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Biomedical subjects

R J Morgan

Publications and source records attributed to R J Morgan.

At least 109 records · Page 6Linked to original sources
PubMed1996

Thrombelastographic evaluation of coagulation in transurethral prostatectomy.

OBJECTIVE: To assess the changes in overall coagulation status and define the degree of systemic fibrinolysis occurring in patients undergoing transurethral prostatectomy (TURP). PATIENTS AND METHODS: Thirty patients undergoing TURP, 23 for benign prostatic hyperplasia and seven for prostatic carcinoma, were studied prospectively. Serial venous blood samples were taken using the two-syringe technique. Samples were taken before, during and at intervals up to 72 h and 10-14 days after surgery. Thrombelastography (TEG) was performed on native whole blood samples. Peri-operative blood loss was assessed, until the catheter was removed, by photometric estimation of the haemoglobin content of the irrigant fluid and the measurement of clot volume. RESULTS: There was no evidence of fibrinolysis (TEG Percentage Clot Lysis Ly60 > 15%) in any patient over the whole peri-operative period. There was a significant change in the mean TEG variables towards hypercoagulation from 3 h until 10-14 days postoperatively, compared with the pre-operative values (P < 0.05). There was a significant correlation between blood loss and clot volume. CONCLUSION: These results question the role of systemic fibrinolysis in primary and secondary haemorrhage following TURP and thus the rationale of using antifibrinolytics in these patients. The persistent hypercoagulable state post-operatively indicates a possible role of hypercoagulability in clot retention.

Blood Coagulation↗
PubMed1996

The incidence of minor sequelae following anaesthesia in children.

A survey was performed to estimate the incidence of the minor sequelae of anaesthesia in children. During an eight-month period 266 children, aged five years and over, were personally interviewed by an anaesthetist following recovery from anaesthesia. At interview the child was questioned to ascertain any morbidity suffered and record was made of the operation performed and the anaesthetic administered. Data were then evaluated, using multivariate analysis, to identify risk factors for the more common sequelae. This study revealed a higher incidence of the minor sequelae of anaesthesia in children than had previously been reported. The three most common sequelae recorded were nausea (48.1%), vomiting (35.0%), and sore throat (31.4%).

Anesthesia↗
PubMed1996

Autoradiographic localization of nitric oxide synthase binding sites in normal and diabetic rat corpus cavernosum.

OBJECTIVES: To investigate density and distribution of nitric oxide synthase (NOS) binding sites in rat cavernosal tissue, and to assess any changes brought about by the onset of diabetes mellitus. METHODS: Hyperglycaemic non-ketonuric diabetes mellitus was induced in 5 rats using streptozotocin. The penises were excised from these rats 2 months after the administration of streptozotocin and stored at -70 degrees C. Longitudinal serial sections (6 microns) were cut in a cryostat and thaw mounted onto gelantinized microscope slides. Low- and high-resolution autoradiography was performed using a radioligand for NOS. Densitometric analysis was performed on the autoradiographs and the results compared with those obtained from 5 age-matched no-diabetic rats. RESULTS: NOS binding was primarily localized to the endothelium lining the cavernosal lacunar spaces. Significantly increased binding of NOS was seen in the diabetic cavernosal tissue 2 months after induction of diabetes mellitus. CONCLUSIONS: NOS binding is present on the endothelium of the rat corpus cavernosum and is increased in diabetic rats 2 months after streptozotocin administration. This increase in NOS binding may be part of the endothelial dysfunction which is reported in the corpus cavernosum of diabetic patients or rats.

Animals↗
PubMed1995

Modulation of 5-fluorouracil with high-dose leucovorin calcium: activity in ovarian cancer and correlation with CA-125 levels.

The purpose of this study was to estimate the response rate, response duration, and survival of patients with advanced ovarian cancer treated with a 132-hr continuous infusion of high-dose calcium leucovorin in combination with five consecutive daily bolus doses of 5-fluorouracil (5-FU) and to correlate changes in CA-125 levels with clinical and radiologic assessment of disease progression. Forty-six heavily pretreated patients [median number of previous chemotherapy regimens, 2.5 (range 1-7)] with advanced ovarian cancer received 132-hr continuous infusions of calcium leucovorin (500 mg/m2/day) for 5 1/2 days, with daily bolus doses of 5-FU (370 mg/m2/day) for 5 days beginning 24 hr after initiation of the calcium leucovorin. Twenty-three patients had clinically measurable disease and 23 had evaluable disease; CA-125 levels were performed prior to each treatment course and after the final course of therapy. One of 42 patients had a partial response to combination chemotherapy (duration, 8.9 months); 16/42 had stable disease [median duration, 4.9 months (range, 2.4-9.0 months)]. Toxicity of combination therapy included mild myelosuppression and stomatitis, similar to previously reported toxicity profiles for the 5-FU and calcium leucovorin combinations. Sensitivity of CA-125 levels as a single indicator of disease progression was 55%. The combination of infusional high-dose calcium leucovorin and 5-FU has little activity in refractory ovarian cancer. CA-125 levels incorrectly predict clinical disease activity in about one-third of cases and should not be the sole criterion for determination of clinical response when evaluating chemotherapeutic efficacy in heavily pretreated patients.

Adenocarcinoma↗
PubMed1995

Phase I study of mitomycin C and menadione in advanced solid tumors.

A phase I study of mitomycin C with menadione (2-methyl-1,4-naphthoquinone, a vitamin K analogue which lowers intracellular pools of reduced glutathione) was designed as an approach to overcoming tumor cell resistance to alkylating agent chemotherapy. Patients with refractory solid tumors (n = 51) were treated with a 48-h continuous intravenous infusion of menadione followed by a bolus intravenous dose of mitomycin C at the completion of the menadione infusion. Initial menadione doses of 8.0 and 4.0 g/m2 over 48 h were associated with hemolysis, so subsequent dose levels of menadione ranged from 1.0 to 3.0 g/m2 with mitomycin C from 5 to 20 mg/m2. All three patients treated with menadione at 8.0 g/m2 and the single patient treated at 4.0 g/m2 with mitomycin C at 5 mg/m2 developed clinically significant hemolysis despite the presence of red blood cell glucose-6-phosphate dehydrogenase. Subsequently, a revised escalation scheme for menadione was used, and all patients tolerated menadione doses of 1-2.5 g/m2 over 48 h with mitomycin C doses up to 20 mg/m2. Since the 3.0 g/m2 dose of menadione was associated with mild hemolysis in three of four patients, the maximum tolerated dose of menadione was established at 2.5 g/m2. All of the mitomycin dose levels were tolerated without unexpected toxicities attributable to the combination. Prolonged infusions of menadione at doses which have been associated with lowering of intracellular glutathione pools in short-term exposure are limited by dose-dependent hemolysis, probably due to depletion of erythrocyte glutathione by menadione-related redox cycling. There was no detectable deleterious effect of pre-exposure to menadione on mitomycin C tolerance. We recommend a combination of menadione at 2.5 g/m2 as a continuous intravenous infusion and mitomycin C at 15 mg/m2 for further study in solid tumors, for which treatment with single-agent mitomycin C is appropriate.

Adult↗
PubMed1995

Mitomycin C and menadione for the treatment of lung cancer: a phase II trial.

A phase II trial of menadione [2.5 gm/m2 as a continuous intravenous (i.v.) infusion over 48 hours] followed by mitomycin C (10-20 mg/m2 i.v. bolus) administered every 4 to 6 weeks was performed in 23 patients with advanced lung cancer. Menadione, a vitamin K analog which lowers intracellular pools of reduced glutathione (GSH), was combined with mitomycin C in an attempt to overcome thiol-mediated resistance to alkylating agent chemotherapy. The median age of patients entered on this trial was 62 years; performance status ranged from 60-90%. Two of the 23 patients (9%; 95% confidence interval, 1% to 28%) had objective responses lasting 3.5 months and 13 months respectively, while 4 additional patients developed short unconfirmed responses (lacking follow-up response data to estimate response duration). Median survival for all patients was 5.5 months. Treatment with mitomycin C and menadione was well tolerated except for hematologic toxicity and cardiac events of unclear relationship to the study drugs. Thirty-one percent of treatment courses were complicated by grade 3 or 4 hematologic toxicity including one episode of hemolytic anemia. One patient developed interstitial pneumonitis. Two patients developed a decrease in left ventricular ejection fraction: one patient remained asymptomatic, but the other patient developed congestive heart failure. Although only 9% of patients had confirmed objective responses, 28% (5 of 18) of the patients with non-small cell lung cancer demonstrated biological activity (tumor regression fulfilling the criteria for objective response on a single occasion but 3 patients lacking a follow-up measurement to document response duration) to this combination of mitomycin C and menadione. We conclude that further studies of chemomodulation in non-small cell lung cancer are appropriate.

Adult↗
PubMed1995

Mitomycin C and menadione for the treatment of advanced gastrointestinal cancers: a phase II trial.

A phase II trial of menadione (2.5 g/m2 as a continuous intravenous infusion over 48 h) followed by mitomycin C (10-20 mg/m2 i.v. bolus) administered every 4-6 weeks was performed in 43 patients with advanced gastrointestinal cancer. Menadione, a vitamin K analog that lowers intracellular pools of reduced glutathione, was combined with mitomycin C in an attempt to overcome thiol-mediated resistance to alkylating-agent chemotherapy. The median age of patients entered on this trial was 58 years; performance status ranged from 60%-100%. None of the 43 evaluable patients obtained an objective response to this combination regimen. Median survival was 6.6 months. Treatment with menadione and mitomycin C was reasonably well tolerated except for hematological toxicity. A total of 27% of treatment courses were complicated by grade 3 or 4 hematological toxicity including one episode of hemolytic anemia and one episode of hemolytic uremic syndrome. One patient developed irreversible interstitial pneumonitis, and 1 patient had an asymptomatic decrease in the left-ventricular ejection fraction. Despite preclinical evidence indicating that menadione pretreatment enhances the cytotoxicity of mitomycin C, our study documents the resistance of advanced gastrointestinal cancers, particularly colorectal cancer, to mitomycin C modulated by menadione.

Adult↗
PubMed1995

Prediction of infusion rates of vecuronium using the bolus test dose technique.

Fifty neurosurgical patients were given loading doses of vecuronium 0.1 mg kg-1 followed by boluses of 1, 2 or 4 mg after return of T1 of the train-of-four. Neuromuscular function was assessed simultaneously by palpation of the great toe after peripheral nerve stimulation of the lateral popliteal nerve using a handheld nerve stimulator and also using a Relaxograph attached to one arm. The time taken for the return of T1 after the bolus dose was recorded and an infusion of vecuronium was begun and subsequently adjusted to maintain steady state neuromuscular block. It was possible to predict the infusion rate of vecuronium from the duration of action of a 2-mg or 4-mg but not a 1-mg bolus dose using the handheld stimulator. The infusion rate could also be predicted from the duration of action of the initial loading dose.

Anesthesia, General↗
PubMed1995

The density and distribution of endothelin 1 and endothelin receptor subtypes in normal and diabetic rat corpus cavernosum.

OBJECTIVE: To investigate the density and distribution of endothelin 1(ET-1) and endothelin receptor subtypes in rat cavernosal tissue, and to assess any changes brought about by the onset of diabetes mellitus (DM). MATERIALS AND METHODS: Hyperglycaemic non-ketotic diabetes mellitus was induced in five rats using streptozotocin (STZ). Two months later the penises were excised and stored at -70 degrees C. Longitudinal serial sections (6 microns) were cut using a cryostat and thaw- mounted onto gelatinized microscope slides. Low and high resolution autoradiographs were taken using radioligands for ET-1 and endothelin A (ETA) and endothelin B (ETB) receptors and the autoradiographs analysed densitometrically. These results were compared with those from five age-matched control rats. RESULTS: ET-1 and ETA receptor binding was primarily localized to the endothelium lining the cavernosal lacunar spaces: trabecular corporeal smooth muscle was much less intensely stained. No ETB receptor binding could be demonstrated, but increased binding of ET-1 and ETA receptors was seen in the diabetic cavernosal tissue. CONCLUSION: ET-1 and ETA receptor binding is increased in diabetic rat cavernosal tissue. A reduction in receptor linked nitric oxide (NO) release has previously been reported in diabetic rats. This finding may provide an explanation for the upregulation of ET-1 and ETA receptor binding in the diabetic rat.

Animals↗
PubMed1995

Abdominal pain.

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Abdominal Pain↗
PubMed1995

Effect of low-dose prophylactic dopamine on high-dose cisplatin-induced electrolyte wasting, ototoxicity, and epidermal growth factor excretion: a randomized, placebo-controlled, double-blind trial.

PURPOSE: To evaluate the protective effect of low-dose dopamine given as continuous infusion in patients who undergo chemotherapy with the nephrotoxin cisplatin. PATIENTS AND METHODS: Forty-two patients who received high-dose cisplatin-containing chemotherapy entered a prospective, randomized, double-blind, placebo-controlled trial. Twenty-one patients received dopamine, and 21 received placebo. Patients were to receive either infusional dopamine 2 micrograms/kg/min over 48 hours or placebo. Cisplatin 125 mg/m2 was administered 12 hours after initiating dopamine (group D) or placebo (group P). This schedule was repeated twice, 1 week apart. Measurements of serum creatinine, urinary electrolytes and creatinine, urinary excretion of epidermal growth factor (EGF), ototoxicity, parameters of hematopoietic recovery, and duration of hospitalization were analyzed. RESULTS: We observed an increase in serum creatinine level to a peak of 1.9 mg/dL (range, 0.8 to 7.8) in the dopamine group, in comparison to 1.4 mg/dL (range, 0.9 to 3.3) in the placebo group (P = .04). Urinary magnesium excretion increased and EGF excretion decreased in both groups. Urinary sodium, chloride, and potassium excretion were increased in both groups, but more so in the placebo group. Dopamine had no measurable effect on hearing loss, duration of hospitalization, or hematopoietic recovery. CONCLUSION: The use of prophylactic dopamine increased peak serum creatinine levels relative to placebo and failed to prevent cisplatin-induced renal toxicity or ototoxicity. Determination of whether dopamine could reverse chemotherapy-induced renal damage would require a randomized prospective trial.

Adult↗
PubMed1995

Phase I trial of carboplatin and infusional cyclosporin in advanced malignancy.

PURPOSE: To determine the maximal-tolerated dose (MTD) of infusional cyclosporine (CSA) with fixed-dose carboplatin (CBDCA). PATIENTS AND METHODS: Clonogenic cytotoxicity assays were performed to assess the effect of CSA on reversal of resistance to CBDCA. The phase I study was performed in three phases. In phases 1 and 2, escalating-dose CSA (5, 7.5, 8.8, or 9.5 mg/kg/d) with fixed-dose CBDCA 300 or 250 mg/m2 were administered. Phase 3 required an initial cycle of CBDCA 250 mg/m2 alone, followed by combination therapy with CBDCA 250 mg/m2 and CSA (8.8, 9.5, or 10.0 mg/kg/d). RESULTS: Preincubation of platinum-resistant A2780 human ovarian cancer cells with CSA 2 micrograms/mL significantly enhanced CBDCA cytotoxicity in clonogenic assays. Fifty-one patients received 130 courses of therapy. The phase 1 MTD was thrombocytopenia (CSA 7.5 mg/kg/d and CBDCA 300 mg/m2) attributable to the effects of CBDCA alone. The phase 2 MTD was reversible nephrotoxicity (serum creatinine elevations to 3.6 and 4.4 mg/dL) and neutropenia (CSA 9.5 mg/kg/d and CBDCA 250 mg/m2). In phase 3, headache was observed in five patients and hypertension in one patient at CSA 10 mg/kg/d. The expected change in platelet count predicted for CBDCA alone was compared with the actual change; no excessive thrombocytopenia was observed with addition of CSA. Steady-state CSA levels of 2 micrograms/mL capable of reversing platinum resistance in vitro were observed. Four objective responses were observed. CONCLUSION: CSA is effective in reversing CBDCA resistance in A2780 ovarian cancer cells. Short-term infusions of CSA < or = 8.8 mg/kg/d in combination with CBDCA are well-tolerated for heavily pretreated patients and result in CSA levels known to reverse CBDCA resistance in vitro.

Adult↗