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Biomedical subjects

D L Morris

Publications and source records attributed to D L Morris.

At least 199 records · Page 11Linked to original sources

Venous stasis during laparoscopic cholecystectomy.

The objectives of this research were (a) to determine the effect of insufflation at laparoscopic cholecystectomy to 12 mm Hg on femoral venous blood flow; and (b) to assess the function of intermittent pneumatic compressors (IPC) and intermittent electric calf stimulators (IECS) in the presence of a pneumoperitoneum. Measures of baseline venous blood flow velocity, femoral vein diameter, and maximum blood flow velocity achieved by IPC or IECS were made in the presence or absence of a pneumoperitoneum of 12 mm Hg. The ICP and IECS were randomly allocated to either leg. All measures were made by an experienced sonologist. Insufflation to 12 mm Hg caused a statically significant decrease in femoral blood flow velocity and was accompanied by a significant increase in femoral vein diameter. The IPC and IECS were able to achieve pulsatile venous blood flow despite the presence of a pneumoperitoneum, but they had no effect on the depressed baseline blood flow velocity. We concluded that insufflation to 12 mm Hg causes significant venous stasis in the lower limb and that IPC and IECS cannot completely eliminate this stasis. Further research needs to be done to clarify the optimal methods of prophylaxis in view of the implications for deep venous thrombosis.

Adult↗

Direct effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on human tonsillar lymphocytes.

Murine lymphocyte function is quite sensitive to TCDD. However, in contrast to the murine model, the corresponding functional studies have not been undertaken with human lymphocytes. One laboratory has recently demonstrated that human tonsillar lymphocytes (HTL) possess the aryl hydrocarbon (Ah) receptor which mediates many of the effects of TCDD. This observation suggested that HTL may be sensitive to TCDD. In mitogen stimulated HTL, TCDD induced a dose-dependent increase in 7-ethoxyresorufin-O-deethylase (EROD) synthesis. Because we recently demonstrated that background proliferation in HTL and murine splenocytes was suppressed by TCDD, we purified human and murine B-cells into high density and low density populations. In low density human B-cells, TCDD suppressed background proliferation and IgM secretion from 0.3 to 30 nM. Interestingly, TCDD produced comparable effects on background proliferation and IgM secretion in purified low density murine B-cells. When low density human B-cells were stimulated with LPS and TRF, TCDD suppressed both proliferation and IgG secretion in a dose-dependent manner from 0.3 to 30 nM, although the suppression was modest when compared to the magnitude of suppression of the background responses. In contrast, TCDD did not alter background or stimulated proliferation in high density human B-cells. These results indicate that TCDD has a direct effect on human tonsillar lymphocyte activity and suggest that low density B-cells are a sensitive cellular target.

Animals↗

Abnormal transcription factor induction through the surface immunoglobulin M receptor of B-1 lymphocytes.

Populations of murine peritoneal B-1 and splenic B-2 cells, highly purified by negative selection techniques, were used to demonstrate that B-1 cells completely fail to enter cell cycle in response to surface immunoglobulin M (sIgM) crosslinking without any decrease in cell number or viability. This failure of B-1 cell responsiveness appears to represent a specific defect in sIgM-derived signaling inasmuch as stimulation to enter S phase occurs normally in response to activated and fixed T cells, and to lipopolysaccharide (LPS). The level at which sIgM signaling fails was determined by evaluating the nuclear expression of the transcription factor complex, NF-kappa B, whose sIgM-mediated induction in B-2 cells is dependent on protein kinase C (PKC) activation but is independent of protein synthesis. There was no induction of nuclear NF-kappa B in B-1 cells stimulated by sIgM crosslinking, although NF-kappa B was stimulated by phorbol myristate acetate and by LPS. In contrast, NF-kappa B was induced in B-2 cells by all three stimuli. Thus, in B-1 cells, the sIgM-mediated induction of a transcription factor that is substantially stimulated by anti-IgM in B-2 cells is blocked. However, all sIgM-derived signaling in B-1 cells was not impaired inasmuch as anti-IgM increased I-A antigen expression. These results strongly suggest that sIgM receptor-mediated signaling in B-1 cells is interrupted early in the signal transduction pathway, at a point proximal to the activation of PKC. These results further demonstrate that transcription factor induction can be used to analyze the level at which receptor-mediated signaling is blocked.

Animals↗

Myocardial infarct artery patency and reocclusion rates after treatment with duteplase at the dose used in the International Study of Infarct Survival-3. Burroughs Wellcome Study Group.

Duteplase, 98% double-chain recombinant tissue-type plasminogen activator, was administered intravenously in 488 patients with acute myocardial infarction in a multicenter, open, safety and patency study. Duteplase dosing was based on body weight. Duteplase was administered as a bolus of 0.04 MIU/kg of thrombolytic activity followed by 0.36 MIU/kg over 1 hour and 0.067 MIU/kg/hour for 3 additional hours. The patency rate of the infarct-related artery at 90 minutes was 69% (330 of 478). The reocclusion rate at 3 to 48 hours was 6% (18 of 301). Reinfarction occurred in 7.6% of patients (37 of 488), but 12 reinfarctions occurred after coronary angioplasty. Serious bleeding occurred in 7.6% of patients (37 of 488), predominantly at the catheterization entry site. There were 3 instances of central nervous system bleeding, 1 fatal. Fibrinogen levels declined to 83% of baseline at 24 hours. Weight-based dosing may explain the low incidence of serious bleeding in this study. The in-hospital mortality was 6.6% (32 of 488). This study documents that the dose of duteplase used in the International Study of Infarct Survival-3 results in a 90-minute coronary artery patency rate and safety profile comparable to those reported in published studies on the approved dose of alteplase.

Coronary Angiography↗

Upward fixation of the patella in cattle: 38 cases (1984-1990).

Case records of cattle admitted to 2 university veterinary hospitals during 6 years were evaluated to determine the age, breed, sex, and treatment of cattle with upward fixation of the patella. Affected cattle were compared with those from the respective hospital populations of cattle admitted during the same time. Of 38 cattle with upward fixation of the patella, 34 were treated surgically. Follow-up evaluation was obtained from owners of 28 of the treated cattle. Surgery was successful in eliminating all clinical signs in 25 of the 28 cattle. There was an increased risk of upward fixation of the patella associated with Brahman and Brahman-type cattle, compared with non-Brahman cattle.

Animals↗

Dose-ranging study with a new two-chain rt-PA in patients with acute myocardial infarction: a multicenter trial.

Tissue-type plasminogen activator (t-PA) derived from a melanoma cell line was first used in patients with acute myocardial infarction in the early 1980s. Recombinant DNA technology then allowed production of large amounts of t-PA. The TIMI-I trial used a two-chain recombinant (rt-PA) product. A predominantly single-chain rt-PA (alteplase) was used in the majority of the TIMI II trial. The present study used a different form of two-chain rt-PA (duteplase) to determine the effective dose for thrombolysis at 60 min, and to evaluate time to reperfusion, reocclusion at 72-96 h, coagulation profiles, and bleeding events. Duteplase was given intravenously to 75 patients a mean of 3.8 +/- 1 h after the onset of myocardial infarction. Following angiography demonstrating coronary occlusion, 23 patients received a low dose of duteplase [0.16-0.29 million international units per kilogram (MIU/kg)] over 60 min followed by a 5-h infusion in conjunction with heparin, 25 patients received a middle dose (0.30-0.41 MIU/kg) and 23 patients received a high dose (0.43-0.74 MIU/kg). Angiography was then performed every 15 min x 4. Progressive recanalization occurred over 60 min (median 45 min) with an overall success rate of 59% (mean 60-min dose: 0.37 MIU/kg). No dose-response relationship was observed. The reocclusion rate was 9% at 72-96 h. Reductions in fibrinogen and plasminogen correlated with dose, but clinical events did not.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Laboratory and animal model evaluation of the Cryotech LCS 2000 in hepatic cryotherapy.

Hepatic cryotherapy is increasingly used in the treatment of patients with multiple hepatic metastases, particularly from colorectal cancer. The Cryotech LCS 2000 system, with insulated shaft-circulated liquid nitrogen probes, was designed for this purpose and was evaluated on the bench and in an animal model. The 9-mm probe was considerably more effective than the 5-mm probe when judged on time to create an iceball of a given diameter. The use of thawing gas reduced the time until the probe could be removed from 25 to 5 min but heated gas only produced a further reduction of 2 min. In the animal model, significant reduction in treatment times occurred with vascular inflow occlusion. The zone of necrosis as a percentage of the original iceball diameter was significantly higher following a twin freeze/thaw cycle. The relationship of the edge of the iceball to the eventual zone of hepatic necrosis was studied using different unabsorbable markers. India ink and sutures proved unreliable but a Teflon cannula was more successful and the margin was only of the order of 2 mm. The discrepancy between this observation and the percentage of the original iceball diameter which apparently becomes necrotic (64 and 82%) for single- and double-freeze lesions, respectively, suggests that the cryolesion undergoes shrinkage within 1 month and that the diameter of necrosis underestimates the true zone of destruction.

Animals↗

Avid thallium-201 uptake in hepatic carcinoid metastases.

While radiolabelled somatostatin analogues sensitively detect extrahepatic carcinoid tumour, intrahepatic metastases are frequently not visualised due to somatostatin accumulation in normal hepatic tissues. We report a case of avid thallium-201 uptake in multiple hepatic carcinoid metastases using single-photon emission tomography (SPET) and compare this to a SPET technetium-99m sulphur colloid scan in the same patient. The 99mTc sulphur colloid images demonstrate multiple focal defects at the site of known metastases in the hepatic right lobe (confirmed on both CT and surgery). However, there is avid uptake of thallium in the metastases on comparative SPET slices. 201Tl may be a useful agent for the detection and localisation of carcinoid tumour and in particular of intrahepatic carcinoid metastases.

Adult↗

Evaluation of the clastogenic effects of 2-methoxyethanol in mice.

2-Methoxyethanol (ethylene glycol monomethyl ether; EGME) is present in many industrial and consumer products, therefore, many individuals in the population are exposed to EGME. Although the toxicity of this compound is well documented its genotoxicity has not been adequately investigated using updated cytogenetic procedures. We have conducted studies to determine the clastogenic effects of EGME and its metabolite, methoxyacetaldehyde (MALD), in bone-marrow cells of B6C3F1 mice after their acute and subchronic exposure to the chemicals by the oral route. In addition, the effects after acute intravenous treatment with EGME were investigated. Mice treated with cyclophosphamide (CP) under similar experimental conditions were used as positive controls. Mice treated acutely with EGME or MALD were also implanted with bromodeoxyuridine tablets to label cells so that only cells at their first post-treatment mitoses were selected for chromosome analyses. Our data show that none of the concentrations of EGME (35-2500 mg/kg body weight) nor MALD (20-1000 mg/kg) caused any induction of chromosome aberrations even though cytotoxic doses were used. On the other hand, CP caused significant increases in chromosome damage. The data suggest that EGME and MALD are either non-clastogenic in vivo or that our mice are able to detoxify the two chemicals. In order to clarify these possibilities, pharmacokinetic and metabolic studies need to be conducted.

Acetaldehyde↗

Case report: emphysematous tuberculous pancreatitis diagnosis by ultrasound and computed tomography.

We describe a case of simultaneous tuberculous and pyogenic infection of the pancreas in a 58-year-old Asian man who presented with a pyrexia of unknown origin. There was no evidence of disseminated tuberculosis or immuno-deficiency. The diagnosis was confirmed by ultrasound-guided percutaneous pancreatic aspiration and subsequent progress assessed by sequential computed tomography (CT) and ultrasonography. Complete recovery was achieved on anti-tuberculous chemotherapy without surgical intervention.

Emphysema↗

Screening for gastric carcinoma in coal miners.

This study aimed to determine the prevalence of dyspeptic symptoms and premalignant gastric lesions in coal miners and sex matched population control subjects. Retired coal miners and men from the general population in north Nottinghamshire were sent a dyspepsia questionnaire to fill in, and those with upper gastrointestinal symptoms were invited for gastroscopy and biopsy. A total of 1272 men from the general population and 2099 retired coal miners aged 50-75 years took part in the study. Some 977 of 1272 (76.8%) control subjects and 1715 of 2099 (81.7%) miners replied to the questionnaire. A total of 308 of 977 (31.5%) controls and 620 of 1715 (36.2%) miners were positive for at least one symptom. There was a highly significant difference between the numbers of surface mine and underground workers who reported dyspeptic symptoms (66 of 300 (22%) v 425 of 1083 (32.2%) of p < 0.0001). Histology showed that significantly more miners than controls had acute on chronic gastritis (22 v 11%; p = 0.01) and intestinal metaplasia (23 v 8%; p = < 0.0001). Coal miners may be a suitable group for gastric premalignancy screening using an upper gastrointestinal symptom questionnaire and upper gastrointestinal endoscopy.

Age Factors↗

The impact of cardiac index on cerebral hemodynamics.

BACKGROUND AND PURPOSE: Current noninvasive testing allows accurate assessment of cerebrovascular hemodynamics. The cardiovascular influence on the noninvasive assessment of cerebrovascular studies has not been defined. This study was designed to determine the effect of cardiac index (CI) on cerebral blood flow velocities, ocular pulse amplitude, ophthalmic systolic pressure, and ocular blood flow (OBF) as currently estimated by noninvasive laboratories. METHODS: Based on a retrospective study of 181 patients, we prospectively evaluated 45 patients undergoing right heart catheterization for hemodynamic monitoring to correlate the relation between CI, transcranial Doppler sonography, and ocular pneumoplethysmography. Patients with hemodynamic instability, severe carotid stenoses, massive cerebral infarct, or sepsis were ineligible for the study. Simultaneous recordings of systemic blood pressure, ophthalmic systolic pressure, heart rate, ocular pulse amplitude, middle cerebral artery blood flow velocities, and cardiac output were obtained on all patients. OBF was calculated from the heart rate and ocular pulse amplitude. RESULTS: The relation between OBF and CI is expressed by the equation CI = 2.36 + 0.61 x OBF (r = .47, P = .0010). The middle cerebral artery peak systolic velocities and CI had a correlation of .36 (P = .0181). The equation, derived from the linear relation between OBF and CI, was then validated on a sample of 15 patients. With the apparent linear relation between OBF and CI, we used the derived equation to predict CI from OBF. The OBF determination predicted CI within 30% in all patients and within 20% in 53.3% of the patients. CONCLUSIONS: We demonstrated that OBF and middle cerebral artery systolic velocity decrease with diminishing CI. Our findings suggest that CI may be potentially estimated in selected patients by noninvasive assessment of OBF using ocular pneumoplethysmography.

Blood Pressure↗

Azithromycin clinical pharmacokinetics.

Azalide antibiotics, of which azithromycin is the first demonstrated, have different pharmacokinetics from other antibiotics currently used. The bioavailability of the drug is approximately 37%. Extensive and rapid distribution from serum into the intracellular compartments is followed by rapid distribution to the tissues. Tissue concentrations exceed serum concentrations by up to 100-fold following a single azithromycin 500mg dose. Concentration of the drug within phagocytes aids in its ability to combat infections. High concentrations of azithromycin are found in the tonsil, lung, prostate, lymph nodes and liver, with only small concentrations found in fat and muscle. A 500mg dose on day 1, followed by 250mg daily on days 2 to 5, has been demonstrated to maintain azithromycin concentrations at sites of infection and continues to be effective for several days after administration has ceased. The pharmacokinetics of azithromycin make it a drug with diverse therapeutic applications.

Azithromycin↗