Search PubMed⌕ Search

Biomedical subjects

J Hodge

Publications and source records attributed to J Hodge.

At least 19 recordsLinked to original sources
PubMed2006

Unexpected relationship between plasma protein binding and the pharmacodynamics of 2-NAP, a CCK1-receptor antagonist.

UNLABELLED: WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT?: * Two chemically diverse CCK1 receptor antagonists have been shown clinically to inhibit CCK-evoked contraction of human gallbladder [2, 3]. These studies have not examined the relationship between plasma concentration and effect, the latter usually considered to be predictive from the free drug concentration [8]. * We wanted to examine our novel CCK1 receptor antagonist in this validated model and also to explore its PK-PD relationship. WHAT THIS STUDY ADDS: * 2-NAP inhibited CCK-evoked human gallbladder contraction in vivo but at a plasma free concentration that was, in theory, too low to have achieved adequate CCK1 receptor occupancy. * The study serves as a caveat to the assumption that free plasma concentration can be used to predict pharmacological effect. AIMS: To study the pharmacokinetics and pharmacodynamics of 2-NAP (2-naphthalenesulfonyl-L-aspartyl-(2-phenethyl)amide), a selective CCK1 receptor antagonist in healthy volunteers. METHODS: 2-NAP was given to 12 healthy male volunteers in an ascending dose, safety and PK phase 1a study by 1 h i.v. infusion (0.6-9.6 mg kg(-1) h(-1)). A further 12 healthy male volunteers received i.v. CCK-8S (6.25 pmol kg(-1) h(-1)) to produce gallbladder contraction, measured by ultrasound recordings of gallbladder volume, and the effect of concurrent i.v. 2-NAP administration was studied. Plasma protein binding in vitro and ex vivo was measured by ultrafiltration and by equilibrium dialysis. RESULTS: 2-NAP was generally well tolerated, displayed linear pharmacokinetics and a very high degree of plasma protein binding (99.9%). A 105 min i.v. CCK-8S infusion induced a reduction in gallbladder volume of 14.9 (+/-7.0) ml during placebo co-infusion and this was reduced to 2.4 (+/-5.9) ml when 2-NAP was co-infused with CCK-8S (P = 0.00024, paired t-test, mean change 12.5 ml; 95% CI For mean 7.4, 18.3 ml). This extent of inhibition was consistent with a 2-NAP total plasma concentration of 36 microm, but when protein binding corrections were made, the 'free concentration' of 2-NAP was only 0.04 microm, a value much less than the average equilibrium dissociation constant of 2-NAP for human CCK1 receptors ( approximately 0.7 microm). CONCLUSIONS: The pharmacological effect of a drug is usually considered to be determined by its free concentration. However, the complete inhibition of CCK-8S-evoked gallbladder contraction by a free plasma concentration of 0.04 microm 2-NAP was much greater than would have been predicted from simple drug-receptor occupancy theory and cautions against the general use of free concentration of drug for predicting pharmacological effect.

Adolescent↗
PubMed2004

Health information privacy and syndromic surveillance systems.

The development of syndromic surveillance systems to detect potential terrorist-related outbreaks has the potential to be a useful public health surveillance activity. However, the perception of how the Health Insurance Portability and Accountability Act of 1996 (HIPAA) Privacy Rule applies to the disclosure of certain public health information might affect the ability of state and local health departments to implement syndromic surveillance systems within their jurisdictions. To assess this effect, a multiple-question survey asked respondents to share their experiences regarding patient confidentiality and HIPAA Privacy Rule requirements when implementing syndromic surveillance systems. This assessment summarizes the results of a national survey of state terrorism-preparedness coordinators and state epidemiologists and reflects the authors' and others' experiences with implementation.

Bioterrorism↗
PubMed2001

Acquisition of CD80 (B7-1) by T cells.

Activation of T cells usually requires two signals. Signal 1 is mediated via a peptide-MHC on the APC; signal 2 is mediated via a costimulatory molecule on the APC surface. We demonstrate here that naive CD4(+) T cells actually acquire the costimulatory molecule CD80 (B7-1) from syngeneic APCs after activation. This phenomenon was demonstrated showing acquisition of CD80 by T cells from CD80/CD86 (B7-2) knockout mice, and by treating T cells with cyclohexamide to further rule out endogenous expression of CD80 by T cells. Moreover, no CD80 mRNA could be detected in T cells that had acquired CD80. The amount of acquisition of CD80 by T cells was shown to be directly related to both the strength of signal 1 and the amount of CD80 on the APC. Specificity of this acquisition was also shown by the lack of acquisition by T cells from CD28 knockout mice (implicating CD28 in this process), the lack of acquisition of CD40 (another molecule on the APC surface) by T cells, and confocal microscopy studies. We demonstrate for the first time that 1) naive T cells, following acquisition of CD80 from APCs, were themselves shown to be capable of acting as APCs; and 2) memory T cells that have acquired CD80 from APCs undergo apoptosis in the presence of increased levels of signal 1. Thus we demonstrate both immunostimulatory and immunoregulatory functions as a result of CD80 acquisition by different T cell populations.

Animals↗
PubMed1999

The metabolism of native and randomized butterfat chylomicrons in the rat is similar.

Reportedly, randomly rearranging the position of fatty acids (FA) in butterfat triacylglycerol (TAG) by interesterification, thereby lowering the proportion of saturated FA in the sn-2 position, reduces its hypercholesterolemic and hypertriglyceridemic properties when fed to humans. The aim of this work was to determine if these reductions in plasma cholesterol and TAG could be explained by an improved rate of clearance from the plasma of chylomicrons composed of randomized butterfat, using a rat model. Acute chylomicron clearance studies demonstrated no differences in fractional clearance rates of cholesteryl esters and TAG from the plasma of rats infused with chylomicrons produced from gastric feeding of either native (NBF) or randomized (RBF) butterfat. Although there was a 14% decrease in the level of saturated FA occupying the sn-2 position of TAG in RBF compared with NBF, this difference became negligible (approximately 5%), following digestion of the fat and subsequent repackaging of TAG into chylomicrons. These observations suggest that the previously observed reduction in hypercholesterolemic properties of randomized butterfat in rat is unlikely to be explained by improved clearance of chylomicron TAG.

Animals↗
PubMed1997

Clinicopathologic variables predictive of residual dysplasia after cervical conization.

OBJECTIVE: To evaluate the clinicopathologic variables that are important for predicting residual dysplasia after cervical conization or the loop electroexcisional procedure. STUDY DESIGN: A retrospective review of 80 cases was performed on patients with squamous dysplasia in the conization specimen, endocervical curettage (ECC) performed immediately after resection, margin status reported by the pathologist and adequate postprocedure follow-up. RESULTS: Twelve patients had residual dysplasia. No case progressed to invasive carcinoma. A multivariate analysis was performed with presence or absence of residual dysplasia as the dependent variable and patient age, type of procedure (cold knife conization or loop excision), grade of dysplasia, margin status and ECC status as independent variables. Margin status was the strongest predictor of residual disease, followed by ECC status. Patient age had a minimal association with persistence. Of the 12 patients with residual dysplasia, 11 had a positive margin, and 8 had a positive ECC. Only 38% of patients with a positive margin had residual disease, but 67% with a positive margin and ECC had residual dysplasia. CONCLUSION: Margin status and ECC are useful in predicting residual dysplasia after conization.

Adolescent↗
PubMed1996

Ontogeny of copepod predation in juvenile squid (Loligo opalescens).

Copepods are the major prey of juvenile squid, and small species of squid such as Loligo opalescens face a great challenge in catching these erratically moving crustaceans. We studied the ontogeny of copepod predation in laboratory-reared animals and found that mastery of copepod capture develops progressively, starting shortly after hatch with strong attacks of a simple type. Modifications of the initial basic attack lead to more specialized strategies that effectively extend the range of capture to both longer and shorter distances. This progression culminates, by approximately 40 days post-hatching, in adult-like prey capture behavior involving tentacle extension and retraction. Squid raised exclusively on easily captured Artemia nauplii and introduced to a copepod diet 40 days after hatching displayed only basic attack behavior, characteristic of very young squid. All of these attacks were unsuccessful, and very few of these animals survived the transition. Copepod capture thus appears to be a skill that must be acquired in an experience-dependent manner early in post-hatching life.

Animals↗
PubMed1996

The enemy within: diarrheal rates among British and Australian troops in Iraq.

British and Australian medical teams working in Northern Iraq in 1991 providing primary care to refugees and the war wounded were subjected to a descriptive retrospective survey, 5 weeks after arriving in Iraq. The aim was to document different rates of diarrhea in British and Australian troops. The British, who were not taking daily doxycycline and did not enforce a plate- and hand-washing routine, experienced higher rates of diarrhea (69% of British troops compared with 36% of Australian troops), which was more severe and of a longer duration (p < 0.001) and resulted in twice as many days being lost (p < 0.001) in spite of the British team being half the size of the Australian contingent, and the region having enteropathogens with a high rate of antibiotic resistance. Vigorous hand- and plate-washing routines along with doxycycline prophylaxis appear to significantly reduce incapacitation from diarrhea in this military setting and have an important implication for operational effectiveness.

Anti-Bacterial Agents↗
PubMed1995

Managing diversity in the health care industry: a conceptual model and an empirical investigation.

Between 1985 and 2000, 8 out of every 10 new entrants to the work force will be minorities, immigrants, or women. If the U.S. health care industry has to retain a competitive edge, it will have to effectively attract and manage the diverse talent that will characterize its new work force. This article analyzes the authors' cultural awareness survey results and suggests a strategic model for managing diversity in the health care industry.

Aged↗
PubMed1993

Differential utilization of eicosapentaenoic acid and docosahexaenoic acid in human plasma.

It has recently been shown that the omega 3 fatty acid status in humans can be predicted by the concentration of eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids in plasma phospholipids [Bjerve, K.S., Brubakk, A.M., Fougner, K.J., Johnsen, H., Midjthell, K., and Vik, T. (1993) Am. J. Clin. Nutr., in press]. In countries with low intake of omega 3 fatty acids, the level of EPA in plasma phospholipids is often only about one-fifth the concentration of DHA. The purpose of this study was to investigate whether this difference in the concentration of these two fatty acids was due to a selective loss of EPA relative to DHA or to a lower dietary intake of EPA. Seven female volunteers ingested four grams of MaxEPA daily for 2 wk and in the following 4 wk they ate a diet almost completely devoid of the long-chain omega 3 fatty acids. The concentrations of the omega 3 fatty acids in the plasma cholesteryl esters, triglycerides and phospholipids and the high density lipoprotein phospholipids were examined at weekly intervals throughout the study. There was a more rapid rise in the concentration of EPA than in DHA levels in the supplementation period in all lipid fractions, but there was a disproportionate rise in DHA relative to EPA in the plasma lipids compared with the ratio in the supplement. In the depletion phase there was a rapid disappearance of EPA from all fractions, such that pre-trial levels were reached by one week post-supplementation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Appraisal of the clinical value of serotoninergic drugs.

Principal objectives in obesity management comprise the prevention of weight gain, the promotion of weight loss, and the treatment of obesity-related complications, including diabetes, hypertension, and depression. Serotonin agonists reduce food intake. The resultant weight loss is variable and there appears to be no way of predicting good responders, nor is there evidence that additional weight loss attributable to drug therapy is sustained once treatment is discontinued, although nonpharmacological strategies for preventing weight regain are worthy of exploration. Serotonin agonists are of clinical value if there is a short-term need for weight reduction or if long-term pharmacotherapy can be justified. This implies that sometimes the dangers of the obese state outweigh the potential hazards of drug treatment. Clearly, if the same agent also improves diabetic control, blood pressure, or depression then a longer term usage is more readily justified. The extent to which this may be achieved by the currently available 5-HT agonists is discussed.

Appetite Depressants↗
PubMed1992

Case report: myiasis--the botfly boil.

Cutaneous furunculoid myiasis arises from the infestation of skin or mucous membranes with dipterous larvae. Myiasis from the botfly Dermatobia hominis is a common parasitic disease of the tropics of Central and South America, and may present in the United States. With increasing travel by U.S. citizens, there is potential for increased occurrence; it is important to be able to accurately diagnose myiasis and differentiate it from entities with similar presentations, such as leishmaniasis. The authors describe four cases of myiasis from D. hominis infestation and review clinical features, differential diagnosis, and treatment.

Adult↗
PubMed1986

Synthesis and bioevaluation of alkyl 2-cyanoacryloyl glycolates as potential soft tissue adhesives.

A series of alkyl 2-cyanoacryloyl glycolate tissue adhesives were synthesized and characterized by NMR. Physical properties and bond strengths are presented. Within the series, bond strength decreased with increasing molecular weight. Corresponding polymers were evaluated by in vitro and in vivo techniques for biocompatibility. In general, in vitro biocompatibility increased with molecular weight. Based on in vitro and in vivo results, the isobutyl and isoamyl derivatives gave polymers that were most biocompatible, however, the entire series was found to be less reactive than poly(methyl 2-cyanoacrylate) and only the isopropyl derivative polymers more reactive than poly(isobutyl 2-cyanoacrylate). Approximately one-third of the isobutyl polymer biodegraded in vivo after 6 weeks.

Adhesiveness↗
PubMed1986

Synthesis and bioevaluation of a rapidly biodegradable tissue adhesive: 1,2-isopropylidene glyceryl 2-cyanoacrylate.

A rapidly biodegradable tissue adhesive, 1,2-isopropylidene glyceryl 2-cyanoacrylate, was synthesized and characterized by NMR. Bond strength was determined. Three types of corresponding polymers were prepared and evaluated for in vitro and in vivo toxicity. The polymers were generally found to be in the moderately toxic and toxic groups similar to the lower alkyl 2-cyanoacrylates.

Adhesiveness↗
PubMed1986

Impaired 6-phosphofructokinase activity in mononuclear leukocytes from patients with type II diabetes mellitus.

Seven cytoplasmic enzyme activities were measured in extracts of mononuclear leukocytes (lymphocytes plus monocytes) obtained from 19 type II diabetic humans and 10 healthy control subjects. 6-Phosphofructokinase activity was significantly decreased in cell extracts from diabetics, while other enzyme activities were similar in diabetics and controls. Since the effects of starvation on enzyme activities are sometimes similar to the effects of diabetes, the studies were repeated in 5 control subjects after a 2-day fast. This short period of starvation did not mimic the effect of diabetes on 6-phosphofructokinase activity. The decreased enzyme activity was not correlated with percent specific insulin binding to monocytes in the same cell preparations nor to clinical variables such as obesity or the broad range of fasting plasma glucose values encountered among the diabetics. We conclude that 6-phosphofructokinase activity in mononuclear leukocytes, as in other tissues, may be a marker for a postreceptor lesion associated with the insulin resistance found in type II diabetes mellitus.

Adult↗