Changes in antioxidant status and biochemical parameters after orally cadmium administration in females rats.

The research was conducted to investigate the toxic effects of cadmium chloride (CdCl2), administered during gestation period on female Wistar rats. Pregnant rats received CdCl2 (20 mg/l, orally) from Day 6 to Day 19 of pregnancy. Results showed that Cd treatment induced a decrease in body weight gain. The relative liver weight increased significantly, with a marked decrease of glycogen and total lipids content. The administration of Cd induced hepatotoxicity as indicated by elevations in plasma alanine aminotransferase (ALT), aspartate aminotransferase and lactate dehydrogenase (LDH) activities (p < 0.05). Treatment with CdCl2 caused a significant (p < 0.05) increase in glucose. A significant increase was observed in the level of MDA and 8-oxodGuo tissues in the cadmium-exposed group compared to the control group (p < 0.05). Results showed that cadmium given to dams led to an oxidative stress and DNA damage in tissues of pregnant rats.

Withdrawal from dialysis: a palliative care perspective.

A retrospective chart review was conducted in this pilot study of 35 patients who withdrew from dialysis and were followed by a palliative care team. Data included etiology of end-stage renal disease, comorbid illnesses, mode of dialysis and duration, survival time after withdrawal, reason for withdrawal, mental competency, symptom management, and the nature of death. Mean survival time was 10 days. The most frequent symptoms following withdrawal were confusion, agitation, pain and dyspnea. 1/3 of the sample were cognitively impaired at the time of the withdrawal decision. 17% experienced suffering during the withdrawal period, 24% had unrelieved symptoms, 19% psychological distress, while just over 1/3 of patients died alone. With the provision of palliative care, symptom prevalence in the last 24 hours dropped from 53 to 20% for pain, 68 to 33% for agitation and 46 to 26% for dyspnea. Opioids and benzodiazepines were used in the treatment of over 90% of patients. Palliative medicine has the potential to improve the care of patients who discontinue dialysis.

The mitochondrial-dependent pathway is chronically affected in testicular germ cell death in adult rats exposed in utero to anti-androgens.

In utero exposure to exogenous anti-androgenic compounds induces a wide range of abnormalities of the reproductive system, including hypospermatogenesis, cryptorchidism and hypospadias. By using rats exposed in utero to the anti-androgenic compound flutamide (0.4, 2 or 10 mg/kg per day), it has been shown that hypospermatogenesis in adult testes could be related to (i) a long-term apoptosis in germ cells but not in somatic Leydig and Sertoli cells as evidenced by the TUNEL approach and (ii) alterations in the mRNA and protein expression of pro- (Bax, Bak, Bid) and anti-apoptotic (Bcl-2, Bcl-w) members of the Bcl-2 family. Indeed, the number of apoptotic germ cells increased with the dose of flutamide administered and the apoptotic germ cells were mainly detected at androgen-dependent stages VII-VIII. Moreover, for the Bcl-2-related proteins that were expressed mainly in the germ cells, a decrease in the levels of anti-apoptotic peptides Bcl-w (60%, P=0.003) and Bcl-2 (90%, P=0.0001) was observed at 2 mg/kg per day flutamide and an increase in levels of the pro-apoptotic Bax (2.3-fold, P=0.0004) was detected at 10 mg/kg per day. In contrast, the levels of pro-apoptotic peptide Bak that was mainly expressed in somatic cells decreased (70%, P=0.0008) at 10 mg/kg per day. Such alterations in Bcl-2-related peptides occurred mainly at the protein level except for Bcl-2 (72%, P=0.0001) and Bak (43%, P=00002) transcripts. Together, these results showed that the apoptosis observed in adult germ cells from rats exposed in utero to flutamide may result from a long-term alteration in the balance between pro- and anti-apoptotic Bcl-2-related molecules in favour of pro-apoptotic proteins. These data further supported the concept of an androgen-dependent fetal programming that is in relation with an alteration of the expression of Bcl-2-related genes/proteins promoting apoptosis in testicular germ cells of adult rats with fetal androgen disruption.

Regulation of aromatase gene expression in purified germ cells of adult male rats: effects of transforming growth factor beta, tumor necrosis factor alpha, and cyclic adenosine 3',5'-monosphosphate.

Estrogens are key regulators of sexual differentiation and development in vertebrates. The P450 aromatase (P450arom) is the steroidogenic enzyme responsible for the synthesis of estrogens from androgens. In the adult rat testis, aromatase transcripts and activity have been observed in somatic cells and germ cells, including pachytene spermatocytes (PS) and round spermatids (RS), but little is known concerning regulation of the aromatase gene expression, especially in germ cells. The quality of germ cell preparations was assessed by the absence of androgen-binding protein and stem cell factor transcripts, two specific markers for Sertoli cells. By employing a competitive quantitative reverse transcriptase-polymerase chain reaction technique, we confirmed that germ cells contained P450arom transcripts and demonstrated that the aromatase gene was up-regulated by cAMP. Conversely, transforming growth factor (TGF) beta1 inhibited Cyp19 gene expression in a dose- and a time-dependent manner in both PS and RS. The addition of tumor necrosis factor (TNF) alpha to purified germ cells induced an increase of the amount of P450arom mRNA in PS, although an inhibitory effect was observed in RS. When PS were treated with dexamethasone (Dex), a similar enhancement of the aromatase transcript level was observed, whereas an inhibitory effect was recorded for RS. Furthermore, in either TGFbeta1- or TNFalpha-treated germ cells, the addition of Dex stimulated the aromatase gene transcription. Experiments using 5' rapid amplification of cDNA ends suggested that promoter PII is mainly concerned in the regulation of the aromatase gene expression in germ cells of adult male rats; however, the presence of other promoters could not be excluded.

Attitudes of terminally ill patients toward euthanasia and physician-assisted suicide.

BACKGROUND: In jurisdictions that permit euthanasia or physician-assisted suicide, patients with cancer comprise the largest group to die by these methods. We investigated the personal attitudes toward these practices of patients receiving palliative care for advanced cancer. METHODS: Seventy patients (32 men and 38 women; median survival, 44.5 days) took part in a survey using in-depth semistructured interviews. The interviews were audiotaped for transcription and content analysis of themes. RESULTS: Most participants (73%) believed that euthanasia or physician-assisted suicide should be legalized, citing pain and the individual's right to choose as their major reasons. Participants who were opposed to legalization cited religious and moral objections as their central concerns. Forty (58%) of the 69 participants who completed the entire interview also believed that, if legal, they might personally make a future request for a hastened death, particularly if pain or physical symptoms became intolerable. Eight of these individuals (12%) would have made such a request at the time of the interview. These 8 participants differed from all others on ratings of loss of interest or pleasure in activities, hopelessness, and the desire to die (Ps<.02). They also had a higher prevalence of depressive disorders (P<.05). However, they did not differ on ratings of pain severity. CONCLUSIONS: Many patients with advanced cancer favor policies that would allow them access to both euthanasia and physician-assisted suicide if pain and physical symptoms became intolerable. For patients who would actually make requests for a physician-hastened death, however, psychological considerations may be at least as salient as physical symptoms.

Sedation for intractable distress in the dying--a survey of experts.

Terminal sedation is a phrase that has appeared in the palliative care literature in the last few years. There has not been a clear definition proposed for this term, nor has there been any agreement on the frequency with which the technique is used. A postal survey of 61 selected palliative care experts (59 physicians, two nurses) was carried out to examine their response to a proposed definition for 'terminal sedation', to estimate the frequency of this practice and the reasons for its use, to identify the drugs and dosages used, to determine the outcome, and to explore the decision-making process. Opinions on physician-assisted suicide and voluntary euthanasia were also sought. Eighty-seven per cent of the experts responded from eight countries, although predominantly from Canada and the United Kingdom. Forty per cent agreed unequivocally with the proposed definition, while 4% disagreed completely. Eighty-nine per cent agreed that 'terminal sedation' is sometimes necessary and 77% reported using it in the last 12 months--over half of these for up to four patients. Reasons for using this method included various physical and psychological symptoms. The most common drugs used were midazolam and methotrimeprazine. Decision making usually involved the patient or family, and varied with respect to the ease with which the decision was made. The use of sedation was perceived to be successful in 90 out of 100 patients recalled. Ninety per cent of respondents did not support legalization of euthanasia. In conclusion, sedating agents are used by palliative care experts as tools for the management of symptoms. The term 'terminal sedation' should be abandoned and replaced with the phrase 'sedation for intractable distress in the dying'. Further research into the management of intractable symptoms and suffering is warranted.

The Social Security safety net.

Is it possible to build a stronger future for Social Security while, at the same time, protect the well being of the vulnerable elderly and maintain critical protection for families? Contrary to those who call for radical measures, the evidence is mounting: Social Security can be made stronger for the long-term with a package of modest, responsible reforms.

The use of nebulized opioids for breathlessness: a chart review.

Breathlessness secondary to both cancer and non-malignant disease is a distressing, exhausting symptom which, to date, has been difficult to control. This paper reports a chart review undertaken on patients referred to the Ottawa Civic Hospital's Palliative Care Service over the 18-month period from 1 January 1992 to 30 June 1993. The intent of the review was to assess the recorded efficacy and safety of nebulized opioid use on patients with complaints of dyspnoea. Fifty-four patients were treated and subjective data have been compiled. The treatment was found to be effective, safe and convenient for the majority of the patients studied. In addition, nebulized opioids have been demonstrated as a treatment modality which is feasible for self-administration by the patient at home.

Clinical application of nebulized opioids for treatment of dyspnoea in patients with malignant disease.

This article describes our experience in the clinical use of nebulized opioids for the management of dyspnoea in patients with terminal cancer by reviewing three specific patient case studies in which this treatment was found to be both safe and effective in controlling breathlessness. The patients were treated with morphine, hydromorphone or anileridine in various doses according to their prior use of opioids. Additional formal studies are being initiated at this Centre.

Case studies outlining use of nebulized morphine for patients with end-stage chronic lung and cardiac disease.

This article describes the use of nebulized morphine in the management of dyspnea in two patients with end-stage chronic lung disease, and two patients with end-stage heart failure. All four patients had relief of breathlessness. Arterial blood gas results and vital signs were monitored pre- and postnebulized morphine in two of the patients and demonstrated little change. Nebulized morphine appears to be well tolerated in this patient population.

Correlating visual acuity and electrooculogram recordings in Best's disease.

The visual function in 54 eyes of 27 patients with Best's disease was analyzed by retrospectively examining the Snellen visual acuities and the electrooculogram (EOG). Visual acuities, generally well maintained in most patients, were 20/40 (0.5) or better in 41 of 54 (75.9%) eyes, and showed no correlation with age. Those in the cicatricial stage had worse visual acuities than those in the previtelliform stage. The EOG was abnormal in 47 eyes (87.0%) with a subnormal light peak/dark trough (Lp/Dt) ratio less than 1.85. Seven eyes (13.0%) with an Lp/Dt ratio 1.85 or higher had significantly smaller Dt values compared with those with a low Lp/Dt ratio. The Lp/Dt ratio did not correlate with patient age or disease stage. No correlation existed between visual acuities and Lp/Dt ratios. The Lp/Dt ratio did not reflect the severity of the macular lesions. The results indicate that not only a low Lp/Dt ratio but also a low dark trough value in cases with a normal Lp/Dt ratio are helpful in diagnosing Best's disease.

Premedication with piroxicam in patients having dental surgery under general anaesthesia with halothane or isoflurane.

Pain, analgesic requirements, mouth opening and emesis were assessed in 60 patients who received either piroxicam 40 mg or placebo before dental surgery under general anaesthesia which included breathing either halothane or isoflurane. Patients went home on the day after surgery and completed a questionnaire concerning pain and emesis. There were four groups of 15 subjects: piroxicam-halothane, piroxicam-isoflurane, placebo-halothane or placebo-isoflurane. Pain increased at 2 and 4 h and had reduced by 18 h after surgery; there were no significant differences between the groups in pain scores. After operation, fewer patients in the piroxicam-isoflurane group required papaveretum compared with the piroxicam-halothane and placebo-halothane groups. Mouth opening was reduced between 2 and 4 h after surgery, but was less restricted after piroxicam-isoflurane than placebo-halothane. There was no difference between the groups in the incidence of emesis within 18 h of surgery. The postal questionnaire suggested that pain and emesis were reduced significantly during the 3 days after surgery in patients who had received piroxicam before surgery, compared with those who had received placebo.

Effect of passive hyperventilation on seizure duration in patients undergoing electroconvulsive therapy.

The influence of end-expired carbon dioxide concentration (E'CO2) on seizure duration was studied in 30 depressed patients undergoing electroconvulsive therapy (ECT) on three separate consecutive occasions. Unpremedicated patients breathed 100% oxygen before the induction of anaesthesia with methohexitone and the provision of partial neuromuscular blockade with suxamethonium. They then received no further ventilation, 10 breaths, or 20 breaths of hyperventilation with 100% oxygen from a non-rebreathing system with a high fresh gas flow. Transcutaneous oxyhaemoglobin saturation (SaO2) was monitored continuously and E'CO2 was measured before and after the seizure. Observation of an isolated forearm was used to time the seizure duration. SaO2 remained greater than 90% in all patients. Passive hyperventilation with 20 breaths significantly reduced E'CO2 and prolonged seizure duration. E'CO2 before the seizure and change in E'CO2 during the seizure did not correlate significantly with seizure duration.

Parkinson's disease: a pharmacological update.

The primary biochemical defect in Parkinsonism is dopamine depletion. Anticholinergics (except in the elderly) and amantadine are useful in treating early symptomatic disease. L-dopa remains the most effective drug, but experience has led to more modest use due to its late complications, particularly dyskinesias. Bromocriptine, a dopamine agonist, is relatively effective, but when it should be used is undecided. Beta-blockers may control tremor. Treatment should be tailored to each patient, and focus on functional motor ability. Dyskinesias and neuropsychiatric complications are the major limiting factors with most of these drugs. Several drugs are under investigation.

Role selection by nurses: managerial interests and personal attributes.

The relationship between interest in management roles and personality, demographic, and career background characteristics of 122 female nurses was investigated. The study tested the proposition that women in nursing seek roles within the profession that permit the expression of their personalities. The subjects, first-quarter master's degree students, were classified into management or non-management groups, based upon their scores on the business management scale of the Strong-Campbell Interest Inventory (SCII). Results of a multivariate analysis of variance (MANOVA) for unequal N's showed significant group differences on seven of the 11 scales of the Vocational Preference Inventory (VPI). Findings indicated that those who exhibited managerial interests were more practical-minded, sociable, conforming, dominant, expressive, and had more occupational interests than those who did not demonstrate such interest. Women lacking managerial interests showed a greater preference for "feminine," low-status occupations. No significant group differences were found on any of the 19 demographic and career background variables.