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Biomedical subjects

J A Davis

Publications and source records attributed to J A Davis.

At least 109 records · Page 6Linked to original sources

Faecal enzymes: in vivo human skin irritation.

Digestive enzymes in faeces have been reported to possess skin irritation potential. The present study was designed to investigate the in vivo irritant potentials of faecal concentrations of proteolytic and lipolytic digestive enzymes in bile salt mixtures. In a 21-day cumulative irritation assay, clinical evaluation and noninvasive bioengineering techniques were used. 5 days occlusive exposure to phosphate buffer (pH = 8) caused no visual skin damage but reflectance spectroscopy demonstrated significant vasodilation (p < 0.01) and increases in transepidermal water loss (TEWL) and skin pH were also observed (p < 0.01). These increases were still present at days 12 and 19. Occlusive exposure to physiologic concentrations of faecal enzymes resulted in significant visual and objective scores at day 5, 12, and 19, with increased readings as a function of exposure time (p < 0.01). The enzyme mixture containing lipase caused delayed onset of skin erythema and epidermal barrier disruption compared to elastase and chymotrypsin containing solutions. Prolonged occlusive exposure to digestive enzymes in faecal concentrations caused severe skin erythema and epidermal barrier disruption in a human model, suggesting a possible etiologic role of digestive enzymes in perianal, circumstomal or diaper dermatitis.

Adult↗

Prognosis in cystic fibrosis treated with continuous flucloxacillin from the neonatal period.

All newborn infants in East Anglia are screened for cystic fibrosis by blood immunoreactive trypsin assay at 7 days. Thirty eight infants with cystic fibrosis were randomised to treatment with either continuous oral flucloxacillin 250 mg/day (group P, n = 18) or with episodic antimicrobials as clinically indicated (group E, n = 20). Their progress was monitored from diagnosis to 24 months by a nurse coordinator who visited all infants regularly, at home and in hospital, to collect anthropometric, dietary, clinical, and microbiological data. Mean (range) age of confirmation of diagnosis was 5.7 weeks (1-14 weeks). There was no significant difference in birth weight, genotype, immunoreactive trypsin concentration, neonatal history, symptoms at diagnosis, pancreatic enzyme supplementation, or parental smoking history between the groups. Infants in group E had more frequent cough and a greater number of Staphylococcus aureus isolates than infants in group P. More infants of group E were admitted to hospital, had higher admission rates during the second year (19 v 5), for longer periods (6.4 v 2.2 days), despite receiving more than double the number of courses of antibiotics than group P infants (in addition to flucloxacillin). Continuous prophylactic flucloxacillin from early diagnosis of cystic fibrosis is associated with improved clinical progress during the first two years of life.

Bacterial Infections↗

Role of intracellular pH during cytoprotection of proximal tubule cells by glycine or acidosis.

Lowering extracellular pH to less than 7.0 strongly protects isolated proximal tubules against ATP depletion and Ca(2+)-induced injury, but there is little information about alterations of intracellular pH (pHi) in renal tubules during either injury or its modification by decreasing medium pHi or other potent protective factors such as glycine. pHi was assessed with 2',7'-bis-(2-carboxyethyl)-5-carboxyfluorescein during proximal tubule injury produced by simple ATP depletion with the electron transport inhibitor antimycin or by large increases of cytosolic free Ca2+ induced by treatment with the calcium ionophore ionomycin, alone and in combination with antimycin. Freshly isolated rabbit proximal tubules studied under superfusion conditions in the presence of probenecid were suitable for monitoring pHi during relatively prolonged and severe injury states. Probenecid, used to promote the retention of intracellular fluorophores, only minimally modified the injury response by transiently delaying lactate dehydrogenase release during antimycin treatment. The tubules did not exhibit spontaneous decreases of pHi during simple ATP depletion, but pHi fully equilibrated with cytoprotective decreases of medium pH. Irrespective of the presence of antimycin, ionomycin induced intracellular alkalinization in Ca(2+)-replete medium, which may have further enhanced the severity of injury. When medium Ca2+ was buffered to 100 nM, ionomycin induced intracellular acidification, which likely resulted from a combination of Ca2+/H+ exchange activity of the ionophore and H+ uptake during Ca(2+)-ATPase-mediated extrusion of Ca2+ released by ionomycin from intracellular pools. Alterations of pHi did not contribute to glycine cytoprotection because glycine did not affect the behavior of pHi during treatment with antimycin, ionomycin, or both agents in combination.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗

The influence of food on the absorption and metabolism of drugs.

Food-drug interactions can lead to a loss of therapeutic efficacy or toxic effects of drug therapy. Generally, the effect of food on drugs results from a reduction in the drug's bioavailability; however, an alteration in drug clearance can occur due to the effect of certain foods on drug metabolism. The proportion of adverse drug reactions due to food-drug interactions is not known and unfortunately only when a serious adverse drug reaction follows a food-drug interaction does the matter usually receive any significant attention. In order to improve therapeutic efficacy and to help prevent adverse drug reactions, it is necessary that clinicians be knowledgeable of the important food-drug incompatibilities and risk factors related to the increased likelihood of developing an adverse drug reaction due to food-drug interactions.

Biological Availability↗

Conservation of structure in ATP-depleted proximal tubules: role of calcium, polyphosphoinositides, and glycine.

Increases of intracellular free Ca2+ (Caf) may mediate phospholipid hydrolysis and disintegration in energy-compromised cells; on the other hand, glycine and related amino acids preserve structure. We have examined the effects of increased Caf on phospholipids and structure in ATP-depleted cells, as well as how these actions may be modified by glycine. Incubation of isolated proximal tubules with antimycin A led to ATP depletion, delayed increases of Caf to micromolar levels, polyphosphoinositide (PPI) hydrolysis by phospholipase C, and generalized disintegration of cell structure. Glycine inhibited PPI hydrolysis and preserved cell structure in entirety but did not apparently modify the Caf increases. When overwhelming increases of Caf were induced by the additional presence of a Ca2+ ionophore, glycine did not inhibit either the hydrolysis of PPI or disruption of mitochondria and microvilli. However, the cells remained integrated and unbroken. Incubation in low-Ca2+ medium prevented Caf increases, inhibited PPI hydrolysis, and preserved the structure of mitochondria and microvilli. Nevertheless, there was lethal damage by disintegration of all other membranes. This damage was prevented specifically and completely by glycine. Thus compartments of cells were shown to be differentially susceptible to injury from increased Caf or lack of glycine. Although damage by either factor occurs by distinct mechanisms, glycine also appears to have effects that suppress the deleterious effects of Ca2+ so long as Caf increases are not overwhelming. Our results also suggest that the PPI have a major structural role, which may be compromised by Caf increase during ATP depletion.

Adenosine Triphosphate↗

Applied physiology of female soccer players.

Women's soccer is in its infancy as a sport and research into its physiological demands and the physical characteristics of players is somewhat limited. There is now an increasing demand for scientific investigation of the female game and of the players, match analysis and role variations requiring particular attention. Current research suggests that the demands of the game for women are similar to those placed on male players. Women are reported to cover a similar distance (mean 8471m) to their male counterparts during a game and much the same proportions of the game appear to be devoted to exercise of varying intensities. Furthermore, female and male players appear to tax the aerobic and anaerobic energy systems to a similar level. The physical and physiological characteristics of female soccer players are comparable with those of other female games players and are more favourable than average for the population. Mean body fat percentages of between 19.7 and 22.0% and VO2max values of between 47.1 and 57.6 ml/kg/min have been reported for elite female players, while faster than average sprint times are also characteristic of them.

Body Composition↗

Benzocaine-induced methemoglobinemia attributed to topical application of the anesthetic in several laboratory animal species.

In a screening study, a common benzocaine-containing anesthetic was topically applied to the following species: dogs (n = 11), domestic shorthair cats (n = 38), Long-Evans rats (n = 22), Sprague-Dawley rats (n = 11), ferrets (n = 6), rhesus monkeys (n = 10), cynomolgus monkeys (n = 10), owl monkeys (n = 10), New Zealand White rabbits (n = 18), miniature pigs (n = 9), ICR mice (n = 4), C3H mice (n = 4), and C57BL/10SnJ mice (n = 24). All animals, except mice and rats, received a 2-second spray to the mucous membranes of the nasopharynx for an estimated dose of 56 mg. A 2-second spray to rodents' oral mucous membranes delivered too great a volume of fluid for these animals; therefore, an equivalent dose was applied to the oral mucosa membranes by use of a 23-gauge needle and syringe. Initial (baseline) blood samples, as well as 4 blood samples taken every 15 minutes after drug application, were analyzed for methemoglobin (MHb), using an oximeter. Positive MHb response (> 3 SD above baseline) was seen in individuals of all groups. The study was repeated in dogs several months later to confirm low response. Response to benzocaine spray was observed in most animals tested, with response peaking between 15 and 30 minutes after dosing. Positive MHb response ranged from 3.5 to 38%, was detected in > 95% of individual animals, and ranged from 15 to 60 minutes after drug administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Topical↗

Evaluation of butorphanol tartrate and buprenorphine hydrochloride on the inflammatory reaction of the Sereny Test.

Invasion of the ocular epithelia of guinea pigs by virulent Shigella organisms, eliciting keratoconjunctivitis, is the basis of the Sereny Test (ST). This test has been used to ascertain the virulence of Shigella strains and more recently to screen candidate Shigella vaccines for efficacy. This test undoubtedly causes pain in test animals; however, recommendation for use of local analgesics/anesthetics has not been accepted because of concern that these topical agents may affect the ability of the Shigella organisms to invade the ocular epithelia or have a physiologic effect on the inflammatory process. Similarly, investigators are hesitant to use systemic analgesics in conjunction with the ST. Two blinded studies were conducted to evaluate the effects of selected systemic analgesics on the ST in outbred Hartley guinea pigs. Study 1 evaluated the recommended dosages for two systemic analgesics; study groups consisted of those receiving butorphanol tartrate (n = 16), those receiving buprenorphine hydrochloride (n = 16), and untreated controls (n = 5). Study 2 evaluated a low-dose buprenorphine hydrochloride group (n = 16) and an untreated control group (n = 5). All animals were inoculated with Shigella flexneri, strain 2a 2457T, onto the cornea and conjunctiva of each eye. At the onset of clinical signs, analgesics were administered to test groups. The degree of keratoconjunctivitis was evaluated per standard procedure; animals were weighed daily. After 7 days, animals were euthanatized and the eyes were removed for histologic morphometric evaluation.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute-Phase Reaction↗

Anatomical and roentgenographic features of atlantooccipital instability.

An anatomical study using six fresh, human cadaveric cervical spine specimens was performed. After the dissection of all soft tissue, flexion-extension radiographs were obtained to verify initial stability. A sagittal plane bone cut was then made, centered on the odontoid and sparing the alar ligaments, the tectorial membrane, and the atlantooccipital (AO) ligaments. Repeat flexion-extension radiographs and photographs were taken to document maintenance of stability of these hemisections. The occipital-atlantoaxial ligaments were then individually and sequentially incised, maintaining all other structures each time. After the sectioning of each ligament, flexion-extension radiographs and photographs were obtained to identify subsequent motion patterns. Both gross anatomical and roentgenographic examinations demonstrated the important stabilizing role of the tectorial membrane in flexion. Additionally, contact between the posterior arch of C1 and the occiput limited hyperextension as a secondary restraint once the tectorial membrane was sectioned. Furthermore, the AO ligaments proved to play an insignificant role in the preservation of AO stability through a flexion-extension arc of motion. Under normal circumstances, the AO articulation is not excessively stressed. However, acute AO injury, as well as the insidious failure of these ligaments, has been documented in several cases involving various pathologies. This study demonstrates a mechanism of instability and highlights the essential role of the tectorial membrane in maintaining upper cervical spine stability.

Atlanto-Occipital Joint↗

Uvulopalatopharyngoplasty for obstructive sleep apnea in adults: clinical correlation with polysomnographic results.

The success of Uvulopalatopharyngoplasty (UPPP) for Obstructive Sleep Apnea (OSA) can be assessed by a variety of parameters including clinical evaluation and polysomnography (PSG). Patients are often reluctant to undergo post-operative testing and insurance companies are often unwilling to reimburse for expensive overnight sleep studies. Due to the reality of these medical and economical problems, can a clinician be confident of the success of UPPP based solely on clinical evaluation? Sixty patients underwent UPPP for the treatment of OSA from July 1987 through June 1992. Patients treated with tracheostomy or other methods were not included in this study. Fifty-three patients (88%) reported an improvement in their symptoms of snoring, daytime somnolence, morning headache and apnea. Twenty-one patients (35%) had post-operative PSG. Eighteen of 21 patients (85%) reported improvement in their symptoms. Eleven of 21 patients (57%) showed objective improvement in their sleep apnea. The objective findings of PSG do not correlate, in a significant number of patients, with subjective clinical improvement of patients treated with UPPP.

Adult↗

Fistula injury to the bladder at repeat cone biopsy by laser.

A 33-year-old woman underwent repeat cone biopsy of the cervix with a carbon dioxide (CO2) laser. At operation the laser caused multiple full thickness fenestrations of the bladder, creating multiple small vesico-vaginal fistulae. The cone biopsy was completed and the fistulae were converted into a single defect which was immediately repaired. The patient went home 'dry'. We believe this is the first such report in the English-language literature.

Adult↗

Pre-season physiological characteristics of English first and second division soccer players.

This investigation was undertaken in an effort to establish physiological characteristics of soccer players and to relate them to positional roles. A total of 135 footballers (age 24.4 +/- 4.6 years) were assessed for body mass, % body fat, haemoglobin, maximal oxygen uptake (VO2 max), leg power, anaerobic capacity and speed prior to an English league season. The sample included 13 goalkeepers, 22 full-backs, 24 centre-backs, 35 midfield players and 41 forwards. The goalkeepers were significantly heavier (86.1 +/- 5.5 kg; P < 0.01) than all groups except the centre-backs, had significantly higher estimated body fat percentages than centre-backs, forwards, midfield players (P < 0.01) or full-backs (P < 0.05), significantly lower estimated VO2 max values (56.4 +/- 3.9 ml kg-1 min-1; P < 0.01) and were slowest over 60 m (12.71 +/- 0.42 s). The midfield players had the highest predicted VO2 max values (61.4 +/- 3.4 ml kg-1 min-1), this being significantly greater (P < 0.05) than for the centre-backs. The forwards were the fastest group over 60 m (12.19 +/- 0.30 s), being significantly quicker than goalkeepers or centre-backs (P < 0.01) and full-backs (P < 0.05). Anaerobic power, as well as knee extensor torques (corrected for body mass) and extensor-flexor ratios, were similar between groups. No difference in estimated body fat percentage was observed between any of the outfield players, and haemoglobin concentrations were similar among players of all positions.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Thrombotic thrombocytopenic purpura complicating systemic lupus erythematosus. Case report and literature review from the plasmapheresis era.

Although thrombotic thrombocytopenic purpura (TTP) has been described in patients with systemic lupus erythematosus (SLE), the relationship between these 2 diseases is controversial. We recently treated a patient with longstanding SLE who developed TTP. The patient responded to therapy with aggressive plasmapheresis. Review of the literature revealed that TTP may occur in the setting of either active or inactive SLE. Survival in SLE associated TTP correlated with the use of plasma therapy (plasma infusion or plasmapheresis) rather than with the activity of the underlying autoimmune disease. We conclude that TTP and SLE represent distinct clinical entities that may occur together in an immunologically predisposed host. The use of plasma therapy appears to have had a significant impact on survival in these patients.

Adolescent↗

Protection of human umbilical vein endothelial cells by glycine and structurally similar amino acids against calcium and hydrogen peroxide-induced lethal cell injury.

Cultured human umbilical vein endothelial cells treated with either the calcium ionophore, ionomycin, or ionomycin plus cyanide-m-chlorophenylhydrazone had immediate severe depletion of adenosine triphosphate, (ATP) and increases of cytosolic free calcium (Caf) and then sustained lethal cell injury as manifested by release of lactate dehydrogenase and failure to exclude vital dyes within 15 minutes. Inclusion of glycine in the experimental medium prevented the enzyme leakage for at least 60 minutes without altering the ATP depletion or increases of Caf. The physiologic glycine concentration of 0.25 mmol/l gave 50% protection, and protection was complete at 1 mmol/l. Several other small neutral amino acids, L- and D-alanine, beta-alanine, 1-aminocyclopropane-1-carboxylate, alpha-aminoisobutyrate, and L-serine, had effects similar to glycine, but other amino acids and metabolic substrates did not. The endothelial cells were relatively resistant to damage from hydrogen peroxide, but sensitivity could be increased by preloading with Fe2+. In both non-loaded and Fe(2+)-loaded cells, hydrogen-peroxide-induced lactate dehydrogenase (LDH) release developing over 180 minutes was prevented by glycine in a fashion analogous to that seen with ionomycin damage. Mn2+ also partially protected against hydrogen peroxide injury but was not required for glycine's effects. These data demonstrate that striking modulatory effects of glycine and structurally similar amino acids that have previously been characterized in most detail using kidney tubule cells are strongly expressed in human umbilical vein endothelial cells and are involved in their response to Ca2+ and oxidant-mediated damage. These amino acid effects must be considered in the design of in vitro studies of endothelial cell injury and may contribute to endothelial cell pathophysiology in vivo.

Amino Acids↗

Prevalence of Chlamydia trachomatis infection in women having cervical smear tests.

OBJECTIVE: To determine the prevalence of sexually transmitted diseases in patients with normal and abnormal cervical smears. DESIGN: A prospective study of asymptomatic women with normal cervical smears attending their general practitioner and newly referred patients with abnormal smears attending a colposcopy clinic. SETTING: A hospital based colposcopy clinic and an urban general practice (list size 5500) in north west Glasgow. SUBJECTS: 197 asymptomatic women attending their general practitioner for cervical smear tests and 101 randomly selected patients attending the colposcopy clinic for investigation of abnormal smears. MAIN OUTCOME MEASURES: Presence of various sexually transmitted infections as determined by culture and serological tests. RESULTS: Of the 101 women with cytological abnormalities, six had current chlamydial infection proved by culture and none had gonococcal infection; of the 197 women with normal smears, 24 (12%) had a chlamydial infection and two had gonorrhoea. Serological studies for Chlamydia trachomatis specific antibody also indicated that a large proportion of patients had been exposed to this agent in both groups. There was no significant difference between the groups in the prevalence of any sexually transmitted disease studied. CONCLUSION: A high prevalence of chlamydial infection is present in women in north west Glasgow irrespective of their cervical cytological state.

Adult↗