Biomedical subjects

D Howes

Publications and source records attributed to D Howes.

At least 19 recordsLinked to original sources

PubMed2004

A penny for your thoughts: small bowel obstruction secondary to coin ingestion.

We report a case of small bowel obstruction secondary to coin ingestion. A 22-year-old woman presented to the Emergency Department (ED) with a 3-week history of abdominal pain. Upon initial history the patient denied any foreign body ingestion. Only after computed tomography (CT) scanning of the abdomen and pelvis did the patient admit to deliberate ingestion of a single United States penny coin. During surgical evaluation it was found that the coin had lodged near the ileocecal valve and an inflammatory mass had formed around the intraluminal coin, causing a 10 x 7 cm fibrous tumor to completely obstruct the small bowel. It is thought that oxidation of the coin, with subsequent exposure of its high zinc content, instigated the inflammatory cascade.

Abdomen, Acute↗

PubMed2001

Fate of ethanol topically applied to skin.

Ethanol is a major component of many aerosol sprays and consumer products that are designed to contact the skin. It is theoretically possible that small amounts of ethanol from alcohol-based sprays can be absorbed across the skin or inhaled during spraying. In order to assess the potential systemic dose, three parameters were measured: the evaporation of [14C]ethanol from the skin surface, the in vitro penetration of [14C]ethanol through excised pig skin and the ethanol concentration in the blood of human volunteers following simulated use of an alcohol based deodorant spray. The rate of evaporation from Benchkote and whole pig skin was similar (t(1/2)=13.6 sec and 11.7 sec, respectively) while that from glass was longer (t(1/2)=24.8 sec). Ethanol penetration through pig skin in vitro was greater in occluded cells than in non-occluded cells (2.19 mg/cm(2) and 0.10 mg/cm(2) in 24 hours, respectively). At the maximum flux seen in this experiment under occlusion, the amount of ethanol penetrating from a 1 m(2) area of skin would give a blood alcohol level of about 4 mg% in a 70-kg man. In the human use study, none of the blood samples taken from 16 human volunteers exhibited a detectable level of alcohol. These studies provide evidence that a systemic dose of ethanol is likely to be very low after the use of formulations delivering ethanol to the skin.

Administration, Topical↗

PubMed2001

The absorption, distribution and excretion of 1- and 2-.

Human breast milk is rich in 2-palmitoyl 1,3 unsaturated triacyglycerols and during the neonatal period, when milk is the sole source of nutrients, their role could be particularly important. Betapol is a novel triacylglycerol mix resembling human breast milk in its high palmitic acid content and positional distribution. The total fat absorption from Betapol has been shown to be higher than fat from conventional infant milk formulas and closer to human breast milk in infants. However, the relative fate of purified palmitic acid esterified to glycerol in the 1-, 3- and 2-positions in neonatal and young animals has not previously been established. Therefore, the fate of orally administered 1-[1-14C]palmitoyl, 2,3 dioleoyl glycerol ([14C]POO) and 1,3 dioleoyl,2-[1-14C]palmitoyl glycerol (O[14C]PO) was investigated in suckling and weanling rats using liquid scintillation counting of tissues and expired air and whole-body autoradiography. The results obtained indicate that orally administered [14C]POO and O[14C]PO are extensively absorbed from the gut, probably either as palmitic acid or as a palmitoyl glyceride in both suckling and weanling rats. Radioactivity initially concentrated in brown fat with apparent migration to the white fat of weanling rats by 96 h. Levels of 14C were low in blood, brain and other tissues. Excretion of 14C was mainly by expiration of CO(2) (approximately 72% in 96 h), indicating beta-oxidation as a major route of metabolism. Urine and faeces accounted for only approximately 6% of the excreted radioactivity. The design and size of the experiment did not allow tests of statistical significance between the absorption and excretion of OPO and POO to be conducted. However, the absorption, distribution, beta-oxidation and excretion appeared to be similar.

Animals↗

PubMed2000

The safety evaluation of phytosterol esters. Part 6. The comparative absorption and tissue distribution of phytosterols in the rat.

As part of an extensive safety evaluation programme, a series of studies has been conducted to determine the fate of phytosterols in the rat. Rats were dosed by oral gavage with 14C-labelled samples of cholesterol, beta-sitosterol or beta-sitostanol or (3)H-labelled samples of beta-sitostanol, campesterol, campestanol or stigmasterol dissolved in sunflower seed oil. Urine and faeces were collected for up to 96 hours after dosing. There was no quantification of biliary excreted material in these studies. Animals were sacrificed and either prepared for whole body autoradiography or tissues and carcass remains were assayed for 14C or (3)H. The overall absorption of phytosterols was low as judged by tissue and carcass levels of radioactivity. Elimination from the body was mainly in the faeces and was initially very rapid, but traces of material were still being excreted at 4 days after dosing. While total absorption of the phytosterols could not be fully quantified without biliary excretion data, it was clear that cholesterol was absorbed to the greatest extent (27% of the dose in females at 24 hours). Campesterol (13%) was absorbed more than beta-sitosterol and stigmasterol (both 4%) which were absorbed more than beta-sitostanol and campestanol (1-2%). The absorption of phytosterols was slightly greater in females than males. For each test material, the overall pattern of tissue distribution of radioactivity was similar, with the adrenal glands, ovaries and intestinal epithelia showing the highest levels and the longest retention of radioactivity.

Animals↗

PubMed2000

Percutaneous penetration and dermal metabolism of triclosan (2,4, 4'-trichloro-2'-hydroxydiphenyl ether).

triclosan is widely used in many products that contact the skin of consumers. This study compares in vivo and in vitro skin absorption of triclosan and determines the potential of skin to metobolize it prior to entering the blood stream. After in vivo topical application of a 64.5mM alcoholic solution of [(3)H]triclosan to rat skin, 12% radioactivity was recovered in the faeces, 8% in the carcass 1% in the urine, 30% in the stratum corneum and 26% was rinsed from the skin surface at 24 hours after application. Free triclosan and the glucuronide and sulfate conjugates of triclosan were found in urine and faeces. triclosan penetrated rat skin more rapidly and extensively than human skin in vitro. 23% of the dose had penetrated completely through rat skin into the receptor fluid by 24 hours, whereas penetration through human skin was only 6.3% of the dose. Chromatographic analysis of the receptor solutions showed that triclosan was metabolized to the glucuronide, and to a lesser extent to the sulfate, during passage through the skin. triclosan glucuronide appeared rapidly in the receptor fluid whereas triclosan sulfate remained in the skin. Although the major site of metabolism was the liver, conjugation of triclosan in skin was also demonstrated in vitro and in vivo, particularly to the glucuronide conjugate which was more readily removed from the skin. The in vitro system provides a reasonable estimate of dermal absorption in vivo for the rat. Therefore by extrapolation of the comparative in vitro data for human and rat skin it is reasonable to deduce that dermal absorption in human of triclosan applied at the same dose is about one-third of that in the rat in vivo.

Administration, Cutaneous↗

PubMed2000

How to use the Internet to improve care delivery--without changing the way physicians work.

Martin's Point Health Care is a nonprofit organization with more than 30 primary care physicians and 280 health care professionals serving 43,000 patients in four sites in Maine and New Hampshire. Like many medical group practices, Martin's Point believed its patients needed more channels to communicate with their physicians. An increasing number of patients wanted more in-depth advice from their doctors, and many already used the Internet to obtain health care information. This article describes how Martin's Point developed an interactive Web communications program to build physician/patient relationships and improve practice efficiency.

Confidentiality↗

PubMed1997

Percutaneous penetration of N-nitroso-N-methyldodecylamine through human skin in vitro: application from cosmetic vehicles.

The human skin penetration of N-nitroso-N-methyldodecylamine (NDOMA) from isopropyl myristate (IPM) and two vehicles representative of cosmetic/personal care formulations was determined in vitro. When applied as an infinite dose in IPM (1 microgram/microliter) the average total absorption over 48 hr was 0.10 +/- 0.01% of the applied dose (all data are expressed as means +/- SE). When applied as a finite dose in a representative oil-in-water emulsion formulation the average total absorption over 48 hr was 4.66 +/- 0.76% of the applied dose. When applied as a finite dose in a representative shampoo formulation for 10 min, followed by rinsing (to represent in-use exposure conditions), the average total absorption over 48 hr was 0.75 +/- 0.17% of the applied dose. Approximately 72% of the NDOMA in the applied shampoo formulation was removed by rinsing. The overall data indicated that NDOMA could penetrate the skin but that penetration was low. The rate and extent of absorption, however, could be affected by differences in the vehicle of application, time of exposure and whether the formulation is (and the conditions are designed to mimic) a rinse-off or leave-on product.

Carcinogens↗

PubMed1997

Percutaneous penetration of octyl salicylate from representative sunscreen formulations through human skin in vitro.

The human skin penetration of [14C]octyl salicylate from two representative sunscreen vehicles was determined in vitro. 3H-sucrose was incorporated into all formulations and provided a marker for membrane integrity. When applied as a finite dose in an oil-in-water emulsion vehicle containing 5% (w/w) octyl salicylate, the average total absorption of 14C over 48 hr was 0.65+/-0.16% of the applied dose (representing a total amount permeated of 1.58+/-0.36 microg/cm2). When applied as an infinite dose in the oil-in-water emulsion vehicle the average total absorption of 14C over 48 hr was 0.47+/-0.22% of the applied dose (representing a total amount permeated of 27.54+/-13.91 microg/cm2). When applied as a finite dose in a representative hydroalcoholic formulation containing 5% (w/w) octyl salicylate, the average total absorption of 14C over 48 hr was 0.59+/-0.09% of the applied dose (representing a total amount permeated of 1.58+/-0.25 microg/cm2). When applied as an infinite dose in the hydroalcoholic formulation the average total absorption of 14C over 48 hr was 0.23+/-0.05% of the applied dose (representing a total amount permeated of 11.28+/-2.55 microg/cm2). The penetration of [14C]salicylic acid [applied at a concentration of 2.7% (w/w), in the oil-in-water emulsion] was also determined. When applied as a finite dose the average total absorption of 14C over 48 hr was 1.14+/-0.23% of the applied dose (representing a total amount permeated of 1.65+/-0.39 microg/cm2). These results suggest that the in vitro human skin permeation of octyl salicylate is relatively low. The amounts of octyl salicylate and salicylic acid permeated when applied in similar vehicles were remarkably similar over 48 hr (1.58 microg/cm2 and 1.65 microg/cm2, respectively). This suggests the possibility that the 14C label appearing in the receptor fluid may, in both cases, represent salicylic acid. If this is the case, then it is possible that the amount of octyl salicylate permeating through the skin is much less than that suggested by the data obtained here. This supposition is, however, entirely speculative and has yet to be confirmed experimentally.

Administration, Cutaneous↗

PubMed1995

Diverse mechanisms of calcium mobilization by peroxisome proliferators in rat hepatocytes.

The ability of six peroxisome proliferators to modulate Ca2+ homeostasis was studied in freshly isolated rat hepatocytes. Clofibrate and bifonazole (0.5 mM) caused a transient increase in cytosolic-free Ca2+ concentration ([Ca2+]i) by releasing the intracellular inositol 1,4,5-trisphosphate-sensitive Ca2+ pool. However, the mobilization of this pool by clofibrate was only transient; a subsequent exposure of the cells to the endoplasmic reticulum Ca(2+)-ATPase inhibitor thapsigargin resulted in a second release of the same Ca2+ store, indicating that this pool could refill from the cytosol, independently of extracellular Ca2+. By contrast, bifonazole-exposed hepatocytes no longer responded to a stimulation by thapsigargin. Bifonazole also strongly inhibited Ca2+ influx. Ciprofibrate and nafenopin (0.5 mM) produced increases in [Ca2+]i that were sustained, even in the absence of extracellular Ca2+. The [Ca2+]i response was not due to release of the inositol 1,4,5-trisphosphate-sensitive Ca2+ pool and was not inhibited by prior treatment with the protonophore carbonyl cyanide 4-(trifluoromethoxy) phenylhydrazone, but was slightly antagonized by prior exposure to the Ca2+ ionophore ionomycin. Pretreating the cells with nafenopin completely abolished the response elicited by ciprofibrate, and vice versa. By contrast to the other peroxisome proliferators, WY-14,643 and bezafibrate (1 mM) increased cytosolic free Ca2+ only by approximately 30 nM. In conclusion, the structurally diverse peroxisome proliferators tested in this study all produced changes in [Ca2+]i in hepatocytes but through the redistribution of different internal Ca2+ pools. Further studies are needed to determine whether any of the observed Ca2+ changes have a role in the pleiotropic effects elicited by peroxisome proliferators.

Animals↗

PubMed1995

Prediction of the percutaneous penetration and metabolism of dodecyl decaethoxylate in rats using in vitro models.

Percutaneous absorption of a lipophilic surfactant, dodecyl decaethoxylate, can be predicted using in vitro models. In vivo, dermal penetration of dodecyl decaethoxylate was found to be 22.9% in 48 h. All of the absorbed dodecyl decaethoxylate in the rat was metabolised and excreted in expired air as carbon dioxide, or in the urine and faeces. Using rat skin mounted in the unoccluded flow-through diffusion cell with MEM as receptor fluid, in vivo absorption was predicted by the percentage of the applied dose recovered in the stratum corneum, epidermis, dermis and receptor fluid at 24 h (25%). Conversely, the penetration of dodecyl decaethoxylate was over-predicted in the unoccluded static diffusion cell using aqueous ethanol (50% v/v) as the receptor fluid where 49.4% recovered in the receptor fluid at 24 h. In vitro models may be used to predict percutaneous absorption and reduce animal use, provided a suitable receptor fluid is used in which the penetrant is soluble. Dermal metabolism of dodecyl decaethoxylate was low and not considered to influence dermal absorption.

Administration, Topical↗

PubMed1995

Percutaneous penetration of dimethylnitrosamine through human skin in vitro: application from cosmetic vehicles.

Human skin penetration of N-dimethylnitrosamine (DMN) from three vehicles has been determined in vitro. When applied as an infinite dose in isopropyl myristate (IPM, 1 microgram/microliter) the average total absorption over 48 hr was 2.6 +/- 1.2% of the applied dose (all data presented are expressed as means +/- standard errors). When applied as a finite dose in a representative oil-in-water emulsion vehicle the average total absorption over 48 hr was 4.0 +/- 0.3% of the applied dose. When applied as a finite dose in a representative shampoo vehicle for 10 min followed by rinsing (i.e. to represent in-use exposure conditions) the average total absorption over 48 hr was 1.1 +/- 0.1% of the applied dose. Approximately 72% of the DMN in the applied shampoo vehicle was removed by rinsing. There was considerable evaporative loss of DMN from the IPM and oil-in-water emulsion vehicles, such that absorption was complete within 3 hr of application. The overall data indicate that DMN can penetrate the skin rapidly but that in practice the amount actually available for penetration is significantly reduced by high permeant volatility. In contrast, application of N-nitrosodiethanolamine (NDELA) at a concentration of 1 microgram/microliter as an infinite dose generated an average total absorption over 48 hr of 23.6 +/- 6.4%, representing a total flux of 103.9 +/- 28.4 micrograms/cm2. In the case of NDELA, no evaporative loss was evident.

Carbon Isotopes↗

PubMed1995

The effect of epidural anaesthesia on peripheral resistance and graft flow following femorodistal reconstruction.

OBJECTIVE: To determine the extent to which epidural anaesthesia influences peripheral resistance and graft blood flow following femorocrural reconstruction. DESIGN: Prospective, controlled study measuring blood flow, arterial pressure and peripheral resistance in femorocrural bypass grafts for 20 min following onset of epidural anaesthesia with 15ml of 0.25% bupivacaine. PATIENTS: Twenty patients undergoing femorocrural reconstruction for critical lower-limb ischaemia with in situ long saphenous vein, under general anaesthesia. Ten patients had epidural cannulae inserted preoperatively and injected with bupivacaine after completion of the graft. RESULTS: Peripheral resistance fell in all 10 patients receiving epidural anaesthesia from a mean (range) of 1.07 PRU (0.32-2.2) to 0.49 PRU (0.19-0.72), compared to control values of 0.95 PRU (0.39-2.0) to 0.91 PRU (0.41-1.51; P < 0.01, Wilcoxon). There was a tendency for blood pressure to fall in the study patients (not significant) but graft blood flow still increased from 98 ml min-1 (41-221) to 160 ml min-1 (101-250), compared to flow in the control patients of 101 ml min-1 (45-176) at baseline to 104 ml min-1 (56-168; p < 0.01) at 20 min. CONCLUSIONS: Epidural anaesthesia significantly decreases peripheral resistance and increases graft blood flow in femorocrural grafts and would appear, therefore, to be of benefit for patients undergoing femorodistal reconstruction.

Aged↗

PubMed1992

Influence of single and concurrent clofibrate and phenobarbital administration on cytochrome P450-dependent mixed function oxidase activities and peroxisome proliferation in male rat liver.

The influence of both single and concurrent administration of phenobarbital and clofibrate on hepatomegaly, cytochrome P450-dependent mixed function oxidase activities, and peroxisome proliferation in male rat liver have been studied. Both xenobiotics separately increase the liver: body weight ratio and their combined administration results in greater hepatomegaly than either compound alone. Both compounds induce NADPH-cytochrome c(P450) reductase activity and laurate omega- and omega-1-hydroxylase activities, but only phenobarbital induces pentoxyresorufin-O-dealkylase. None of the drug treatments induced microsomal cytochrome b5. Phenobarbital did not cause peroxisome proliferation and inhibited the corresponding clofibrate-dependent proliferation. Taken collectively, our studies have demonstrated that concomitant treatment with phenobarbital and clofibrate are largely permissive with respect to the hepatic mixed function oxidase system but have opposing effects on the phenomenon of peroxisome proliferation in the same tissue.

Animals↗

PubMed1987

Metabolism in the rat of potassium nonan-5-sulphate, a symmetrical anionic surfactant.

1. The metabolism of potassium nonan-5-[35S]sulphate, a symmetrical secondary alkylsulphate ester, was investigated in the rat. Oral administration of the radiolabelled ester was followed by the elimination of the majority of radioactivity in the urine. 2. Potassium nonan-5-[35S]sulphate is degraded in vivo to produce at least three radiolabelled sulphate esters. 3. The same metabolites were produced by isolated rat livers perfused with potassium nonan-5-[35S]sulphate. 4. The three radioactive metabolites were identified by combined g.l.c.-mass spectroscopy as the unchanged parent ester, nonan-1-ol-5-sulphate and nonanoate-5-sulphate. 5. The nature of the latter two metabolites indicates that potassium nonan-5-sulphate is metabolized by omega-oxidation only and, moreover, the alkylsulphate ester is metabolized only at one end of the molecule.

Anesthesia↗

PubMed1984

The mode of action of ethyl lactate as a treatment for acne.

We have shown that an alcoholic lotion containing ethyl lactate when applied topically to rat skin under occlusion became localized in the follicles and sebaceous glands. When applied to human facial skin the ethyl lactate was hydrolysed to ethanol and lactic acid, and thereby lowered the skin pH. Under such conditions the growth of recoverable skin bacteria, in particular the anaerobe Propionibacterium acnes, was inhibited, and the hydrolysis of sebum to free fatty acids by lipase derived from the bacteria was greatly impaired. These effects of ethyl lactate would account for its observed clinical efficacy in acne vulgaris.

Acne Vulgaris↗

PubMed1982

The effect of configuration of the sulphate moiety on the metabolism of potassium octan-2-sulphate in the rat.

1. A comparison was made of the metabolism of potassium D-(+)-octan 2-[35S]sulphate and potassium L-(-)-octan-2-[35S]sulphate in the rat. 2. Following administration of either enantiomer orally or i.v. the major proportion of the radioactivity was excreted in the urine within 24 h. When either enantiomer was administered i.v. to rats with bile-duct and ureter cannulae, the majority of the radioactivity was eliminated in the urine within six hours with only small amounts in bile. 3. Both enantiomers were extensively degraded in vivo. The metabolic products were identical with those previously reported (Maggs et al. 1982). 4. The major difference in the metabolite patterns was with respect to the relative amounts of hexanoate-5-sulphate: male and female urines contained approx. twice as much of this metabolite when the D-(+)-isomer was administered. In addition, isomer and sex-linked differences were observed with respect to the amounts of octanoate-7-sulphate.

Animals↗

PubMed1982

Metabolism in the rat of potassium DL-octan-2-sulphate, a secondary alkyl sulphate.

1. The metabolism of potassium [2-14C]octan-2-sulphate and potassium octan-2-[35S]sulphate was investigated in the rat. Following oral administration, the bulk of the radioactivity was eliminated in the urine within 24 h. 2. Whole-body radioautography showed the liver to be the principal site of tissue accumulation of radiolabel following administration of 14C- or 35S-labelled DL-octan-2-sulphate. 3. Octan-2-sulphate was extensively degraded in vivo. The major urinary components are five sulphate estes, present in urine in essentially the same proportions regardless of label. The relative proportions of radioactivity associated with the urinary components showed considerable differences between male and female rats. 4. Three of the components have been identified as butanoate-3-sulphate, hexanoate-5-sulphate and octanoate-7-sulphate. The remaining metabolite was tentatively identified as an aldehyde derivative of octan-2-sulphate, a possible intermediate in the formation of octanoate-7-sulphate.

Animals↗

PubMed1979

"Satellite" haemodialysis.

Thirty of the 39 patients treated at the Blacktown Dialysis Centre, the first "satellite" dialysis centre in the greater metropolitan Sydney, had been referred from four Sydney renal units for long-term dialysis therapy. The move save approximately 150 kilometres in travelling and eight hours time each week for each of these patients. The cost of running the unit was approximately $10,000 per patient per year in the first year--no greater than that of home dialysis, and less than that of dialysis in a teaching hospital. The advantages of establishing satellite dialysis centre, the method of operation, and the results of the first year of operation of the Blacktown Dialysis Centre are described.

Adult↗