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Biomedical subjects

J A Davis

Publications and source records attributed to J A Davis.

At least 163 records · Page 9Linked to original sources

Pharmacotherapy of allergic rhinitis.

The pathophysiology, clinical manifestations and diagnosis, and pharmacotherapy of allergic rhinitis are reviewed. Allergic rhinitis is an immunologically mediated disease initiated by an antigen-antibody reaction in sensitized persons. Clinical manifestations include nasal obstruction, rhinorrhea, itching of the nose and eyes, coughing, and sneezing and may be perennial or seasonal. Diagnosis is confirmed by challenging the patient with suspected allergens in skin-prick tests. Avoidance of offending allergens is the cornerstone of therapy. Antihistamines and decongestants provides only minimal relief when used alone and are more effective when combined with other agents. Two newer antihistamines, astemizole and terfenadine, lack the sedative and anticholinergic properties of older antihistamines. Intranasal corticosteroids are particularly effective in relieving symptoms; beclomethasone diproprionate and flunisolide do so without producing systemic adverse effects. Cromolyn sodium is effective in relieving nasal symptoms and is the prototype of a new noncorticosteroidal class of compounds termed antiallergy drugs. Drugs under investigation for the treatment of allergic rhinitis include histamine H2-receptor antagonists, nonsteroidal anti-inflammatory agents, anticholinergic agents, and beta-adrenergic receptor agonists. Immunotherapy is a helpful adjunctive treatment. Treatment with drugs may be necessary for those patients with allergic rhinitis who find it difficult or impossible to avoid the offending allergen. The severity of symptoms and the adverse effects of agents should be considered when individual therapeutic plans are being established.

Humans↗

Relationship between cell adenosine triphosphate and glutathione content and protection by glycine against hypoxic proximal tubule cell injury.

We designed studies to characterize metabolic aspects of the protective effects of glycine and glutathione against hypoxic proximal tubule cell injury b clarifying the relationship between protection and preservation of tubule cell adenosine triphosphate (ATP) and glutathione levels. The tubule preparation was glutatione depleted as isolated although some recovery occurred during incubation at 37 degrees C, and this recovery was enhanced by treatment with glutatione precursors. Increasing the duration of hypoxia from 30 minutes to 60 minutes produced increasingly extensive lethal tubule cell injury that was almost completely prevented, even at the 60-minute duration, by inclusion of either 2 mmol/L glutathione or 2 mmol/L glycine in the tubule incubation medium. Cell ATP levels decreased to the same extent and at the same rate in protected and unprotected hypoxic tubules. Glycine- and glutathione-protected tubules maintained higher cell glutathione levels than unprotected tubules at all durations of hypoxia studied. However, completely eliminating this increment of glutathione with either the gamma-glutamylcysteine synthetase inhibitor, buthionine sulfoximine, or the glutathione reductase inhibitor, 1,3-bis(2-chloroethyl)-1-nitrosourea, did not prevent protection. The data indicate that the striking protection against hypoxic injury to the isolated tubules provided by treatment with glycine or glutathione is independent of preservation of tubule cell ATP and glutathione levels, to the extent that difference of these levels can be discriminated in intact cells with present methods.

Adenosine Triphosphate↗

Gastric emptying: influence of prolonged exercise and carbohydrate concentration.

Gastric emptying: influence of prolonged exercise and carbohydrate concentration, Med. Sci. Sports Exerc., Vol. 21, No. 3, pp. 269-274, 1989. The purpose of this study was to examine the effects of serial feedings of different concentrations of carbohydrate (CHO) on gastric emptying and to compare the rates of gastric emptying at rest and during prolonged exercise. Solutions of 0, 6, 12, and 18 g. 100 ml-1 (WP, CHO-6, CHO-12, and CHO-18, respectively) were tested. Ten trained male cyclists performed five trials involving 120 min of cycling. The first 105 min were at 70% of VO2max, and the final 15 min were an all-out self-paced performance ride. In one of the five trials, the subjects rode intermittently, completing seven 15-min rides at 70% of VO2max, with 3 min of rest between each ride. Every 15 min, approximately 150 ml (8.5 ml.kg-1.h-1) of one of the four test solutions were consumed. (In the intermittent trial, the CHO-12 solution was used.) Subjects were also tested during 120 min of seated rest using the above feeding schedule (6% solution). Gastric residue was determined by stomach aspiration following the performance ride. The volumes emptied during the CHO-12 and CHO-18 trials (1,049.8 and 889.2 ml) were significantly different from each other and were less than during the WP and CHO-6 trials (1,210.3 and 1,185.6 ml) (P less than 0.05). CHO delivery was significantly higher in the CHO-12 and CHO-18 trials (126 and 160 g) compared to the CHO-6 trial (71.1 g).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Pulmonary surfactant. I. In immature and mature babies.

Lung surfactant was obtained by postmortem lavage from: (A) premature babies: 34 dying acutely within 2 days of birth from Hyaline Membrane Disease (HMD), 20 dying several days after birth with HMD and its consequences, 8 dying from causes other than HMD; (B) mature babies: 24 dying stillborn, 15 dying soon after birth and 16 dying between 2 weeks and 1 year of age with minimal lung pathology. The phospholipid composition of the surfactant was analysed. Compared to the surfactant of babies dying acutely from HMD, that of the babies dying later from HMD contained significantly higher proportions of phosphatidylcholine (PC) and significantly lower proportions of sphingomyelin while that of the mature babies contained significantly higher proportions of PC and phosphatidylglycerol but significantly lower proportions of sphingomyelin and combined phosphatidylinositol and phosphatidylserine. The surfactant of premature babies dying of causes other than HMD was similar and intermediate to that of both groups of babies dying from HMD. The PC fraction composition of the surfactant of the babies dying acutely from HMD contained significantly lower proportions of the disaturated fraction than those of the babies dying later from HMD, stillborn babies or mature babies.

Female↗

Pulmonary surfactant. II. In sudden infant death syndrome.

The lung surfactant phospholipid composition of lavage samples from 102 babies dying from Sudden Infant Death Syndrome (SIDS) (one-third with minor signs of inflammation) was compared with that of: 34 babies dying from Hyaline Membrane Disease (HMD), 15 mature babies dying soon after birth, 16 mature babies dying in the same age range as the sudden infant death syndrome cases, 13 babies dying from pneumonia and 6 from septicaemia. The surfactant of the two groups of babies dying from SIDS was identical and approximated that obtained from babies dying from HMD, pneumonia or septicaemia. Compared to that obtained from mature babies, the surfactant of babies dying from SIDS contained significantly lower proportions of phosphatidylcholine (PC) and significantly higher proportions of lyso-PC and sphingomyelin. The proportion of disaturated PC was similar to that of the surfactant of the age-matched mature babies. The surfactant composition of the babies dying from SIDS did not change appreciably after death nor vary with age at death. The surfactant phospholipid composition of postmortem samples from mature babies was similar to that of aspirates from living babies and infants and to that of bronchoalveolar lavage samples from living adults.

Female↗

Calcium compartmentation in isolated renal tubules in suspension.

Substantial increases of total cell Ca2+ have been observed in suspensions of isolated rabbit proximal tubules subjected to hypoxic injury or treated with exogenous ATP followed by apparent recovery with reoxygenation of the hypoxic tubules or continued incubation of ATP-treated tubules. Ca2+ compartmentation studies using digitonin and metabolic inhibitors were done to clarify the basis for these changes. Digitonin, 40-90 micrograms/mg tubule protein, rapidly permeabilized the tubule cells and did not impair mitochondrial Ca2+ sequestration. Most of the increases of tubule cell Ca2+ produced by hypoxia and ATP were accounted for by pools which could be rapidly removed by exposure of tubules to EGTA and the uncoupler carbonyl cyanide m-chlorophenyl hydrazone without concomitant use of digitonin, suggesting that the changes of Ca2+ predominantly reflect sequestration by mitochondria in severely damaged cells or mitochondria already released to the medium from them. The time course of uptake followed by spontaneous release of mitochondrial Ca2+ from tubule cells deliberately permeabilized with digitonin, then incubated for prolonged periods, indicated that the decreases of tubule cell Ca2+ during reoxygenation of hypoxic suspensions and prolonged incubation of ATP-treated tubules were likely to be attributable to loss of Ca2+ from free mitochondria and those in damaged cells rather than to extrusion by intact cells.

Adenosine Triphosphate↗

Randomized trial of artificial surfactant (ALEC) given at birth to babies from 23 to 34 weeks gestation.

Artificial surfactant (ALEC) composed of dipalmitoylphosphatidylcholine and unsaturated phosphatidylglycerol in a ratio of 7:3 (w/w) and a dose of 50-100 mg was suspended in 1 ml of cold saline and used at birth as a prophylaxis against the respiratory distress syndrome and its complications in a two centre randomized prospective trial involving 341 babies from 23 to 34 weeks gestation regardless of their antenatal problems. The surfactant had little effect in babies above 29 weeks gestation and was most beneficial in babies under 30 weeks gestation (67 controls and 69 surfactant treated babies). In this subgroup the artificial surfactant significantly reduced the inspired oxygen and peak ventilator pressure requirements during the first 96 h, the incidence of intraventricular haemorrhages from 40% to 19% (P less than 0.01), the overall mortality from 36% to 17% (P less than 0.02), the mortality due to RDS from 31% to 9% (P less than 0.01), the need for more than 28 days oxygen from 37% to 21% (P = 0.05) and the use of pancuronium in ventilated babies from 52% to 27% (P less than 0.01). There were no apparent side effects. This protein free, artificial surfactant should be a useful addition to the therapy of babies under 30 weeks gestation to reduce the severity of their RDS and the incidence of serious complications.

1,2-Dipalmitoylphosphatidylcholine↗

Urodynamic findings following radiotherapy for cervical carcinoma.

Forty patients were assessed urodynamically 5 to 11 years after radiotherapy for cervical carcinoma and compared with 27 patients prior to treatment. The mean volume of first bladder sensation after radiotherapy was significantly lower than the mean volume before treatment, as was the mean maximum cystometric capacity. The mean filling detrusor pressure was higher after radiotherapy than before treatment. Unstable detrusor contractions were found only in the 12 symptomatic patients. There was a significant reduction in maximal urethral closure pressure and functional profile length in the post-radiotherapy group. Detrusor instability was a common finding following radiotherapy. The reduction in bladder capacity alone was not sufficient to account for the symptoms of frequency, urgency and urge incontinence.

Female↗

Factors associated with maternal choice to provide breast milk for low birthweight infants.

Factors associated with maternal choice to provide milk for premature infants were investigated in 925 mother/infant pairs in five hospitals. A well educated, married, primiparous mother aged 20 or over who delivered a baby boy by caesarean section was nearly 1000 times more likely to choose to express her milk than a mother who was poorly educated, single, multiparous, and aged under 20, delivering a female infant vaginally. Evidence from the five centres suggested that hospital staff have little influence on a mother's choice of feeding method. The major differences between the populations of babies whose mothers do or do not choose to provide milk, raise important issues concerning the interpretation of data from non-randomised clinical trials of feeding premature infants.

Birth Order↗

Modulation of cell nucleotide levels of isolated kidney tubules.

The mechanisms responsible for the large increases of intracellular ATP levels seen after isolated rabbit proximal tubules are treated with exogenous adenine nucleotides were studied. Exogenous ATP was rapidly degraded via adenosine as far as hypoxanthine. Degradation of AMP to adenosine was substantially inhibited by beta-glycerol phosphate. In studies of the ability of individual exogenous purines to increase intracellular ATP levels, single large doses of adenosine were less effective than equimolar doses of exogenous ATP but were substantially more effective than exogenous inosine or hypoxanthine. Exogenous guanine derived compounds increased only cell GTP. Incremental delivery of smaller doses of adenosine to maintain medium levels greater than 5 microM or inhibition of adenosine deaminase with erythro-9-[3-(2-hydroxynonyl)]adenine or 2'-deoxycoformicin enhanced the nucleoside's effectiveness. However, the initial increase of cell ATP was still greater after treatment with exogenous ATP than after adenosine and, in the presence of adenosine deaminase inhibition, larger increases of cell ATP were produced by 50 microM adenosine than by 250 microM adenosine. These observations are most consistent with substrate inhibition of adenosine kinase by adenosine. Furthermore, the adenosine kinase inhibitor, 5-iodotubercidin, prevented the increases of cell ATP resulting from exogenous adenosine or exogenous ATP. These studies demonstrate how the differential uptake and utilization characteristics of nucleosides and bases can fully account for the increases of intracellular nucleotides produced in isolated tubules by exogenous purines.

Adenine↗

Autocrine stimulation of Nb2 cell proliferation by secreted, but not intracellular, prolactin.

We have introduced expression constructs for mouse PRL (mPRL) or a nonsecreted form of mPRL into the PRL-responsive Nb2 rat lymphoma cell line. Cell lines resulting from transfection of Nb2 cells with the wild type mPRL construct synthesize and secrete mPRL. These cells are able to grow independently of added lactogens, and conditioned media and cell extracts from these cultures stimulate the growth of Nb2 cells. In contrast, cells synthesizing the nonsecreted mPRL do not proliferate in the absence of added lactogenic hormones, and conditioned media from these cell cultures do not have PRL-like activity in the Nb2 cell growth assay. PRL protein is detected in these nonsecreting cell lines; however, extracts from these lines are generally unable to stimulate Nb2 cell proliferation. These results indicate that cells can respond in an autocrine fashion to PRL, but that an intracellular form of PRL is unable to activate Nb2 cell growth.

Animals↗

A paracostal approach for splenectomy in the sheep.

A modified left paracostal approach was developed to splenectomize sheep. This approach was found to be superior to the described approaches for removal of the spleen by rib resection. Since the diaphragm is in close approximation to the last rib, resection of the last rib can result in entry of the thoracic cavity, which will complicate the surgical procedure. Furthermore, rib resection necessitates the use of analgesics, due to the pain commonly associated with any orthopedic procedure, and thereby extends postoperative recovery time. The paracostal abdominal approach provides excellent exposure, ease of manipulation, reduced anesthetic time, and fewer related problems such as postoperative pain control and thoracic evacuation. A major benefit of the paracostal approach is the minimal need for analgesic support as evidenced by the animals' rapid return to normal function. This bypasses the need for extended recovery, as required in the rib resection approach, and allows earlier utilization of the animal for research.

Animals↗

Delayed cutaneous hypersensitivity response in tetanus toxoid sensitized rhesus monkeys: predictor of anergy and value in tuberculin skin testing.

The primary problem in using the tuberculin skin test in nonhuman primates is the clinical uncertainty concerning the animal's ability to elicit a delayed cutaneous hypersensitivity response. A negative tuberculin skin test can only be meaningful if the animal can produce a delayed cutaneous hypersensitivity reaction. Veterinarians deliberately sensitize animals to antigens in the form of prophylactic vaccination. Therefore, if nonhuman primates were deliberately sensitized to an antigen capable of producing a hypersensitivity response, that antigen should serve as a positive control for delayed cutaneous hypersensitivity reactions. Tetanus toxoid was chosen because repeated immunizations with this antigen is recommended routine medical practice for nonhuman primates housed outdoors. Twenty juvenile, male rhesus (Macaca mulatta) monkeys were selected for this study. The monkeys were assigned randomly to one of two groups of ten animals. The test group was vaccinated with tetanus toxoid intramuscularly at 1 month intervals for a total of three vaccinations. The control group was treated the same except saline was administered rather than tetanus toxoid. Following sensitization, the two groups of animals were challenged with tetanus toxoid intradermally. Eight of the ten monkeys in the test group responded to the tetanus toxoid while none of the control groups responded to the tetanus toxoid. Elicitation of a delayed cutaneous response in animals sensitized to tetanus antigen before challenge may serve as a positive control for delayed cutaneous hypersensitivity. This simple test may serve as a useful adjunct in making objective clinical decisions concerning anergy-suspect animals.

Animals↗

Ameloblastic odontoma in a cynomolgus monkey (Macaca fascicularis).

An ameloblastic odontoma occurred in an adult cynomolgus monkey (Macaca fascicularis). The neoplasm involved the upper left maxilla as a disfiguring, fleshy growth. The tissue and cellular changes were consistent with an ameloblastic odontoma which is rare in man, nonhuman primates (NHP), and other vertebrate animals. The monkey was one of 50 adult, single-caged housed cynomolgus monkeys. No additional clinical signs of disease were present. Hematology and serum chemistries were within normal limits. There have been three reports in the literature of ameloblastic odontomas in NHP; however, this is the first reported case of an ameloblastic odontoma in a cynomolgus monkey.

Animals↗

Surgical excision of an ameloblastic odontoma in a cynomolgus monkey (Macaca fascicularis).

A surgical approach used for removal of maxillary tumors in humans was modified to excise a maxillary tumor in a cynomolgus monkey (Macaca fascicularis). This is an effective technique for excising tumors, recovering fractured canine teeth, or other health problems of the maxillary region in Macaca sp. The described approach limits facial disfigurement and enhances the probability of return to required function for future research utilization. This approach minimizes the extensive degree of post-operative intensive care.

Animals↗