Humoral control of water and electrolyte excretion during water restriction

The goals of the present study were twofold: first, to assess the renal excretory and hormonal responses to chronic water restriction in dogs whose sodium retaining mechanisms had been stimulated through dietary sodium (Na+) deprivation; second, to determine the mediator(s) of the natriuresis which was observed with water restriction in these sodium deprived dogs. Three groups of dogs maintained on a low Na+ diet (5 mEq/day) for two weeks underwent a three day period of water restriction. In normal, intact dogs Group 1 (N = 5), water restriction resulted in a significant increase in Na+ excretion with a net cumulative loss of 26.3 +/- 2.6 mEq over three days. The natriuresis was associated with a significant increase in plasma vasopressin (PAVP) (1.7 to 10.2 pg/mliter) and a significant fall in plasma aldosterone (PALDO) from the levels observed with Na+ restriction alone (24.9 to 12.4 ng/dliter). The natriuresis could not be explained by decreases in food intake as determined by control studies in four dogs. Group 2 (N = 6) dogs had a decrease in PALDO with water restriction that was prevented by means of continuous i.v. aldosterone infusion (6.0 micrograms/kg/day). Dogs in this group failed to demonstrate a natriuresis during three days of water restriction, despite the fact that PAVP rose from 3.3 +/- 0.8 to a peak level of 14.95 +/- 1.9 pg/mliter. Group 3 (N = 6) dogs underwent selective neurohypophysectomy, thus preventing the rise in PAVP during three days of water restriction. In this group, PALDO also remained unchanged from the Na+ deprived level during water restriction, and no natriuresis was observed. We conclude: 1) that the natriuresis which occurs with water restriction is a potent physiological response that occurs even in the Na+ restricted state; and 2) this natriuresis can be explained by a fall in PALDO and not the rise in PAVP.     

A literature review exploring how healthcare professionals contribute to the assessment and control of postoperative pain in older people

Little research has examined the care older people receive in the acute surgical setting. Although pain assessment and management are judged to be a priority in nursing, often pain, in older people, is undermanaged for a variety of reasons. Factors such as stoicism, communication and ageism can shape both the patients’ and nurses’ attitude towards the perception of pain which subsequently affects pain management. Through a review of the literature, this paper aims to: (i) identify how healthcare professionals contribute to the assessment and control of postoperative pain in older people and (ii) explore potential barriers to achieving more advantageous pain control in this group. It is suggested that to improve pain management there is a need to individualize pain assessment for older people and to assist clinicians with enhancing their education and decision‐making abilities in this field. This may best be achieved by supporting a programme of change to develop the skills of staff and encouraging learning through reflective practice. There is however a need for further research in this area.     

Phospho-akt expression is associated with a favorable outcome in non-small cell lung cancer.

Akt, a Serine/Threonine protein kinase, mediates growth factor-associated cell survival. Constitutive activation of Akt (phosphorylated Akt, P-Akt) has been observed in several human cancers, including lung cancer and may be associated with poor prognosis and chemotherapy and radiotherapy resistance. The clinical relevance of P-Akt in non-small cell lung cancer (NSCLC) is not well described. In the present study, we examined 82 surgically resected snap-frozen and paraffin-embedded stage I to IIIA NSCLC samples for P-Akt and Akt by Western blotting and for P-Akt by immunohistochemistry. P-Akt protein levels above the median, measured using reproducible semiquantitative band densitometry, correlated with a favorable outcome (P = 0.007). Multivariate analysis identified P-Akt as a significant independent favorable prognostic factor (P = 0.004). Although associated with a favorable prognosis, high P-Akt levels correlated with high tumor grade (P = 0.02). Adenocarcinomas were associated with low P-Akt levels (P = 0.039). Akt was not associated with either outcome or clinicopathologic variables.Cytoplasmic (CP-Akt) and nuclear (NP-Akt) P-Akt tumor cell staining was detected in 96% and 42% of cases, respectively. Both CP-Akt and NP-Akt correlated with well-differentiated tumors (P = 0.008 and 0.017, respectively). NP-Akt also correlated with nodal metastases (P = 0.022) and squamous histology (P = 0.037).These results suggest P-Akt expression is a favorable prognostic factor in NSCLC. Immunolocalization of P-Akt, however, may be relevant as NP-Akt was associated with nodal metastases, a known poor prognostic feature in this disease. P-Akt may be a potential novel therapeutic target for the management of NSCLC.     

Lethal tracheal dissolution during treatment for thyroid lymphoma

Background - A case of primary thyroid T cell lymphoma leading to lethal tracheal perforation during chemotherapy is described.     

A phase I/II study of continuous infusion suramin in patients with hormone-refractory prostate cancer : toxicity and response

 Introduction: Suramin is a synthetic polysulfonated naphthylurea which has been used for the treatment of African trypanosomiasis and onchocerciasis, but since the mid-1980s has received attention as a possible antiretroviral and antineoplastic agent. Objective: This clinical trial of suramin was undertaken as a phase I/II study in patients with hormone-refractory prostate cancer, with the hypothesis that the intensity of therapy with suramin could be increased significantly if measures were undertaken to maintain the plasma concentrations of the drug under 300 μg/ml. Methods: We report the clinical results of this trial, wherein patients were treated at three different targeted plasma suramin concentrations (275, 215 and 175 μg/ml) for varying periods of time (2, 4 or 8 weeks), with delivery of the drug by continuous intravenous infusion. Results: The major toxicity observed in this trial was neurologic, consisting of a motor and sensory peripheral neuropathy that resulted in both paresis and paralysis of the limbs. Nearly all of this severe (CTEP grade III, IV) neurologic toxicity was observed in the patients treated at a plasma suramin concentration of 275 μg/ml for 4 or more weeks. A single patient treated at 215 μg/ml for 8 weeks developed moderate (CTEP grade III) proximal lower extremity weakness, and no patient treated at 175 μg/ml developed this toxicity. The second most common toxicity observed was infection of the central venous catheter. The overall response rate for all of the evaluable patients was 17% (13 of 75 patients). In addition, prostate-specific antigen (PSA)-defined responses were observed in six patients receiving therapy at 175 μg/ml, but these responses were confounded by cessation of therapy with flutamide during suramin treatment. Conclusions: In summary, although plasma suramin concentrations were maintained below 300 μg/ml, neurologic toxicity nonetheless occurred with high frequency in patients treated at 275 μg/ml for 4 or more weeks. Therapy at 215 and 175 μg/ml was in general well tolerated, but central venous catheter-related infection, as well as the inconvenience and expense of continuous infusional therapy, make this method of drug delivery impractical. Only moderate antitumor activity was observed during this trial, but it is possible that both continuation of flutamide and flutamide withdrawal during suramin therapy confounded the assessment of suramin’s activity in hormone-refractory prostate cancer. Received: 9 June 1995/Accepted: 18 March 1996