Gene probe for P0 messenger RNA used to index acrylamide toxic neuropathy in rats.

Cumulative exposure to the neurotoxicant acrylamide produces axonal damage in the distal ends of both central (CNS) and peripheral (PNS) nerve fibers and subsequent hind-limb paralysis. The messenger RNA which codes for the PNS myelin glycoprotein P0 (P0-mRNA) was used to monitor this toxic neuropathy in Sprague Dawley rats prior to, concurrent with, and subsequent to, ultrastructurally and immunocytochemically defined nerve damage. Rats were dosed every other day with acrylamide (50 mg/kg, IP) and sampled intermittently throughout a 4 week exposure period. Slot blot and Northern gel analyses of the proximal and distal sciatic nerve were used to determine a quantitated measure of P0-mRNA. Twenty-four hours after the first treatment, in the absence of ultrastructural damage, P0-mRNA increased 55% over control levels in the distal sciatic nerve. After 12 treatments, and concomitant with the appearance of spinal cord and PNS neuropathic damage and hindlimb dysfunction, P0-mRNA decreased 45% below control levels. Levels of P0-mRNA from rats exposed to 12 treatments of acrylamide but allowed to recover for 40 days, returned to 79% of control values to reflect the regeneration and remyelination occurring in the distal sciatic nerve. In spite of these fluctuations in levels of P0-mRNA, immunocytochemical staining of P0 protein in plastic sections of the distal sciatic nerve was present throughout all sample times. These results suggest that changes in neural specific mRNAs are sensitive to neurotoxic damage and can be used to monitor the pathogenesis of nerve degeneration.     

Central corticotropin releasing factor reduces natural cytotoxicity. Time course of action

Corticotropin-releasing factor (CRF) administered intracerebroventricularly produced both a rapid, greater than 50% reduction in splenic natural killer (NK) cytotoxicity and a prolonged elevation in plasma corticosterone levels. In the first 60 minutes following CRF, fivefold increases in corticosterone levels were associated with the suppression of NK activity. However, NK activity returned to control levels at later time points even though elevated plasma corticosterone levels persisted. These data augment the findings that central CRF reduces natural cytotoxicity and establish a time course for the effect in acutely treated rats.     

Gastric and duodenal obstruction in patients with cholangiocarcinoma in the porta hepatis: increased prevalence after radiation therapy.

OBJECTIVE. Our objective was to study the imaging findings in patients who had gastric and duodenal obstruction as a long-term complication of cholangiocarcinoma and to determine if the obstruction was associated with radiation therapy. MATERIALS AND METHODS. Between 1973 and 1989, 96 patients had either curative resection or palliative stenting for cholangiocarcinoma involving the hepatic duct bifurcation. Sixty-three (66%) also received adjuvant radiation therapy ranging from 4960 to 7220 rad (cGy). Gastric outlet or duodenal obstruction or both developed subsequently in seven of the 63 patients treated with radiation therapy. Radiographic studies, including upper gastrointestinal series and CT, and medical and surgical records for these seven patients were retrospectively reviewed. RESULTS. Upper gastrointestinal series in the seven patients with obstruction showed narrowing of the lumen, deformity and enlargement of gastric and duodenal mucosal folds, and delayed gastric emptying. CT performed in five of the seven patients showed thickening of the wall of the gastric antrum and small bowel and retained food and fluid within the stomach. All seven patients required gastrojejunostomy; at surgery, dense adhesions and fibrosis were found, and it was not evident whether the obstruction was due to the tumor or to radiation fibrosis. However, because this complication was seen only after radiotherapy, it was presumed to be radiation fibrosis. CONCLUSION. Our experience suggests that radiation therapy increases the risk of postoperative gastric and duodenal obstruction in patients undergoing surgery for cholangiocarcinoma.     

Central alpha 2-adrenoceptor responsiveness in borderline hypertensive rats.

Increased dietary NaCl intake increases the responsiveness of central nervous system alpha 2-adrenoceptors which regulate the neural control of renal function in spontaneously hypertensive rats (SHR) but not Wistar-Kyoto (WKY) normotensive rats. The borderline hypertensive rat (BHR) is the first filial offspring of the SHR and the WKY. With increased dietary NaCl intake, the BHR develops hypertension and expresses other characteristics of the hypertensive SHR parent. This investigation sought to determine whether increased dietary NaCl intake in the BHR enhances the responsiveness of central nervous system alpha 2-adrenoceptors. Six weeks of increased dietary NaCl intake (8% versus 1% NaCl) in BHR augmented the depressor, bradycardic, renal sympatho-inhibitory and diuretic responses to intracerebroventricular administration of graded doses (5, 25 and 125 micrograms) of the alpha 2-adrenoceptor agonist, guanabenz. The results suggest that the potential for an increased responsiveness of central nervous system alpha 2-adrenoceptors is genetically transmitted to the BHR by the SHR and may be exposed in the BHR by increased dietary NaCl intake.     

The need for basic sciences in the understanding and practice of anaesthesia

We conducted a survey using an unstructured, then a structured, questionnaire to determine the attitudes of 78 postfellowship anaesthetists to the Basic Sciences component of the part I examination for the FRCA. Seventy-two per cent replied. These anaesthetists felt that about 65% of the basic science syllabus was essential to the understanding and practice of everyday anaesthesia, but there was varying opinion as to the importance of specific topics. Cardiovascular, respiratory, central nervous system and renal physiology were all regarded as essential, as was the pharmacology of anaesthetic drugs. Topics regarded as irrelevant included biochemistry, endocrinology, membrane theory and immunology. Paradoxically, there were many topics which anaesthetists regarded as essential but on which they were unable to give a tutorial. There was little difference between the responses of consultants and trainees. This survey may help to identify a core syllabus on which the majority of anaesthetists agree but also suggests that the current syllabus is overloaded with detail that has no place in clinical practice.     

Phase II trial of high-dose cisplatin with sodium thiosulfate nephroprotection in patients with advanced carcinoma of the uterine cervix previously untreated with chemotherapy.

Cisplatin is one of the most active single agents in the treatment of advanced cancer of the cervix. The concurrent administration of the nephroprotective agent, sodium thiosulfate, has enabled exploitation of the therapeutic potential of cisplatin. To explore the role of cisplatin dose intensity in the treatment of patients with cancer of the uterine cervix, patients with persistent/recurrent measurable disease were treated with cisplatin at 200 mg/m2 as a 2-hr infusion with sodium thiosulfate given at 3.3 g/m2 1 hr prior to cisplatin and 6.6 g/m2 during the cisplatin infusion. Treatment was repeated monthly. Due to the known cumulative toxicity of cisplatin, treatment beyond two cycles (400 mg/m2) was given only to those patients who had at least demonstrated a PR. Audiologic evaluation was done prior to each cycle of treatment. Eleven patients were entered with a median age of 43 years (range, 25-57), a median KPS of 80% (range, 60-90%), and nine epidermoid and two adenocarcinoma, and all patients had received previous pelvic irradiation. Twenty-eight cycles of treatment were given: 1, five cycles; 3, three cycles; 7, two cycles. No greater than or equal to 3+ hematologic, neurologic, or renal toxicity was demonstrated. Ototoxicity was demonstrated in the mild to moderate hearing loss range (3000-8000 Hz). The greatest threshold shift occurred after the first course of cisplatin. There were three PRs with a maximum duration of 4 months. Due to the significant toxicities encountered, the low response rate, and the limited duration of responses, this trial was closed early to accrual.     

Death,portry, psychotherapy and clinical supervision (the contribution of psychodynamic psychotherapy to palliative care nursing)*

This paper explores one facet of a therapeutic relationship with a woman suffering from inoperable cervical cancer. The psychotherapy sessions were conducted in both hospital and the family home and continued on a weekly basis until final termaination immediately prior to the woman's death. Through a ‘suspense structure’ case study narrative, the writer, a nurse psychotherapist, describes the way in which the humanities art and poetry can provide a means through which to understand seemingly incomprehensible feelings related to reviewing past events as a preparation for death. While no explict critique is made of the twin psychoanalytical concept of transference and countertransference, the occurrence is woven into the text. The essential nature of clinical supervision is illustrated in context. The author proposes that engagement in a therapeutic relationship with a dying person presents the worker with parallel struggles manifesting in elementary feelings which require discernment. The central recommendation of this paper is that the rich symbolic language and metaphors, redolent in art and poetry, be harnessed as a potent therapeutic and metaphors, redolent in art and poetry, be harnessed as a potent therapeutic tool. Throughout the discussion, the terms counseling and psychotherapy are used interchangeably.     

Project 2000: perceptions of the philosophy and practice of nursing: shifting perceptions—a new practitioner?

This is the first of two papers which address aspects of the findings of a large scale study commissioned by the English National Board which set out to examine the impact of Project 2000 on perceptions of the philosophy and practice of nursing. The findings presented here suggest that there have been fundamental shifts in perceptions of the nature and discipline of nursing. Students and diplomates of the course perceive themselves as knowledgeable doers, with their practice well grounded in theory and research. They value the interpersonal skills teaching and place the patient firmly at the centre of care delivery, viewing the patient holistically and being prepared to be fierce patient advocates where necessary. It is difficult to determine the extent to which these shifts can be attributed to the Project 2000 course, although the Project 2000 approach to education appears to be an important factor.