate and lower activities of citrate synthase and cytochrome c oxidase than those from m. gluteus and m. quadriceps. In contrast, cell cultures obtained from the three muscles were mutually comparable with regard to these mitochondrial activities. 3. Although cell cultures only reached a low differentiation grade (judged by the total creatine kinase activity and percentage isoenzyme-MM) they are well comparable with the original biopsies with respect to citrate synthase activity and capacity of palmitate oxidation. The activity of cytochrome c oxidase was clearly lower in the cultured cells. 4. Palmitate was more completely oxidized in intact myotubes than in homogenates of myotubes. Apparent Km and Vmax values of palmitate oxidation did not differ significantly in homogenates and intact preparations of myotubes.

14CO2 production is no adequate measure of [14C]fatty acid oxidation.

Palmitate oxidation was comparatively assayed in various cell-free and cellular systems by 14CO2 production and by the sum of 14CO2 and 14C-labeled acid-soluble products. The 14CO2 production rate was dependent on incubation time and amount of tissue in contrast to the total oxidation rate. The 14CO2 contribution to the oxidation rate of [1-14C]palmitate varied with homogenates from 1% with rat liver to 28% with rat kidney and amounted to only 2-4% with human muscles. With cellular systems the 14CO2 contribution varied between 20% in human fibroblasts and 70% in rat muscles and myocytes. Addition of cofactors increased the oxidation rate, but decreased the 14CO2 contribution. Various conditions appeared also to influence to a different extent the 14CO2 production and the total oxidation rate with rat tissue homogenates and with rat muscle mitochondria. Incorporation of radioactivity from [1-14C]palmitate into protein was not detectable in cell-free systems and only 2-3% of the sum of 14CO2 and 14C-labeled acid-soluble products in cellular systems. Assay of 14CO2 and 14C-labeled acid-soluble products is a much more accurate and sensitive estimation of fatty acid oxidation than assay of only 14CO2.

Fatty acid oxidation in human and rat heart. Comparison of cell-free and cellular systems.

Oxidation rates of palmitate and activities of the mitochondrial marker enzymes cytochrome c oxidase and citrate synthase have been determined in homogenates, isolated mitochondria and slices of human and rat heart and in calcium-tolerant rat cardiac myocytes. Homogenates and mitochondria from rat heart showed a 6- and 2.5-fold higher palmitate oxidation rate than the corresponding preparations from human heart. From the palmitate oxidation rates and cytochrome c oxidase and citrate synthase activities as parameters, the mitochondrial protein contents of human and rat heart were calculated to be about 18 and 45 mg/g wet weight, respectively. Based on citrate synthase activities, the fatty acid oxidation rates were about the same in homogenates and isolated mitochondria, much lower in myocytes and lowest in slices. In the cellular systems the palmitate molecule was more completely oxidized than in homogenates or isolated mitochondria. Fatty acid oxidation rates were concentration-dependent in slices, but not with myocytes. With the cellular systems, palmitate oxidation was synergistically stimulated by the addition of carnitine, coenzyme A and ATP to the incubation medium. This stimulation could be attributed only partly to an increased oxidation in damaged cells.