Search PubMed⌕ Search

Biomedical subjects

J Horton

Publications and source records attributed to J Horton.

At least 37 records · Page 2Linked to original sources
PubMed2000

Albendazole: a review of anthelmintic efficacy and safety in humans.

This comprehensive review briefly describes the history and pharmacology of albendazole as an anthelminthic drug and presents detailed summaries of the efficacy and safety of albendazole's use as an anthelminthic in humans. Cure rates and 0% egg reduction rates are presented from studies published through March 1998 both for the recommended single dose of 400 mg for hookworm (separately for Necator americanus and Ancylostoma duodenale when possible), Ascaris lumbricoides, Trichuris trichiura, and Enterobius vermicularis and, in separate tables, for doses other than a single dose of 400 mg. Overall cure rates are also presented separately for studies involving only children 2-15 years. Similar tables are also provided for the recommended dose of 400 mg per day for 3 days in Strongyloides stercoralis, Taenia spp. and Hymenolepis nana infections and separately for other dose regimens. The remarkable safety record involving more than several hundred million patient exposures over a 20 year period is also documented, both with data on adverse experiences occurring in clinical trials and with those in the published literature and/or spontaneously reported to the company. The incidence of side effects reported in the published literature is very low, with only gastrointestinal side effects occurring with an overall frequency of just >1% . Albendazole's unique broad-spectrum activity is exemplified in the overall cure rates calculated from studies employing the recommended doses for hookworm (78% in 68 studies: 92%, for A. duodenale in 23 studies and 75% for N. americanus in 30 studies), A. lumbricoides (95% in 64 studies), T. trichiura (48% in 57 studies), E. vermicularis (98% in 27 studies), S. stercoralis (62% in 19 studies), H. nana (68% in 11 studies), and Taenia spp. (85% in 7 studies). The facts that albendazole is safe and easy to administer, both in treatment of individuals and in treatment of whole communities where it has been given by paramedical and nonmedical personnel, have enabled its use to improve general community health, including the improved nutrition and development of children.

Adolescent↗
PubMed2000

An analysis of the safety of the single dose, two drug regimens used in programmes to eliminate lymphatic filariasis.

This review of the safety of the co-administration regimens to be used in programmes to eliminate lymphatic filariasis (albendazole + ivermectin or albendazole + diethylcarbamazine [DEC]) is based on 17 studies conducted in Sri Lanka, India, Haiti, Ghana, Tanzania, Kenya, Ecuador, the Philippines, Gabon, Papua New Guinea, and Bangladesh. The total data set comprises 90,635 subject exposures and includes individuals of all ages and both genders. Results are presented for hospital-based studies, laboratory studies, active surveillance of microfilaria-positive and microfilaria-negative individuals, and passive monitoring in both community-based studies and mass treatment programmes of individuals treated with albendazole (n = 1538), ivermectin (9822), DEC (576), albendazole + ivermectin (7470), albendazole + DEC (69,020), or placebo (1144). The most rigorous monitoring, which includes haematological and biochemical laboratory parameters pre- and post-treatment, provides no evidence that consistent changes are induced by any treatment; the majority of abnormalities appear to be sporadic, and the addition of albendazole to either ivermectin or DEC does not increase the frequency of abnormalities. Both DEC and ivermectin show, as expected, an adverse event profile compatible with the destruction of microfilariae. The addition of albendazole to either single-drug treatment regimen does not appear to increase the frequency or intensity of events seen with these microfilaricidal drugs when used alone. Direct observations indicated that the level of adverse events, both frequency and intensity, was correlated with the level of microfilaraemia. In non microfilaraemic individuals, who form 80-90% of the 'at risk' populations to be treated in most national public health programmes to eliminate lymphatic filariasis (LF), the event profile with the compounds alone or in combination does not differ significantly from that of placebo. Data on the use of ivermectin + albendazole in areas either of double infection (onchocerciasis and LF), or of loiais (with or without concurrent LF) are still inadequate and further studies are needed. Additional data are also recommended for populations infected with Brugia malayi, since most data thus far derive from populations infected with Wuchereria bancrofti.

Albendazole↗
PubMed2000

Quality of life after adjuvant chemotherapy for breast cancer.

PURPOSE: To evaluate the quality of life of breast cancer patients previously treated with adjuvant chemotherapy. METHOD: Registry data were used to recruit a sample of breast cancer patients (N = 61; mean age = 51.6 years) with no current evidence of disease who had completed adjuvant chemotherapy between 3 and 36 months earlier (average = 15.87 months). In addition, a peer nomination procedure was used to recruit an age-matched comparison group of women with no history of cancer (N = 59; mean age = 51.5 years). Both groups were mailed a survey to complete that included the Medical Outcomes Study Short Form 36 (SF-36) and the Center for Epidemiologic Studies Depression Scale (CES-D). These data were used to test the hypothesis that breast cancer patients previously treated with adjuvant chemotherapy experience impaired quality of life relative to their peers and to identify demographic and medical factors associated with individual differences in patient quality of life. RESULTS: Consistent with predictions, the postchemotherapy group scored poorer than the noncancer comparison group on the CES-D and on six of the eight subscales as well as the physical component summary scale of the SF-36 (p < 0.05). With regard to individual differences in patient quality of life, younger age and unmarried status were positively related to poorer mental well-being and greater depressive symptomatology (p < 0.05). Time since cancer diagnosis and chemotherapy completion were also positively related to greater depressive symptomatology (p < 0.05). In contrast, none of the demographic or medical variables assessed were related to physical well-being (p > 0.05). CONCLUSIONS: Breast cancer patients appear to experience problems in multiple quality of life domains following the completion of adjuvant chemotherapy treatment. Demographic and medical characteristics explain individual differences in mental but not physical aspects of patient quality of life. These findings demonstrate the need for interventions to improve the quality of life in breast cancer patients previously treated with adjuvant chemotherapy.

Adult↗
PubMed2000

Increased cardiomyocyte intracellular calcium during endotoxin-induced cardiac dysfunction in guinea pigs.

Septic shock is a complex pathophysiologic state characterized by circulatory insufficiency, multiple system organ dysfunction, and frequent mortality. Although profound cardiac dysfunction occurs during sepsis, the pathogenesis of this dysfunction remains poorly understood. To determine whether abnormalities in intramyocyte calcium accumulation might contribute to the development of cardiac dysfunction, we measured myocyte intracellular calcium during peak cardiac dysfunction after an endotoxin challenge. Intraperitoneal administration of Escherichia coli lipopolysaccharide 4 mg/kg to adult guinea pigs resulted in significantly impaired cardiac performance (Langendorff preparation) 18 h after challenge compared with control. This included diminished left ventricular pressure development (56 +/- 7 versus 95 +/- 4 mm Hg, p < 0.05), maximal rate of left ventricular pressure rise (998 +/- 171 versus 1784 +/- 94 mm Hg/s, p < 0.05) and left ventricular pressure fall (1014 +/- 189 versus 1621 +/- 138 mm Hg/s, p < 0.05). Assay of intracellular calcium in fura-2AM-loaded cardiac myocytes demonstrated increased intracellular calcium concentration in myocytes obtained from lipopolysaccharide-challenged animals compared with controls (234 +/- 18 versus 151 +/- 6 nM, p < 0.05). Inhibition of calcium-release channel (ryanodine receptor) opening by administration of dantrolene prevented the increase in intracytoplasmic calcium (159 +/- 8 versus 234 +/- 18 nM, p < 0.05) and partially ameliorated systolic and diastolic ventricular dysfunction. These data indicate that abnormalities of intracellular calcium contribute to the development of endotoxin-induced myocardial dysfunction.

Animals↗
PubMed2000

Pharmacokinetics of fluticasone propionate inhaled via the Diskhaler and Diskus powder devices in patients with mild-to-moderate asthma.

OBJECTIVE: The aim of these studies was to compare the pharmacokinetics of inhaled fluticasone propionate (FP) after repeated administration via the Diskus or Diskhaler dry powder inhalers (DPIs) to patients with mild-to-moderate asthma. METHODS: Both studies evaluated the pharmacokinetics of inhaled administration of FP via a DPI to patients with mild-to-moderate asthma, according to a randomised, double-blind, placebo-controlled design. In the first study, FP 100 microg or 500 microg was administered twice daily via the Diskhaler for 6 weeks and, in the second, FP 500 microg was administered via the Diskus or Diskhaler for 12 weeks. RESULTS: In the first study, plasma FP concentrations could be detected consistently only with the higher dose; the lower dose produced concentrations close to or below the 0.025 microg/L quantification limit of the radioimmunoassay used. From detailed analysis of a subgroup of patients receiving the 500 microg dosage, steady-state plasma FP concentrations were attained within one week of commencing treatment. After 4 weeks, the maximum plasma FP concentration (Cmax) in this subgroup was 0.096 microg/L [95% confidence interval (CI) 0.066-0.141] and the area under the plasma FP concentration-time curve up to the last quantifiable concentration (AUClast) was 0.491 microg/L x h (95% CI: 0.256-0.940). The steady-state to single dose accumulation ratio for FP after twice-daily administration varied between patients: a ratio of approximately 1.7 was recorded after comparison of Cmax at week 4 and day 1. In the second study, the point estimate of the Diskus to Diskhaler ratio for Cmax in all patients was 0.91 (90% CI: 0.76-1.10) after 4 weeks' treatment. From a detailed analysis of a subgroup of patients, the corresponding ratio for AUClast at the same time point was 1.15 (90% CI: 0.69-1.94), indicating no significant difference in systemic exposure to FP between the 2 devices. Steady-state kinetics were achieved by week 1: the point estimate ratios of Cmax and AUClast at week 4 compared with week 1 were 0.88 (90% CI: 0.66-1.16) and 0.95 (90% CI: 0.66-1.36), respectively. Administration of FP via either DPI had no effect on plasma cortisol levels over the 12-hour postdose period. CONCLUSION: In patients with asthma receiving repeated inhaled doses of FP, the systemic exposure (AUC) after inhalation from the Diskus was similar to that from the Diskhaler, with no difference between the DPIs in the effects on cortisol suppression. The 2 DPIs therefore have very similar pharmacokinetic profiles.

Administration, Inhalation↗
PubMed1999

The role of albendazole in programmes to eliminate lymphatic filariasis.

Citing earlier advances in the treatment of lymphatic filariasis [particularly the effectiveness of single-dose diethylcarbamazine (DEC) in reducing microfilaraemia and its enhanced effectiveness when co-administered with single-dose ivermectin], Eric Ottesen, Mahroof Ismail and John Horton consider recent studies on the antifilarial activity of albendazole that have led to the current recommendations for its use in single-dose regimens in conjunction with either DEC or ivermectin for large-scale control/elimination programmes. Furthermore, the potential of albendazole as a macrofilaricide for treating individual patients with lymphatic filarial infections is emphasized as one of a number of important research questions that remain to be explored.

Albendazole↗
PubMed1999

Fatigue in women receiving adjuvant chemotherapy for breast cancer: characteristics, course, and correlates.

This study investigated the characteristics, course, and correlates of fatigue in women receiving adjuvant chemotherapy for breast cancer. Fifty-four patients were assessed before the start of chemotherapy and during the first three treatment cycles. An age-matched sample of women with no cancer history was assessed at similar time intervals for comparison purposes. Results indicated that breast cancer patients experienced worse fatigue than women with no cancer history. These differences were evident before and after patients started chemotherapy. In addition, fatigue worsened among patients after treatment started. More severe fatigue before treatment was associated with poorer performance status and the presence of fatigue-related symptoms (e.g., sleep problems and muscle weakness). Increases in fatigue after chemotherapy started were associated with continued fatigue-related symptoms and the development of chemotherapy side effects (e.g., nausea and mouth sores). These findings demonstrate the clinical significance of fatigue in breast cancer patients before and during adjuvant chemotherapy treatment. Results also suggest that aggressive management of common side effects, such as nausea and pain, may be useful in relieving chemotherapy-related fatigue.

Adult↗
PubMed1999

Loading technique comparison in permanent 125I prostate implants.

Treatment of prostate cancer utilizing iodine 125 (125I) interstitial seed implants has become an accepted and widely used modality. Numerous variations in 125I seed implant loading distribution techniques have developed as a result of the preferences of individual institutions implementing the modality. No particular universal standard is currently used for 1251 seed implants. A major concern with 125I seed implants is coverage of the prostate with the desired dose and the minimization of dose to the urethra. A variation of seed distribution per individual anatomy is desirable. Historically, brachytherapy relied on dosimetry systems, such as the Paris, Quimby, and Manchester systems to achieve the desired dose distribution. Use of various peripherally loaded 125I seed implant distributions to accommodate anatomic variations within the same institution prompted the interest of how the results compare to the Manchester system.

Brachytherapy↗
PubMed1999

Albendazole generics--a comparative in vitro study.

PURPOSE: We sought to determine whether disintegration and dissolution behavior differs among various albendazole generic formulations obtained from third world countries and to compare them with the innovator's product. METHODS: Dissolution behavior of various albendazole formulations was studied with USP Apparatus 2 in SGFsp and in a modified SGFsp which contained 0.1% of the nonionic surfactant Triton X 100. Disintegration was tested according to the European Pharmacopoeia. RESULTS: Dissolution experiments in SGFsp showed a wide range in rate and extent of albendazole dissolution. The innovator product released 81 percent within two hours, a profile matched by only one other formulation. For other formulations 32 to 64% was released within two hours. Use of a modified SGFsp, containing 0.1% Triton X 100 to simulate the surface tension of gastric juice, resulted in less discrimination between products. The innovator product again showed the fastest and most complete dissolution, with ninety percent released within two hours. The generic formulations released between 67 and 82%, except for one formulation which achieved only 43% release. The results in SGFsp plus Triton X 100 may be more meaningful than in SGFsp since the surface tension of the medium is closer to the physiological value. All formulations passed the disintegration test according to the European Pharmacopoeia, with disintegration times ranging from 2.5 to 11 minutes. CONCLUSIONS: Generic albendazole products vary widely in their dissolution behavior. Differences among products were greater in SGFsp than in SGFsp plus Triton X 100. These differences were not reflected in the disintegration behavior of the products.

Albendazole↗
PubMed1999

Randomized dose-ranging study of the safety and efficacy of WR 238605 (Tafenoquine) in the prevention of relapse of Plasmodium vivax malaria in Thailand.

WR 238605 is an 8-aminoquinoline developed for the radical cure of Plasmodium vivax. Forty-four P. vivax-infected patients were randomly assigned to 1 of 4 treatment regimens: 3 groups received a blood schizonticidal dose of chloroquine followed by WR 238605: group A (n=15) received 300 mg daily for 7 days; group B (n=11), 500 mg daily for 3 days, repeated 1 week after the initial dose; group C (n=9), 1 dose of 500 mg. A fourth group (D; n=9) received chloroquine only. Among patients who completed 2-6 months of follow-up (n=23), there was 1 relapse in group B (day 120) and 1 in group C (day 112). Among patients treated with chloroquine only, there were 4 relapses (days 40, 43, 49, and 84). WR 238605 was safe, well tolerated, and effective in preventing P. vivax relapse.

Adolescent↗
PubMed1999

Albendazole therapy for loiasis refractory to diethylcarbamazine treatment.

Although diethylcarbamazine is curative in approximately 60% of patients who acquire loiasis as long-term visitors to an endemic area, some individuals continue to have signs and symptoms of infection despite multiple courses of diethylcarbamazine. On the basis of a study of albendazole treatment of loiasis in microfilaremic patients that suggested a macrofilaricidal effect of the drug, we treated three patients who had symptomatic loiasis refractory to more than four courses of diethylcarbamazine with albendazole. At the time of treatment, all patients had persistent symptoms despite decreasing titers of antifilarial antibodies and normal eosinophil counts. Symptoms resolved in all three patients following albendazole therapy. In one patient, nonspecific symptoms recurred 2 years later, but unlike her symptoms before albendazole therapy, they were not accompanied by the appearance of subcutaneous nodules containing adult worms. The other two patients have been symptom-free in the 8 years after albendazole treatment. In summary, albendazole may be useful for the treatment of loiasis when diethylcarbamazine is ineffective or cannot be used.

Adult↗
PubMed1999

Oral combination chemotherapy in the management of AIDS-related lymphoproliferative malignancies.

An oral combination chemotherapy regimen initially developed for AIDS-related non-Hodgkin's lymphoma includes lomustine (CCNU), etoposide, cyclophosphamide, and procarbazine. This regimen takes advantage of oral administration, the in vitro synergy of these drugs and their first-line efficacy in lymphoma, and the ability of lomustine and procarbazine to cross the blood-brain barrier. This regimen was used to treat 38 patients with AIDS-related non-Hodgkin's lymphoma. The overall objective response rate was 66% (34% complete response rate) with a 5% CNS relapse rate, and a median survival duration of 7.0 months. One-third of the patients survived for 1 year, 11% for 2 years, and half of the patients survived free from progression of their lymphoma. On the basis of these results, this oral regimen was modified and administered to 5 patients with AIDS-related primary CNS lymphoma as part of a sequential combined-modality chemotherapy and radiation regimen. Rapid progression of CNS disease was observed in this group of patients, with a median survival duration of 1.0 month. The identical regimen was administered to 7 patients with AIDS-related Hodgkin's disease: we observed a 71% partial remission rate and a median survival duration of 7.0 months. Myelosuppression remains the most significant clinical toxicity. Our results with this oral regimen appear comparable to those of standard intravenous combination chemotherapy regimens in patients with AIDS-related non-Hodgkin's lymphoma.

Administration, Oral↗
PubMed1999

Impact of third molar removal on demands for postoperative care and job disruption: does anaesthetic choice make a difference?

A prospective cohort study was undertaken to investigate the influences of anaesthetic modality and surgical difficulty on social reintegration and demands on health services after third molar removal. The study was undertaken at the Oral and Maxillofacial Surgery Department, Cardiff Dental Hospital. Of 444 patients, 266 (60%) had their third molars removed. The main outcome measures included anaesthetic modality, surgical difficulty (WHARFE scores), utilisation of health services, effects on work, school and home life. In all, 101 (40%) patients were treated under local anaesthesia (LA) +/- intravenous (i.v.) sedation and 165 (60%) under general anaesthesia (GA); 81 (49%) as inpatients and 84 (51%) as day cases. Of these patients, 38 (14%) returned to the hospital and 74 (28%) utilised primary care services postoperatively in addition to a standard review appointment. Patients treated under GA made more demands on primary care services (chi 2 = 6.41, df = 2, P < 0.05) and took more time away from work (P < 0.05). Patients underestimated the time they needed to recover. There was similar disruption to job, college and home life. There were no links between disruption and particular anaesthetic modalities and surgical difficulty. Surgery under GA was linked to increased postoperative demands on primary care, but not secondary care, and to longer job disruption. This could not fully be attributed to surgical difficulty.

Adolescent↗
PubMed1998

Molecular epidemiology of HTLV-II among United States blood donors and intravenous drug users: an age-cohort effect for HTLV-II RFLP type aO.

Molecular subtyping was used to investigate the epidemiology of human T-lymphotropic virus type II (HTLV-II) in the United States. Nested polymerase chain reaction of the HTLV-II long terminal repeat region followed by restriction fragment length polymorphism (RFLP) analysis was performed on HTLV-II seropositive subjects including 97 U.S. blood donors without major risk factors for HTLV-II infection, 53 injection drug users (IDU), and 10 American Indian blood donors. Three new HTLV-II RFLP types were confirmed with DNA sequencing and phylogenetic analysis. HTLV-II RFLP type aO (Switzer classification) was associated with older age [adjusted odds ratio (OR) 1.06 per year of age, 95% confidence interval (CI) 1.02-1.09] and with Black (OR 5.24, 95% CI 1.90-14.47) and White (OR 4.43, 95% CI 1.67-11.75) race/ethnicity. These data are consistent with an age-cohort effect for HTLV-II RFLP type aO among older White and Black IDU and blood donors. This finding could be explained by an epidemic of non-aO HTLV-II RFLP types among younger persons of Hispanic and other race/ethnicity, superimposed upon endemic HTLV-II RFLP type aO among older Black and White persons.

Adolescent↗
PubMed1998

The effect of sequential injuries on splanchnic perfusion and eicosanoid release.

BACKGROUND: This study examines the hypothesis that sequential burn injury followed by intraabdominal sepsis induces significantly greater splanchnic hypoperfusion and reduced intestinal PGI2 release than either injury independently. MATERIALS AND METHODS: Anesthetized Sprague-Dawley rats were randomized to one of four groups: BURN (45% body surface area scald burn) + cecal ligation and puncture (CLP); BURN alone; CLP alone; or uninjured controls (SHAM). Twenty-four hours following injury, superior mesenteric artery (SMA) blood flow was measured with a doppler flow probe. Splanchnic eicosanoid release (6-keto-PGF1alpha, metabolite of PGE2; TxB2, metabolite of TxA2; and PGE2) was measured in mesenteric venous effluent utilizing an isolated, perfused bowel preparation. RESULTS: SMA blood flow was no different than that of controls 72 h following BURN injury alone; whereas CLP alone resulted in a 80% reduction in splanchnic blood flow when compared with controls (P < 0.001). SMA blood flow in animals sustaining BURN + CLP was only modestly reduced from controls (P = 0.04) and 3.6 times greater than that of animals sustaining CLP alone (P < 0.001). PGI2 was the dominant eicosanoid released by the intestine with levels 10 times greater than TxB2 and nearly 50 times greater than PGE2. CLP either alone or when combined with BURN was associated with a 60% decrease in splanchnic PGI2 release when compared to controls (P < 0.05). CONCLUSIONS: These data suggest that moderate BURN injury in rats attenuates the severe reduction in splanchnic perfusion associated with intraabdominal sepsis and that this occurs despite profound reductions in the release of the endogenous splanchnic vasodilator PGI2.

Animals↗
PubMed1998

Choice of anaesthetic and healthcare facility for third molar surgery.

A prospective investigation was carried out to find out which factors affected the choice of anaesthetic for 444 consecutive patients (153 male, 291 female, age range 15-85) listed for extraction of third molars. Two hundred and seventy-two were listed for treatment under general anaesthesia, 120 (44%) as inpatients and 152 (60%) as day cases. The remaining 144 (32%) patients were to be treated under local anaesthesia and 28 (6%) with additional intravenous sedation. Logistic regression analysis showed that difficulty of surgery, patients' anxiety, patients' preferences, medical history, and number of teeth to be removed were important predictors of choice of anaesthetic. From an anaesthetist's perspective, many more patients should have been treated under local anaesthesia with intravenous sedation and fewer should have been listed for inpatient extraction under general anaesthesia.

Adolescent↗
PubMed1998

Effect of altered serum lipid concentrations on the IC50 of halofantrine against Plasmodium falciparum.

Halofantrine (Hf) is a highly lipophilic antimalarial which significantly associates with triglyceride (TG) rich plasma lipoproteins, and this is likely manifest as a decrease in the free fraction of drug. This study assessed the effect of using growth media containing 10% serum containing different concentrations of TG (i.e. TG-rich plasma lipoproteins) on the IC50 of Hf determined using continuous in vitro culture of Plasmodium falciparum. Serum was collected from a human subject in either a fasted state or at various times after ingestion of a fatty meal. There was a linear and statistically significant 2.5-fold increase in the IC50 of Hf across a 6-fold range of increasing TG concentrations, with the increased IC50 values being ascribed to a decreased free fraction of Hf in the growth media due to sequestration by TG-rich lipoproteins. Chloroquine diphosphate, which is hydrophilic and not significantly bound by TG-rich lipoproteins, was used as a control and its IC50 values were independent of TG concentrations. These data indicate that consideration should be given to the adoption of standard conditions for the collection of serum with respect to pre- or postprandial states, and that subject- and disease-related factors which alter plasma lipoprotein profiles should be considered when interpreting the IC50 profile of Hf (and possibly other lipophilic antimalarials). Furthermore, although food is known to affect the pharmacokinetics of Hf, these data suggest that altered plasma lipoprotein profiles could also influence its pharmacodynamic profile.

Animals↗