Search

We performed a retrospective study of 90 consecutive cases with inoperable carcinoma of the oesophagus treated with definitive chemoradiation at a single cancer centre between 1995 and 2002. For the last 4 years, 73 patients have received therapy according to an agreed protocol. This outpatient-based regimen involves four cycles of chemotherapy, cycles 3 and 4 given concurrently with 50 Gy external beam radiotherapy (XRT) delivered in 25 fractions over 5 weeks. Cisplatin 60 mg m(-2) day(-1) is given every 3 weeks together with continuous infusional 5-fluorouracil 300 mg m(-2) day(-1), reduced to 225 mg m(-2) day(-1) during the XRT. In all, 45 (50%) patients suffered one or more WHO grade 3/4 toxicity, grade 3 in 93% cases. Patients received more than 90% of the planned chemoradiation schedule. The median overall survival was 26 (15, >96) months, 51% (41, 64) and 26% (13, 52) surviving 2 and 5 years, respectively. Advanced stage, particularly T4 disease, was associated with a worse prognosis. Patients considered not suitable for surgery for reasons other than their disease, mainly co-morbidity, had a significantly better outcome, median survival 40 (26, >96) months, 2- and 5-year survivals 67% (54, 84) and 32% (13, 79), respectively (P

The most common reason for women being referred to colposcopy clinics is an abnormal smear suggesting pre-cancerous change within the cervix. It has been demonstrated that in women with low-grade lesions, smoking cessation led to a reduction in size of the cervical lesion over a 6-month period. Smoking is also recognised as an independent risk factor for treatment failure of cervical intraepithelial neoplasia. As 'stop smoking' services have become an integral part of the colposcopy clinic at St John's Hospital, Livingston, a national survey was undertaken. The aim of the survey was to establish what smoking cessation information, advice and support is available in colposcopy clinics throughout Scotland, and if staff had attended standardised training on raising the issue of smoking. The study demonstrated that 52% of colposcopy clinics in Scotland always establish smoking status but only 37% of clinics discuss the benefits of smoking cessation in relation to abnormal cervical smears. There was inaccurate and inconsistent written and verbal advice given on the benefits of cessation and whether women should cut down or stop smoking completely. The majority of staff had not attended standardised training on how to raise the issue of smoking and very few clinics have established referral pathways for smoking cessation support.

Aims Paclitaxel, a radiosensitiser, has significant activity in oesophageal cancer. We aimed to conduct a feasibility study of preoperative chemoradiation using paclitaxel, cisplatin and 5-fluorouracil (5-FU). Materials and methods Sixteen eligible patients were enrolled. Infusional 5-FU, paclitaxel and cisplatin were given for 6 weeks before and concurrent with radiation. Conformal radiotherapy was delivered in two phases (45Gy in 25 fractions). Results A total of 62.5% of the patients experienced Grade 3–4 toxicities, 50% required admission; one patient died during the neo-adjuvant phase. Twelve (75%) patients had oesophagectomy, and two (12.5%) died after surgery. Pathological complete remission (PCR) and minimal residual disease were observed in 25% (95% CI 0.5–49.5%) and 18% (95% CI 0–38%) of patients, respectively, who underwent surgery. The median survival was 39.7 months (95% CI 15, not reached); 1-, 2-, 3-, and 4-year survivals were 75% (95% CI 56.5–99.5), 56.3% (36.5–86.7), 50% (30.6–81.6), and 50% (30.6–81.6), respectively. Conclusion Paclitaxel, cisplatin and 5-FU (TCF)-chemoradiation is an active regimen; the current dose schedule tested is associated with unacceptable toxicity, and cannot be recommended for routine clinical use.

We examined the effects of the synthetic matrix metalloproteinase inhibitor batimastat (BB-94) on lung colonization and spontaneous metastasis of a rat mammary carcinoma, HOSP.1P. This tumor expresses both latent and active forms of the matrix metalloproteinases MMP-2 and MMP-9, although the former, as in human breast cancer, is the most prominent. Administration of batimastat (6 x 30 mg/kg i.p.) inhibited by up to 80% both the number and median weights of HOSP.1P lung colonies following i.v. inoculation of cells. This implies an effect both on seeding efficiency and subsequent tumor development. In spontaneous metastasis assays, limited treatment with batimastat (commencing when s.c. tumors were established and continuing until 5 or 14 days after their surgical removal) significantly inhibited lung metastasis but had little effect on lymphatic metastasis. However, when treatment was initiated 2 days prior to surgery and continued until day 70, 100% of animals survived to day 120 when there was no evidence of metastatic disease. All control animals (n = 25) in two separate experiments died before day 100 with lymphatic, lung, and extrapulmonary metastases. Taken together, these data suggest that lymphatic dissemination by HOSP.1P tumor cells is less susceptible to inhibition by batimastat than vascular invasion, but that long-term treatment can effectively prevent the outgrowth of putative micrometastases in both lymph nodes and lungs, allowing sustained tumor-free survival.

The enzyme carboxypeptidase G2 (CPG2) was conjugated to the rat IgG2a monoclonal antibody (mAb) ICR12, which recognizes the external domain of the human c-erbB2 protooncogene product. The conjugate retained antigen-binding and enzyme activity. Radiolabeled conjugate localized efficiently and stably to MDA MB 361 breast carcinoma xenografts, which overexpress the c-erbB2 gene product p185. Radiotracer determinations and plasma enzyme activity studies in nu/nu mice gave conjugate blood clearance rate half-lives of approximately 4 days. In separate antibody-directed enzyme prodrug therapy regimes, one dose of the 4-[(2-chloroethyl)(2-mesyloxyethyl)amino]benzoyl-L-glutamic acid prodrug was administered to nu/nu mice bearing established MDA MB 361 tumors (mean volume, 170-260 mm3). In mice which had received ICR12-CPG2 12-14 days previously, sustained dose-dependent tumor stasis or regressions were effected, which in some cases persisted throughout observation periods of up to 90 days. In control mice which had received the isotype-matched irrelevant mAb ICR16-CPG2 conjugate, tumors grew progressively, as did those in mice treated with prodrug alone, or treated simultaneously with ICR12-CPG2 and prodrug at the maximum tolerated dose. Control chemotherapy with conventional drugs proved toxic and induced only minimal growth delays.

Drug-naive schizophrenic patients lacked abnormal involuntary movements. Chronic neuroleptic treatment was associated in 4% of the cases with Tardive Dyskinesia (TD). These findings suggest that schizophrenia, at least in its early stages, is not contributing to the appearance of Tardive Dyskinesia, and also underscore the importance of using the lowest effective neuroleptico dose to reduce the risk of that syndrome.

Fetal cardiorespiratory changes during spontaneous prelabor uterine contractions (called contractures) were studied in 12 chronically catheterized fetal sheep at 120 to 143 days' gestation. During contractures the carcass blood flow increased significantly from 27 +/- 2 (SEM) to 32 +/- 3 ml/min/100 gm. There were no significant changes in combined ventricular output or in blood flow to the umbilical circulation, brain, heart, adrenal glands, gut, kidney, and lung. Fetal arterial blood pressure increased from 57 +/- 2 to 62 +/- 1 mm Hg (p less than 0.001) during contractions. There were no significant changes in fetal heart rate. In the fetal femoral artery during contractures the oxygen content decreased from 6.1 +/- 0.2 to 5.4 +/- 0.2 ml/dl of blood (p less than 0.001), and carbon dioxide tension increased significantly from 44 +/- 0.4 to 45 +/- 0.4 mm Hg (p less than 0.001). The pH did not change. The increase in carcass blood flow during contractures suggests that there was an increase in fetal skeletal muscular activity or tone. An increase in fetal skeletal muscle activity, together with a decrease in uterine blood flow could explain the small decrease in fetal oxygen content that occurs with each contracture. Fetal compression and/or changes from rapid eye movement to synchronized sleep or arousal observed during contractures are possible stimuli causing increased fetal skeletal muscle tone or activity. Since contractures periodically result in neuromuscular activity in the fetus in its protected fluid-filled environment, they may play a key role in fetal neuromuscular development by stimulating "exercising" in the fetus in utero.

Surgical procedures which involve the pregnant uterus are associated with preterm labor contractions in the postoperative period. Because uterine contractions decrease fetal oxygen tension, we investigated the effect of maternal ritodrine infusion on fetal oxygen consumption in catheterized fetal sheep 5 h postoperatively. During ritodrine infusion, uterine activity promptly abated, but the oxygen tension in the umbilical vein and descending aorta decreased. The arterial-venous oxygen content difference, the umbilical blood flow, and consequently, fetal oxygen consumption did not change significantly. We conclude that fetal oxygenation is not improved by eliminating uterine activity with maternal ritodrine infusion in the postoperative period.

Measures of oxygenation in the chronically prepared fetus have shown considerable variation when reported by different investigators despite apparent physiological ‘resting’ conditions. This variation has been compounded by differences in the blood vessels sampled and varying accuracy of biochemical methodology, so was consequently assumed to reflect methodological error and variability. However, development of continuously recording systems for oxygen pressure and hemoglobin saturation has confirmed the continuously varying values of oxygenation. It is the purpose of this review to examine the biological causes and associations of the variations in basal oxygenation.

Forty-six pregnant patients with potential diabetes were studied to compare the use of glucose and a glucose polymer for carbohydrate tolerance testing. The first 26 patients had a glucose tolerance test and a glucose polymer tolerance test in randomized order an average of one week apart. The mean tolerance curves and insulin curves were similar for both agents. Patients preferred glucose polymer to glucose because of a lower incidence of associated nausea. A second group of 20 patients was randomly divided so that patients had two glucose tolerance tests or two glucose polymer tolerance tests an average of one week apart. Comparison of the variability and correlation of the incremental areas under the paired tolerance curves showed that the reproducibility of the glucose polymer tolerance test exceeded that of the glucose tolerance test.

During contractures there are decreases in fetal oxygen tension. In order to determine if there are concomitant changes in fetal oxygen consumption, we calculated the latter during contractures from measurements of the umbilical blood flow and venous arterial oxygen content differences across the umbilical circulation. There were decreases in both the umbilical venous (from 8.8 +/- 0.2 (SEM) to 8.5 +/- 0.2 ml.dl-1, P less than 0.01) and umbilical arterial (5.9 +/- 0.1 to 5.2 +/- 0.2 mg.dl-1, P less than 0.001) oxygen contents. The umbilical venous-arterial oxygen content difference increased from 2.9 +/- 0.1 to 3.3 +/- 0.2 ml.dl-1 (P less than 0.005). Umbilical blood flow was 194.3 +/- 4.5 ml.min-1 kg-1 during relaxation and was unchanged during contractures. Fetal oxygen uptake increased from 5.7 +/- 0.3 to 6.5 +/- 0.4 ml.min-1 kg-1 (P less than 0.005) during contractures. This observation is consistent with our previous speculation that there is increased muscular activity of tone associated with contractures.

Forty-eight of 100 pregnant women received a 100-g (nonfasting) glucose screening test at about 28 weeks' gestation, followed by a 100-g glucose tolerance test. Another 52 received a 100-g (nonfasting) glucose polymer screening test followed by a 100-g glucose polymer tolerance test. Mean plasma glucose one hour after the glucose screening test was significantly lower than after the glucose polymer screening test. A further 178 women received a glucose polymer screening test and a glucose polymer tolerance test (230 in total). These women and the infants they delivered were studied to derive diagnostic criteria for the 100-g glucose polymer tolerance test by correlating maternal carbohydrate tolerance with indexes of neonatal metabolic performance, and to determine an adequate method of screening for carbohydrate intolerance of pregnancy (gestational diabetes). Diagnostic criteria similar to those of O'Sullivan and Mahan were also developed for the glucose polymer tolerance test. These values are up to 5% lower than those recommended by the National Diabetes Data Group (1979) for the 100-g glucose tolerance test.

The EEG examination of 45 patients with vascular headache and 44 patients with tension headache showed abnormal EEG's in 71% of the cases with migraine and 35% of the cases with tension headache. The examination of morphology and topography of alpha-rhythm and driving-effect during photic stimulation showed statistically significant differences between both groups. Applying specific characteristics in the EEG it is possible to differentiate both types of headache.

Hypoxaemia in fetal sheep causes a decrease in vascular resistance of the heart, brain and adrenal gland which results in increased blood flow to these organs. Placental blood flow is maintained. To investigate whether increased beta-adrenergic activity during hypoxaemia is involved in these changes, the effects of propranolol on organ blood flows (using the microsphere method) and other cardiovascular variables were studied during fetal hypoxaemia (50% reduction of fetal haemoglobin saturation) in 5 chronically catheterized fetal sheep at 126 to 130 days of gestation. Beta-blockade during hypoxaemia caused a fetal bradycardia and a 30% drop in cardiac output. Placental and myocardial blood flows fell by 39% and 37% respectively. Total peripheral resistance increased by 35% mainly due to increased fetal placental vascular resistance. Heart and lung vascular resistances increased following propranolol. In 3 similarly catheterized animals, propranolol administered in the absence of hypoxaemia led to a 9% drop in cardiac output and placental blood flow but no redistribution of blood flow to fetal organs. It is concluded that the increased beta-adrenergic activity associated with fetal hypoxaemia limits the negative chronotropic effects of concomitantly increased vagal activity, maintains placental blood flow through its inotropic and chronotropic activity as well as by maintenance of placental vasodilatation and may be one of several factors which increase myocardial blood flow during hypoxaemia.

Axonal transport of acetylcholinesterase (AChE) was measured in the median and sural nerves of a subject who suffered from dystrophia myotonica and in a control subject. It was found that the basal activity of AChE was increased in myotonic nerves while its proximodistal transport was inhibited.

A report on a patient with clinical hyperthyroidism associated with hydatidiform mole is presented. Some biochemical characteristics of the thyroid stimulator isolated from the tumour are discussed.