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Biomedical subjects

S Walker

Publications and source records attributed to S Walker.

At least 343 records · Page 19Linked to original sources
PubMed1985

Foetal and neonatal development of cytochrome P-450 and cytochrome P-448 catalysed mixed function oxidases in the rat: induction by 3-methylcholanthrene.

Benzphetamine N-demethylase (cytochrome P-450) and ethoxyresorufin O-deethylase activities (cytochrome P-448) were determined in the growing neonate and foetus of control and 3-methylcholanthrene-pretreated rats. Ethoxyresorufin O-deethylase activity was highest in the 1-2-week-old animals and then decreased with age. The inducibility of this activity by 3-methylcholanthrene was low in the young animals, but increased with age. In contrast, benzphetamine N-demethylase activity in the control animals was low at birth and increased with age, and was not induced by 3-methylcholanthrene. In the foetal liver, ethoxyresorufin O-deethylase was the only activity present at higher levels than in the maternal liver. Transplacental administration of 3-methylcholanthrene failed to induce the foetal activities while the maternal liver showed the expected response. These observations demonstrate that cytochrome P-448 may be a predominant hepatic form in the foetus and neonate but cytochrome P-450 becomes a major form as the animal grows. The implications of these findings in chemical toxicity are discussed.

Age Factors↗
PubMed1985

Radiation exposure rates near brachytherapy patients containing 137Cs sources.

For 30 brachytherapy patients, whose lateral pelvic diameters, 2r, ranged from 28 to 47 cm, and who contained activities Ac of 137Cs expressed in equivalent milligrams of 226Ra, the normalized exposure rates, X(r)/Ac, in mR h-1 (mg Ra eq)-1 at 1 m lateral from the midline of the pelvis, can be expressed by X(r)/Ac = (1.3 +/- 0.5)e-(0.07 +/- 0.02)r. Patient and applicator effects that contribute to the large uncertainties in the model coefficients are identified.

Brachytherapy↗
PubMed1985

Familial complex autosomal translocations involving chromosomes 7, 8, and 9 exhibiting male and female transmission with segregation and recombination.

A family showing a complex translocation between chromosomes 7, 8, and 9 with breakpoints at 7q21, 7q33, 8p23, and 9p23 is described. The proband had been referred because of repeated spontaneous abortions. This is only the second family to be ascertained in this way. Twenty-three other cases of complex translocations are briefly reviewed, eight of which were de novo in origin and 15 familial. All but one of the familial cases showed maternal transmission only. The present family shows both maternal and paternal transmission and is thought to be the first exhibiting recombination from a male carrier. The origin and transmission of the complex translocation is followed through three generations.

Abortion, Habitual↗
PubMed1985

Absorption of urso- and chenodeoxycholic acid and their taurine and glycine conjugates in rat jejunum, ileum, and colon.

Chenodeoxycholic acid (cheno) and ursodeoxycholic acid (urso) dissolve cholesterol gallstones in man. Comparative studies of the absorption of cheno and urso are not available. The absorption of urso and cheno and their glycine and taurine conjugates in jejunum, terminal ileum, and colon of the rat were therefore determined in an open in situ perfusion system. Absorption of unconjugated urso and cheno in jejunum, ileum, and colon was similar. In the jejunum conjugated urso and cheno were absorbed only in minimal amounts. In the ileum glycine-conjugated urso was absorbed to a lower extent than glycine-conjugated cheno (6.5 +/- 0.4 vs. 8.6 +/- 0.6 nmol/cm X h at 25 mumol/l bile acid concentration, p less than 0.05) and taurine-conjugated urso was absorbed less than taurine-conjugated cheno (6.4 +/- 0.5 vs. 8.1 +/- 0.7 nmol/cm X h, p less than 0.05). In the colon glycourso and taurourso were not absorbed, while glycocheno and taurocheno were absorbed in small amounts. The low reabsorption rates of urso conjugates in ileum and colon may contribute to the relatively low urso content in bile during urso treatment.

Animals↗
PubMed1985

Absorption of 7-ketolithocholic acid in rat jejunum, ileum and colon.

7-Ketolithocholic acid is a bile acid which is formed in the intestine of man by bacterial oxidation of chenodeoxycholic acid and ursodeoxycholic acid. In contrast to deoxycholic acid and lithocholic acid 7-ketolithocholic acid after its intestinal absorption may be reduced in the liver to chenodeoxycholic acid or ursodeoxycholic acid. In the present study absorption of 7-ketolithocholic acid in jejunum, ileum, and colon was measured. When 7-ketolithocholic acid was perfused with a concentration of 0.025 mmol/l the absorption in the jejunum was 6.2 +/- 0.9 nmol/cmxh (mean +/- SD), in the ileum 8.1 +/- 0.2 nmol/cmxh, and in the colon 11.2 +/- 1.7 nmol/cmxh. The absorption of 7-ketolithocholic acid in jejunum, ileum, and colon was equal to the absorption of ursodeoxycholic and chenodeoxycholic acid. The equal absorption rates of 7-ketolithocholic, ursodeoxycholic, and chenodeoxycholic acid indicate, that substitution of the 7-hydroxyl group by the 7-keto group has no influence on the intestinal absorption of bile acids. The excellent colonic absorption of 7-ketolithocholic acid demonstrates, that not only the small intestine but also the colon contributes to the enterohepatic circulation of bile acids.

Animals↗
PubMed1984

A totally implanted injection port system for blood sampling and chemotherapy administration.

We evaluated a totally implanted system consisting of a subcutaneous injection port connected to a silicone elastomer central venous catheter for vascular access, including blood drawing, in 35 patients with cancer. All patients lacked peripheral venous access sites and were undergoing aggressive chemotherapy programs. The cumulative duration of successful access exceeded 2,900 days (for individual patients: range, five to 203 days; median, 61 days). In no instance were infusions or injections unsuccessful. Blood-sampling attempts were successful 90% of the time. The system did not require flushing between uses, being filled with heparinized saline after each entry. There were no instances of irreversible catheter occlusion or shear and no system-related infections. Thus, this device appears to have advantages over other central venous catheters in terms of patient acceptance and lack of maintenance between uses.

Adolescent↗
PubMed1984

Regional chemotherapy of colorectal cancer metastatic to the liver.

Ninety-three patients with biopsy-proven colorectal cancer metastatic to the liver were treated with hepatic arterial infusion of 5-fluorodeoxyuridine (FUDR). There were 52 men and 41 women (median age, 60 years). Forty-two patients (45%) had failed prior systemic chemotherapy. Catheters were operatively placed and multiple catheters were used if dictated by hepatic arterial anatomy in order to obtain perfusion of the entire liver. The drug was delivered by a totally implanted INFUSAID model 400 pump and patients received cyclic therapy consisting of 2 weeks of 0.3 mg/kg/d FUDR alternating with 2 weeks of saline. Patients with extrahepatic tumor or patients whose hepatic tumor failed to respond to FUDR were given a 30 minute intraarterial infusion of mitomycin C, 15 mg/m2, every 6 to 8 weeks in addition to FUDR. Fifty of the 93 evaluable patients presented with metastatic tumor confined to the liver. Of these 50 patients, 83% demonstrated a significant reduction in tumor size with a median duration of response of 13 months and a median survival of 25 months from diagnosis of liver metastases. Twenty-four of these 50 patients remain alive. Forty-three patients presented with extrahepatic metastases in addition to their liver tumor, and 74% had a response with a median duration of 6 months and a median survival of 14 months. Only six patients of those presenting with extrahepatic tumor remain alive. None of the 93 patients died solely of uncontrolled liver tumor, and only 9 died as a result of uncontrolled liver metastases and disseminated extrahepatic tumor. The duration of survival for both groups was determined by the uncontrolled progression of extrahepatic tumor. In patients with metastatic colorectal cancer involving only the liver, hepatic arterial FUDR alone and with the addition of mitomycin C provided excellent control of hepatic tumor. Survival appeared to be prolonged in this uncontrolled study.

Antineoplastic Agents↗
PubMed1984

Constant intraperitoneal 5-fluorouracil infusion through a totally implanted system.

Five-day continuous intraperitoneal (ip) infusions of 5-fluorouracil (FU) were injected into five patients as part of a phase I clinical pharmacology study. They received 20 courses through a totally implanted catheter/injection port system. Six courses are evaluable for kinetic parameters and all courses are evaluable for toxicity. In each course a 2 to 3 log FU concentration differential in favor of the peritoneal cavity was achieved and maintained. Steady-state venous plasma FU concentrations averaged 0.34 microM, whereas steady-state ip FU concentrations averaged 697 microM. Mean total body clearance (TBC) in these patients was 18.4 l/min and mean permeability-area (PA) product for diffusion from the peritoneum was 13.7 ml/min. Mean TBC of 20 l/min with ip FU infusion was observed in one patient who also received a 24-hr IV FU infusion for comparison. The TBC during the later infusion was 5.9 l/min. In this patient, calculations indicate 75% extraction of drug during the passage from the peritoneum to the systemic circulation, presumably representing in large part hepatic extraction of FU taken into the portal venous circulation. Ip constant infusion and bolus kinetics were compared in one patient. TBC for the ip bolus was 14.3 l/min, which was approximately half of the TBC of 29.5 l/min determined during the 5-day constant ip infusion. Thus constant ip infusion of FU (l gm/day) can provide an improved regional advantage over bolus ip FU because of an increased TBC. Toxicity was acceptable in all courses. Dose limiting toxicity was regional, namely moderate chemical peritonitis seen in two of the five patients on repeated courses. There was no myelosuppression, alopecia, nausea, or vomiting.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1984

Ratio of cut surface area to leaf sample volume for water potential measurements by thermocouple psychrometers.

Evaporative losses from the cut edge of leaf samples are of considerable importance in measurements of leaf water potential using thermocouple psychrometers. The ratio of cut surface area to leaf sample volume (area to volume ratio) has been used to give an estimate of possible effects of evaporative loss in relation to sample size. A wide range of sample sizes with different area to volume ratios has been used. Our results using Glycine max L. Merr. cv Bragg indicate that leaf samples with area to volume values less than 0.2 square millimeter per cubic millimeter give psychrometric leaf water potential measurements that compare favorably with pressure chamber measurements.

Journal Article↗
PubMed1984

Definition of hepatic tumor microcirculation by single photon emission computerized tomography (SPECT).

Single photon emission computerized tomography coupled with Tc-99m MAA hepatic-arterial perfusion scintigraphy has been used to examine the density of the functional microcirculation of hepatic tumors relative to normal liver in 24 patients. In both colorectal and carcinoid tumors we have demonstrated an average three-fold greater arteriolar-capillary density in areas of tumor proliferation. The depth of the evoked tumor hypervascularity was found to extend about 4 cm. Tumors greater than 8-9 cm in diameter were uniformly found to have a central hypovascular core. These observations are of importance in the design of selective strategies utilizing therapeutic microspheres directed against the hypervascular proliferating regions of human tumors.

Adult↗
PubMed1984

Calmodulin.

The two best-defined intracellular signalling systems are cAMP and calcium. It is clear that the actions of cAMP depend on its interaction with an enzyme--cAMP-dependent protein kinase. One of the major developments in recent years has been the recognition that many of the intracellular actions of calcium occur through its binding to and activation of calmodulin.

Adenylyl Cyclases↗
PubMed1983

Further experience of vitamin supplementation for prevention of neural tube defect recurrences.

In accordance with a previous protocol, a second cohort of 254 mothers with a history of previous neural tube defect (NTD) births was before a subsequent conception and continued until the time of the second missed menstrual period. There were 2 NTD recurrences (0.9% of 234 infants/fetuses examined), which is significantly fewer than the 11 NTD recurrences (5.1% of 215 infants/fetuses examined) born to 219 unsupplemented (US) mothers in the same centres over the same period. When the data for the two cohorts were combined, the overall recurrence rates were 0.7% for 454 fully supplemented (FS) mothers and 4.7% for 519 US mothers. The recurrence rates after 1 previous NTD were 0.5% for FS and 4.2% for US mothers: after 2 or more previous NTDs, 2.3% for FS and 9.6% for US. There were no recurrences among the offspring of a further 114 mothers whose duration of supplementation fell short of the full regimen (partially supplemented, PS).

Female↗
PubMed1983

Improved regional selectivity of hepatic arterial mitomycin by starch microspheres.

Biodegradable starch microspheres, 40 microns in diameter, were administered through hepatic arterial catheters in 16 subjects with primary and metastatic liver tumors. These microspheres temporarily obstruct blood flow at the precapillary arteriole (microcirculation) level. Our study was undertaken to determine whether such occlusion would enhance hepatic deposition of, and thereby decrease systemic exposure to, simultaneously administered hepatic arterial mitomycin C (mito). When mito (10 mg/m2 over 1 min) was given with 90 X 10(6) microspheres (10 subjects), there was a 17% to 70% reduction in systemic mito exposure. When mito (10 mg/m2 over 1 min) was given with 36 X 10(6) microspheres (six subjects), there was a 15% to 60% reduction in systemic exposure, which may correlate with dose-dependent shunting (8% to 29%) through the liver to the lung (and hence to the systemic circulation), attributed to the starch microspheres. No life-threatening myelosuppression was noted; hepatic toxicity consisted of transient pain and elevation of liver enzymes.

Adult↗
PubMed1983

Hepatic arterial streptozocin: a clinical pharmacologic study in patients with liver tumors.

Hepatic arterial infusions of streptozocin (STZ) were compared with peripheral venous infusions administered for 3 h at a dose rate of 0.5 or 1.0 g/m2 . h in five patients with liver-predominant neoplastic disease. Peripheral venous plasma STZ levels were measured during and for 3 h after completion of all infusions. Steady-state was achieved at 2 h and the elimination half-life was 35-40 min, the total body clearance was 400 ml/min, and the volume of distribution of STZ was 20-22 liters in these patients. Comparison of steady-state drug levels demonstrated minimal hepatic extraction (mean 5%). Assuming a hepatic arterial blood flow of 100-200 ml/min with a total body clearance of 400 ml/min, hepatic arterial administration of STZ can be expected to result in a three- to sixfold greater exposure of tumor in the liver compared with the intravenous route. Toxicity was minimal and two patients had evidence of response.

Adult↗
PubMed1983

A comparison of the attitudes of students and non-students toward the disabled in Ghana.

A comparison of attitudes toward the disabled in Ghana was made between 146 college students (majoring in general education, special education administration and medicine) and 128 non-students. The study focuses on an analysis of responses to a select number of attitude statements which revealed the following: Students responded more favorably than non-students to statements emphasizing the value of educating the disabled. Students were less likely to blame the disabled or his/her family for the presence of a disability. On the other hand, both students and non-students were least favorable to social interaction with the disabled. A major finding of the study was that all scores fell within or above the moderately positive range. However, analysis of data revealed an inconsistency between the cognitive and affective attitude components. These findings suggest the influence of traditional beliefs on attitudes toward the disabled.

Administrative Personnel↗