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Biomedical subjects

J Wright

Publications and source records attributed to J Wright.

At least 451 records · Page 25Linked to original sources
PubMed1988

Treatment of advanced non-small cell lung cancer with cisplatin, 5-fluorouracil, and mitomycin C.

Thirty patients with advanced non-small cell lung cancer (NSCLC) were treated with cisplatin (P), mitomycin C (M), and 5-fluorouracil (5-FU) chemotherapy. Twelve patients (40%) achieved major responses to therapy (11 partial, one regression). The median duration of partial response was 20 weeks. Median survival for the entire group was 29 weeks. Toxicity with this combination was moderate, with myelosuppression being the most significant toxic effect. Acute hematologic toxicity was generally mild, with 74% of patients having a leukocyte nadir greater than or equal to 2000/microliter and 67% with a platelet count nadir of greater than or equal to 100,000/microliter. There were, however, two toxic deaths during periods of treatment-induced cytopenia, 40% of patients developed significant anemia necessitating blood transfusions, and 33% had episodes of prolonged neutropenia. Nonhematologic toxicities were generally mild, although one patient developed a cardiac arrest of unclear etiology during day 4 of cycle 3 of treatment and died, for a total treatment mortality rate of 10% (three of 30). This drug combination produced a response rate comparable to those noted with other two or three drug cisplatin-based regimens in NSCLC but does not appear to offer any substantial advantage given its moderate toxicity, short duration of response, and necessity for substantial hospitalization.

Adult↗
PubMed1988

Surveillance of antibody to measles, mumps, and rubella by age.

Before the introduction of measles, mumps, and rubella vaccine a survey was carried out to measure antibody prevalence to the three viruses by age. A total of 8716 samples of serum collected by five public health laboratories in different parts of England during 1986-7 were tested. Despite the current measles vaccination programme 60% of children aged 1-2 years did not have measles antibody and over 80% did not have antibodies to mumps and rubella. In the 3-4 year age group 17% of the children were susceptible to measles, 55% to mumps, and 73% to rubella. The results suggest that vaccinating children early in the second year of life will be necessary to eliminate the three diseases. The survey provides baseline data for continuing surveillance of the immediate and long term effects of the new vaccination strategy.

Adolescent↗
PubMed1988

Direct enhancement by cigarette smoke of asbestos fiber penetration and asbestos-induced epithelial proliferation in rat tracheal explants.

Tracheal explants from Sprague-Dawley rats were briefly exposed to cigarette smoke or air (control) and then to amosite asbestos. Asbestos fibers in or under the tracheal epithelium were counted and extent of hyperplastic lesions was ascertained at 24 hours, 72 hours, and 1 week after exposure. Smoke-exposed cultures showed significantly greater numbers of fibers in the epithelium and greater proliferative activity compared to findings in cultures not exposed to smoke. These observations indicate that very short exposure to cigarette smoke can directly affect the response of the epithelium to asbestos fibers and that smoke exposure need not be concurrent with asbestos exposure for such event to occur. These reactions may play a role in the greater incidences of lung cancer and asbestosis seen in asbestos-exposed workers who smoke.

Animals↗
PubMed1988

Chronic unilateral optic neuropathy: a magnetic resonance study.

We studied the clinical, electrophysiological, and magnetic resonance imaging (MRI) features of 20 patients with chronic unilateral optic neuropathy (CUON): progressive unilateral visual failure lasting a minimum of 6 months. The patients, 10 male and 10 female, ranged in age from 12 to 77 years (mean 44) and had a mean duration of symptoms of 22 months. All had signs of optic nerve dysfunction. Each patient was studied with MRI using a short TI inversion recovery (STIR) sequence to delineate the optic nerve from surrounding orbital tissue. Three distinct groups of patients with CUON were identified using MRI. In the first group (8/20) the optic nerve was compressed by an extrinsic mass, whereas in the second group (5/20) CUON resulted from an intrinsic tumor of the optic nerve or sheath. In both groups STIR sequences compared favorably with computed tomography in identifying mass lesions. MRI was superior in delineating distortion of the optic nerve by mass or tumor extension beyond the orbit. In the third group (7/20) no mass was evident on MRI. However, STIR sequences revealed altered signal (long T1) in clinically symptomatic nerves. In 4 of the patients T2-weighted cerebral MRI disclosed periventricular lesions suggestive of disseminated white matter disease. We conclude that MRI complements clinical and electrophysiological testing in the assessment of CUON.

Adolescent↗
PubMed1988

The role of the Na+/H+ antiporter in human neutrophil NADPH-oxidase activation.

The Na+/H+ antiporter has been shown to regulate activation of the human neutrophil. To delineate the role of the antiporter in the stimulation cascade, superoxide [O2-) generation was observed in PMA-stimulated neutrophils in which intracellular pH (pHi) was artificially manipulated by the use of nigericin, a K+/H+ ionophore, with and without use of the Na+/H+ antiporter inhibitor, dimethylamiloride (DA). Decreased O2- generation was observed in a Na+-free, 140 mM K+ buffer, but addition of nigericin restored this parameter of neutrophil activation to levels found in physiologic Na+ media. Further, the inhibitory effects of DA on O2- generation by cells incubated in a 10 mM Na+, 130 mM K+ buffer were totally reversed by a similar concentration of nigericin. O2- generated by a membrane preparation of the NADPH-oxidase, made from cells incubated under the same experimental conditions, paralleled whole cell studies, but the activity of the oxidase did not vary when suspended in the various reaction mixtures. These experiments support the role of the Na+/H+ antiporter in neutrophil activation as a metabolic regulator of pHi that influences receptor-coupled reactions proximal to expression of the NADPH-oxidase itself.

Antiporters↗
PubMed1988

Ultrasound detection of oesophageal varices--comparison with endoscopy.

In a prospective study of 100 patients for the detection of oesophageal varices, real-time ultrasound was both sensitive (sensitivity 82%) and specific (specificity 91%) compared with upper gastrointestinal endoscopy. All patients with large and medium sized varices were correctly identified by ultrasound. Ultrasound should be considered as an alternative to endoscopy and radiology for detection of oesophageal varices.

Esophageal and Gastric Varices↗
PubMed1988

Induction of phagocyte cytochrome b heavy chain gene expression by interferon gamma.

Phagocytic cells, such as macrophages and polymorphonuclear leukocytes, produce a "respiratory burst" in which oxygen is reduced to superoxide and other active oxygen species responsible for many of the microbicidal, tumoricidal, and inflammatory activities of these cells. Interferon gamma has been shown to augment phagocyte superoxide production, but the molecular mechanisms underlying this effect have remained unknown. Recently a key component of the oxidase, phagocyte cytochrome b, has been characterized as a heterodimer of a 91-kDa glycoprotein and a 22-kDa polypeptide. The present studies examined the effects of human recombinant interferon gamma on the expression of the genes for these components of the cytochrome b. In vitro treatment with interferon gamma substantially increases the level of phagocyte cytochrome b heavy chain gene transcripts in normal polymorphonuclear leukocytes, normal monocyte-derived macrophages, and the monocytic leukemia cell line THP-1. Light chain gene transcripts are less affected. In monocyte-derived macrophages and THP-1 cells, the enhanced expression of the heavy chain gene appears in large part attributable to increased rates of transcription. Treatment of monocyte-derived macrophages with human recombinant interferon alpha (a down-regulator of the respiratory burst) decreased the heavy chain transcript levels; interferon beta produced no detectable change. These findings demonstrate the responsiveness of one essential component of the phagocyte oxidase system to activation by interferon gamma and provide a rationale for its use to augment phagocytic function in chronic granulomatous disease.

Cytochrome b Group↗
PubMed1988

Architecture of the sarcomere matrix of skeletal muscle: immunoelectron microscopic evidence that suggests a set of parallel inextensible nebulin filaments anchored at the Z line.

Nebulin, a giant myofibrillar protein (600-800 kD) that is abundant (3%) in the sarcomere of a wide range of skeletal muscles, has been proposed as a component of a cytoskeletal matrix that coexists with actin and myosin filaments within the sarcomere. Immunoblot analysis indicates that although polypeptides of similar size are present in cardiac and smooth muscles at low abundance, those proteins show no immunological cross-reactivity with skeletal muscle nebulin. Gel analysis reveals that nebulins in various skeletal muscles of rabbit belong to at least two classes of size variants. A monospecific antibody has been used to localize nebulin by immunoelectron microscopy in a mechanically split rabbit psoas muscle fiber preparation. Labeled split fibers exhibit six pairs of stripes of antibody-imparted transverse densities spaced at 0.1-1.0 micron from the Z line within each sarcomere. These epitopes maintain a fixed distance to the Z line irrespective of sarcomere length and do not exhibit the characteristic elastic stretch-response of titin epitopes within the I band domain. It is proposed that nebulin constitutes a set of inextensible filaments attached at one end to the Z line and that nebulin filaments are in parallel, and not in series, with titin filaments. Thus the skeletal muscle sarcomere may have two sets of nonactomyosin filaments: a set of I segment-linked nebulin filaments and a set of A segment-linked titin filaments. This four-filament sarcomere model raises the possibility that nebulin and titin might act as organizing templates and length-determining factors for actin and myosin respectively.

Actins↗
PubMed1988

Diffuse histiocytic lymphoma: the 20-year experience of an Australian teaching hospital.

There is a paucity of information regarding the natural history and treatment outcome of diffuse histiocytic lymphoma (DHL) in Australia. Case records from 80 patients treated for DHL at the Royal Adelaide Hospital between 1965 and 1985 were reviewed to determine treatment outcome and prognostic information. Pathological review of biopsy specimens confirmed the correct diagnosis in 78 patients. The Ann Arbor staging criteria were unsatisfactory for prognostic purposes. We identified three prognostic groups: Localised disease (82% five-year survival), Advanced disease marrow negative (36% five-year survival), and Advanced disease marrow positive (11% five-year survival). An elevated plasma lactate dehydrogenase (LDH) and calcium (Ca++) predicted a poorer outcome; no patient with a LDH greater than 500 IU achieved longterm survival (p less than 0.001). Survival was identical for patients reclassified histologically as intermediate grade or high grade (Working Formulation). Localised disease was associated with a good prognosis (82% five-year survival) regardless of treatment modality. The outcome of patients with advanced disease has markedly improved over the last two decades, particularly with the introduction of combination chemotherapy containing doxorubicin in 1974 (p less than 0.005). Using these regimens, complete remission was achieved in 65% of patients, with a 39% five-year survival.

Adult↗
PubMed1988

Ectopic release of GHRH and ACTH from an adenoid cystic carcinoma resulting in acromegaly and complicated by pituitary infarction.

A 23 year old man presented with a tumour mass in the lung. Subsequent investigation showed ectopic secretion of adrenocorticotrophic hormone (ACTH) and growth hormone releasing hormone (GHRH) from an adenoid cystic carcinoma. The patient progressed to show the clinical effects of long term exposure to high blood levels of both growth hormone and cortisol. The case was complicated by pituitary infarction. The very high blood levels of ACTH, growth hormone (GH) and GHRH proved resistant to treatment with the somatostatin analogue, SMS 201-995, and a possible side effect of the drug is reported. To our knowledge this is the first reported case of ectopic hormone secretion by an adenoid cystic carcinoma.

Acromegaly↗
PubMed1988

Effect of chronic propranolol on growth of newborn beagle puppies.

To evaluate the effect of chronic propranolol on body growth and organ size, newborn beagle puppies were assigned to each of three treatment groups: high propranolol (18 mg/kg/day); low propranolol (6 mg/kg/day), and control. Heart rate and systolic blood pressure were significantly lower in animals receiving propranolol (p less than 0.001). There were no significant differences between groups at any time during the 6 months of observation in length, weight and necropsy wet weights or histology of brain, heart, kidney, lung, liver, thyroid, pancreas, adrenal, pituitary, prostate or gonad, or in humerus and femur length. Chronic propranolol therapy had no apparent effect on body growth and individual organ size of normal newborn beagle puppies.

Administration, Oral↗
PubMed1988

Effects of cigarette smoke on tissue uptake and retention of iron oxide in the guinea pig.

We have previously shown that cigarette smoke increases retention and tissue penetration of asbestos, a pathogenic dust. To determine whether these same phenomena occur with an inert dust, we administered iron oxide particles to guinea pigs by intratracheal instillation. Half of the animals were exposed to cigarette smoke. Animals were killed at 1 day, 1 wk, and 1 month. Numbers of particles in airway epithelia and walls were counted in histologic sections of one lung, and the other lung was analyzed chemically for iron content. In both smoke-exposed and nonexposed groups, the chemically determined concentration of iron in the lung tissue decreased between 1 day and 1 month; however, the concentration of iron was significantly greater in the smoke-exposed group at 1 day and 1 wk. By 1 month, there was no significant difference between the 2 groups. The number of particles in the epithelia of respiratory bronchioles also decreased in both smoke-exposed and nonexposed groups between 1 day and 1 month, but the smoke-exposed group had significantly more intraepithelial particles at 1 day and 1 wk than did the nonexposed group. The number of particles in the walls of respiratory bronchioles increased between 1 day and 1 month in both smoke-exposed and nonexposed groups; the difference between these groups was significant only at 1 wk, when airway walls of the smoke-exposed animals contained more particles.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Effects of recombinant human granulocyte-macrophage colony-stimulating factor on intracellular pH in mature granulocytes.

We studied the effects of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSFrh) on the internal pH of granulocytes using the fluorescent probe BCECF. GM-CSFrh did not directly alter the resting pH of granulocytes isolated from the peripheral blood; however, when the cells were preincubated for 90 minutes with the growth factor and then activated with the chemotactic peptide N-formyl met leu phe (fMLP), they exhibited both an acceleration in the initial rate of acidification and a marked delay in realkalinization. The kinetic changes both in initial acidification and in subsequent realkalinization induced by GM-CSFrh priming were not prevented by protein synthesis inhibitors and were observed in granulocytes harvested from patients with both sex-linked and autosomal recessive chronic granulomatous disease (CGD). By directly quantitating H+ ion secretion, by monitoring the effects of sodium repletion on intracellular pH, and through use of the sodium channel inhibitors amiloride and dimethyl amiloride and the Na+/K+-ATPase inhibitor ouabain, we showed that the altered kinetics of intracellular acidification and alkalinization following fMLP stimulation of GM-CSFrh-primed granulocytes could not be accounted for by changes in transmembrane proton exportation regulated by the Na+/H+ antiport channel. Although the initial acidification following fMLP was abrogated by 2-deoxy-D-glucose in both GM-CSFrh-pretreated and GM-CSFrh-untreated granulocytes, retardation of the subsequent phase of alkalinization was observed in GM-CSFrh-primed cells even after inhibition of both glycolytic and mitochondrial metabolism. Our data indicate that the increased cytosolic acidification following fMLP stimulation in granulocytes "primed" with GM-CSFrh does not result from disordered proton excretion but instead from increased release of intracellular free acid which is only partially coupled to glucose catabolism or to the generation of superoxide anion (O2-).

Amiloride↗
PubMed1988

Evaluation of Cassia obtusifolia (sicklepod) seed consumption in Holstein calves.

Fifteen Holstein bull calves weighing 135-160 kg (300-350 lb) were randomly assigned to 3 groups of 5 animals each. Each calf was individually fed free choice Bermuda grass hay and 3.63 kg (8 lb) of a commercial 14% crude protein ration/day. Group 1 (control) received no Cassia obtusifolia seed, group 2 (low exposure) received 0.45 kg (1 lb) of C obtusifolia seed (12.5% of ration and approximately 0.27% of body weight) and group 3 (high exposure) received 1.81 kg (4 lb) C obtusifolia seed (50% of ration and approximately 1.19% of body weight) from day 0-9, and then received 1.36 kg (3 lb) (37.5% of ration and 0.89% of body weight) from day 10-24. The effects of low and high C obtusifolia seed contamination were intermittent feed refusal, diarrhea, and decreased weight gain. Average daily weight gains (ADG) for the control, low exposure and high exposure groups, were 0.76, 0.53, 0.31 kg/day, respectively. The ADG of the control calves was significantly greater than the ADG of the high exposure calves (p less than 0.0001) and the low exposure calves (p less than 0.0059). The ADG of the low exposure calves was significantly greater than the ADG of the high exposure calves (p less than 0.0209). No change was observed in serum aspartate aminotransferase, creatine phosphokinase, lactic dehydrogenase activity, and histologic examination showed no evidence of muscle necrosis.

Animals↗
PubMed1988

Changes in anal sphincter tone at induction of anaesthesia.

Changes in anal pressure have been monitored during the induction of anaesthesia. Falls in pressure accompany loss of consciousness following bolus doses of commonly used intravenous and inhalational anaesthetic agents. Subsequent rises in pressure towards pre-anaesthetic levels are usually associated with the time taken to correct responses and initial recovery. Premedication, including anticholinergic drugs in conventional dosage, does not affect anal pressure.

Alfaxalone Alfadolone Mixture↗