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Biomedical subjects

D Gordon

Publications and source records attributed to D Gordon.

At least 397 records · Page 22Linked to original sources
PubMed1985

Antibiotic-associated colitis due to Clostridium difficile: double-blind comparison of vancomycin with bacitracin.

A randomized double-blind study was carried out in patients with unresolving antibiotic-associated colitis due to Clostridium difficile, to compare the effect of bacitracin (80,000 U/day) with vancomycin (500 mg/day) on the resolution of symptoms, clearance of organism, and prevention of relapse. Forty-two patients with colitis, 9 of whom had a pseudomembrane, were randomized, 21 patients to each treatment group. The two groups were comparable in age, disease severity, and antibiotic exposure. For a 50% reduction in stool frequency the mean times (+/- SE) were 4.1 +/- 0.4 days for bacitracin and 4.2 +/- 0.4 days for vancomycin. Sixteen patients (76%) had symptom resolution after 7 days of treatment with bacitracin, compared with 18 patients (86%) given vancomycin. Patients who failed to respond were crossed over (blind) to the alternative antibiotic, but tended to be refractory to the alternative medication as well. Vancomycin-treated patients had negative toxin (83% vs. 53%, p = 0.04) and negative stool cultures (81% vs. 52%, p = 0.02) more frequently than did those patients given bacitracin. Similar numbers of patients in each group had symptomatic relapse during 1 mo of follow-up, but most of them relapsed yet again after blinded crossover therapy. Although bacitracin was significantly less effective than vancomycin in clearing C. difficile from the stools, both were of similar value in the control of symptoms in a group of patients with predominantly nonpseudomembranous colitis. In view of its low cost, bacitracin is a reasonable first-line alternative to vancomycin in the treatment of antibiotic-associated colitis.

Adult↗
PubMed1985

Correlation between prostaglandin and thromboxane levels and clinical signs in cyclosporine A-treated guinea pigs with acute experimental allergic encephalomyelitis.

Prostaglandin E, prostaglandin F2 alpha and thromboxane B2 levels were measured in the spinal cord and cerebellum of guinea pigs with acute experimental allergic encephalomyelitis treated with Cyclosporine A in a schedule which delayed the onset of the disease and completely suppressed it in 40% of the animals. A correlation was found between the eicosanoid levels in the central nervous system and clinical signs of the disease. Where lesions were completely suppressed the levels of eicosanoids were normal. The number of lesions found correlated well with the clinical state of the animals.

Animals↗
PubMed1985

Intrarenal prostaglandin release: effects of arachidonic acid and hyperchloremia.

We measured the release of PGE2, 6kPGF1 alpha, PGF2 alpha, and TXB2 into urine (U) and renal hilar lymph (L) to assess the possible roles of intrarenal prostaglandins (PGs) in arachidonic acid (AA)-induced renal vasodilation and Cl-induced renal vasoconstriction, (a model of tubuloglomerular feedback, TG). AA caused an ipsilateral fall in renal vascular resistance (RVR) and diuresis and increased release of all PGs into U; release of 6kPGF1 alpha into L increased ninefold. Hypertonic NaCl infusion caused ipsilateral vasoconstriction and decreased GFR; the release of TXB2 into U and L increased, but other PGs were not altered consistently. During a background infusion of AA, hypertonic NaCl infusion again evoked TXB2 release into U and L without significant changes in other PGs. AA attenuated the NaCl-induced renal vasoconstriction in dogs with the highest rates of PGE2 release into L. Changes in RVR correlated with the ratio of excretion of vasodilator PG (PGE2 + 6kPGF1 alpha) to TXB2 (r = -0.74). Indomethacin administration blunted, but did not abolish, the Cl-induced increase in RVR. In conclusion, (1) AA evokes the release of PGs, especially prostacyclin, into renal cortex; (2) hypercholoremia increases RVR and evokes a rather selective release of renal TX; (3) the production of vasodilator PGs by AA may attenuate Cl-induced renal vasoconstriction; (4) renal vasodilator and vasoconstrictor PGs can be released relatively independently--their balance could modulate RVR during activation of the TG response.

6-Ketoprostaglandin F1 alpha↗
PubMed1985

A smooth muscle-specific monoclonal antibody recognizes smooth muscle actin isozymes.

Injection of chicken gizzard actin into BALB/c mice resulted in the isolation of a smooth muscle-specific monoclonal antibody designated CGA7. When assayed on methanol-Carnoy's fixed, paraffin-embedded tissue, it bound to smooth muscle cells and myoepithelial cells, but failed to decorate striated muscle, endothelium, connective tissue, epithelium, or nerve. CGA7 recognized microfilament bundles in early passage cultures of rat aortic smooth muscle cells and human leiomyosarcoma cells but did not react with human fibroblasts. In Western blot experiments, CGA7 detected actin from chicken gizzard and monkey ileum, but not skeletal muscle or fibroblast actin. Immunoblots performed on two-dimensional gels demonstrated that CGA7 recognizes gamma-actin from chicken gizzard and alpha- and gamma-actin from rat colon muscularis. This antibody was an excellent tissue-specific smooth muscle marker.

Actins↗
PubMed1985

Assessment of autonomic function in humans by heart rate spectral analysis.

Spectral analysis of spontaneous heart rate fluctuations were assessed by use of autonomic blocking agents and changes in posture. Low-frequency fluctuations (below 0.12 Hz) in the supine position are mediated entirely by the parasympathetic nervous system. On standing, the low-frequency fluctuations increase and are jointly mediated by the sympathetic and parasympathetic nervous systems. High-frequency fluctuations, at the respiratory frequency, are decreased by standing and are mediated solely by the parasympathetic system. Heart rate spectral analysis is a powerful noninvasive tool for quantifying autonomic nervous system activity.

Adult↗
PubMed1985

Hemodynamic regulation: investigation by spectral analysis.

We investigated the hypothesis that beat-to-beat variability in hemodynamic parameters reflects the dynamic interplay between ongoing perturbations to circulatory function and the compensatory response of short-term cardiovascular control systems. Spontaneous fluctuations in heart rate (HR), arterial blood pressure, and respiration were analyzed by spectral analysis in the 0.02- to 1-Hz frequency range. A simple closed-loop model of short-term cardiovascular control was proposed and evaluated in a series of experiments: pharmacological blockades of the parasympathetic, alpha-sympathetic, beta-sympathetic, and renin-angiotensin systems were used to open the principal control loops in order to examine changes in the spectral pattern of the fluctuations. Atrial pacing was used to examine blood pressure variability in the absence of HR variability. We found that respiratory frequency fluctuations in HR are parasympathetically mediated and that blood pressure fluctuations at this frequency result almost entirely from the direct effect of centrally mediated HR fluctuations. The sympathetic nervous system appears to be too sluggish to mediate respiratory frequency variations. Low-frequency (0.02-0.09 Hz) fluctuations in HR are jointly mediated by the parasympathetic and beta-sympathetic systems and appear to compensate for blood pressure fluctuations at this frequency. Low-frequency blood pressure fluctuations are probably due to variability in vasomotor activity which is normally damped by renin-angiotensin system activity. Blockade of the alpha-adrenergic system, however, does not significantly alter low-frequency blood pressure fluctuations.

Animals↗
PubMed1985

Studies of intestinal lymphoid tissue. IX. Dose-dependent, gluten-induced lymphoid infiltration of coeliac jejunal epithelium.

Jejunal biopsy specimens from coeliac patients who had received small, oral doses (100-1500 mg) of a peptic-tryptic gluten digest were analysed by morphometric methods. An increase in the total number of surface epithelial lymphocytes, maximal at 12 h after challenge, was dose-dependent, the mean percentage rise at this time being 53% (p less than 0.005), 44% (p = 0.01), and 25% (p greater than 0.05) with 1500, 1000, and 500 mg of gluten digest, respectively. This effect was not accompanied by any increased mitotic activity or blast transformation among the infiltrating lymphocytes, nor was there any demonstrable alteration in mucosal structure-that is, reduction in surface or increase in crypt epithelial volumes. The results of this controlled morphometric analysis indicate that oral gluten challenge causes an increase in the lymphocyte population of surface epithelium in coeliac disease but that this effect does not necessarily result in mucosal damage.

Celiac Disease↗
PubMed1985

The use of captopril to control hypertension in post-transplant renal artery stenosis.

Captopril is a new orally active angiotensin converting enzyme inhibitor that is useful for the treatment of hypertension. Prior reports have cautioned against its use for the control of blood pressure in patients with transplant renal artery stenosis since it caused a reversible renal failure. We describe a four year old child with radiographically proven transplant renal artery stenosis and severe hypertension that was safely managed with long-term administration of captopril. This case highlights the continued therapeutic role of this drug in the treatment of post-transplant hypertension, provided one carefully monitors the renal function in such patients.

Captopril↗
PubMed1985

Prolactin dynamics and tumour size in the prediction of surgical outcome for prolactinoma.

Each of 62 females were studied for a period of between two and 72 months (mean 36 months) following the removal of a prolactinoma by transsphenoidal pituitary surgery. Our aims were to define the relationships between pre- and post-operative features, the operative findings and the functional outcome. Pre-operative serum prolactin (PRL) concentrations correlated with tumour diameter (r = 0.55, p less than 0.001). Following surgery two groups of patients were identified: Group 1, 46 spontaneously and regularly menstruating patients and Group 2, 16 patients with persistent amenorrhoea. The patients in Group 1 had significantly lower pre-operative and post-operative serum (PRL) concentrations (p less than 0.02 and p less than 0.001 respectively) and significantly greater PRL responses to thyrotrophin releasing hormone (TRH) and metoclopramide stimulation after surgery (p less than 0.001). There was not a significant difference in tumour size between the groups. Forty-four (96 per cent) of the patients in Group 1 had normal post-operative serum PRL concentrations within one week of surgery. By comparison (p less than 0.001) only 42 and 20 per cent respectively of Group 1 patients who were tested had normal TRH and metoclopramide evoked PRL secretion following surgery. Return of regular menstruation was associated with cessation of galactorrhoea in 44 patients (96 per cent) and ovulation occurred in 37 of 38 menstruating patients for whom data are available. All patients with normal TRH and metoclopramide stimulation tests menstruated spontaneously. Nevertheless most patients who menstruated did so in spite of retaining suppressed PRL responses. Of 46 patients followed to date whose serum PRL was normal one week after surgery, seven later were found to have an elevation of serum PRL outside the normal range but in only two has this been persistent. We suggest that a single measurement of serum PRL one week following transsphenoidal pituitary surgery for prolactinoma provides a good basis for deciding about the future management of patients who desire menstruation and pregnancy.

Female↗
PubMed1984

Immunologic analysis of intraocular mononuclear cell infiltrates in uveitis.

The pathogenesis of chronic idiopathic uveitis is not known. Analysis of inflammatory site (ie, intraocular) lymphocytes in the aqueous humor and/or vitreous cavity was performed with monoclonal antibodies and a cell sorter. The mononuclear cell population within the aqueous humor of eyes with acute idiopathic uveitis resembled that observed in the peripheral blood. In contrast, eyes with chronic idiopathic uveitis displayed a scarcity of T cells within the vitreous. Eyes with chronic uveitis of presumed infectious cause did not show similar changes. These observations are consistent with the hypothesis that intraocular T-cell immunoregulation of B-cell function may be defective in some stages of chronic idiopathic uveitis.

Aqueous Humor↗
PubMed1984

Effects of piroxicam on mononuclear cells. Comparison with other antiarthritic drugs.

Piroxicam and other antiarthritic drugs were compared with respect to their effects on T-lymphocyte/monocyte/rheumatoid synovial cell interactions leading to inflammatory mediator production. Piroxicam inhibited PGE2 formation by blood mononuclear cells, but was less potent than indomethacin. Both drugs enhanced suboptimal phytohemagglutinin (PHA)-stimulated tritiated thymidine (3H-TdR) incorporation by mononuclear cells, although optimal responses were less affected. Exogenous interleukin-2 (IL-2) enhanced suboptimal but not optimal PHA responses, and the effects of the cyclo-oxygenase inhibitors were overcome by exogenous PGE2. Thus piroxicam and indomethacin prevented the inhibition by endogenous monocyte-derived PGE2 of IL-2 secretion and activity. Other antiarthritic drugs, including antimalarials, immunosuppressive agents and gold salts, inhibited PHA-induced lymphocyte proliferation regardless of the level of stimulation. Mepacrine and chloroquine were more effective in inhibiting the release of mononuclear cell factor (MCF) that stimulated PGE2 synthesis by synovial cells. Cyclosporin-A, azathioprine and 6-mercaptopurine were more potent as antiproliferative agents than as inhibitors of mediator release. Sodium aurothiomalate and aurothioglucose selectively interfered with lymphocyte-mediated amplification of MCF release, whereas auranofin inhibited spontaneous production of monocytes and the action of MCF on synovial cells. In rheumatoid synovial cells, piroxicam and indomethacin inhibited PGE2 production but not collagenase release. Suppression of MCF release could lead indirectly to reduction of IL-2 and collagenase as well as PGE2 production and consequently to more profound inhibition of immunologically-mediated inflammation.

Anti-Inflammatory Agents↗
PubMed1984

Evidence for fibroblasts as the major source of prostacyclin and prostaglandin synthesis in dental cyst in man.

Periodontal cysts synthesize large amounts of prostaglandins and collagenase which probably cause the localized bone destruction essential for intraosseous cyst growth. Fragments of cyst wall, and fibroblasts cultured from them, synthesized prostacyclin (PGI2) in addition to prostaglandin E2 (PGE2), PGF2 alpha and collagenase in vitro. Soluble products from cultures of unstimulated and phytohaemagglutinin-stimulated blood mononuclear cells enhanced the synthesis of these prostaglandins in monolayer cultures of cyst-wall fibroblasts. It is therefore proposed that cyst capsule fibroblasts are the major source of these bone-resorbing factors, acting under the stimulus of lymphocytes and monocytes in chronically inflamed cysts. Cysts which were not infiltrated by chronic inflammatory cells (follicular cysts, a keratocyst, an ameloblastoma, and an aneurysmal bone cyst) also produced prostaglandins and collagenase, indicating that the stimulatory mechanism for the production of bone-resorbing factors in these cysts may differ from that in periodontal cysts.

6-Ketoprostaglandin F1 alpha↗
PubMed1984

Prostaglandin and thromboxane levels in central nervous system tissues from rats during the induction and development of experimental allergic encephalomyelitis (EAE).

Prostaglandin (PG) and thromboxane levels were measured in the spinal cords and cerebellums of rats during the induction, disease and recovery periods of experimental allergic encephalomyelitis (EAE). In spinal cords PGE and 6-oxo-PGF1 alpha increased to maximum with the onset of neurological symptoms, 11-12 days after inoculation. However, the levels returned to normal at the height of clinical disease, despite the persistence of inflammatory lesions. After an initial fall, PGF2 alpha increased to normal limits, 11-12 days after inoculation, and remained at this level throughout the experiment. In contrast, the cerebellum content of all the eicosanoids decreased prior to the appearance of clinical EAE. PGF2 alpha and 6-oxo-PGF1 alpha concentrations subsequently increased but the PGE and thromboxane levels remained depressed for the duration of the study. The role of the eicosanoids in modulating the immune response to neuroantigen is discussed together with our recent findings in guinea pigs with acute EAE.

6-Ketoprostaglandin F1 alpha↗
PubMed1984

The developmental expression of neurofilament and glial filament proteins in the human pituitary gland: an immunohistochemical study with monoclonal antibodies.

Monoclonal antibodies (MA) specific for neurofilaments (NF) and glial filaments (GF) were used to study the development of the normal human pituitary gland in fetuses, premature infants and adults. A total of 16 serially sectioned pituitary glands was examined. The expression of both NF and GF proteins correlated with maturation of the pituitary gland. Axons, but not cell bodies, were observed to contain immunoreactive NF proteins and these labeled axons were restricted almost exclusively to the pars nervosa. However, in early stages of development, intra-axonal NF proteins were not detectable. Aggregates of NF material in ' blobs ' were also observed in the pars nervosa of adults and a premature infant who survived 6 months following birth. They were never observed in more immature pituitary glands. Cells containing immunoreactive GF proteins were present in all subdivisions of the pituitary gland and they were more common in later stages of development. However, such cells represented only a minority of those present in the pituitary gland and cells in the pars distalis did not express GF protein until after birth. ' Blobs ' comprised of immunoreactive GF proteins were also seen. They were restricted to the pars nervosa and appeared later in development.

Adult↗