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Biomedical subjects

S Hill

Publications and source records attributed to S Hill.

At least 163 records · Page 9Linked to original sources
PubMed1994

Low-dose tumour necrosis factor-alpha (TNF-alpha) and melphalan in hyperthermic isolated limb perfusion. Results from a pilot study performed in the United Kingdom.

Nine patients with soft tissue tumours of the lower limb not amenable to treatment other than by isolated limb perfusion (ILP) or amputation underwent ILP at the level of the superficial femoral vessels, using a combination of recombinant TNF-alpha and melphalan. In seven patients in whom tumours were superficial, sloughing and necrosis were apparent within 48 h of perfusion. All patients experienced a complete tumour response. There were no systemic side effects associated with the use of TNF-alpha, although local side effects, particularly oedema, were pronounced. Four patients ultimately required amputation, three because of large soft tissue defects resulting from necrosis of tumour and overlying skin and one because of tumour recurrence.

Adult↗
PubMed1993

Low-dose tumour necrosis factor alpha and melphalan in hyperthermic isolated limb perfusion.

Nine patients with soft tissue tumours of the lower limb not amenable to treatment other than by isolated limb perfusion or amputation underwent hyperthermic isolated limb perfusion at the level of the superficial femoral vessels, using a combination of recombinant tumour necrosis factor (TNF) alpha and melphalan. In seven patients with superficial tumours, necrosis and sloughing was apparent within 48 h of perfusion. All patients experienced a complete tumour response. There were no systemic side-effects associated with the use of TNF-alpha although local side-effects, particularly oedema, were pronounced. Three patients ultimately required amputation because of the large soft tissue defects that resulted from necrosis of the tumour and overlying skin.

Adult↗
PubMed1993

Flavone acetic acid (FAA) with recombinant interleukin-2 (rIL-2) in advanced malignant melanoma: I. Clinical and vascular studies.

A trial of FAA and rIL-2 has been performed both to study the clinical efficacy of this combination and to determine whether they cause haemorrhagic necrosis by acting upon tumour vasculature. FAA and rIL-2 were given to 23 patients with progressing metastatic melanoma. FAA 4.8 gm m-2 was given as a 1 h infusion without urine alkalinisation on days 1, 8 and 15. rIL-2 (6-18 x 10(6) IU/m2/day) was given as a continuous infusion days 8-12 and 15-19 (nine patients) or days 8-12 only (14 patients). Treatment was repeated after 2 weeks unless there was disease progression. Of the 21 assessable patients there have been one complete (skin and liver) and two partial responses (skin and liver, skin and nodes) lasting 20 + 17 + and 15 months, overall response rate 14%. Unexpectedly severe hypotension after the third FAA, when given 2-4 days after RIL-2, was the major toxicity (8/15 grade 3 or 4). No alteration in coagulation parameters were seen during therapy of the first ten patients. No increase in tumour necrosis was seen in any of the 15 biopsies taken from ten patients after therapy. This suggests that FAA does not have similar vascular effects in human as it does in murine tumours.

Adult↗
PubMed1993

Bromodeoxyuridine-labelled apoptosis after treatment with antimetabolites in two murine tumours and in small intestinal crypts.

Antimetabolites are S-phase specific anticancer drugs. Administration of bromodeoxyuridine (BrdUrd) to tumour bearing mice was followed by treatment with cytosine arabinoside or hydroxyurea. Anti-BrdUrd immunocytochemistry visualised susceptible tumour and intestinal crypt cells at electron microscope level, showing unequivocally that cells that were in S-phase at the time of administration of the drugs subsequently died by apoptosis.

Animals↗
PubMed1993

A randomized, double-blind, multi-centre, parallel-group study comparing the tolerability and efficacy of moclobemide and dothiepin hydrochloride in depressed patients in general practice.

A randomized, double-blind, multi-centre, parallel-group study compared the tolerability and efficacy of 450 mg of moclobemide and 75-150 mg of dothiepin in the management of depressed patients in general practice. Patients who fulfilled the DSM-III-R criteria for major depressive disorder and who scored 13 or more on the Hamilton Depression Rating Scale were admitted. The trial lasted six weeks. The dose of moclobemide was 150 mg three times daily and that of dothiepin was 75 mg daily for the first two weeks and 150 mg thereafter. Assessments were made at baseline and after one, three and six weeks using the HDRS, the Zung SRS and the CGI. Adverse events and vital signs were monitored at each visit, and laboratory screening tests performed at the beginning and end of the study. Sixty-four general practitioners from four centres recruited 345 patients: 175 received dothiepin and 170 moclobemide; 265 completed six weeks of treatment. Thirty-eight dothiepin-treated patients (22%) and 42 who received moclobemide (25%) dropped out, most commonly because they experienced adverse events. More patients on dothiepin (24) than on moclobemide (16) dropped out for this reason; the incidence of adverse events was 10% higher in the dothiepin-treated group and of "side effects" more than 10% higher, the latter difference being statistically significant. Both treatments resulted in significant improvement; this was greater in the dothiepin-treated group and the difference was statistically significant, although clinically small.

Adolescent↗
PubMed1993

Oxygen inhibition of nitrogenase activity in Klebsiella pneumoniae.

A purpose-built oxystat has been used to study reversible inhibition of nitrogenase by O2 in the facultative anaerobe Klebsiella pneumoniae. C2H2-reducing activity in samples from either an anaerobic glucose-limited or an O2-limited diazotrophic chemostat culture was completely inhibited by exposure to a dissolved O2 concentration (DOC) of 1.5 microM or above. Subsequently, under anaerobic conditions, C2H2-reducing activity returned in the absence of de novo protein synthesis. The amount of activity returning never reached 100% of the initial anaerobic activity before O2 treatment. The degree of reversibility was inversely proportional to the log of DOC during exposure and was decreased by increasing the time of exposure to O2 (about 60% reversibility occurred after a 20 min exposure to 6 microM-O2). The failure to obtain complete recovery of activity was apparently not due to inactivation of the very O2-sensitive pyruvate-flavodoxin oxidoreductase (nifJ product) which provides electrons for nitrogenase activity in vivo. Samples from the O2-limited culture behaved similarly to those limited by glucose. Thus, 'training' of the organism to use O2 during growth does not influence the tolerance of nitrogenase to O2. Since the behaviour towards O2 reported here for K. pneumoniae differs from that known to occur in Azotobacter, the mechanism of protection of nitrogenase from O2 damage may differ in these organisms.

Anaerobiosis↗
PubMed1993

The Colorado Tobacco-Free Schools and Communities Project.

This article defends the appropriateness of tobacco-free school policies as an effective tool toward ensuring young people develop into healthy and intellectually strong adults, and demonstrates how such a policy can be introduced into a school district. Health education efforts to eliminate tobacco use are widely considered more effective when carried out in concert with school policies and adult role models offering the consistent message that tobacco use is unhealthy and unacceptable. Studies indicate students who attend schools with strict smoking policies are less likely to begin smoking than students who attend schools without such policies. Through research, support, and guidance, the Colorado Tobacco-Free Schools and Communities Project successfully has assisted almost half the 176 school districts in Colorado to adopt such policies.

Adolescent↗
PubMed1993

Tackling language delay: a groupwork approach.

Communication, Articulation and Terrific fun adds up to Speech. Jacqueline Cox and Sylvia Hill describe CATS, a speech and language group for language-delayed children run by health visitors.

Child, Preschool↗
PubMed1993

Treatment of cutaneous metastases from malignant melanoma using the carbon-dioxide laser.

Between October 1988 and September 1991, 60 patients with cutaneous metastases from malignant melanoma have been treated palliatively using carbon-dioxide laser ablation. The number of lesions per patient varied between 3 and 450; accordingly treatment was performed under local or general anaesthesia. The post-operative complication rate was low and the majority of wounds healed within 6 weeks. Control of in-transit metastatic disease and palliation of disseminated cutaneous melanoma can be achieved by carbon-dioxide laser ablation which provides a simple and effective alternative to isolated limb perfusion. Eighteen of the 32 patients in this series with stage IIIa disease were controlled by three or fewer laser treatments in the first year. We advocate laser vaporization as the initial treatment for non-nodal regional recurrence in the knowledge that isolated limb perfusion can be offered at a later stage for patients who cannot be controlled by the laser.

Adult↗
PubMed1992

Regulation of integrin gene expression by substrate adherence.

Under substrate adherent conditions, integrin gene expression can be regulated by transforming growth factor-beta, interleukin-1 beta, and prostaglandins. This report demonstrates a new mechanism that can differentially control the expression of several integrins. When MG-63 osteosarcoma cells are maintained in suspension, up-regulation of several integrin alpha-subunits takes place. Within as little as 4 h, the mRNA levels for both the alpha 2- and alpha 4-subunits are increased 4- and 6-fold, respectively. It was found that mRNA levels for the alpha 2-, alpha 4-, and alpha v-subunits were markedly increased in several differentiated cell lines under nonadherent conditions; however, cells that did not express a given integrin under substrate adherent conditions also did not express this integrin when maintained in suspension. The alpha 5-subunit did not upregulate during suspension growth. By immunocytochemistry, changes in integrin mRNA levels were confirmed at the protein level. Both cytochalasin B and a phorbol ester were found to induce the expression of the alpha 2-subunit, but not the alpha 4- and alpha 5-subunits, in a dose-dependent fashion. Many investigators have documented changes in gene expression that result from changes in "cell shape." These phenomena may result from up-regulation of integrin gene expression induced by the lack of substrate adherence.

Base Sequence↗
PubMed1992

Reactions of nitrosonitrobenzenes with biological thiols: identification and reactivity of glutathion-S-yl conjugates.

1,3-Dinitrobenzene (1,3-DNB) but not 1,2-dinitrobenzene (1,2-DNB) or 1,4-dinitrobenzene (1,4-DNB) is a potent testicular toxicant in rats. In vitro metabolism studies have established that 1,3-DNB is reduced to 3-nitroso-nitrobenzene (3-NNB), 3-nitrophenylhydroxylamine (3-NP) and 3-nitroaniline (3-NA) in testicular cytosol and Sertoli cell cultures. To establish a potential role for endogenous glutathione (GSH) in the detoxification of the electrophilic metabolite 3-NNB, we examined the chemical reaction of this compound with biological thiols, including GSH. The effect of pH and thiol concentration upon the reaction were studied. The reaction of GSH with 3-NNB was complex and gave three distinct products. These were identified as 3-NP, 3-NA and a glutathionyl derivative containing a covalently linked S-N bond. The hydroxyl amine and the amine were isolated and fully characterised. The glutathion-S-yl derivative was characterised in solution by proton NMR (400 MHz), infra-red and mass spectroscopy to establish its structure as the semimercaptal, N-(glutathion-S-yl)-N-hydroxy-3-nitroaniline (GSNOH-3NA). Similar reactions were performed with 4-nitrosonitrobenzene (4-NNB) to ascertain the reactivity of this chemical towards thiols. The addition of GSH to 4-NNB resulted in the rapid formation of 4-nitrophenylhydroxylamine (4-NP) and an adduct that was identified as the semimercaptal N-(glutathion-S-yl)-N-hydroxy-4-nitroaniline (GSNOH-4NA).

Acetylcysteine↗