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J Francis

Publications and source records attributed to J Francis.

At least 91 records · Page 5Linked to original sources
PubMed1994

The effect of anticonvulsant drugs on GABA-stimulated chloride uptake.

Eight anticonvulsant drugs-including clonazepam, diazepam and phenobarbital-were tested for their effects on GABA-stimulated chloride uptake in rat cerebral cortical microsacs (unfiltered synaptoneurosomes). "Mid" and "high" therapeutic concentrations were screened, and, if significant enhancement was found, full concentration-response tests were done. In the initial screens, enhancement of GABA-stimulated uptake was found only with phenobarbital, clonazepam and diazepam. In subsequent concentration-response tests, the effects of phenobarbital were found to occur throughout the range of normal, anticonvulsant concentrations, whereas the effects of clonazepam and diazepam were observed only above the concentrations normally used for the chronic control of seizures or anxiety. These data suggest that phenobarbital's anticonvulsant effects are mediated via the GABAA receptor complex, but that the low-dose effects of the benzodiazepines may be mediated via some other mechanism.

Animals↗
PubMed1994

The use of market research to design healthcare offerings. A case study of a senior citizen community.

With a growing elderly population, there is little argument that the healthcare system in the United States must understand the needs and wants of its elderly consumers. This is especially important in a rural community where services can be limited and access to these services is difficult for consumers. Marketing research is one way in which rural healthcare facilities can gain market information not only to enhance their product offerings, but also to ensure that proper and sufficient services are provided. This article presents a case study of a long-term healthcare facility using marketing research.

Aged↗
PubMed1994

Rat C-reactive protein causes a charge modification of LDL and stimulates its degradation by macrophages.

We have previously shown the binding of low-density lipoprotein (LDL) to immobilized rat C-reactive protein (CRP) and the formation of a fluid-phase complex between these two proteins. In this report we used immunoelectrophoresis and agarose gel electrophoresis to show increased anodic migration of the LDL particle as a result of the modification of LDL by rat CRP. The degradation of the modified 125I-LDL by rat peritoneal macrophages was increased more than twofold in the presence of rat CRP. The increase in rat CRP-mediated 125I-LDL degradation by macrophages was dependent on the concentrations of 125I-LDL and rat CRP. This increased 125I-LDL degradation was inhibited by phosphorylcholine. In contrast, the degradation of 125I-acetyl-LDL by macrophages was not affected by rat CRP, although acetylated LDL inhibited the rat CRP-stimulated degradation of 125I-LDL. Increasing concentrations of LDL did not affect the degradation of rat 125I-CRP by the macrophages, which suggested that the rat CRP and the modified LDL did not enter the cell as a complex. Our results suggested that the increased degradation of 125I-LDL was caused by the charge modification of 125I-LDL by rat CRP, due to a fluid-phase complex formation between 125I-LDL and rat CRP, and that the degradation involved the scavenger receptor present on the macrophages.

Animals↗
PubMed1993

Selective dopamine D-1 receptor agonists, SK&F 38393 and CY 208-243 reduce sucrose sham-feeding in the rat.

Gastric-fistulated rats were trained to sham-feed a 10% sucrose solution in a 60 min test. The selective dopamine D-1 receptor agonists, SK&F 38393 (3 and 10 mg/kg, s.c.) and CY 208-243 (1 and 3 mg/kg, s.c.) both produced dose-related reductions in sham-feeding. These effects were present in the first 5 min of the test period, and persisted throughout the remainder of the test. The data confirm and extend results for an anorectic effect of SK&F 38393 and demonstrate, for the first time, a similar anorectic effect of CY 208-243.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1993

A microstructural analysis of the effects of presatiation on feeding behavior in the rat.

Rats were familiarized with eating a sweetened mash, and were divided into three groups. Before a test meal, the animals were allowed to eat the mash for 0, 2.5, or 5 min, respectively, to vary the degree of their satiation. Their subsequent consumption of the meal and their behavior over the course of a 30-min period was observed, to provide a microstructural description of the behavioral changes that are characteristic of increasing satiation. Presatiation, as expected, reduced the size of the test meal, and did so predominantly by reducing the duration of feeding, especially during the first 5 min of the test period. There was a slight reduction in the rate of eating as a function of presatiation, and a tendency for the latency to initiate feeding to increase. When other responses were considered separately, there was little effect of presatiation on their microstructural parameters. However, the duration of a composite category (comprising rearing, grooming, and stationary) did increase significantly as a function of presatiation. These data provide a behavioral template for satiation, against which to compare treatments that purport to manipulate feeding satiation.

Animals↗
PubMed1993

Vitamin K coagulation status in surgical newborns and the risk of bleeding.

The vitamin K coagulation status in surgical newborns, who may be at increased risk of developing hypocoagulability and hemorrhage, has not previously been studied. Therefore, we measured the combined activity of the plasma vitamin K-dependent coagulation factors (Thrombotest), total prothrombin, PIVKA II, plasma vitamin K1, fibrinogen, D-Dimer, and platelets in 49 newborns admitted to a neonatal surgical intensive care unit. All infants had significant pathology, and treatment involved surgery in all but two. Twenty-three infants (47%) underwent surgery on two or more occasions. Intravenous or oral antibiotics were used in all patients and many received more than one course. All infants had vitamin K1 prophylaxis at birth. At day 0 (date of birth), the mean Thrombotest and total prothrombin levels were 51% (range, 20% to 100%) and 40% (range, 24% to 59%), respectively. Coagulation activity decreased on day 1 (P > .1) and was followed by a graduate increase in clotting activity, reaching normal adult levels (> 60%) at day 5 for Thrombotest and day 24 for total prothrombin. Only three infants had a Thrombotest less than 20%. PIVKA II was detected in 20 cases (41%). However, levels were within normal limits (< 0.9%) in 17 of these, and between 1.0 and 4.8% in the remaining three infants. There was no relationship between elevated PIVKA levels and coagulation activity in these patients. Plasma vitamin K1 was very high, particularly in the first days of life.(ABSTRACT TRUNCATED AT 250 WORDS)

Birth Weight↗
PubMed1992

Time dependency of cognitive recovery with cobalamin replacement: report of a pilot study.

OBJECTIVE: To examine the effects of cobalamin repletion on cognition in elderly subjects with low serum cobalamin and evidence of cognitive dysfunction. DESIGN: Time series data collected in an open trial of parenteral cobalamin therapy. SETTINGS: Outpatient geriatric assessment centers, inpatient geropsychiatry unit, and tertiary care university hospital. PARTICIPANTS: Twenty-two subjects with low serum cobalamin (less than 150 pmol/L) and evidence of cognitive dysfunction were entered consecutively over an 8-month period of time. Eighteen subjects completed the study. INTERVENTIONS: Subjects received 1000 micrograms of cyanocobalamin intramuscularly daily for 1 week, then weekly for 1 month, then monthly thereafter for a minimum of six months. OUTPATIENT MEASURE: The Mattis Dementia Rating Scale (DRS) was administered both before and at least 6 months after full cobalamin replacement therapy. The hypothesis that cognitive improvement was dependent on the duration of cognitive symptoms was formulated a posteriori. RESULTS: After a minimum of 6 months of cobalamin therapy, 11 of 18 patients showed cognitive improvement. There was a striking correlation between duration of cognitive symptoms and response to therapy. Patients symptomatic for less than 12 months gained an average of twenty points on the DRS (paired t test P = 0.0076), whereas patients symptomatic greater than 12 months lost an average of three points (paired t test P = .34). Two patients symptomatic for only 3 months normalized their DRS scores, gaining 31 and 28 points, respectively. CONCLUSION: There may be a time-limited window of opportunity for effective intervention in patients with cognitive dysfunction and low serum cobalamin.

Aged↗
PubMed1992

Prognosis after hospital discharge of older medical patients with delirium.

OBJECTIVE: To determine survival, functional independence, and cognitive performance of older patients 2 years after an episode of delirium. DESIGN: Descriptive cohort study. SETTING: General medical wards of a teaching hospital. PATIENTS: Two hundred twenty-nine consecutive patients aged 70 years or older who had been community-dwelling prior to admission. Fifty patients met criteria for delirium (cases); these were compared to patients without delirium (controls). Two-hundred twenty-three patients survived hospitalization (46 cases, 177 controls) Of these, 92% were followed greater than or equal to 2 years. MAIN OUTCOME MEASURES: Vital status, place of residence, activities of daily living (ADL), and cognitive performance were determined by telephone interview of patients or care-givers 2 years after discharge. Independent community living was defined as survivorship outside of an institution and without dependence in any of four basic ADL (bathing, dressing, transfers, eating). RESULTS: Two-year mortality in the entire population was 39% for cases and 23% for controls (relative risk 1.82, 95% confidence interval 1.04-3.19). Delirium identified those patients at risk for loss of independent community living, even after adjustment for potential confounding variables (adjusted odds ratio 2.56, 95% confidence interval 1.10-5.91). Follow-up cognitive testing in a subset of patients with high baseline performance revealed a greater decline in performance among cases of delirium than controls (P = 0.023). CONCLUSIONS: Delirium identifies older patients at risk for mortality or loss of independence. Delirium may also identify patients at risk for future cognitive decline.

Activities of Daily Living↗
PubMed1992

[3H]Phenytoin identifies a novel anticonvulsant-binding domain on voltage-dependent sodium channels.

The voltage-dependent sodium channel has been proposed as a specific target for the actions of the anticonvulsant drug phenytoin. Working at 0-4 degrees, we previously reported the existence of specific [3H]phenytoin binding sites in rat brain membranes. In the present study, the binding of [3H]phenytoin was assessed at 22 degrees, a temperature favorable to the binding of sodium channel ligands. At 22 degrees, the site had a Kd of 1.5 microM, which is in the relevant therapeutic concentration range for anticonvulsant activity (1-10 microM), and a calculated Bmax of 4.5 pmol/mg of protein, which is similar to previous estimates of sodium channel concentration in brain membranes. In competition experiments, specific [3H]phenytoin binding was found to be inhibited by drugs that interact with the sodium channel, including antiarrhythmics, local anesthetics, anticonvulsants, and site-specific neurotoxins (the steroidal alkaloid activators, beta-scorpion venoms, and brevetoxin-3). Diazepam, used clinically in the management of tonic-clonic status epilepticus, and flunarizine, a calcium channel blocker with anticonvulsant activity, potentiated [3H]phenytoin binding at micromolar concentrations. Other drugs and ligands, including neurotransmitters, neuromodulators, and ligands for other ion channels, had no effect. Depolarization with KCl showed [3H]phenytoin binding to be voltage sensitive. Experiments with batrachotoxin (a specific site 2 toxin) and anticonvulsants demonstrated that the interactions between these compounds and the [3H]phenytoin binding site are allosteric in nature. These results provide direct evidence that phenytoin interacts with the voltage-dependent sodium channel and indicate that such interactions take place at therapeutic concentrations. They support previous proposals, based on toxin-binding and electrophysiological studies, that the therapeutic effects of phenytoin result from a selective inhibition of voltage-dependent sodium flux.

Animals↗
PubMed1991

A case control study of trisomy 21 and maternal pre-conceptual radiography.

A case control study of 67 infants with trisomy and 67 apparently normal controls matched to each case for sex, date of birth and age of mother at birth has been carried out. Cases were compared with controls for exposure of their mothers to medical radiography prior to conception as recorded in medical records. The total number and type of radiographs were similar in both groups. The relative risk of trisomy for a radiographic examination, involving direct irradiation of the ovaries, prior to conception was 0.8 (95% confidence interval 0.34-1.83). The estimated mean nominal ovarian doses for case and control mothers were 2.19 and 2.41 mGy respectively. Therefore this study does not show an increased risk of giving birth to a child with trisomy for mothers whose ovaries have been exposed to medical radiation. However, because of the small numbers of cases studied and the limited data available a risk cannot be excluded. It is unlikely that a radiograph involving direct exposure of the maternal gonads could increase the risk of a subsequent pregnancy affected by trisomy by more than two.

Case-Control Studies↗
PubMed1991

Carbachol-stimulated phosphorylation of a 170-kDa endogenous protein in avian salt gland cells.

The effect of cholinergic stimulation of cellular protein phosphorylation was studied using an intact cell preparation isolated from the avian salt gland. Isolated cells were allowed to incorporate 32Pi into the cellular ATP pool and then challenged with compounds known to induce ion secretion in this tissue. Addition of carbachol resulted in a time- and concentration-dependent (EC50 = 500 nM) increase in 32Pi content of a 170-kDa protein (pp170). The stimulated phosphorylation could be blocked by the inclusion of atropine (100 microM). Subcellular fractionation studies localized pp170 to the plasma membrane fraction of the tissue. The integral nature of this protein was demonstrated by detergent-solubilization experiments with Triton X-100. The possibility that carbachol stimulates phosphorylation of pp170 via activation of protein kinase C (PKC) was investigated. Incubating salt gland cells with 4 beta-phorbol 12-myristate 13-acetate (PMA; 1 microM) or carbachol (100 microM) resulted in a translocation of soluble PKC from the cytosol to a plasma membrane fraction. Addition of either PMA (1 microM) or ionomycin (1 microM) alone did not enhance phosphorylation of pp170. A 4.5-fold increase in the phosphorylation state of pp170 was only observed when PMA and ionomycin were added concurrently. Preincubation of salt gland cells with PKC inhibitors H-7 (50 microM) or staurosporine (10 microM) inhibited the carbachol-stimulated phosphorylation of pp170. These findings suggest that carbachol mediates its secretomimetic effects via activation of PKC and that pp170 may represent a novel integral membrane PKC substrate protein.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1990

A prospective study of delirium in hospitalized elderly.

The prevalence, risk factors, and outcomes of delirium were studied in 229 elderly patients. Fifty patients (22%) met criteria for delirium; nondelirious elderly constituted the control group. Abnormal sodium levels, illness severity, dementia, fever or hypothermia, psychoactive drug use, and azotemia were associated with risk of delirium. Patients with three or more risk factors had a 60% rate of delirium. Delirious patients stayed 12.1 days in the hospital vs 7.2 days for controls and were more likely to die (8% vs 1%) or be institutionalized (16% vs 3%). Illness severity predicted 6-month mortality, but the effect of delirium was not significant. Delirium occurs commonly in hospitalized elderly, is associated with chronic and acute problems, and identifies elderly at risk for death, longer hospitalization, and institutionalization. The increased mortality associated with delirium appears to be explained by greater severity of illness.

Activities of Daily Living↗
PubMed1990

The anorectic effect of SK&F 38393, a selective dopamine D1 receptor agonist: a microstructural analysis of feeding and related behaviour.

An observational study was undertaken to provide a microstructural analysis of the effects of the selective dopamine D1 receptor agonist, SK&F 38393, on feeding and associated behaviours in the rat. Adult, male non-deprived rats were adapted to eating a meal of sweetened mash in a 30-min period. SK&F 38393 (3.0 and 10 mg/kg, SC) significantly reduced food consumption). It also reduced the frequency of feeding bouts and the local rate of eating, while there was an increase, at 10 mg/kg, in the mean duration of individual feeding episodes. The D1 receptor agonist also reduced the total duration of locomotor activity, but did not affect the total duration of rearing, grooming, sniffing, oral behaviours (other than feeding), or resting. The frequency of bouts of locomotion, rearing, grooming, and sniffing were reduced by SK&F 38393. Consideration of the time-courses for the several responses suggested that SK&F 38393 did not materially affect the form and sequence of behavioural responses in the test, although some changes occurred.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1990

In vitro activity of ramoplanin on staphylococci.

Approximately 1000 strains of staphylococci isolated from the skin of patients before and after coronary artery by-pass surgery were speciated using the API-Staph system, and tested for susceptibility to ramoplanin and teicoplanin. In addition flucloxacillin MICs were available for 750 strains. MICs were performed by incorporating dilutions of antibiotics in 'Isosensitest' Agar (Oxoid) and applying approx 10(4) cells by a multi-point inoculator. The strains tested (numbers in brackets) included: Staph. epidermidis (352), Staph. haemolyticus (133), Staph. simulans (104), Staph aureus (69), Staph. hominis (54), Staph. warneri (39), Staph. capitis (23), Staph. saprophyticus (12), Staph. cohnii (6) and Staph. sciuri (2). The overall MICs were: ramoplanin MIC 50%: 0.5 mg/l, MIC 90%: 1 mg/l; teicoplanin MIC 50%: 2 mg/l, MIC 90%: 8 mg/l. Ramoplanin MICs of greater than 2 mg/l were only found for 17 strains from eleven patients which included: Staph. simulans (6), Staph. haemolyticus (4) and Staph. epidermidis (2). The maximum MIC however was only 8 mgl, so no strains were ramoplanin-resistant. There was no relationship between ramoplanin and flucloxacillin MICs; but despite their differing modes of action, the strains with higher ramoplanin MICs also had higher teicoplanin MICs.

Anti-Bacterial Agents↗
PubMed1990

Procoagulant activity in whole blood from patients with breast and colorectal cancer.

Whole blood procoagulant activity was determined by measuring the endotoxin-induced shortening of the celite-activated whole blood recalcification time in patients with breast cancer (n = 29), colorectal cancer (n = 18), benign breast disease (n = 26), benign colorectal disease (n = 10), normal volunteers (n = 17) and surgical in-patients with non-malignant and non-inflammatory conditions (n = 18). Using this method, patients with breast and colorectal cancer produced significantly more procoagulant activity than normal controls (P less than 0.001), surgical in-patients (P less than 0.005) and patients with benign breast (P less than 0.001) and benign colorectal (P = 0.05) disease respectively. The difference between subjects classified as 'cancer' or 'non-cancer' was highly significant (P less than 0.0001). There were no significant differences in total white cell or absolute monocyte counts between subject groups, and in individual patients, there was no correlation between these parameters and the procoagulant activity. It is concluded that the activated whole blood recalcification time is a more reproducible way of measuring whole blood procoagulant activity than the original technique, and that using this method, patients with cancer show higher procoagulant activity than corresponding benign controls.

Adult↗