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Biomedical subjects

S Morgan

Publications and source records attributed to S Morgan.

At least 109 records · Page 6Linked to original sources

Time-course of adhesion molecule expression in rectal mucosa of gluten-sensitive subjects after gluten challenge.

Adhesive interactions between endothelium and circulating cells, such as monocytes, neutrophils and lymphocytes, are crucial for localizing the inflammatory response. We investigated the inflammatory response of rectal mucosa to local gluten challenge as a dynamic model of antigen-induced tissue injury, during which the expression of adhesion molecules on leucocytes and endothelial cells could be sequentially observed. Expression of ELAM-1, ICAM-1 and VCAM-1 was monitored in 10 treated and eight untreated patients with gluten sensitivity (coeliac disease), and in five disease controls for up to 4 h (short challenge), while a further seven treated coeliacs were monitored for up to 24 h (long challenge) following rectal gluten challenge. In the former, the expression of VCAM-1 and ELAM-1 was significantly raised 4 h after gluten challenge compared with controls. VCAM-1 and ELAM-1 expression was also increased in mucosae of treated patients, but to a lesser extent. VCAM-1 expression continued to increase for up to 24 h after gluten, while ELAM-1 had begun to wane by 4 h, reaching basal levels by 24 h. In contrast, the expression of ICAM-1 did not change in any of the disease groups studied. These findings relate to significant increases in lymphocytes (CD3+ cells) after 8 h, and neutrophils (CD15+ cells) after 4 h in the lamina propria. This approach has permitted novel studies of the inflammatory response to a defined antigen in sensitized (gluten-sensitive) human patients.

Celiac Disease↗

A family with autosomal dominant polycystic kidney disease not linked to chromosome 16p13.3.

A family of Sicilian origin with autosomal dominant polycystic kidney disease (APKD) has been shown to be unlinked to chromosome 16 markers. LOD scores for the polymorphic markers 3'HVR and SM7 flanking the PKD 1 locus, were -1.4 and -2.33 respectively, and theta max was 0.5 for each marker. The clinical phenotype of this family is consistent with that of the other non-linked families with APKD reported in the literature, all outside the United Kingdom, which have a milder progression than those linked to 16p13.3. Assuming that a clinic population represents the most severe forms of a disease and non PKD-1 is a less aggressive phenotype, the degree of genetic heterogeneity for APKD in the population may well be much greater than at present suggested.

Aged↗

Morphometric analysis of intestinal mucosa. V. Quantitative histological and immunocytochemical studies of rectal mucosae in gluten sensitivity.

To study changes in rectal mucosa that might be attributable to the effects of gluten, rectal biopsy specimens from untreated and treated gluten sensitised subjects were analysed morphometrically and by immunohistochemical techniques and were compared with a series of disease control mucosae. Although morphometry showed increased populations of plasma cells, lymphocytes, and mast cells in the mucosae of untreated patients, which were reduced (except for mast cells) by dietary gluten restriction, immunohistochemical techniques were far more sensitive in defining these changes. There were highly significant increases in CD3+ and gamma delta+ lymphocytes within both the lamina propria and the epithelium while neutrophils (CD15+ cells) were not at all prominent. Activated (CD25+) lymphocytes expressing interleukin (IL)-2 receptors were increased in lamina propria, usually subjacent to basal lamina, although a few IL-2R+ intraepithelial lymphocytes were found: other IL-2R+ cells were deemed to be macrophages (CD68+). These results clearly indicate that in untreated, gluten sensitised subjects the rectal mucosa shows a lymphoplasmacytoid reaction that is responsive to gluten restriction. The absence of neutrophilia suggests that this lesion is not a conventional inflammatory type proctitis, but rather one presumed to be induced by gluten antigen(s) present in the faecal stream--that is, a cell mediated form of response.

CD3 Complex↗

Experimental infections and natural outbreaks of eperythrozoonosis in pigs identified by PCR-DNA hybridizations.

Eperythrozoon-specific DNA amplification reactions and subsequent hybridizations with an eperythrozoon DNA probe (KSU-2) were used in experimental infection studies to identify Eperythrozoon suis DNA in the blood of splenectomized and nonsplenectomized pigs. The results indicate that E. suis DNA is present in nonsplenectomized pigs at levels that can be amplified by polymerase chain reaction (PCR) and identified in DNA hybridizations within 24 hours after infection. The ability of the E. suis PCR/hybridization assay to detect eperythrozoonosis was further demonstrated in blood samples collected from pigs in 2 separate natural outbreaks in Oklahoma. Results from these initial samplings indicate that pigs infected with E. suis from geographically distinct locations can be identified using the eperythrozoon-specific PCR/hybridization assay, which offers many advantages over conventional laboratory procedures for diagnosing eperythrozoonosis in pigs.

Animals↗

Plasma inorganic fluoride levels with sevoflurane anesthesia in morbidly obese and nonobese patients.

Administration of several of the inhaled anesthetics result in plasma inorganic fluoride concentrations that are higher in obese compared to nonobese patients. Sevoflurane, a new inhaled anesthetic, is metabolized to inorganic fluoride; however, plasma inorganic fluoride levels with sevoflurane anesthesia in obese subjects have not been evaluated. We studied plasma inorganic fluoride concentrations during and after sevoflurane surgical anesthesia in morbidly obese (n = 13, body mass index > 35) and nonobese (n = 10) patients. Sevoflurane anesthesia in 60% nitrous oxide/40% oxygen was administered with a semiclosed circle absorption system. Mean anesthetic duration was 1.4 minimum alveolar anesthetic concentration (MAC) hours (sevoflurane MAC = 2.05%) for both groups. Pre- and postoperative blood urea nitrogen, creatinine, and liver function tests were evaluated. Venous blood samples were obtained during and after anesthesia for plasma inorganic fluoride analysis. In six morbidly obese and nonobese patients arterial blood samples were obtained during and after sevoflurane anesthesia for determining sevoflurane blood concentration. Plasma fluoride concentrations during and after anesthesia did not differ between morbidly obese and non-obese groups. Peak plasma inorganic fluoride ion concentrations were 30 +/- 2 mumol/L (mean +/- SEM) in obese and 28 +/- 2 mumol/L in nonobese patients 1 h after discontinuing anesthesia. The hourly rate of change of fluoride ion concentration in plasma during anesthesia was similar between the groups. The maximal recorded plasma fluoride concentrations were 49 mumol/L in an obese patient and 42 mumol/L in a nonobese patient. Pre- and postoperative hepatic and renal tests did not differ significantly in either group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Double-blind trial of pyridoxine (vitamin B6) in the treatment of steroid-dependent asthma.

Pyridoxine has been reported to largely correct an abnormality of tryptophan metabolism present in patients with bronchial asthma and to reduce the symptoms of asthma in long-term studies. We enrolled 31 patients requiring steroids (oral or inhaled) for the treatment of their asthma in a double-blind, placebo-controlled assessment of 9 weeks' treatment with pyridoxine 300 mg per day (13) or placebo (18). Outcome variables included PEFR, FEV1, asthma symptom scores, 24 hour urinary 5-HIAA, skin test reactivity to histamine and compound 48/80 and blood serotonin levels. Plasma pyridoxine levels indicated overall patient compliance with a mean change from baseline to the end of the study of 82.5 +/- 27.7 ng/mL in patients on pyridoxine and -2.9 +/- 10.3 for those on placebo (P = .0001). Furthermore, patients routinely treated with theophylline had lower (10 +/- 8 ng/mL) plasma pyridoxine levels at baseline than those not on it (19 +/- 6 ng/mL; P = .01), suggesting that theophylline may lower plasma pyridoxine levels. There was no significant difference between the pyridoxine and placebo groups in the change from baseline to the last 2 weeks of treatment phase in any of the outcome variables. We conclude that under the conditions of the study, treatment with oral pyridoxine failed to improve the outcome variables in patients requiring steroids for the treatment of their asthma. The results of this study suggest that prescription or usage of oral pyridoxine for the treatment of asthma cannot be justified in such patients.

Administration, Inhalation↗

Time-dependent neuroplasticity in mesostriatal projections after unilateral removal of vibrissae in the adult rat: compartment-specific effects on horseradish peroxidase transport and cell size.

In adult rats the mystacial vibrissae were clipped on one side of the snout, and the influence of this sensory deprivation on crossed and uncrossed striatal afferents from the substantia nigra, ventral tegmental area, and retrorubral area was examined with the horseradish peroxidase tract tracing technique. Unilateral removal of vibrissae was found to affect crossed and uncrossed nigrostriatal projections in a time-dependent manner. One to three days after hemivibrissotomy an apparent neuronal asymmetry was found in the crossed nigrostriatal projection arising in the rostral part of the substantia nigra, with more labeled neurons in the projection to the caudate-putamen on the side of vibrissae removal. This asymmetry resulted mainly from an asymmetry in the subset of nigrostriatal neurons reported to project to the striatal matrix ("dorsal cell type"). In contrast, 4-20 days after hemivibrissotomy reversed asymmetries were found in crossed and uncrossed nigrostriatal projections, with more labeled neurons in the projections to the caudate-putamen of the hemisphere opposite to vibrissae removal (the sensory deprived hemisphere). The asymmetry in the uncrossed projection was found throughout the substantia nigra, but was also most substantial in the projection from its rostral part. The asymmetry in the crossed projection was again restricted to the rostral substantia nigra; interestingly, however, it was limited to the subset of neurons reported to terminate in the striosomes ("ventral cell type"). Evidence was also found for time-dependent changes in size of neurons of the crossed nigrostriatal projections, as well as for changes in striatal afferents from the ventral tegmental area. The time course of these apparent changes in strength of mesostriatal projections is similar to the known time course of recovery from behavioral asymmetries induced by hemivibrissotomy, which is suggestive of a functional relationship between neuronal and behavioral changes. Moreover, the finding of a differential influence of hemivibrissotomy on nigrostriatal afferents to striosomes and matrix is indicative of a functional dissociation of these two systems.

Analysis of Variance↗

The transoral approach to the cervical spine.

The transoral surgical approach is useful for operating on structures at the base of the brain and the upper cervical spinal cord. For example, this route has been used for resecting spinal tumors and clipping vertebrobasilar aneurysms. In the past, this surgical approach was not advocated due to concerns about exposure and infection. However, the availability of the microscope, computed tomography, computed myelotomography, magnetic resonance imaging and intraoperative radiography as well as more effective techniques have improved the diagnosis of pathology of the craniovertebral junction and surgical performance. An understanding of the operative procedures involved with this approach assists the neuro-science nurse in preoperative teaching and anticipating potential postoperative complications.

Arthritis, Rheumatoid↗

Plasma inorganic fluoride with sevoflurane anesthesia: correlation with indices of hepatic and renal function.

The biotransformation and plasma inorganic fluoride ion production of sevoflurane (the new volatile anesthetic) during and after surgical anesthesia was studied in 50 ASA I or II surgical patients. Twenty-five additional patients served as controls by receiving isoflurane. Sevoflurane or isoflurane was administered with a semiclosed (total gas flow, 2 L/min O2) circle absorption system for durations of 1.0 to greater than 7.0 minimal alveolar concentration (MAC) hours for surgical anesthesia (sevoflurane MAC, 2.05%; isoflurane MAC, 1.15%). Preoperative and postoperative blood urea nitrogen and creatinine concentrations were determined. Blood samples were obtained during and after anesthesia in both groups for determining anesthetic blood concentration analysis and plasma fluoride level. Plasma fluoride concentrations did not significantly increase during isoflurane anesthesia. Sevoflurane biotransformation produced a mean peak plasma inorganic fluoride concentration of 29.3 +/- 1.8 mumol/L, 2 h after anesthesia, which decreased to 18 mumol/L concentration by 8 h after anesthesia. The peak plasma inorganic fluoride ion concentration correlated with duration of sevoflurane anesthetic exposure. Five patients given sevoflurane had peak levels transiently exceeding 50 mumol/L, and one of these had a history of ingesting drugs potentially producing hepatic enzyme induction. No increases in postoperative levels of creatinine, blood urea nitrogen, direct bilirubin, or hepatic transaminase and no changes in serum electrolyte level occurred in either anesthetic group. Indirect bilirubin concentration increased significantly after sevoflurane anesthesia, but the increase was not of clinical significance (from 0.30 +/- 0.03 to 0.38 +/- 0.06 mg/dL). Indirect bilirubin concentrations did not increase after isoflurane anesthesia; the concentrations reached 0.31 +/- 0.04 mg/dL and did not differ significantly from those found with sevoflurane.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Inhalation↗

Abdominal wound closure using a running, looped monofilament polybutester suture: comparison to Smead-Jones closure in historic controls.

OBJECTIVE: To determine whether abdominal wound closure with a running, looped monofilament polybutester suture was as effective, inexpensive, and rapid as Smead-Jones closure using the same material. METHODS: Between April 19, 1990 and August 29, 1991, 154 patients undergoing major gynecologic surgery had wound closure using a running, looped monofilament polybutester suture. Controls were 154 patients undergoing similar surgical procedures in the 15 months immediately preceding the study period (January 5, 1989 to April 18, 1990) whose wounds were closed with 0 polybutester using the Smead-Jones technique. All patients received prophylactic cephalosporin antibiotic therapy and external pneumatic leg compression perioperatively. The subcutaneous tissues were not sutured after fascial closure, and the skin was closed with stainless-steel staples. There was no difference between the groups when compared by mean weight, mean ponderal index, number of previous abdominal operations, operative blood loss, or the use of chemotherapy or radiotherapy in the pre- or postoperative period. Both groups had similar rates of complicating medical conditions including insulin-dependent and non-insulin-dependent diabetes mellitus, hypertension, obstructive pulmonary disease, atherosclerotic coronary disease, or peripheral vascular disease. RESULTS: The use of a running closure with looped monofilament polybutester suture in the study patients resulted in a reduction in operating time when compared with controls. The rates of superficial separation and wound infection were similar in both groups. In the study group, there was one minor fascial separation and one wound dehiscence, which occurred when the running suture was inadvertently snipped during debridement of a superficial infection. CONCLUSION: Running closure with looped polybutester is an acceptable, inexpensive, and expeditious method of abdominal wound closure.

Abdomen↗

Changes in the nigrostriatal projection associated with recovery from lesion-induced behavioral asymmetry.

Possible neuronanatomical changes correlated with recovery from lesion-induced behavioral asymmetry were examined. Rats, with 6-OHDA injected into the substantia nigra (SN) on one side, were either assigned to a group with a 48-hour survival period, or one with a 15-day recovery period. Control groups, without a lesion, were also included. All animals were tested for behavioral asymmetry and, at the end of the survival period, had horseradish peroxidase (HRP) deposited in the caudate-putamen (CPU) ipsilateral to the lesion (right or left CPU in the controls). Both substantia nigrae of all animals were examined for HRP-labeled cells. Animals given a 15-day recovery period had more HRP-labeled cells in the SN ipsilateral to the HRP deposition site than those given a 1-day recovery period. Also animals which showed behavioral recovery had more HRP-labeled cells in their ipsilateral SN than either those which showed no recovery or those which were not given time to recover. Thus, our results suggested that behavioral recovery from lesion-induced asymmetry was associated with an increase in HRP uptake and retrograde transport by the remaining nigrostriatal terminals. Animals which recovered showed the expected decrease in ipsiversive, and increase in contraversive turning with time. Unexpectedly, animals which did not recover exhibited an increase in ipsiversive, and a decrease in contraversive turning with time.

Animals↗

Preparation, properties, and plasma retention of human hemoglobin derivatives: comparison of uncrosslinked carboxymethylated hemoglobin with crosslinked tetrameric hemoglobin.

Human hemoglobin A has been crosslinked by diisothiocyanatobenzenesulfonate to give a limited number of products in a yield of approximately 70%. The predominant product was crosslinked between subunits within a tetramer and had a Mr of 64,000; no higher Mr species were formed. This product had one crosslink per tetramer located between the NH2 termini of its alpha chains, as established by HPLC analysis, amino acid analysis, Edman degradation, and mass spectrometry. This crosslinked derivative had a slightly increased oxygen affinity [P50 = 9 mmHg (1 mmHg = 133 Pa); P50 for unmodified hemoglobin = 11 mmHg], and the retention time of this derivative in the circulation of rats was 2.9 and 3.3 hr at two hemoglobin concentrations (7 g/dl and 14 g/dl, respectively). The half-life of an uncrosslinked carboxymethylated derivative, which has a low oxygen affinity (P50 = 28 mmHg), was 0.6 and 0.7 hr under the same conditions. Therefore, prolongation of the plasma-retention time of infused hemoglobin is dependent on the crosslinking of the tetramer but independent of the oxygen affinity of the derivative.

Allosteric Regulation↗

The clinical effects of prolonged treatment of patients with advanced cancer with low-dose subcutaneous interleukin-2 [corrected].

Thirty-five patients with advanced malignant disease have been treated as outpatients with increasing doses (0.1-100 mcg) of interleukin 2 (IL2) by once daily self-administered subcutaneous (s.c.) injection, 5 days weekly for 8 weeks followed by a 4 week observation period. Systemic side effects were not experienced by patients at the 3 lower doses. Three patients required dose reduction from 100 mcg daily because of intolerance (fever, rash, lethargy, nausea and vomiting) and one patient was discontinued because of dyspnoea. We observed immunological effects at the 100 mcg dose (but not at the lower doses). These consisted of (a) a modest sustained lymphocytosis, (b) eosinophilia in six (out of nine) patients and (c) a significant rise in IL2-stimulated peripheral blood lymphocyte activated killer (LAK) cell activity in six (out of nine) patients to a mean of 2.0 times pretreatment levels (P less than 0.01). Two (out of nine) patients with renal cell carcinoma treated with 100 mcg daily had partial responses of duration 4 and 9 months respectively and a further three had disease stabilisation for at least 3 months. Low dose long-term s.c. IL2 is clinically and immunologically active, and in comparison to other IL2 regimens it has minor toxicity and is easy to administer. These characteristics make low dose s.c. IL2 suitable for study in the adjuvant setting.

Adult↗

The interhemispheric projection from the substantia nigra to the caudate-putamen as depicted by the anterograde transport of [3H]leucine.

The organization of the interhemispheric projections from the substantia nigra to the caudate-putamen was examined after [3H]leucine had been injected into the substantia nigra on one side. There was not a strict correspondence between the regions of termination of the crossed and homolateral nigrostriatal projections. Although the leucine predominantly labeled the lateral parts of the ipsilateral caudate-putamen, terminal labeling was also found in the medial and lateral parts of the contralateral caudate-putamen. The crossed nigrostriatal projection terminated in discrete areas of variable size in the contralateral caudate-putamen. The patterns made by the silver granules in the caudate-putamen contralateral to the [3H]leucine injection appeared to be heterogeneous.

Animals↗