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Biomedical subjects

D J Morris

Publications and source records attributed to D J Morris.

At least 19 recordsLinked to original sources

The interrupted-continuous microsurgical suture technique.

Interrupted microsurgical sutured anastomoses are the standard to which all new anastomotic techniques must be compared. In 1902, Alexis Carrel described a continuous suture technique for large vessels that initially triangulated the anastomosis with three stay sutures. Our technique is a modification of Carrel's original technique combined with other previously published microvascular methods. This is an attempt to address the inherent problems associated with the standard interrupted technique and previously described continuous suture techniques.

Anastomosis, Surgical

Transtibial transposition of gastrocnemius muscle and musculocutaneous flaps.

The medial and lateral gastrocnemius muscle flaps have become the workhorses of proximal calf reconstruction since their initial description by McCraw et al. in 1977. Since that time many authors have presented varying and often ingenious techniques by which the range of these flaps can be expanded. This report adds another modification of the standard gastrocnemius muscle flap: transtibial transposition of the muscle through the posterior cortex.

Aged

Effects of carbenoxolone administered acutely to adrenalectomized rats (in vivo) on renal and hepatic handling of corticosterone by 11 beta-hydroxysteroid dehydrogenase.

The in vivo effect(s) of carbenoxolone (CS) on renal 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD), hepatic 11 beta-OHSD, and 5 beta-reductase enzymatic activity was investigated, under conditions previously shown to confer mineralocorticoid (MC)-like activity on the glucocorticoids cortisol and corticosterone; it has been suggested that this Na+ retention is linked to inhibition of renal 11 beta-OHSD. The results show that acute administration of CS [2.5 mg/rat for 0.5 or 2 hours; and 10 or 25 mg/rat for 2 hours subcutaneously (sc)] to rats caused no inhibition of 11 beta-OHSD activity in kidney homogenates, minces, and microsomes when compared with controls. However, addition of 50 nM CS to the incubation medium completely inhibited the 11 beta-OHSD activity in kidney homogenates and microsomes (from controls or CS-injected rats). In contrast, hepatic microsomal 11 beta-OHSD was significantly inhibited after in vivo treatment with CS (P < 0.05) using 2 microM and 50 microM corticosterone, as was 5 beta-reductase (P < 0.05) using 4 microM corticosterone as substrate. However, chronic glycyrrhizin administration (15 mg/rat/day sc for 14 days) significantly inhibited renal 11 beta-OHSD activity when assayed in minces or homogenates. Thus, it appears that when CS is administered acutely, its effects are primarily on hepatic 11 beta-OHSD and 5 beta-reductase with no inhibition of renal 11 beta-OHSD.(ABSTRACT TRUNCATED AT 250 WORDS)

11-beta-Hydroxysteroid Dehydrogenases

Detection of false seroconversions in cytomegalovirus seronegative platelet donors by serial complement fixation or IgG-specific radioimmunosorbent tests.

A panel of 421 cytomegalovirus (CMV) seronegative-platelet donors was followed using complement-fixation (CFT) and IgG-specific radioimmunosorbent tests (RIST) to detect seroconversion. During 4623 person-months of observation 2452 serum specimens were tested, and the annual rate of seroreactivity detected by RIST was 56%. However, most of the positive RIST results were followed by negative results with later serum samples. CFT seroreactivity was a poor predictor of RIST seroreactivity. The high rate of transient seroreactivity detected by RIST may have reflected the lack of absolute specificity of the test. Alternatively, the results could illustrate the difficulty of determining whether an individual harbours latent CMV infection using antibody tests when some seronegative individuals appear to be latently infected. In the light of our observations recommendations for CMV antibody testing of blood donors are proposed.

Antibodies, Viral

Effect of carbenoxolone sodium on steroid-induced sodium transport in the toad bladder: further studies.

The licorice derivative, carbenoxolone sodium, is a potent inhibitor of the enzyme 11 beta-hydroxysteroid dehydrogenase. When this enzyme is suppressed or is absent, endogenous glucocorticoids induce mineralocorticoid-like sodium retention by the kidney. Carbenoxolone sodium administered in vivo to an adrenalectomized rat has also recently been shown to enhance the mineralocorticoid response to submaximal concentrations of aldosterone, deoxycorticosterone (DOC) and 11-dehydrocorticosterone (compound A). In the present studies conducted on the urinary bladder isolated from the Dominican toad, Bufo marinus, a concentration of carbenoxolone sodium shown previously to increase glucocorticoid-induced sodium transport (2.5 x 10(-5) M) did not appear to alter the response to submaximal concentrations of aldosterone 10(-8) M, DOC 10(-7) M, or compound A 10(-5) M. These findings are consistent with the view that in the whole animal carbenoxolone sodium may modify additional steroid metabolic pathways and/or physiological processes in several organs to produce the enhanced renal response to mineralocorticoids and compound A.

Aldosterone

Protective and specificity-conferring mechanisms of mineralocorticoid action.

Several experiments using both the in vivo rat bioassay and the isolated toad bladder preparation have been reported that lend support to the hypothesis that the enzyme 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD), in mineralocorticoid (MC) target tissues, acts as a "protective" mechanism that prevents endogenous glucocorticoids (GCs) from causing MC receptor-mediated effects on Na+ and K+. Additional experiments have also indicated that a second distinct protective mechanism exists that prevents endogenous MCs from eliciting excessive MC receptor-mediated Na+ retention. This second protective mechanism may involve steroid-metabolizing enzymes other than 11 beta-OHSD. Since the specific GC agonist, RU28362, can elicit Na+ retention and K+ secretion, it is possible that a third protective mechanism exists whereby renal 11 beta-OHSD prevents endogenous GCs from eliciting GC receptor-mediated effects on Na+ and K+.

11-beta-Hydroxysteroid Dehydrogenases

Detection of glycyrrhetinic acid-like factors (GALFs) in human urine.

Patients with the syndrome of apparent mineralocorticoid excess and those who ingest licorice show markedly decreased 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD) and 5 beta-reductase activity; both are important for the deactivation of glucocorticoids and other steroid hormones. Glycyrrhetinic acid (GA), present as its glycoside in licorice, is a potent inhibitor of both 11 beta-OHSD and 5 beta-reductase and, as we have also shown, confers Na(+)-retaining properties on glucocorticoids and amplifies those of aldosterone and deoxycorticosterone. We report the results of our initial studies demonstrating the presence of naturally occurring substances, which inhibit both 5 beta-reductase and 11 beta-OHSD as does GA, in partially purified extracts of urine from normotensive men and nonpregnant and pregnant women. Since these substances exhibit GA-like activity, we have termed them GA-like factors (GALFs). This "inhibitory" material is heat stable and does not react with ninhydrin; the majority is not extractable with ethyl acetate and thus is not a "free" steroid. When further purified by high-performance liquid chromatography with a methanol/water gradient, the majority of these GALFs appeared in two regions of inhibitory activity. The chemical nature of this material is currently being investigated. These experiments indicate that normal human urine contains GALFs that may play a role in Na+ homeostasis and regulation of blood pressure.

11-beta-Hydroxysteroid Dehydrogenases

Effect of high calcium diet on the development of high blood pressure in intact spontaneously hypertensive rats and in adrenalectomized spontaneously hypertensive rats treated with aldosterone.

The current investigation was designed to study the effect(s) of high calcium diet on the development of high blood pressure (BP) in both young intact spontaneously hypertensive rats (SHRs) and in young adrenalectomized (ADX) male SHRs treated with aldosterone (ALDO). Weaned SHRs were fed either a control calcium diet (0.5% Ca as PO4) (CCaDiet), a high calcium diet (2.5% Ca, 0.5% as PO4 and 2% as CO3) (HCaDiet), or Agway ProLab rat food containing 2.5% Ca (HCaPLDiet). The HCaDiet significantly blunted the development of high BP in young intact SHRs (P less than 0.001; n = 8 to 10). At 6 weeks of age, BP was 117 +/- 2 mm Hg (HCaDiet) compared with 135 +/- 3 mm Hg (CCaDiet); by 12.7 weeks of age, BP was 192 +/- 4 mm Hg (HCaDiet) compared with 233 +/- 3 mm Hg (CCaDiet). Similar results were observed in age-matched SHRs fed the HCaPLDiet. The results show that subcutaneous infusion of ALDO (1.0 microgram/d, osmotic pumps) for 2 weeks to young ADX male SHRs raised on the CCaDiet caused a significant increase in systolic BP when compared with SHRs implanted with Sham pumps (P less than 0.001). High BP associated with ALDO infusion was attenuated by the HCaDiet (BP after 2 weeks was 138 +/- 8 mm Hg for the HCaDiet group compared with 200 +/- 5 mm Hg for the CCaDiet group, P less than 0.001; n = 4 to 6). The results show that the HCaDiet blunts the development of high BP in intact SHRs and may protect against the development of ALDO hypertension in ADX young SHRs.

Adrenalectomy

Sensitive non-isotopic DNA hybridisation assay or immediate-early antigen detection for rapid identification of human cytomegalovirus in urine.

A sensitive non-radioactive DNA hybridisation assay employing digoxigenin-labelled probes was compared with immediate-early antigen detection and conventional virus isolation for the identification of human cytomegalovirus (HCMV) in 249 urine samples. Of 44 specimens yielding HCMV by virus isolation, more were positive by DNA hybridisation (32; 73%) than by immediate-early antigen detection (25; 52%) (P = 0.05). The specificity of the hybridisation assay in 45 apparently falsely positive specimens was supported by detection of HCMV DNA in 40 of these specimens using the polymerase chain reaction. Many urine specimens may thus contain large amounts of non-viable virus or free viral DNA. Evaluation of various protocols for the extraction and denaturation of virus DNA prior to hybridisation showed that proteinase K digestion with phenol/chloroform extraction was the most sensitive and reliable procedure. We conclude that the non-radioactive DNA hybridisation assay described is a potentially valuable routine diagnostic test.

Antigens, Viral