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Biomedical subjects

S Wright

Publications and source records attributed to S Wright.

At least 19 recordsLinked to original sources

The pathophysiology of cardiorespiratory arrest and principles of post-resuscitation intensive care.

Oxygen supply to the tissues is dependent on both cardiac output (which is determined by blood volume and myocardial function) and the oxygen tension of arterial blood (which reflects respiratory status). Abnormalities of these parameters may occur individually or together to progress ultimately to combined cardiorespiratory collapse. Life support measures are then required to restore the oxygen supply to vital organs, such as the brain, heart, kidneys and liver while attempts to restore normal cardiorespiratory status are made. Survival following cardiorespiratory arrest is enhanced if resuscitation is promptly instituted by skilled resuscitators, and a clear understanding of the mechanisms of cardiorespiratory collapse are essential to the efficient management of these patients.

Arrhythmias, Cardiac

Proof of differentiative mode of action of all-trans retinoic acid in acute promyelocytic leukemia using X-linked clonal analysis.

Using X-linked clonal analysis, mechanism of action of all-trans retinoic acid (ATRA) was sought in a 16-year-old female with relapsed clonally evolved acute promyelocytic leukemia (APL), who achieved complete remission. On ATRA, metamorphosis of peripheral blood leukemic promyelocytes to mature neutrophils was observed, despite the persistence of t(15;17) in 100% of bone marrow metaphases. DNA was extracted from fractionated serial blood specimens, collected at diagnosis, in first complete remission (CR), relapse, and during ATRA treatment. Using a phosphoglycerokinase (PGK) probe, the patient was heterozygous for both Bgl I and Bst XI PGK polymorphisms. Methylation analysis showed monoclonal leukemic promyelocytes with a polyclonal first CR achieved by standard chemotherapy. Subsequent examination, in relapse, of granulocytes appearing during ATRA treatment showed these to be monoclonal, proving these were derived from the neoplastic clone. The X-linked clonal analysis methodology has provided in vivo evidence of cellular differentiation as the mechanism of action of ATRA. Parallel studies of cytogenetic and clonal analysis showed a regression of the t(15;17) cytogenetic abnormality and return of a polyclonal PGK methylation pattern in 5 weeks, indicating a repopulation of marrow by normal stem cells. As standard cytogenetic techniques are inappropriate for nondividing cells, X-linked clonal analysis provides a marker system to allow insight into mechanism of drug action in malignant hematologic disease.

Adolescent

Comparison of staining and concentration techniques for detection of Cryptosporidium oocysts in cat faecal specimens.

Modified Ziehl-Neelsen (MZN), auramine-phenol (A-P) and fluorescein isothiocyanate-labelled (FITC-labelled) monoclonal antibody (MAb) techniques were compared for detection of Cryptosporidium parvum oocysts in cat faecal specimens inoculated with known numbers of C. parvum oocysts. Of the three techniques, the FITC-labelled MAb technique detected more oocysts than the MZN and A-P techniques (P < 0.05), but A-P was more efficient than MZN (P < 0.05). Comparison of sucrose flotation, zinc sulphate (ZnSO4) flotation and formol-ether (F-E) sedimentation techniques revealed that F-E was the most efficient of the three (P < 0.05) for concentration of C. parvum oocysts from cat faecal specimens. On average, the F-E technique recovered 37% of oocysts from the original sample, whereas the sucrose and ZnSO4 flotation techniques recovered 33% and 11%, respectively. The findings of this study suggest that MZN and A-P staining are both useful for screening C. parvum oocysts in cat faecal materials containing 10(6) oocysts or more, but FITC-labelled MAb should be used when the number of oocysts is low. Also, the F-E sedimentation technique is recommended for concentrating oocysts in cat faecal specimens.

Animals

The effect of topical steroids on cutaneous oxygen tension.

The precise mode of action of topically applied steroids is unknown. We have applied clobetasol propionate 0.05% ointment (Dermovate; Glaxo Pharmaceuticals) under occlusion to the forearm skin of 10 healthy volunteers for 6 h and monitored transcutaneous oxygen tension at the site for 19 h after its removal. Compared to the ointment base, the steroid-treated area was significantly hypoxic up to 13 h after application. The profound hypoxia present at the site of application of clobetasol propionate 0.05% ointment may account for some of its anti-inflammatory effects, and its atrophogenicity.

Administration, Topical

Reproductive and developmental hazards and employment policies.

The task of informing workers of hazards in the workplace is seldom more difficult than with the subject of reproductive and developmental hazards. Occupational health staff and physicians are faced with a paucity of relevant medical information. Workers, kept aware of the thalidomide spectre with every media report of the latest descriptive epidemiology study, are anxious to know more. Employers, knowing that few agents are regulated on the basis of reproductive hazards, are encouraged to lessen workplace exposure to all agents but need guidance from government and scientists in setting priorities. Understandable ethical and scientific limitations on human studies require researchers to study animals and cells. The difficulties of extrapolating the results of this research to humans are well known. The scientific, medical, and workplace difficulties in dealing with reproductive and developmental hazards are mirrored in the regulatory positions found in North America. Some regard fetal protection policies as sex discrimination whereas others consider such policies as reasonable. Guidelines are provided to allow employers and medical practitioners to consider this difficult problem.

Abortion, Spontaneous

Assessment of papain-induced lung injury in isolated lungs by measurements of aerosol deposition and mixing.

Aerosol bolus inspirations were used to assess lung injury in 15 isolated dog lungs exposed to low (0-375 units) or high doses (600-1,200 units) of papain. Effective air space size (EAD) was determined from aerosol deposition during a 5-s breath hold. Convective mixing was assessed by the spreading of the expired bolus with respect to expired volume, quantified by a coefficient of dispersion (CD) equal to the square root of the difference in the variances of the expired and inspired boluses divided by the volumetric penetration of the bolus. After exposure, CD measured with deeply penetrating boluses increased by an average of 2.5% in the low-exposure group (P greater than 0.05) and 28.0% in the high-exposure group (P less than 0.0001). CD measured with shallowly penetrating boluses decreased by 4.3% (P less than 0.0001) in the low-exposure group and increased by an average of 18.3% in the high-exposure group (P less than 0.05). Papain exposure caused EAD to increase in some lungs and decrease in others. For deep bolus penetrations, EAD changed by an average of -0.8% in the low-exposure group (P greater than 0.05) and +21.1% in the high-exposure group (P greater than 0.05). Both EAD and CD appeared to be sensitive to lung injury. However, changes in EAD were less consistent than those in CD, possibly due to changes caused by lung injury in the regional distribution of inspired aerosol.

Aerosols

Acute cauda equina syndrome from a ruptured aneurysm in the sacral canal. Case report.

The case is presented of a young woman with acute cauda equina syndrome from a ruptured aneurysm in the sacral canal. The lesion was associated with pathological enlargement of the lateral sacral arteries bilaterally, which presumably occurred to provide cross-pelvic collateral flow in response to the diversion of the right internal iliac artery for renal transplantation. The patient presented with signs and symptoms of spontaneous spinal epidural hemorrhage. The radiographic features of this lesion are described. In addition to angiography and partial embolization of the vascular supply, contrast-enhanced high-resolution computerized tomography was essential in the diagnosis and treatment of this unique aneurysm.

Acute Disease

Premature termination of transcription from the P1 promoter of the mouse c-myc gene.

Modulation of transcriptional elongation within the c-myc gene is thought to play a major role in determining levels of c-myc mRNA in both normal and tumor cells. A discrete site of blockage to transcriptional elongation has previously been localized at the 3' end of exon 1 of the mouse and human c-myc genes. We here identify an additional site of transcriptional attenuation that is located between the P1 and P2 promoters of the c-myc gene and that mediates premature termination of transcripts initiating from the P1 promoter. A 95-nucleotide DNA fragment derived from this region prematurely terminated transcription when placed downstream from the promoter of the H-2Kbm1 gene and assayed by expression in Xenopus oocytes. We also show that the previously identified attenuation signal in exon 1 of the mouse c-myc gene can mediate premature termination of P1-initiated transcripts. Premature termination of P1-initiated transcripts presumably increases transcription from the downstream P2 promoter; aberrant regulation of this termination may explain the increased use of the P1 promoter that is characteristic of certain tumors in which myc is overexpressed.

Animals

Cryptosporidium infection in cats: prevalence of infection in domestic and feral cats in the Glasgow area.

A clinical and post mortem survey of domestic and feral cats in the Glasgow area revealed that 19 of 235 (8.1 per cent) were infected with Cryptosporidium species. More kittens than adults were infected (P less than 0.01), and of 51 of the cats which had diarrhoea, four also had cryptosporidium infection. Of seven domestic cats with cryptosporidium infection, two were also positive for feline immunodeficiency virus. There was no significant difference between the prevalence of cryptosporidium infection in domestic and feral cats. Cryptosporidium oocysts were detected in faecal and mucosal impression smears stained with auramine-phenol and modified Ziehl-Nielsen techniques. Endogenous developmental stages of cryptosporidium were found in the microvillus region of enterocytes of eight of 19 positive cats in sections stained with haematoxylin and eosin. The results suggest that cryptosporidium infection is common among young and newborn kittens, and that the disease is usually asymptomatic.

Age Factors

Vaccination of sheep with a live incomplete strain (S48) of Toxoplasma gondii and their immunity to challenge when pregnant.

Sixty-four ewes were vaccinated with tachyzoites of an incomplete strain (S48) of Toxoplasma gondii grown either in the peritoneal cavity of mice (group 1) or vero cell culture (group 2) and 30 ewes (group 3) were not vaccinated. All the ewes were mated 77 days later and challenged orally with 2000 sporulated oocysts at 89 to 90 days of gestation. Ten additional unvaccinated (group 4) and 10 vaccinated (group 5) control ewes were not challenged. The unvaccinated ewes developed a characteristic febrile response to challenge while in the vaccinated ewes the fever commenced earlier but was less severe and of shorter duration. After challenge, the antibody titres against T gondii rose rapidly to high values in the vaccinated ewes while the ewes in group 3 responded more slowly. Only eight of the 45 fetuses/lambs (17.8 per cent) from group 3 were viable compared with 72.3 per cent of those in group 1 and 80.8 per cent of those in group 2. Gestation in the unvaccinated challenged ewes was shortened and the mean birthweight of their single, viable offspring was significantly lower than the weight of single lambs from the vaccinated (groups 1 and 2) and control ewes (groups 4 and 5). Examination of precolostral sera showed that almost two-thirds of the lambs from the vaccinated ewes were infected in utero. The 20 control ewes appeared clinically normal at all times and lambed normally. The two vaccine preparations were equally effective.

Abortion, Veterinary

The effect of human immunodeficiency virus type 1 antibody status on military applicant aptitude test scores.

The authors conducted a population-based study to attempt to estimate the effect of human immunodeficiency virus type 1 (HIV-1) seropositivity on Armed Services Vocational Aptitude Battery test scores in otherwise healthy individuals with early HIV-1 infection. The Armed Services Vocational Aptitude Battery is a 10-test written multiple aptitude battery administered to all civilian applicants for military enlistment prior to serologic screening for HIV-1 antibodies. A total of 975,489 induction testing records containing both Armed Services Vocational Aptitude Battery and HIV-1 results from October 1985 through March 1987 were examined. An analysis data set (n = 7,698) was constructed by choosing five controls for each of the 1,283 HIV-1-positive cases, matched on five-digit ZIP code, and a multiple linear regression analysis was performed to control for demographic and other factors that might influence test scores. Years of education was the strongest predictor of test scores, raising an applicant's score on a composite test nearly 0.16 standard deviation per year. The HIV-1-positive effect on the composite score was -0.09 standard deviation (99% confidence interval -0.17 to -0.02). Separate regressions on each component test within the battery showed HIV-1 effects between -0.39 and +0.06 standard deviation. The two Armed Services Vocational Aptitude Battery component tests felt a priori to be the most sensitive to HIV-1-positive status showed the least decrease with seropositivity. Much of the variability in test scores was not predicted by either HIV-1 serostatus or the demographic and other factors included in the model. There appeared to be little evidence of a strong HIV-1 effect.

Aptitude Tests

Cryptosporidium parvum: investigation of sporozoite excystation in vivo and the association of merozoites with intestinal mucus.

Enteric cryptosporidiosis was studied in the small intestine of five-day-old sucking mice after infection with 10(6) Cryptosporidium parvum oocysts. It was shown that excystation and the majority of subsequent endogenous stages occurred predominantly in the ileum. During the first three days of infection the number of merozoites collected in ileal washings increased over 100-fold to approximately 10(6) merozoites per mouse on the third day. In contrast to control mice, wash fluid from infected mice contained numerous strands of dislodged mucus. Estimates of mucus in the ileal washings of infected mice were similar to those made in controls until day 4 after infection when they increased and remained high throughout the remainder of the experiment. This study describes a method whereby ileal mucus washings from C parvum infected infant mice could be used as a rich source of merozoites.

Animals

Idiopathic scrotal calcinosis is idiopathic.

The appearance of calcific masses within the dermis of scrotal skin is generally referred to as idiopathic scrotal calcinosis. There has been some debate about the pathogenesis of these calcium deposits. This debate centers on the question of whether the calcium deposition is truly idiopathic or whether it occurs as a result of preexisting epidermal cysts. We have performed immunohistochemical staining for keratin in nine patients with apparent idiopathic scrotal calcinosis and have found no evidence of keratin in the dermal tissue immediately adjacent to the calcium deposits. We conclude that idiopathic scrotal calcinosis is idiopathic.

Adolescent

Cyclic adenosine monophosphate-phosphodiesterase activity in cultured keratinocytes from patients with atopic eczema.

A number of previous studies have documented an increase in cyclic adenosine monophosphate-phosphodiesterase activity in patients with atopic dermatitis. We have studied the activity of this enzyme in keratinocytes cultured from patients with atopic dermatitis compared to keratinocytes from non-atopic controls. Results show that these pure preparations of keratinocytes express only one form of cyclic adenosine monophosphate phosphodiesterase with a Km of 1.9 microM, and a Vmax of 17 pmol/min/mg of substrate converted. We conclude that cyclic adenosine monophosphate-phosphodiesterase activity in cultured keratinocytes from patients with atopic eczema does not differ from controls.

3',5'-Cyclic-AMP Phosphodiesterases

Reactive astrogliosis is widespread in the subcortical white matter of amyotrophic lateral sclerosis brain.

Widespread astrogliosis exists in the subcortical white matter in amyotrophic lateral sclerosis (ALS). As revealed by glial fibrillary acidic protein (GFAP) immunostaining, the gliosis has the morphological properties of an active process. It is present in the midfrontal, inferior parietal, temporal, cingulate, and occipital cortices, as well as in the motor cortex. Compared to matched regions from other neurological diseases, the gliosis in ALS does not appear to be the nonspecific result of a progressive, degenerative disease. In cell number and apparent cell size, the gliosis is comparable to that present in neurological diseases known to have white matter gliosis. Cytologically, the gliosis most closely resembles that present in cases of cerebral infarction. The basis for this similarity is unknown.

Aged