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Biomedical subjects

S MacPhail

Publications and source records attributed to S MacPhail.

11 recordsLinked to original sources

Laparoscopic radical nephrectomy in first-trimester pregnancy.

We present a case of a 30-year-old pregnant woman with renal cell carcinoma who underwent successful laparoscopic radical nephrectomy at 11 weeks of gestational age. The remainder of the pregnancy was uncomplicated, and the patient gave birth to a healthy baby boy at term. Although previous cases of successful nephrectomy performed in pregnancy for renal cell carcinoma have been reported, we believe this is the first case in which it has been performed laparoscopically. We suggest that when the expertise is available, laparoscopic nephrectomy is a safe alternative to open surgery, with the additional benefits of minimal access surgery.

Adult↗

A cost analysis of untoward incidents in a medium secure unit.

All untoward incidents perpetrated by 36 patients--residents in a medium-secure hospital--over a period of six months were examined using a prospective design. Demographic and psychiatric details of patients involved in incidents were compared with those of patients not involved in incidents. Financial costs associated with incidents were calculated. A minority of patients were found to be responsible for the majority of incidents. Patients detained under criminal sections of the Mental Health Act 1983 were involved in disproportionately more incidents than their civil section counterparts. The female patients involved in untoward incidents all had a diagnosis of personality disorder and were over-represented in the number of incidents. However, most of the financial burden of untoward incidents was incurred by those incidents perpetrated by male patients. Likewise, although patients detained under the legal category of psychopathic disorder were involved in a higher number of incidents, higher costs were associated with incidents perpetrated by patients detained under the category of mental illness.

Antisocial Personality Disorder↗

Low concentrations of nitroimidazoles: effective radiosensitizers at low doses.

PURPOSE: There have been various reports that nitroimidazole radiosensitizers are less effective modifiers of radiation response in the clinically relevant x-ray dose regions (0-4 Gy) than they are at doses used in classical in vitro experiments. Our studies at low concentrations of etanidazole led us to question this generalization, and our purpose was to further investigate low concentrations at low doses, using the microscopic location of cells to facilitate these experiments. The observations are compared with data on these drugs in the literature using other methods and systems. METHODS AND MATERIALS: Survival of V79 cells after irradiation in hypoxia +/- drug at various concentrations was assessed using the Cell Analyser (DMIPS) for low doses, in comparison with the standard clonogenic assay (higher doses). Enhancement ratios (ERs) were calculated at 80% and 2% survival, respectively. RESULTS: Etanidazole (SR-2508) consistently gave higher ERs at low doses (measured at 80% survival) than at high doses (survival 2%), when cells were exposed to drug concentrations below approximately 2 mM (e.g., at 1 mM, ER80% = 2.2, ER2% = 1.8 in CHO cells after 1 h preincubation at 37 degrees C). Preincubation of cells for 1 h or 15 min at 37 degrees C with etanidazole prior to irradiation increased the ERs at high and low doses but did not change the "cross-over" behavior (ER80% > ER2% at low concentrations, ER2% > ER80% above 2 mM, regardless of pretreatment at 37 degrees C or cell line, CHO and V79 cells), whereas the 5-nitroimidazole nimorazole consistently gave the same ERs whether determined at high or low radiation doses (e.g., at 1 mM, 1 h preincubation at 37 degrees C ER80% = ER2% = 1.3). This crossover behavior also occurred after irradiation/preincubation at 0 degrees C. The 2-nitroimidazole predecessor, misonidazole, shows the same cross-over behavior. CONCLUSION: Two nitroimidazoles at low concentrations appear to be as effective sensitizers (or better) at low doses (80% S); at high doses (2% S).

Animals↗

Sodium-lithium countertransport kinetics in normal and hypertensive human pregnancy.

Erythrocyte sodium-lithium countertransport activity is increased in a subgroup of patients with essential hypertension but activity also rises temporarily during normal pregnancy. It is not known if the mechanism of raised activity is the same in both of these situations. Standard sodium-lithium countertransport activity and its kinetic characteristics (sodium affinity and maximum velocity) were measured in 15 women with a normal pregnancy. The mechanism of raised sodium-lithium countertransport activity was an increase in maximum velocity. There was no change in sodium affinity. This contrasts with essential hypertension where the mechanism is increased sodium affinity. Sodium-lithium countertransport activity was also measured in 14 primigravidae whose pregnancies were complicated by hypertension, and mean activity was not significantly higher than in normal pregnancy. However, six women had increased sodium affinity suggestive of essential hypertension and a different underlying mechanism of hypertension to those with normal sodium affinity. Prospective measurement of sodium-lithium countertransport kinetics may lead to a better understanding of the pathophysiology of hypertension in pregnancy.

Adult↗

Pregnancy induced hypertension and sodium pump function in erythrocytes.

OBJECTIVE: To determine if erythrocyte sodium pump function is altered with the onset of pregnancy induced hypertension. DESIGN: A prospective descriptive study. SUBJECTS: Thirty-two primigravid women with pregnancy-induced hypertension (17 had proteinuria) and 32 gestation-matched normotensive primigravid pregnant women were studied and measurements repeated 20 weeks after delivery. INTERVENTION: Erythrocyte sodium, ouabain-sensitive sodium flux and the sodium pump rate constant were measured in whole blood and the maximum velocity and sodium affinity of the sodium pump were measured in vitro. RESULTS: Blood pressure remained higher after delivery in the women who had been hypertensive during pregnancy. In normal pregnancy erythrocyte sodium was decreased, and ouabain-sensitive sodium flux, the sodium pump rate constant and maximum velocity (Vmax) were increased compared with 20 weeks after delivery. In pregnancy-induced hypertension erythrocyte sodium and sodium pump changes were the same as in normal pregnancy. The possibility of a positive association between changes in erythrocyte sodium and in blood pressure was excluded. The rate constant of the sodium pump in blood was related to its Vmax measured in vitro but the relation had greater variance in the hypertensives with 7 of the 32 women having rate constants greater than expected from their Vmax. CONCLUSION: There was no evidence of sodium pump inhibition or a rise in intracellular sodium associated with increased blood pressure in pregnancy. There may have been stimulation of the sodium pump by a plasma factor in some hypertensive women.

Adult↗

The prediction of fetal compromise and acidosis by biophysical profile scoring in the small for gestational age fetus.

In a prospective blind study, 133 fetuses suspected of being small for gestational age (SGA), defined as an estimated fetal weight less than the 10th centile for gestation, were monitored by weekly biophysical profile assessment. Perinatal outcome was assessed by umbilical venous blood pH estimation and compared with the profile score determined within seven days of delivery. The positive and negative predictive values of the full biophysical profile score were not significantly better than combinations of two or three of the individual components in this group of fetuses. The use of amniotic fluid volume, non-stress testing and either fetal movement or breathing offers an acceptable alternative to full biophysical profile assessment in the fetus suspected of being small for gestation.

Acidosis↗

Interaction of platinum drugs with clinically relevant x-ray doses in mammalian cells: a comparison of cisplatin, carboplatin, iproplatin, and tetraplatin.

Whereas the interaction between radiation and platinum complexes has never been pronounced in radiobiological experiments (to 30 Gy in mammalian cells), there have been reports of interest in this combination in the clinic, where fractionated doses of approximately 2 Gy are used. Our studies on the marked interaction in hypoxia at the 80% survival level (1-2.5 Gy) with cisplatin have been extended to second generation platinum drugs of clinical interest. The studies in the lower radiation dose region have been facilitated by the use of the cell analyzer DMIPS to identify individual cells and follow them microscopically to assess for clonogenic ability. Chinese hamster V79 cells were used, which were exposed to drug for 1 hr prior to irradiation in hypoxia (or air). None of the drugs give an enhancement ratio (ER) greater than 1.3 in the high radiation dose region, whereas all can produce ER80% (ER calculated at iso-survival of 80%) of 2 or higher at low doses in hypoxic cells. The enhancement of radiation kill in oxic V79 cells (ER's to 1.1 at 1-2% S) disappears at low doses (ER80% = 1.0) except for tetraplatin, where a moderate ER80% (to 1.64) was measured. Comparison of the hypoxic interaction on a concentration basis suggests that cisplatin is the best drug at low x-ray doses and low concentrations, but the interaction reaches a plateau at ER80% approximately 2.0. Tetraplatin continues to give better interaction with increasing concentration (up to ER80% = 3.7 at 25 microM). Interaction of radiation with the less toxic drugs, iproplatin and carboplatin, used at around 100 microM can be improved by longer exposure times prior to irradiation. Comparison on the basis of toxicity, for which the plating efficiency was used, suggests that cisplatin gives a better interaction than the three newer drugs for a given level of toxicity in hypoxic V79 cells.

Animals↗

The effect of blood transfusion on the immune response and renal graft survival in the Chacma baboon.

There is uncertainty about the role of blood transfusion of potential kidney graft recipients. In this study baboons were transfused under conditions mimicking the clinical situation and then callenged with kidney allografts. Eleven baboons were transfused 10 times with blood from different donors. Lymphocytotoxic antibodies induced against the separated B and T cells of a panel of 12 normal baboons were as follows: B-T- 30%; B+T- 3%; B-T+ 1% and B+T+ 66%. Kidney transplantations were done from donors against which the recipients had negative B-T- cross-matches. Median allograft survival time (MST) of 12 days in this group, which was immunosuppressed with azathioprine and prednisolone, was not prolonged when compared with non-transfused, immunosuppressed animals (MST 12 days). A second group of 14 animals was screened for cytotoxins after each transfusion against a panel of five to six normal baboons. The antibody profile of 80 combinations tested after three transfusions was as follows: B-T- 65%; B+T- 16%, B-T+ 0% and B+T+ 19%. Transplantation was with donors against which the transfused recipient had formed B+T- antibodies. Kidney allograft survival was again not prolonged (MST 13 days) but the mean serum creatinine level 8 days after transplantation was significantly lower than that observed in the first group.

Animals↗