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Biomedical subjects

A J Ward

Publications and source records attributed to A J Ward.

At least 37 records · Page 2Linked to original sources

Post-traumatic osteoporosis and algodystrophy after external fixation of tibial fractures.

The incidence of two forms of post-traumatic osteoporosis and algodystrophy in the ankle region of 20 patients with displaced diaphyseal fractures of the tibia treated with external fixation were studied. Acute localised osteoporosis (ALO) occurred in 14 (70 per cent) and 5 (25 per cent) developed algodystrophy. ALO was significantly less frequent in matched patients treated by internal fixation or by external plaster-of-Paris (POP) cast. Regional osteoporosis (RO) was most common in POP patients. The presence of ALO may indicate the development of algodystrophy following tibial fracture. Our findings suggest that external fixation may predispose to ALO and algodystrophy.

Acute Disease↗

A sensitivity to oxidative stress is linked to chromosome 11 but is not due to a difference in single strand DNA breakage or repair.

Defects in loci on chromosome 11 have been associated with tumourigenicity, anchorage-independent growth, metastasis and radiosensitive DNA repair in tumour cells. The introduction of normal chromosome 11 into these cells suppresses these responses. In the present study we tested two hypotheses: (1) that microcell fusion of normal chromosome 11 into bladder-carcinoma cells (A1698) can protect the cells against chromosomal damage by oxidative stress; and (2) that insertion of normal chromosome 11 corrects a single-strand (SS) DNA-repair defect. Cultures of A1698 (termed parent) and its microcell-mediated hybrid (termed hybrid) were exposed for 1 h to xanthine/xanthine oxidase (X/XO) or co-incubated with human neutrophils activated with 12-O-tetradecanoyl-phorbol-13-acetate (TPA). Micronucleus frequencies (an indication of chromosomal damage) were significantly higher in parent cultures after treatment than in hybrid (P < 0.0001). The level of single-strand DNA breakage and its repair was assayed in X/XO-treated cultures with the alkaline comet assay. There was no significant difference between parent and hybrid in the amount of SS DNA breakage at treatment (P > 0.1) or after 20 min of repair (P > 0.1). The data support the involvement of a defect in chromosome 11 leading to sensitivity to oxidative stress and suggest this defect is not in the initial amount or rate of rejoining of SS DNA breakage.

Cell Line↗

Theophylline--an immunomodulatory role in asthma?

Theophylline, a drug used for the treatment of asthma, is recognized as an immunomodulator affecting T-lymphocytes both in vitro and in vivo. The effect of slow-release theophylline (Uniphyllin Continus) on the late asthmatic response (LAR) has been compared with placebo before and after 5 wk of treatment in a double-blind, randomized, parallel group study. Nineteen volunteers with stable mild asthma successfully completed the study. All were dual responders with a documented late response to inhaled house dust mite extract. The LAR was assessed both in terms of changes in lung function and in peripheral blood T-lymphocyte subsets. The mean (SEM) maximal late fall in FEV1 before and after treatment was 28.8 (4.1)% and 7.8 (2.0)% with theophylline, versus 35.8 (5.1)% and 29.1 (5.0)% with placebo (p = 0.046; Cl, 0.3-26.9). Corresponding figures for specific airway conductance (SGaw) were 46.4 (8.4)% and 7.2 (8.0)% with theophylline versus 46.2 (7.2)% and 44.8 (7.7)% with placebo (p = 0.008; Cl, 11.2 to 64.1). This was achieved at a mean (SD) trough serum theophylline level of only 7.8 (3.5) micrograms/ml. Airway responsiveness to methacholine was not significantly changed 24 h after the initial allergen challenge. There was a trend towards a decrease in baseline responsiveness after treatment with theophylline compared with that after placebo (p = 0.07). Studies of peripheral blood lymphocytes showed a modifying effect of treatment on the allergen-induced changes in CD4 and CD8 counts 48 h after challenge. Previous studies have shown a protective effect of theophylline on the LAR at serum theophylline concentrations within the conventional range for bronchodilation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adjuvants, Immunologic↗

Algodystrophy and osteoporosis after tibial fractures.

We made a prospective study of the incidence and natural history of algodystrophy and associated changes in bone mineral density in the ankles and feet of 60 consecutive patients who had suffered unilateral fractures of the tibial shaft. At bone union, 18 patients showed signs of algodystrophy. Its development was independent of the type of fracture management and of the severity of injury. Patients with algodystrophy lost significantly more bone mineral than did those without but the degree of this loss was independent of the type of treatment and of the time to fracture union. In most cases the symptoms resolved within six months of fracture union but in four patients they were still present at one year and two of these had not returned to work.

Absorptiometry, Photon↗

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↗