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Biomedical subjects

C R Thomas

Publications and source records attributed to C R Thomas.

At least 109 records · Page 6Linked to original sources
PubMed1991

Controversies in the multimodality management of head and neck cancer.

A number of prospective controlled trials currently exist, with consistent results that help define the current role of chemotherapy in patients with advanced-stage head and neck cancer, and they may offer directions for future research. Neoadjuvant combination chemotherapy appears to offer no survival advantage but does appear to select a subgroup of patients who do not require surgical intervention, thereby resulting in organ preservation. Patients who have received neoadjuvant chemotherapy and obtain a prompt complete response are more likely to realize a significant local control advantage following regional therapy. Randomized studies using simultaneous chemotherapy and radiotherapy have resulted in higher clinical local control and overall survival rates. These studies have used only single agents, however. Phase II trials with drug combinations have been even more encouraging as compared with historical data. By comparing different treatment schemes, such as alternating and sequential, to simultaneous schedules, it is hoped that differences in toxicity, the role of dose-intensity, and regional control rates can be further defined. The information now exists for the formulation of well-designed, prospective randomized clinical trials comparing different schemes of concomitant chemotherapy with standard regional treatment regimens.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Common emergencies in cancer medicine: metabolic syndromes.

Metabolic derangements are fairly common occurrences in cancer medicine. In many instances, they require deft recognition and prompt institution of emergency therapeutic intervention. These syndromes may result from a primary tumor, metastatic disease, or anti-tumor therapy. This article discusses the management of such patients.

Acidosis, Lactic↗
PubMed1991

Update on gastric lymphoma.

Primary gastrointestinal lymphoma is an uncommon entity that can often present like classic adenocarcinoma. The most common organ site involved is the stomach. Important prognostic indicators include location of lymph node involvement, histologic subtype, lymphocyte lineage, gross size, and location of the tumor. Surgical resection is the mainstay of curative therapy. Combination chemotherapy and radiotherapy may have a role either separately or as part of a multimodality treatment program. Clinicians are encouraged to enter patients with primary gastric lymphoma into multi-institutional, cooperative group clinical trials to more clearly define the best treatment strategy.

Humans↗
PubMed1990

Rheumatologic manifestations of malignancy.

The relationship between rheumatologic syndromes and cancer covers a very broad array of both common and distinctly rare manifestations. This discussion has outlined some of the known relationships that do exist. A high index of suspicion by both the primary care physician and subspecialist will enhance the probability of detecting cancer in the patient who may present with rheumatologic complaints.

Adenocarcinoma↗
PubMed1990

Effects of maternal diabetes on placental transfer of glucose in rats.

In situ perfusion of the fetal side of the anesthetized rat placenta was used to monitor glucose fluxes in nondiabetic, streptozocin-induced diabetic (STZ-D), acutely hyperglycemic nondiabetic, and acutely normoglycemic STZ-D rats. STZ-D resulted in increased accumulation of glucose in the perfusate during a single passage through the fetal vasculature compared with nondiabetic rats, and this increase was maintained in normoglycemic STZ-D rats, indicating glucose release from placental stores. The fractional clearance of 3-O-[14C]methylglucose, a nonmetabolizable glucose analogue, across the placenta was decreased in both STZ-D groups compared with nondiabetic rats but unchanged in hyperglycemic nondiabetic rats, implying a reduction in glucose transporters in diabetic placentas. The difference between the transfer of D-[3H]glucose and 3-O-[14C]methylglucose indicated that 17% of the glucose was retained while traversing the placenta of nondiabetic rats, whereas a smaller percentage (8%) but a larger absolute amount (9 vs. 6 mumol/h) of glucose was retained by the placentas of the severely STZ-D rats. This retention was markedly enhanced in hyperglycemic nondiabetic rats and STZ-D rats when rendered normoglycemic. The net accumulation of perfusate glucose was less than that predicted from radiolabeled transfer data, indicating that glucose is also back transferred from the perfusate to the mother's placenta. We conclude that maternal diabetes markedly affects placental glucose flux.

Animals↗
PubMed1990

The use of two in-situ simultaneously-perfused placentas to investigate the effect of carrier proteins on linoleic and palmitic acid transfer in the guinea pig.

By perfusing two placentas concurrently in five animals we have found that linoleic acid is transferred across the guinea-pig placenta more readily than palmitic acid. In the in-situ perfusion this transfer is modulated by the type of albumin used in the perfusate. Removing the associated lipid from the perfusate albumin reduced the amount of non-esterified fatty acid (NEFA) transfer rather than enhanced it. Many researchers use fat free albumin as a protein carrier in in vivo and in-vitro systems, our results indicate that this may not be the most appropriate substance to use.

Animals↗
PubMed1990

The effects of maternal diabetes on placental transfer of essential and non-essential fatty acids in the rat.

Studies were performed on the transfer of essential and non-essential non-esterified fatty acids across the in-situ perfused placenta in normal and diabetic rats in late gestation. Results indicated that increasing maternal glycaemia is associated with a decrease in the unidirectional transfer of both essential and non-essential fatty acids. This reduced transfer is dependent upon the uteroplacental blood flow, which is compromised in the diabetic animals. The transfer of essential fatty acid was always twofold that of non-essential fatty acids regardless of the total amount of lipid transferred, indicating a selective mechanism for the transfer of these moieties.

Animals↗
PubMed1989

The effect of alloxan induced diabetes in the rabbit on placental transfer of glucose and non-esterified fatty acids.

In situ perfusion of the fetal side of the placenta of five normal and eight diabetic anaesthetized rabbits was performed. The does were infused with a mixture of 14C palmitic acid and 3H glucose whilst simultaneous maternal blood and placental perfusate samples were taken for 90 min. Radiolabelled palmitate and glucose levels in the perfusate closely followed levels in the maternal plasma in both normal and diabetic animals. Total placental non-esterified fatty acid transfer was 0.96 mumol/min in the diabetic animals, although due to the considerable variation within the groups this was not statistically significantly more than the 0.58 mumol/min transferred in the normal rabbits. This transfer was significantly affected by maternal uteroplacental blood flow. Total placental glucose transfer was significantly raised in the diabetic (5.0 mumols/min) compared with the normal (1.8 mumols/min) animals, reflecting maternal hyperglycaemia in the diabetic rabbits. Placental glucose transfer was also significantly correlated with maternal uteroplacental blood flow. Maternal diabetes thus increases the placental flux of nutrients to the fetus in the rabbit.

Animals↗
PubMed1987

Decrease in triiodothyronine binding sites in chick embryo erythrocytes during early development.

Specific thyroid hormone (TH) binding sites have been detected in nuclei of erythrocytes obtained from developing chick embryos. The binding characteristics and relative affinities for TH analogs were those expected of TH receptors. Nuclear triiodothyronine (T3) saturation analysis was carried out in vitro by incubating intact erythrocytes in M199 medium with 3-200 pM [125I]T3 for 1 hr at 37 degrees C or 20-24 hr at 21 degrees C. Nuclei were obtained by centrifugation after lysing the erythrocytes in a stabilizing buffer containing 0.3% saponin, followed by addition of Triton X-100 (final concentration 0.2%) to minimize the nonspecific binding. Scatchard analysis of equilibrium binding data suggested that the nuclei possess a single class of binding sites. The binding is reversible and the rate of dissociation is temperature dependent. T3 and T4 appear to bind to the same sites, but the affinity of T3 was 16 times greater. Among TH analogs tested, Triac had the highest affinity followed by L-T3, D-T3, Tetrac, L-T4, D-T4, T2, and rT3. Serial studies performed on different days of chick embryogenesis demonstrated a rapid and significant decrease of the erythrocyte nuclear T3 receptor. On Day 5, the number of T3 binding sites was maximal at 1600 +/- 100 per nucleus. The number declined steadily until, by Day 20, it had reached about 60 +/- 10 sites/nucleus. RBC from adult and baby chickens had less than 1% as many binding sites as those from Day 5 embryos. There was no significant change in the affinity of the sites (Kd approximately equal to 20 pM at 37 degrees C). The reason for the loss of T3 binding sites during embryogenesis is not known. Since the plasma level of the TH increases during embryogenesis, this may reflect down regulation. Another possibility is that the change in erythrocyte population which occurs during this period involves production of erythrocytes which contain fewer T3 binding sites.

Animals↗
PubMed1987

Placental transfer of non-esterified fatty acids in normal and diabetic pregnancy.

The placental transfer of non-esterified fatty acids, predominantly in the direction of mother to fetus, is regulated on a gross scale by the transplacental non-esterified fatty acid gradient. This is maintained by fetal liver lipid uptake and by enhanced lipolysis of circulating triacylglycerol in the pregnant mother. It is also dependent upon maternal placental blood flow, which is reduced in diabetes, upon the fetal umbilical blood flow, upon maternal and fetal albumin concentrations and upon intratrophoblastic fatty acid binding protein, which appears to be altered in diabetes. Circulating maternal triacylglycerols also directly contribute non-esterified fatty acids to the fetus by intraplacental hydrolysis and the hypertriglyceridaemia associated with maternal diabetes, in concert with changes in lipase levels will enhance maternal to fetal lipid flux.

Animals↗
PubMed1987

The interrelationships between circulating maternal esterified and non-esterified fatty acids in pregnant guinea pigs and their relative contributions to the fetal circulation.

The relative contributions of esterified and non-esterified fatty acids to placental lipid transfer were estimated in 7 pregnant guinea-pigs. The fetal side of the placenta was perfused in situ whilst a constant infusion of a mixture of [3H]triacylglycerol emulsion (Intralipid) and [14C]non-esterified fatty acid was given i.v. to the anaesthetised mother. Considerable interconversion of the lipid moieties circulating in the mother was observed. Metabolic turnover rates of triacylglycerol and non-esterified fatty acid were found to be 14.6 mmol/day and 55 mmol/day respectively. No intact triacylglycerol was found to cross the placenta from the mother. Relatively more [3H]non-esterified fatty acid than [14C]non-esterified fatty acid was found in the perfusion fluid when compared with simultaneous circulating maternal levels of these non-esterified fatty acids indicating hydrolysis and direct transfer of [3H]triacylglycerol within the placental tissue. This hydrolysis resulted in the transfer of approximately 0.2 mmol non-esterified fatty acid/day across each placenta at this gestational age (53 days). This is in contrast to the transfer of circulating maternal non-esterified fatty acids, these can be calculated to give a mother to fetus unidirectional transport value of 3.62 mmol/day/placenta, but the total maternal to fetal flux taking into account back transfer to the mother is 1.26 mmol/day/placenta. Results from simultaneous carotid artery and uterine vein samples showed that approximately 40% of the maternal arterial triacylglycerol is removed during a pass through the uterine bed, but the majority of the triacylglycerol re-emerges in the uterine vein as non-esterified fatty acids, and masks the uterine vein uptake of circulating maternal non-esterified fatty acid. The uterine vein non-esterified fatty acid concentration is highly dependent upon levels of circulating maternal triacylglycerols and apparent uterine bed production of non-esterified fatty acid occurs when maternal triacylglycerols are high relative to non-esterified fatty acids.

Animals↗
PubMed1985

Antiserum to rat growth hormone (GH)-releasing factor suppresses but does not abolish antisomatostatin-induced GH release in the rat.

Injection of SRIF antiserum (oA-SRIF) increases serum GH and TSH levels in urethane-anesthetized rats. These responses require an intact hypothalamus with endogenous GH-releasing factor (GHRF) or TRH, respectively. We examined whether pretreatment of rats with an antiserum against rat GHRF (oA-rGHRF) would abolish the GH response to oA-SRIF, since anti-TRH serum has been shown to abolish TSH response to oA-SRIF. Prior injection of oA-rGHRF reduced oA-SRIF-induced GH response in a dose-related manner in a dose up to 1 ml antiserum, but failed to produce any further suppression at higher doses. The maximum suppression of the GH response was approximately 50%. oA-rGHRF also suppresses basal GH levels significantly. On the other hand, oA-rGHRF completely abolished the GH-releasing activity of 1 microgram synthetic rGHRF when incubated for 30 min at room temperature before injection. The results suggest two conclusions: 1) 43-residue rGHRF is a physiological regulator of both basal and stimulated GH release; 2) failure of oA-rGHRF to completely abolish the GH response to oA-SRIF suggests the presence of other physiological GHRFs in the rat.

Animals↗
PubMed1985

Lipid chain length alterations during placental transfer in the guinea pig.

Using an in situ perfusion of the fetal side of the guinea-pig placenta the modification of a non-esterified fatty acid during transfer across the placenta was investigated. Simultaneous constant infusions of [9,10(3)H] palmitic acid and [1-14C] palmitic acid (3 animals) or [9,10(3)H] and [6-14C] palmitic acids (3 animals) or [9,10(3)H] and universal [14C] palmitic acids (3 animals) were given to the mothers and blood samples and perfusion fluid collected over 90 min in each experiment. When expressed as a ratio of perfusion fluid/maternal plasma radioactive counts, no difference between [3H] isotopes results were found for the 3 triplets of experiments. However significant differences were found between the [14C] isotope ratios. More radioactive lipid was found in the perfusion fluid when the label was positioned away from the C1 terminal of the fatty acid chain, i.e. the ratios were [1-14C] less than [6-14C] less than [9,10(3)H] less than universal [14C] palmitic acid. It was concluded that this indicates release of partially oxidised fatty acid products from the fetal side of the placenta, and it was speculated that this partial oxidation takes place in placental peroxisomes.

Animals↗
PubMed1984

Increase in 3,5,3'-triiodothyronine (T3)-binding sites in tadpole erythrocyte nuclei during spontaneous and T3-induced metamorphosis.

The change in T3-binding sites in larval and adult type red blood cell (RBC) nuclei during metamorphosis was studied with the use of Scatchard plots. The number of binding sites per nucleus or the maximum binding capacity (MBC) in the larval type RBC (containing larval hemoglobins) increased from 240 at stage X to 410 at stage XVIII. The apparent Kd also increased from 170 pM at stage X to 260 pM at stage XVIII. At stages XX-XXI, adult type RBCs (containing adult hemoglobins) accounted for 22% of the RBC population. At stage XXII, adult RBCs increased to 54%. In the separated larval and adult RBCs from stage XXII, obtained by Percoll gradient centrifugation, the MBC in larval RBCs had increased to 930 sites/nucleus, a 4-fold increase over stage X, with a Kd of 760 pM; adult RBCs had 1150 sites/nucleus and a Kd of 1530 pM. In contrast, when T3 binding was measured in the whole RBC population from stage XXII tadpoles, the MBC and Kd in larval and adult RBC were estimated at 780 sites/nucleus with a Kd of 640 pM and 1200 sites/nucleus with Kd of 2300 pM, respectively. After metamorphosis, the larval RBCs disappeared and were replaced by adult RBCs. The MBC in adult RBC had declined to 350 sites/nucleus at stage XXV (froglet). The Kd of adult RBC decreased to 790 pM at stage XXV. When stage XVII tadpoles were given a single injection of T3, a 2-fold increase in MBC and Kd was observed after 14 days at 20 C. The values observed for T3-treated animals (870 sites/nucleus with a Kd of 660 pM) were close to the values for the larval RBCs at stage XXII in spontaneous metamorphosis. The MBC and apparent dissociation constant of control animals (400 sites/nucleus; Kd of 270 pM) were almost the same as at stage XVIII in spontaneous metamorphosis. Treatment with PRL (10 micrograms/10 g tadpole every 2 days) had no effect on the T3-binding sites of RBC nuclei. This dose is adequate to stimulate tail fin growth and inhibit hind limb growth. The same dose of PRL did not affect the T3-induced increase in the MBC and Kd of the T3-binding sites. The results are discussed in terms of the positive regulation of the number of T3 receptors by thyroid hormones. The metamorphic response in amphibia appears to require an increase in the number of T3-binding sites (Receptor Induction).

Animals↗
PubMed1984

Contribution of circulating maternal lipids to fetal tissues in the guinea pig.

Using a constant infusion of [1-14C] palmitic acid into 7 late pregnant guinea-pigs the contribution of circulating maternal lipid to the fetuses was assessed. Within the mother plasma radioactivity was found mainly in free fatty acid with only a small amount circulating as triacylglycerol. In contrast in the fetal plasma [14C] was distributed as one-quarter free fatty acid and three-quarters triacylglycerol, with total [14C] levels being four-fold higher than in the maternal plasma after 160 min of infusion. [14C] Triacylglycerol was found in the fetal liver within 10 min of commencing infusion and levels rose to 12 times the levels of [14C] triacylglycerol in the fetal plasma (per/g or ml) by 100-160 min. [14C] Distribution into the lipid moieties of fetal tissues was found to change with time. By 100-160 min the distribution was: liver, triacylglycerol 83%, phospholipid 7%, free fatty acid 4%; fat, triacylglycerol 80%; heart, triacylglycerol 38%, phospholipid 33%, free fatty acid 9%; kidney, triacylglycerol 15%, phospholipid 58%, free fatty acid 10%; muscle, triacylglycerol 70%, phospholipid 10%, free fatty acid 10%; lung, phospholipid 75%; brain, phospholipid 80%. It was concluded that free fatty acid transferred from the mother contributes substantially to fetal lipids in late gestation in this species.

Animals↗