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Biomedical subjects

A J Ward

Publications and source records attributed to A J Ward.

At least 19 recordsLinked to original sources

A clinically relevant modification to existing inhaler therapy.

A modified formulation of inhaled salbutamol and a new inhaler device were studied in a group of 11 moderate-to-severe asthmatic patients. Changes in airway calibre (FEV1, Vmax30) were measured before and after inhalation of the new formulation, and compared with changes following inhalation of conventional salbutamol. A standard Rotahaler was used as a reference for the new inhaler. The study was conducted as a two-part randomized, double-blind cross-over trial. We found a significantly greater bronchodilatation of the larger airways using the modified drug in the Rotahaler. The new inhaler did not show any superiority over the Rotahaler, contrary to expectations from in vitro work. A slightly shorter model may better reflect the in vitro results. The study has implications for inhalation therapy in general.

Adult

Formation of difluorothionoacetyl-protein adducts by S-(1,1,2,2-tetrafluoroethyl)-L-cysteine metabolites: nucleophilic catalysis of stable lysyl adduct formation by histidine and tyrosine.

19F NMR spectroscopy was used in conjunction with isotopic labeling to demonstrate that difluorothionoacetyl-protein adducts are formed by metabolites of the nephrotoxic cysteine conjugate S-(1,1,2,2-tetrafluoroethyl)-L-cysteine (TFEC). To determine which amino acid residues can be involved in adduct formation, the reactivity of TFEC metabolites with a variety of N-acetyl amino acids was also investigated. An N alpha-acetyl-N epsilon-(difluorothionoacetyl)lysine (DFTAL) adduct was isolated and characterized by 19F and 13C NMR spectroscopy and mass spectrometry. N alpha-Acetylhistidine and N-acetyltyrosine were found to act as nucleophilic catalysts to facilitate the formation of both the protein and DFTAL adducts. Adduct formation was greatly reduced when lysyl-modified protein was used as the substrate, indicating that lysyl residues are primary sites of adduct formation. However N alpha-acetyllysine, at concentrations of greater than 100-fold in excess compared to protein lysyl residues, was not effective in preventing binding of metabolites to protein. Therefore, nucleophilic catalysis at the surface of the protein may be an important mechanism for the binding of TFEC metabolites to specific lysyl residues in protein. TFEC metabolites were very reactive with the thiol nucleophiles glutathione and N-acetylcysteine. However, the predicted difluorodithioesters could not be isolated. Both stable difluorothioacetamide and less stable difluorodithioester protein adducts may play a role in TFEC-mediated nephrotoxicity.

Amines

Prenatal stress and childhood psychopathology.

The documentation of levels of prenatal maternal stress and anxiety of four populations of severely emotionally disturbed children and adolescents was retrospectively reviewed to examine their relationship to the later development of childhood psychopathology. Significantly more of those children were born to unmarried mothers who had not planned to become pregnant, felt unhappy about being pregnant, lived in family discord, emotionally rejected being pregnant, and experienced significantly more physical problems than would be expected by chance. This study supports the hypothesis that chronic prenatal stress adds both physiological and psychological risk factors to the later development of childhood psychopathology.

Adolescent

Maxillofacial trauma in severely injured patients.

A study was made of maxillofacial trauma in seriously injured patients to determine the likely role of oral and maxillofacial surgeons working in the regional trauma centres proposed by the Royal College of Surgeons of England. There were 153 patients, aged 70 years or less, who sustained major trauma (injury severity score 16 or more) and were admitted directly to the accident departments of the Bristol Royal Infirmary or Derriford Hospital, Plymouth during 1989. Maxillofacial injuries occurred in 50 (33%) of these patients with lacerations present in 39, burns in 1 and facial bone fractures in 28 (18%); soft tissue abrasions and contusions were excluded. The aetiology, patterns of injury, surgical treatment and outcome were reviewed. The implications for the provision of maxillofacial surgical services in regional trauma centres is discussed.

Accidents, Traffic

Microemulsions as topical drug delivery vehicles: in-vitro transdermal studies of a model hydrophilic drug.

Microemulsions with a 58:42 weight ratio of dioctyl sodium sulphosuccinate: octanol and containing 15, 35, and 68% water have been tested for their ability to transport glucose across human cadaver skin. A flow-through multisample skin diffusion cell showed that both the 35 and 68% water microemulsions caused enhanced (approximately 30-fold) transport of glucose. No transport was discernible for the 15% water microemulsion. Differences in percutaneous glucose transport were shown to parallel differences in the diffusion of water within the microemulsion vehicles before application to the skin.

Administration, Cutaneous

A comparison and analysis of the presence of family problems during pregnancy of mothers of "autistic" children and mothers of normal children.

An examination of a hypothesized relationship between maternal stress experienced during pregnancy and the birth of children who later develop early infantile autism revealed that mothers of autistic children were found to have experienced significantly more family discord and to have had significantly more diagnosed psychiatric problems than mothers of normal children.

Autistic Disorder

Late lengthening of the fibula for malaligned ankle fractures.

We describe a technique of lengthening osteotomy of the fibula for the late treatment of symptomatic malaligned or malunited fractures of the ankle. Good results at two to three years were achieved in five of six cases despite delays of up to four years from the original injury. The method can prevent progressive instability and degenerative arthritis.

Adult

Trauma scoring methods.

Trauma scoring methods are recommended for use in the management of trauma patients. Currently used methods are reviewed for their use in triage, the determination of injury severity and the assessment of prognosis and outcome in comparative evaluation of trauma care within or between institutions.

Critical Care

Treatment of small cell lung cancer by eight weeks chemotherapy.

Eighty-two patients with small cell lung cancer (SCLC), 32 with limited disease, were treated with alternating chemotherapy. Eight courses were administered at weekly intervals, and responding patients received radiotherapy to sites of bulk disease. Overall response rate was 76.8%. Overall median survival was 265 days, 408 days in patients with limited disease. The median symptom free period after chemotherapy was completed was 123 days. These results are comparable with those in reports of chemotherapy of longer duration and warrant the further investigation of short duration treatment in this disease.

Adult

Laxatives after hemorrhoidectomy.

Thirty patients undergoing a standard Milligan-Morgan hemorrhoidectomy were used for a randomized study of the addition of postoperative laxatives or wheat fiber to the diet. Seventeen patients received wheat fiber; 13 were given a laxative regime of sterculia, magnesium sulfate, and mineral oil. There were no differences between the two groups in preoperative or postoperative bowel habits. Patients receiving wheat fiber had a shorter postoperative hospital stay four days (three to five) vs. five days (three to six), median (range), P less than .01, and suffered less pain after defecation on the day of discharge from the hospital (P less than .05). Fecal leakage or soiling was seen less frequently with wheat fiber than in patients receiving the laxative regime (5/17 vs. 10/13, P less than .05). The authors conclude that wheat fiber added to the diet will produce a satisfactory bowel habit after hemorrhoidectomy, with a lower incidence of fecal leakage and reduced pain after defecation than the usual laxative regime.

Cathartics

Investigations of the solubilization kinetics of binary mixtures of non-polar oils by non-ionic surfactants.

An investigation of the solubilization kinetics of binary mixtures of non-polar oils by a non-ionic surfactant has been made using the drop-on-fibre technique. Variables studied were the oil composition, surfactant concentration and the temperature. Rates vary linearly with the surfactant concentration for all oil compositions. The observed rate during nearly total solubilization of each oil drop was constant, implying that in these systems solubilization is non-selective. The rates increase as the lower consolute (cloud) temperature of the surfactant is approached. Activation energies of the solubilization process are shown to be independent of the oil composition for the system studied. This suggests that the important stage of the process involves dissociation of the surfactant micelles.

Hydrocarbons

Solubilization kinetics of n-alkanes by a non-ionic surfactant.

The rates of solubilization of a homologous series of n-alkanes (CnH2n + 2; n = 8-16) into micellar solutions of n-dodecyl hexaoxyethylene glycol ether (C12E6) have been measured at 298 K. A mechanism involving a micellar dissociation-association process previously proposed was found to give an adequate description of the data. Proportionality between the micellar solubilization capacity in the kinetic process and that found at equilibrium could be inferred for such a series of solubilizates which have the same locus of solubilization and packing requirements.

Alkanes

Radiation exposure during dynamic hip screw operation.

Exposure to radiation by surgeon and patient was measured in ten cases during insertion of a dynamic hip screw, using image intensified screening. There were low levels of irradiation of the thyroid and eyes of the surgeon. However, the dominant hand of the surgeon was often exposed to higher levels. The use of a memory during screening significantly reduced the level of radiation measured (P less than 0.05). Recommendations are made for reducing radiation exposure by the surgeon, and a method is described to measure the irradiation of surgeons' hands.

Bone Screws

Estracyt in advanced carcinoma of the breast: a phase II study.

Estracyt, a conjugate of an alkylating agent with an oestrogenic sterol, was given in a dose of 420 mg daily to a group of 44 postmenopausal patients with very advanced breast carcinoma. Thirty-eight of these were in relapse following chemotherapy and 32 had evidence of distant metastases. Seventeen patients had an objective response and marked or complete alleviation of symptoms, four others had a useful symptomatic response but no beneficial effect was observed in the remainder. Three who had shown no response to previous oestrogen therapy also failed to respond to Estracyt as did all nine patients with hepatic metastases. Oestrogen receptor status and age within the postmenopausal group seemed to have no bearing on the result. Side-effects were minimal with nausea in 18 patients but in only two did this necessitate withdrawal of the drug. Bone marrow depression did not occur. Changes in acute-phase reactant proteins suggested that part of the Estracyt was de-esterified in the liver liberating oestrone but the low incidence of vaginal haemorrhage and the recalcification of bony metastases suggested that on the whole Estracyt behaves as an anti-oestrogen as well as an antimitotic.

Aged

The Leeds results for radiotherapy in HBO for carcinoma of the head and neck.

Follow-up data at five years are reported for 24 patients with squamous cell carcinoma of the head and neck, included in a randomised prospective MRC study of radiotherapy in hyperbaric oxygen (10 fractions) or air (15 or 20 fractions). Although few, the data show a significant gain in local control (P less than 0.001) and survival (P less than 0.05) with the use of hyperbaric oxygen but no increased tissue reactions or morbidity.

Aged

Carcinoma of the cervix: results of a hyperbaric oxygen trial associated with the use of the cathetron.

Since 1971, 82 patients with advanced carcinoma of the cervix have been included in a randomised clinical trial in association with the Working Party on Radiotherapy and Hyperbaric Oxygen of the Medical Research Council. External irradiation was given in 10 fractions by an unconventional schedule, either in air or HBO, and combined with three large fractions of intracavitary irradiation using the Cathetron. The results are acceptable overall, with 69% local control, 15% with tumour developing outside the treated volume and 40% survival at five years, but no improvement has been shown with HBO. Symptoms suggestive of some degree of late damage to the small bowel were present in 13% of patients, with a higher but not statistically significant, incidence in the HBO group. It is postulated that the schedule of radiotherapy used has allowed reoxygenation during treatment and that no further gain due to the use of HBO may be achieved. After a review of the results from other centres and taking into account the difficulties of treatment in HBO it is concluded that for advanced carcinoma of the cervix the addition of HBO to radiotherapy is not clinically worthwhile.

Adult