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Biomedical subjects

M L Nicholson

Publications and source records attributed to M L Nicholson.

At least 199 records · Page 11Linked to original sources
PubMed1989

Localization of lower gastrointestinal bleeding using in vivo technetium-99m-labelled red blood cell scintigraphy.

Technetium-99m-labelled red blood cell scintigraphy was used in the investigation of 41 patients with major rectal haemorrhage. Red cells were labelled in vivo with technetium-99m pertechnetate and serial scans (0-36 h) were taken using a large field gamma camera. Twenty-two men and 15 women, mean age 71.3 years (range 32-91 years), and four children were studied. Forty-three scans were performed in all and there were 31 positive and 12 negative results. In each case the accuracy of the scan in localizing the bleeding site was checked either by independent investigations or at laparotomy. A definite bleeding site was identified in 30 cases and red cell scintigraphy correctly localized 29 of these (sensitivity 97 per cent). In the remaining 13 cases a bleeding site was not identified by any of the independent investigations and in this group there were two false positive scans (specificity 85 per cent). The investigation had a high predictive value when both positive (94 per cent) and negative (92 per cent). These data suggest that technetium-99m-labelled red cell scintigraphy should be used more widely in the investigation of patients with suspected lower gastrointestinal haemorrhage.

Adult↗
PubMed1989

Combined abdominal hernia repair and continuous ambulatory peritoneal dialysis (CAPD) catheter insertion.

Out of a series of 290 surgically inserted continuous ambulatory peritoneal dialysis (CAPD) catheters, 19 patients had 24 abdominal hernias repaired at the same time as CAPD catheter insertion. All catheters were used immediately after our normal postoperative break in protocol. There were no fluid leaks from the hernia repair site but 3 catheters failed due to complications unrelated to the hernia repair. CAPD technique survival was not adversely affected in the hernia repair group.

Catheterization↗
PubMed1988

Pancreatic abscess: results of prolonged irrigation of the pancreatic bed after surgery.

The mortality from pancreatic abscess may approach 70 per cent and the survivors often require repeated operations to debride the pancreas and to drain recurrent abscesses. We report the results of prolonged irrigation of the pancreatic bed after surgical débridement in 11 patients. Surgery was performed at an average of 17 days (range 8-25 days) after the onset of symptoms. The pancreatic slough was thoroughly debrided and 2-6 large drains were placed in the pancreatic bed. Irrigation with saline or Diaflex solution (2-6 l/day) was started after 2 days and continued for a mean of 25 days (range 5-54 days). There were three deaths (27.3 per cent) after surgery: one of these patients required reoperation and packing for massive postoperative haemorrhage and all three had some evidence of persisting sepsis at autopsy. Prolonged irrigation of the pancreatic bed after surgical débridement may reduce mortality and the need for repeated drainage procedures in patients with pancreatic abscess, but the detection and treatment of persisting sepsis remains the major problem.

Abscess↗
PubMed1988

Intra-operative inflow resistance measurement: a predictor of steal syndromes following femoro-femoral bypass grafting.

Although femorofemoral bypass grafting was originally used only as a method of limb salvage, it is now used increasingly in patients with claudication. If this trend is to be supported, the haemodynamic consequences of the operation must be carefully assessed. Fifteen patients undergoing femorofemoral grafting were studied prospectively by intra-operative measurement of the inflow resistance (IR) of the donor iliac segment. Three groups were identified by this technique. Patients with an IR less than 0.05 (n = 8) were uncomplicated; those with an IR greater than or equal to 0.05 but less than 0.10 (n = 5) developed a subclinical steal syndrome; and those with an IR greater than 0.10 (n = 2) developed a clinical steal syndrome. High initial IR values were corrected at the time of surgery in two cases. This study demonstrates that steal syndromes can occur after femorofemoral grafting and that the cause is an unmasking of previously unrecognized disease in the donor arterial segment. The measurement of IR allows the prediction of steal syndromes and their correction at the time of surgery. Direct haemodynamic studies are recommended, especially as the availability of balloon angioplasty has made inflow disease amenable to treatment.

Aged↗
PubMed1985

A study of the position of the mandibular foramen in the adult human mandible.

Eighty dry, adult human mandibles of East Indian ethnic origin and bilateral eruption of third molar teeth were examined to measure the location of the mandibular foramen. The position of the foramen was found to be variable. However, the foramen was predominantly located at the anteroposterior midpoint of the ramus halfway between the mandibular notch and the lower surface of the mandible and two thirds of the way down a line joining the coronoid process to the angle of the mandible. In the majority of the mandibles studied the foramen was located below the occlusal surfaces of the molar teeth. It is concluded that the marked variability in the position of the mandibular foramen may be responsible for an occasional failure to block the inferior alveolar nerve.

Humans↗
PubMed1983

Development of resistance to glucocorticoid hormones during rat thymus cell differentiation: proteins associated with emergence of the resistant state.

Two-dimensional gel electrophoresis was used to detect [35S]methionine-labeled newly synthesized proteins from both glucocorticoid-sensitive and -resistant thymus cells. Normal thymic lymphocytes were taken for the sensitive population; the resistant population was composed of medullary thymocytes obtained from rats treated with dexamethasone (10 mg per kg body weight per day) for 3 days. When the proteins from glucocorticoid-sensitive cells are compared to those from resistant cells, the majority of the congruent to 1000 proteins were similar; however, 18 proteins were different. There were 13 proteins that increase in the resistant state and 5 that decrease. One major change is the appearance of a new protein with a molecular weight of about 36,000 in resistant rat thymocytes. This protein is in the same position on the gels as is a protein found in corticosteroid-resistant P1798 mouse lymphosarcoma cells but not in the corticosteroid-sensitive cells. Control experiments indicate that the protein differences are neither components of fibrous tissue associated with the cells nor components of blood. Changes in the synthesis of a common set of proteins that are characteristic of the hormone-resistant state suggest that the presence of one or more of these proteins may confer resistance. The appearance of a single protein in two distinctly different cell types suggests it as the most likely candidate. This coincidence further suggests that tumor cells become resistant by selection of those cells that can express the same gene product as do those normal cells as they undergo immunological commitment.

Animals↗
PubMed1981

Cellular and biochemical actions of adrenal glucocorticoid hormones on rat thymic lymphocytes.

The molecular, biochemical, and cellular effects of adrenal glucocorticoid hormones on thymic lymphocytes are reviewed, with emphasis on their relationship to the growth suppressive and lethal actions that occur in lymphoid tissues when glucocorticoids are administered to the whole animal. The data support the hypothesis that the hormonal inhibition of growth and development is a consequence of its ability to suppress cellular energy production, causing the cells to behave as though they were in a more stringent environment. Slight changes in ratios of adenine and guanine nucleotides appear to account for the reordering of metabolic priorities that occurs, with processes related to growth and development curtailed in favor of those more essential to immediate cell survival. The lethal glucocorticoid actions appear to be the result of the operation of separate mechanisms (unrelated to energy metabolism) that lead to lethal attack at the level of the nuclear membrane. Resistance to the lethal effects appears to occur via the selection (in the case of cancer cells where the animal or patient is undergoing chemotherapy with glucocorticoids) or the normal development (in the case of immunologically noncommitted thymocytes progressing to immunologically committed ones) of cells with hardier membranes. This progression is associated with a change in a few cellular proteins. One such protein appears identical in both kinds of cells, offering itself as a candidate for an intracellular mechanism conferring resistance. Evidence is also presented for the appearance of hormone-induced proteins that could be metabolic regulators that mediate the individual cellular and biochemical actions of glucocorticoids. It is proposed that toxins could alter cellular metabolism through mechanisms similar to those utilized by steroid hormones, or possibly alter the sensitivity of cells to steroids, or vice versa.

Adenosine Triphosphate↗
PubMed1981

Proteins associated with emergence of the resistance to lethal glucocorticoid actions in P1798 mouse lymphosarcoma cells.

Two-dimensional gel electrophoresis was used to detect [35S]methionine-labeled newly synthesized proteins from corticosteroid-sensitive and corticosteroid-resistant P1798 mouse lymphosarcoma cells. When the protein patterns from corticosteroid-sensitive cells are compared with those from highly resistant cells, they are very similar except for seven changes. One of the most obvious changes is the appearance of a new protein with a molecular weight of about 36,000 in highly resistant cells. There are also four other proteins that increase in the resistant state, as well as two that decrease. The control experiments indicate that protein differences are present to approximately the same degree when the sensitive tumor is carried in adrenalectomized animals, suggesting that the protein differences are not induced by endogenous glucocorticoids. Other experiments show that the protein differences are neither components of the small amounts of fibrous tissue that are associated with the cells nor components of blood. These results suggest that resistance of the tumor cells to glucocorticoid killing in vivo could be related to the relative rates of synthesis of a few proteins.

Adrenalectomy↗
PubMed1979

Independence of the lethal actions of glucocorticoids on lymphoid cells from possible hormone effects on calcium uptake.

We have examined the possibility that hormone-induced increases in calcium uptake might initiate the lethal actions of glucocorticoids in two types of lymphoid cells. Hormone-induced increases in nuclear fragility are used as the measure of hormone action, since in both rat thymus cells and in mouse P1798 lymphosarcoma cells increased nuclear fragility (the inability of nuclei to survive lysis of the cells by hypotonic shock) precedes other indices of cellular deterioration by several hours. In the case of the tumor cells, those from corticosteroid-sensitive lines are less able to withstand incubation in vitro than resistant cells. Such differences in cell survival are predicted both by earlier changes in nuclear fragility and also by differences in calcium uptake. However, there is no detectable early glucocorticoid effect on calcium uptake that precedes or coincides with the substantial hormone-induced increases in nuclear fragility that develop in the sensitive cells by 2 h. In rat thymus cells the absence of calcium in the medium does prevent some of the increase in nuclear fragility and cell disintegration that occurs spontaneously during incubation in vitro. Nevertheless, when cells are exposed to hormones the glucocorticoid effect on nuclear fragility develops in the absence of calcium and is similar in magnitude to that seen in the presence of calcium. We conclude that calcium seems to enhance the spontaneous deterioration of lymphoid cells, and there is a large increase in calcium uptake that occurs as cells deteriorate. It nevertheless seems unlikely that hormone-induced changes in calcium uptake initiate the lethal actions of glucocorticoids. The data also support a proposal made earlier [2] that resistance to glucocorticoids in tumor cells may develop by the selection of cells with hardier membranes.

Animals↗
PubMed1978

Effect of glucocorticoid hormones in vitro on the structural integrity of nuclei in corticosteroid-sensitive and -resistant lines of lymphosarcoma P1798.

Exposure of rat thymus cells to glucocorticoids leads to a decreased ability of nuclei to survive the lysis of whole cells by hypotonic shock. In this study, a similar glucocorticoid-induced increase in "nuclear fragility" was found in both corticoid-sensitive and -resistant lines of P1798 mouse lymphosarcoma cells. In corticoid-sensitive cells a small increase in nuclear fragility is seen after a 2-hr exposure to cortisol (10(-6) M); by 3 hr it is 20 to 40% above control values. This effect appears to be a specific glucocorticoid response. Both cortisol and dexamethasone at 10(-7) M produce an effect, 10(-6) M testosterone is inactive, and cortexolone, which binds to glucocorticoid receptors, reduces the effect. Cycloheximide, at concentrations that inhibit protein synthesis, also blocks this effect. While the corticoid-resistant line also demonstrates an effect of similar magnitude, it requires a much longer exposure to the hormone (6 hr). Distinct differences in the "hardiness" of the two cell lines (nuclei of the corticoid-resistant line are less fragile) measurable in the absence of hormones appears to account for the differential susceptibility to steroids. On this basis a new theory of resistance is advanced where the emergence of resistance is related to structural differences in the cells.

Adrenal Cortex Hormones↗
PubMed1977

Effects of peptide anabolic hormones on growth of myoblasts in culture.

The roles of growth hormone and somatomedin in stimulating muscle cell proliferation were investigated in a series of experiments on myoblast growth in culture. At levels 100 times normal circulating concentrations, neither growth hormone nor insulin stimulated growth of rat muscle cells in serum-free medium. In contrast, Temin's Multiplication Stimulating Activity (MSA), a close biological and chemical analog which served as a somatomedin surrogate in this study, was active at concentrations corresponding to the reported circulating levels of the somatomedins; MSA gave consistent stimulation of myoblast proliferation, protein accumulation, and [3H]thymidine incorporation by rat myoblasts and by Yaffe's L6 myogenic cell line. (The unreliability of [3H]thymidine in corporation as a quantitative assay for mitogenic activity is illustrated.) Addition of insulin at physiological concentrations and at the very high levels often used to stimulate cell growth did not enhance the effects of MSA on myoblast proliferation; effects were barely additive. We interpret these results to support earlier indications from studies on diaphragm muscle that the somatomedins are physiologically important mediators of the growth-promoting actions of growth hormone in muscle.

Animals↗
PubMedDate not supplied

Prograf produces a molecular environment favoring antifibrosis, an effect reversed by the addition of rapamune.

Rapamune, an inhibitor of the mammalian target of rapamycin, exhibits antiproliferative actions and is increasingly used as adjuvant therapy with calcineurin inhibitors. This study investigated the effect of Rapamune on functional and molecular markers in a rat model of calcineurin inhibitor-induced graft dysfunction. Prograf (6 mg), with or without addition of Rapamune (1 mg), was administered to salt-depleted male rats (n = 6/group). Urinary protein excretion and serum creatinine were measured. Rats were culled at 28 days, and messenger RNA expression of TGF-beta, MMP-2, MMP-9, TIMP-1, and collagen III was evaluated with reverse transcriptase polymerase chain reaction. Serum creatinine increased with Prograf (P = .01), but not Rapamune (P = .69) treatment, compared to controls at 28 days. The combination of Rapamune and Prograf produced a rise in serum creatinine at 7 (P = .007) and 14 (P = .01) days, but this was not observed at later time points. Urinary protein excretion was unaltered by any drug or combination. While confirming a synergistic effect of Rapamune and calcineurin inhibitors on renal function, these results suggest that sole therapy with Prograf produces inhibition of fibrotic gene expression. Rapamune alone has no deleterious effect on gene expression but addition of Rapamune cancels out the beneficial effects of Prograf.

Animals↗