Biomedical subjects

J C Robinson

Publications and source records attributed to J C Robinson.

At least 55 records · Page 3Linked to original sources

PubMed1996

Indomethacin and epinephrine effects on outflow facility and cyclic adenosine monophosphate formation in monkeys.

PURPOSE: To investigate the effect of indomethacin inhibition of prostanoid production on the epinephrine-stimulated increase in outflow facility and cyclic adenosine monophosphate (cAMP) production in the anterior segment of the monkey eye. METHODS: Topical indomethacin was given 1 hour before the intracameral administration of epinephrine to living cynomolgus monkeys. Outflow facility was measured for 45 to 60 minutes, beginning 3 hours after epinephrine administration, by two-level constant pressure perfusion of the anterior chamber. Cyclic adenosine monophosphate formation was measured in cell membranes isolated from rhesus monkey ciliary muscle, ciliary processes, trabecular meshwork, and iris in the presence of forskolin, indomethacin, epinephrine, or indomethacin and epinephrine combined. RESULTS: Three hours after the intracameral administration of 5.5 micrograms epinephrine, facility increased by approximately 40%, a putatively maximal response, at which time the intracameral epinephrine concentration was approximately 15 microM. Pretreatment with topical indomethacin produced a dose-dependent inhibition of epinephrine's facility-increasing effect; the maximum inhibition of 50% to 70% occurred at an indomethacin dose of 50 to 125 micrograms. Doubling the indomethacin dose (250 micrograms) produced no further inhibition, whereas a fivefold larger epinephrine dose (27.5 micrograms) did not overcome the inhibition. Forskolin and epinephrine both stimulated cAMP production in vitro, whereas [indomethacin] > or = 10(-4) M partially inhibited both basal and epinephrine-stimulated cAMP production in all four tissues. CONCLUSIONS: Approximately half of the epinephrine-induced facility increase is inhibited by indomethacin, but it is unclear whether the indomethacin-inhibitable fraction is mediated by epinephrine-stimulated prostanoid production or release.

Adrenergic Agonists↗

PubMed1995

The growth of medical groups paid through capitation in California.

BACKGROUND: In California, it is common for health maintenance organizations (HMOs) to contract with large medical groups that are paid through capitation and are responsible for managing a full spectrum of medical services. METHODS: We studied six large medical groups in California--Bristol Park Medical, Friendly Hills HealthCare Network, HealthCare Partners Medical Group, Mullikin Medical Centers, Palo Alto Medical Foundation, and San Jose Medical Group--that are paid through capitation and that are growing as a result of contracts with managed-care organizations. We conducted interviews and obtained data on factors such as patient enrollment, capitation and other revenue, numbers of days spent by enrollees in the hospital, and numbers of visits to physicians per enrollee. RESULTS: Between 1990 and 1994, the number of HMO enrollees whose care was paid for through capitation in the six medical groups increased by 91 percent, from 398,359 to 759,474. In 1994, the mean number of hospital days per 1000 HMO enrollees ranged from 120 to 149 for non-Medicare patients and from 643 to 936 days for Medicare patients. By comparison, in 1993 the mean numbers of hospital days per 1000 HMO enrollees not covered by Medicare were 232 for California and 297 for the United States; for HMO enrollees covered by Medicare, the numbers were 1337 for California and 1698 for the United States. In 1994, the average annual number of visits to physicians for HMO patients in the six groups not covered by Medicare ranged from 3.1 to 3.9; for Medicare patients, it ranged from 7.2 to 9.3; these rates were slightly lower than statewide and national rates. Four of the groups have sold their assets (such as facilities, supplies, equipment, and patients' charts) to outside investors; the physicians remain employed by physician-owned professional corporations. CONCLUSIONS: Medical groups paid through capitation offer a model for the status of physicians in managed-care systems that differs from the employee status offered by staff-model HMOs and the subcontractor status offered by HMOs that negotiate directly with individual physicians. Despite their growth, such medical groups in California face substantial challenges, such as obtaining the financial assets necessary to sustain rapid growth.

California↗

PubMed1995

Chromosome 5 suppresses tumorigenicity of PC3 prostate cancer cells: correlation with re-expression of alpha-catenin and restoration of E-cadherin function.

Considerable evidence now exists to support an important role for the E-cadherin-mediated cell-cell adhesion pathway as a suppressor of the invasive phenotype in adenocarcinoma cells. Previous studies have found that this pathway is frequently aberrant in prostate cancers, particularly those that are likely to metastasize. In this study, we report on the effects of re-establishment of this pathway in a prostate cancer cell line, PC-3, in which this adhesion system is dysfunctional by virtue of a deletion of the gene that codes for alpha-catenin, an E-cadherin-associated protein necessary for normal E-cadherin function. Re-expression of alpha-catenin was accomplished either by transfection of PC-3 cells with a copy of the alpha-catenin cDNA under the control of a heterologous promoter or by microcell-mediated transfer of chromosome 5, which contains the alpha-catenin gene and its normal regulatory elements. In both cases, re-expression of alpha-catenin is associated with a similar, dramatic alteration in cell morphology, whereby extensive cell-cell contact is observed. In the case of transfection of the cDNA, this expression is only transient, because the transfected cells either cease to proliferate or, more commonly, revert to the parental phenotype with concomitant cessation of alpha-catenin expression. In contrast, cells containing one or more copies of microcell-transferred chromosome 5 express alpha-catenin in a stable manner and continue to proliferate. Upon injection into nude mice, these latter cells are no longer tumorigenic, or form only slowly growing tumors with greatly extended doubling times when compared to the parental PC-3 cells. During passage in culture, clones that contain only one transferred copy of chromosome 5 reproducibly revert to the parental phenotype. This reversion is associated with loss of the chromosome 5 region containing the alpha-catenin gene and consequent loss of alpha-catenin expression, as well as re-emergence of tumorigenicity. Transfer of chromosome 5 into prostate cancer cells that are E-cadherin negative does not result in either morphological transformation or suppression of tumorigenicity, suggesting that these effects of alpha-catenin expression are dependent upon concomitant expression of E-cadherin. These data demonstrate the tumor suppressive ability of chromosome 5 in the PC-3 prostate cancer cells and suggest that re-expression of alpha-catenin with resultant restoration of E-cadherin function plays a critical role in this process.

Animals↗

PubMed1995

Superior cervical ganglionectomy in monkeys: aqueous humor dynamics and their responses to drugs.

The role of sympathetic innervation in regulating the responses of aqueous humor flow, outflow facility and pupillary diameter to timolol and epinephrine was investigated in cynomolgus monkeys following unilateral superior cervical ganglionectomy. Aqueous humor flow was measured fluorophotometrically under pentobarbital anesthesia before the first and after the ninth of twice-daily topical doses of epinephrine, and under ketamine anesthesia before the first and after the ninth of twice-daily topical doses of timolol, 4-19 months after denervation. Baseline aqueous humor flow rates determined 2-4 months following denervation were 40% greater under ketamine than under pentobarbital anesthesia, with no difference between denervated and control eyes. Epinephrine increased aqueous humor flow by up to 50% in a dose-dependent fashion in both eyes, with a non-significant tendency toward slightly greater potency and efficacy in the denervated eyes. Timolol decreased aqueous humor flow by up to 50% in a dose-dependent fashion with equal maximal efficacy in both eyes, but with slightly and statistically significantly greater potency and efficacy in the control eyes at submaximal doses. Early (1-3 months) but not late (23-27 months) after denervation, baseline pupil diameter under ketamine anesthesia was smaller in the denervated eyes than in the controls. The mydriatic response to 600 micrograms epinephrine was more sensitive in the denervated than the control eye both early (1-3 months) and later on (23-27 months) after denervation; timolol had no effect on pupil diameter in either eye. No striking differences in intraocular pressure or refraction were observed between the eyes under any of these conditions. Resting outflow facility or resistance and perfusion-induced facility increase or resistance reduction, measured by two-level constant pressure perfusion under pentobarbital anesthesia 1.5-4.5 years after unilateral sympathectomy, did not differ significantly between sympathectomized and control eyes. Facility increased (by up to 30-50% beyond washout) and resistance decreased (by up to 20-30% beyond washout) similarly in control and sympathectomized eyes 10-60 min and 3-4 hr after bolus intracameral epinephrine doses of 0.55 and 5.5 micrograms.

Animals↗

PubMed1995

Adverse selection among multiple competing health maintenance organizations.

This study examines risk selection among nine health plans competing for 16,182 employees of one large firm in 1989: one conventional fee-for-service plan, one group-model health maintenance organization (HMO), and seven network and independent practice model HMOs. We develop and compare measures of risk using weights based on HMO and fee-for-service expenditure data, respectively. We use a multiequation statistical model to develop two sets of utilization and expenditure weights for enrollees in each plan. One set of weights, based on discharge abstracts and outpatient records from the large group-model HMO, measures how much each of the nine groups of employees and dependents would have spent, had they been enrolled in a stringently managed plan with no consumer cost sharing. The other set of weights, based on fee-for-service claims data, measures how much each group would have spent, had it been enrolled in an unmanaged health plan with significant coinsurance and deductibles. Predicted annual expenditures per enrollee exhibit a 23% range from lowest (favorable selection) to highest (adverse selection) risk plans using the HMO weights and a 17% range using fee-for-service weights. The fee-for-service plan and group-model HMO with large enrollments have risk mixes near the center of the spectrum. Smaller HMOs exhibit the extreme forms of both favorable and adverse selection. The statistical methods adopted in this study can be used to risk-adjust capitation payments to competing health plans. As mergers among HMOs and group purchasing arrangements among employers increase the average enrollment in each plan from each payor, however, risk differences among plans will be attenuated and the need to risk-adjust payments will be less severe. Key words: health insurance; adverse selection; managed competition; health maintenance organization.

Actuarial Analysis↗

PubMed1995

Risk adjusting community rated health plan premiums: a survey of risk assessment literature and policy applications.

This paper surveys recent health care reform debates and empirical evidence regarding the potential role for risk adjusters in addressing the problem of competitive risk segmentation under capitated financing. We discuss features of health plan markets affecting risk selection, methodological considerations in measuring it, and alternative approaches to financial correction for risk differentials. The appropriate approach to assessing risk differences between health plans depends upon the nature of market risk selection allowed under a given reform scenario. Because per capita costs depend on a health plan's population risk, efficiency, and quality of service, risk adjustment will most strongly promote efficiency in environments with commensurately strong incentives for quality care.

Actuarial Analysis↗

PubMed1995

Health care purchasing and market changes in California.

This paper analyzes the process and outcomes of collective negotiations among large private employers and health maintenance organizations (HMOs) in California. In 1994, prior to collective negotiations, differences in benefit packages, risk mix, and volume of purchasing accounted for only one-third of the variance in premiums among firms and HMOs. The 1995 collective negotiations reduced the variance by 22 percent and the enrollment-weighted mean premium by approximately 9 percent, while enriching the standard benefit package. Savings for the eleven participating firms totaled $36.5 million. Large purchasers are reducing the number of health plans offered to their employees, standardizing the benefit package, using collective negotiations to contain costs, and shifting from vendor to partner relations with HMOs.

California↗

PubMed1994

Phalloidin inhibits epinephrine's and cytochalasin B's facilitation of aqueous outflow.

OBJECTIVE: To determine whether phalloidin, a fungal peptide that inhibits actin filament depolymerization, could inhibit the ability of cytochalasin B and epinephrine to increase the facility of aqueous outflow in the eyes of living cynomolgus monkeys. METHODS: Outflow facility was determined by two-level constant-pressure perfusion of the anterior chamber. After measurement of baseline facility in both eyes, one eye of each animal received intracameral phalloidin (1.3, 13, or 130 mumol/L); the opposite eye received vehicle. Both eyes then received either epinephrine (0.3 mmol/L) or cytochalasin B (0.2 mmol/L), and facility was again measured. RESULTS: Cytochalasin B and epinephrine increased facility by 120% to 190% and 100% to 180%, respectively (uncorrected for 15% resistance washout caused by perfusion itself). Phalloidin itself (13 or 130 mumol/L) did not affect facility, but it inhibited up to 50% of the facility-increasing effect of cytochalasin B and epinephrine. CONCLUSIONS: We conclude that (1) the aqueous humor outflow facilitating effects of cytochalasin B or epinephrine depend in some manner on depolymerization of actin filaments within trabecular meshwork cells, and (2) actin filaments may help regulate aqueous outflow.

Animals↗

PubMed1994

Interleukin-2 transfected prostate cancer cells generate a local antitumor effect in vivo.

In an effort to stimulate host-mediated antitumor response against prostate cancer in an animal model, highly malignant Dunning MAT-LyLu rat prostate carcinoma cells were transfected with the interleukin-2 (IL-2) cDNA, resulting in their ability to secrete large amounts of biologically active IL-2. Although parental cells form lethal tumors when injected subcutaneously into syngeneic hosts at doses of > or = 5,000, injections of IL-2 secreting cells initially formed tumors and regressed completely in each of over 200 animals at all doses tested (10(4)-8 x 10(7) cells). Mixtures of parental and IL-2 transfected cells were similarly rejected, demonstrating the non-cell autonomous nature of the response. Histological analysis of regressing tumors revealed a vigorous, predominantly lymphocytic and macrophage infiltrate at day 2 and marked tumor necrosis by day 6. Immunohistochemical staining of infiltrating lymphocytes at this latter time point demonstrated numerous T cells bearing either CD4 or CD8 surface markers, suggesting these cells as possibly mediating the tumor rejection. The ability of athymic mice to reject the IL-2 secreting tumor cells, however, suggests a non-T-cell-mediated mechanism. Although splenic natural killer (NK) activity is increased following injection of IL2 secreting tumor cells, this activity appears to be unnecessary for tumor elimination since syngeneic animals injected with asialo-GM1 antiserum to decrease NK activity also rejected IL-2 transfected cells, albeit slightly less effectively than untreated animals. Immunization of animals with subcutaneous injections of IL-2 transfected cells protected animals against a subsequent challenge of 10(4) wild-type cells 1 to 2 weeks later in 19 of 51 cases; however, immunization did not confer protection against larger doses of parental tumor. These studies indicate that high local concentrations of IL-2 stimulate the elimination of large local burdens of prostate cancer in this model system, and this elimination results in a weak, but detectable systemic immune response against wild-type prostate cancer cells.

Adenocarcinoma↗

PubMed1994

Apraclonidine and brimonidine effects on anterior ocular and cardiovascular physiology in normal and sympathectomized monkeys.

Apraclonidine and brimonidine administered topically to one eye of ketamine-anesthetized normal cynomolgus monkeys each produced a dose-related bilateral reduction in intraocular pressure which was not dependent on intact sympathetic innervation. Brimonidine was more potent and efficacious (10-12 mmHg maximum intraocular pressure reduction 2 hr after 200 micrograms) but produced a shorter-lasting effect than apraclonidine (4 mmHg maximum intraocular pressure reduction 1-6 hr after 600-1000 micrograms). Apraclonidine had little effect on pupil diameter, but brimonidine produced a dose-related bilateral miosis which was dependent on intact sympathetic innervation. Neither drug significantly affected refractive error. Topical brimonidine, but not apraclonidine, produced a dose-dependent reduction in mean arterial blood pressure, while both drugs lowered heart rate. A dose-dependent bilateral reduction in aqueous humor flow rate calculated over a 6-hr period following drug administration was produced by both topical apraclonidine (maximum 30-35% reduction with 600 micrograms) and brimonidine (maximum 30-45% reduction with 50-250 micrograms), which was not dependent on intact sympathetic innervation. Maintenance of blood pressure by intravenous infusion of angiotensin II had no effect on the aqueous humor flow suppression produced by 100 micrograms of topical brimonidine, but pentobarbital anesthesia abolished it. Intracameral injection of 10 micrograms brimonidine in rhesus monkeys produced an ipsilateral approximately 15% reduction in aqueous humor flow calculated for the 1-3 hr post-injection period. The cardiovascular and contralateral ocular effects observed with both drugs are presumably related to the monkeys' small body weight, and the magnitude of IOP reduction for a given degree of flow suppression would be greater in hypertensive than in normotensive eyes. Caution must therefore be exercised in extrapolating from our data in ocular normotensive monkeys to the glaucomatous human.

Adrenergic alpha-Agonists↗

PubMed1994

Retinal blood flow after superior cervical ganglionectomy: a laser Doppler study in the cynomolgus monkey.

There is a conflicting literature regarding the possible presence of adrenergic innervation of the retinal circulation. The effect of a histologically confirmed left superior cervical ganglionectomy on the total retinal blood flow in eight anaesthetised female cynomolgus monkeys was determined. Near total unilateral ocular sympathetic denervation was confirmed by ipsilateral miosis, supersensitivity of pupillary dilatation to topical phenylephrine and pupillary hyporesponsiveness to topical hydroxyamphetamine. Retinal vein diameters were measured from monochromatic photographs, maximum red cell velocities (Vmax) were measured with a helium-neon laser, using a bidirectional laser Doppler velocimeter technique, and the total retinal blood flow in each eye was determined by summation of measurements of flow in individual retinal veins. Mean (SEM) total retinal blood flow was 32.93 (1.49) and 30.41 (1.86) microliters/min in the eight sympathectomised and normal eyes respectively; the 9% (5%) difference was not statistically significant. Our study suggests that pharmacologically confirmed sympathetic denervation has little if any effect on resting total retinal blood flow.

Animals↗

PubMed1994

Forceps and vacuum extraction.

The proper use of forceps or vacuum extractor, or both, remains a safe and effective modality in achieving the universal goal of a healthy mother and baby. Their use requires continued experience, sharing of information, and possibly attention to subtleties of design. This review looks at the current situation with special emphasis on side effects and selection issues as found in the recent literature.

Birth Injuries↗

PubMed1994

Functional bowel disorders in women with dysmenorrhea.

OBJECTIVES: The relationship between menstrual and bowel symptoms, the overlap between the diagnoses of dysmenorrhea (DYS) and functional bowel disorder (FBD), and markers that may be useful in discriminating functional bowel disorders from DYS were studied in 383 women (20-40 yr of age). METHODS: All women completed the NEO Personality Inventory at intake and completed the Moos' Menstrual Distress Questionnaire and a bowel symptom inventory every 3 months for 12 months. Prostaglandin levels were measured in vaginal dialysate on the first day of menses. RESULTS: DYS was diagnosed in 19.8% of the total sample. Functional bowel disorder, defined as abdominal pain with altered bowel function, was diagnosed in 61% of the DYS group compared with 20% of controls (p < 0.05). Neuroticism scores were significantly higher in subjects with functional bowel disorder with or without DYS. However, bowel symptoms were significantly correlated with menstrual symptoms even after statistically controlling for the effects of neuroticism. Painful menses and water retention distinguished the DYS group from the functional bowel disorder group. Prostaglandin levels were elevated in women with DYS, but did not consistently differentiate the diagnostic groups. CONCLUSIONS: The strong covariation of menstrual and bowel symptoms, along with the overlap in diagnoses of DYS and function bowel disorder, suggest a common physiological basis.

Adult↗

PubMed1994

The changing boundaries of the American hospital.

The American hospital faces two different possible futures. In one, the hospital continues to expand into outpatient, home health, and long-term-care services and remains the center of the changing health care system. In the other, competition in each of these domains from independent health plans, which do not have to contend with the high wages, technological imperatives, and bureaucratic inertia of large hospital organizations, pushes the hospital to a peripheral role as provider of ever-diminishing acute inpatient services. The choice between these two futures will be made based on the efficiencies of vertical integration relative to market contracting. Transactions cost economics is used to analyze the changing boundaries of the hospital organization, particularly with respect to outpatient diagnostic and surgical clinics, home health agencies, and long-term-care facilities.

Ambulatory Care↗

PubMed1993

Homozygous deletion and frequent allelic loss of chromosome 8p22 loci in human prostate cancer.

Allelic loss studies have been instrumental in identifying tumor suppressor gene loci in a variety of cancers. In this study we analyzed prostate cancer specimens from 52 patients for allelic loss using 8 polymorphic probes for the short arm of chromosome 8. Overall, 32 of 51 (63%) informative tumors showed loss of at least one locus on chromosome 8p. The most frequently deleted region is observed at chromosome 8p22-8p21.2. Loss of one allele is identified in 14 of 23 (61%) tumors at D8S163, in 15 of 32 (47%) tumors at lipoprotein lipase, and in 20 of 29 (69%) tumors at MSR, all on 8p22. Loss of one allele is identified in 16 of 27 (59%) tumors at D8S220 at 8p21.3-8p21.2. In addition to frequent loss of one allele at the MSR locus, one metastatic prostate cancer sample demonstrated homozygous deletion of MSR sequences. Loci telomeric and centromeric to this region are largely retained. A chromosome 8p deletion map is constructed and defines the smallest region of overlap to a 14-cM interval at 8p22 between D8S163 and lipoprotein lipase, flanking the MSR locus. Evidence of chromosome 8q multiplication at locus D8S39 was detected in 5 of 32 (16%) tumors, all of which demonstrated loss with at least one probe on chromosome 8p. This study extends the previous finding of frequent loss of chromosome 8p in prostate cancer by defining a common region of loss of heterozygosity at 8p22 and a homozygous deletion of the MSR locus contained within this region. This is the first homozygous deletion identified in the genome of a human prostate cancer and the highest rate of loss yet reported on chromosome 8p in cancer. These results strongly suggest the presence of a tumor suppressor gene in this region which is frequently inactivated in prostate cancer.

Alleles↗

PubMed1993

DNA methylation of the fragile X locus in somatic and germ cells during fetal development: relevance to the fragile X syndrome and X inactivation.

To obtain insights into mechanisms responsible for methylation of CpG islands on the inactive X chromosome of normal females, we examined methylation of the fragile X (FraX) locus in a variety of tissues from normal fetuses and adults, and from males with the FraX syndrome. We identified 20 CCGG sites (MspI-HpaII sites M1-M20) within a 12-kb BglII fragment that includes the CpG island. Sites M3-M18, within the 1.2-kb CpG island are unmethylated on the active X in normal males and females at all ages and in all tissues studied. In contrast, these sites are at least partially methylated on the inactive X chromosome in a variety of tissues from normal females by six weeks from conception. The exceptional tissues are chorionic villi and gonads, which are significantly undermethylated. In addition, fetal germ cells are unmethylated at site M3, which is methylated on the inactive X in other tissues; thus, the methylation imprint of the inactive X has been erased. Methylation of the locus on the fragile X chromosome is similar to that of the normal inactive X but is more extensive and less heterogeneous. This suggests that the expansion of the island and the greater number of CpGs that result from amplification of the CGG repeat enhance the methylatibility of the island. Additional studies show that the chromatin of the CpG island is nuclease hypersensitive on the active X but insensitive on both inactive and FraX.

Adult↗

PubMed1993

Urethral pressure variation in women with vulvar vestibulitis syndrome.

OBJECTIVES: It is hypothesized that patients with vulvar vestibulitis syndrome will demonstrate increased urethral pressure variability. STUDY DESIGN: Twelve patients with confirmed vulvar vestibulitis syndrome were compared with two groups: 13 patients with chronic pelvic pain matched for age and race and 23 asymptomatic unmatched patients. Urodynamic variables studied included maximum urethral pressure, functional urethral length, bladder capacity, and urethral pressure variability. During urethral pressure measurement each patient was given a standard mental exercise. RESULTS: Urethral pressure variability was significantly greater in patients with vulvar vestibulitis than in those with chronic pain or in asymptomatic controls (Wilcoxon test, p < 0.001). Use of a multiple regression model that controlled for age, race, and parity showed that diagnostic group predicted a significant degree of urethral pressure variability (F = 8.18, p < 0.001). CONCLUSIONS: Vulvar vestibulitis syndrome is associated with increased urethral pressure variability, and variation in muscular tone of the urethra is the probable source of this variability. However, the possible relationship with the pathogenesis of vulvar vestibulitis syndrome is unknown at present.

Adult↗

PubMed1993

A comparison of serum and vaginal dialysate concentration of 13,14-dihydro-15-keto-PGF2 alpha in women undergoing 1st trimester therapeutic abortions.

13,14-Dihydro-15-keto-PGF2 alpha(PGFM) levels in serum and vaginal secretion, before, one hour, and 24 hours post abortion were measured in 13 women from 8 to 12 weeks pregnant. The mean metabolite levels in the blood were 61.2 pg/ml pre-termination, 73.1 pg/ml and 121.4 pg/ml one hour and 24 hours post-termination. The vaginal dialysate means were 136.7 pg/ml, 425.7 pg/ml, and 211.7 pg/ml respectively.

Abortion, Induced↗