Functional use of the Nucleus 22-channel cochlear implant in the elderly

A questionnaire was sent to 101 Nucleus 22-channel cochlear implant recipients aged 65 years and older to investigate the perceived impact of cochlear implantation on their quality of life. The questionnaire was designed to gain insight into the patient's daily use of the Nucleus implant. Sixty-seven questionnaires were returned over a 3-month period. The results of the survey showed that elderly cochlear implant patients obtained similar benefits to younger adult patients who were implanted with the same device. We believe that the results of this study will aid other centers when counseling elderly patients on the expected daily functional benefits of this device.     

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.     

Demonstration of low frequency of human papillomavirus DNA in cervical adenocarcinoma and adenocarcinoma in situ by the polymerase chain reaction and in situ hybridization.

There is evidence that cervical adenocarcinoma is increasing in incidence, particularly in young women. In order to assess the possible role of human papillomaviruses in cervical glandular oncogenesis, 16 cases of invasive adenocarcinoma and eight cases of adenocarcinoma in situ have been examined by in situ DNA hybridization using biotinylated probes to human papillomavirus types 6, 11, 16, 18, and 31, and assessed by polymerase chain reaction analysis for human papillomavirus types 11, 16, and 18 sequences. Of the invasive adenocarcinomas, four of 16 contained human papillomavirus type 16 sequences and one of 16 contained type 18 sequences as assessed by polymerase chain reaction analysis. Five of eight cases of adenocarcinoma in situ contained human papillomavirus type 16 sequences by polymerase chain reaction analysis. Only one invasive adenocarcinoma and one case of adenocarcinoma in situ showed a positive in situ hybridization signal. The low rate of carriage of the human papillomavirus sequences examined suggests that these viral types may not play a major role in cervical glandular neoplasia.     

The clearance of a single i.v. bolus of recombinant human erythropoietin from the serum of patients with myelodysplastic syndromes and its effects on erythropoiesis.

The serum erythropoietin (EPO) concentration in patients with myelodysplasia (MDS) varies widely at similar hemoglobin concentrations, although the reasons for this variation are unclear. We have studied the pharmacokinetics of an i.v. bolus of recombinant human EPO in ten subjects with myelodysplasia. Basal serum EPO concentration varied from 210 to 5984 mU/ml. Plasma half-time clearance (t1/2) varied from 3.9 to 20.0 h. A significant positive correlation was found between t1/2 and basal EPO concentration. An increase in immature peripheral blood reticulocytes was found on days 1 and 2 after EPO treatment; this may represent either an effect on hemopoiesis or on reticulocyte release from the bone marrow.     

The interaction of endothelin receptor responses in the isolated perfused rat lung

To gain more insight into the complex pulmonary interactions of endothelins (ET), we studied airway and vascular responses to endothelins in isolated perfused rat lungs in the presence of the novel ET_B-receptor antagonist BQ788. In particular we focused on airway responses and on prostacyclin release. The effectiveness of BQ788 in our system was shown by its ability to concentration-dependently prevent vasoconstriction (IC₅₀ 0.1μM), bronchoconstriction (IC₅₀ 0.1μM) and prostacyclin production (IC₅₀<0.1μM) induced by the ET_B-receptor agonist IRL1620 (1nmol). Airway responses to ET-1: ET-1-induced bronchoconstriction was aggravated by BQ123 (1 or 8μM), while BQ788 pretreatment (1 or 8μM) showed no significant effect. Simultaneous treatment with 8μM BQ123 and BQ788 attenuated the ET-1-induced bronchoconstriction. Vascular responses to ET-1: ET-1 (1nmol)-induced vasoconstriction was potentiated by BQ788 (1 or 8μM), but attenuated by the ET_A-receptor antagonist BQ123 (1μM). In the presence of BQ788 diminished amounts of the stable prostacyclin metabolite 6-keto-PGF_1α were detected in the perfusate. Simultaneous treatment with 8μM BQ123 and BQ788 completely prevented the ET-1-induced vasoconstriction. Conclusions: Both ET_A- and ET_B-receptors contribute to ET-1-induced vasoconstriction and bronchoconstriction. The ET-1-induced vasoconstriction is attenuated by stimulation of ET_B-receptors, a response that is partly mediated by prostacyclin. Due to the mutual interactions between ET_A- and ET_B-receptors, simultaneous inhibition of both receptors is required to prevent the deleterious effects of ET-1 on lung functions. Received: 17 October 1996 / Accepted: 16 May 1997     

Failure of Ro15-4513 to alter an ethanol-induced taste aversion.

The ability of Ro15-4513, an imidazobenzodiazepine inverse benzodiazepine agonist, to attenuate/block the acquisition of an ethanol (ETOH)-induced conditioned taste aversion (CTA) was investigated in two experiments. Experiment 1 examined the effects of Ro15-4513 (3 mg/kg) on rats' consumption of a novel saccharin solution under a traditional CTA paradigm. Experiment 2 examined the effects of Ro15-4513 (3 mg/kg) on rats' consumption of a novel saccharin solution under a preexposure CTA paradigm. Under the preexposure paradigm, rats were given Ro15-4513 immediately before each of five daily consecutive preexposure treatments prior to the initial conditioning day. To obtain maximal preexposure and unconditioned stimulus effects, a 2-g/kg dose of ETOH (20% v/v) was used in the present study. As previously reported, animals given ETOH following 20-min access to a novel saccharin solution established moderate to strong aversions, with the degree of aversion being directly related to the number of conditioning days. Experiment 1 showed that Ro15-4513 failed to alter the CTA induced by ETOH. Experiment 2 further showed that Ro15-4513 failed to block the preexposure effect exerted on the ETOH-mediated CTA. The results confirm previous reports regarding the failure of Ro15-4513 to disrupt an ETOH-induced CTA. These data are in agreement with a number of behavioral studies demonstrating the failure of Ro15-4513 to antagonize certain actions of ETOH. Moreover, the present study along with a previous report suggests that ETOH-induced CTA's do not appear to be mediated via actions at the GABA-BDZ receptor complex.     

Alteration of pancreatic B-cells in Wistar rats treated with non-diabetogenic doses of cyclosporin A.

We have investigated the effect of non-immunosuppressive cyclosporin A (CS-A) doses on glucose tolerance, pancreatic insulin content, insulin content of isolated islets and insulin secretion in vitro in response to glucose. Within 12 weeks animals treated permanently with a dose of 2.5 mg CS-A/kg b.wt. developed glucose intolerance (but not hyperglycaemia) accompanied by a decrease of pancreatic insulin content due to a decrease of islet insulin content, whereas the relative B-cell volume density was not changed. Isolated islets obtained from rats treated for 4 weeks had a diminished sensitivity for glucose, whereas islets obtained from animals treated for greater than 4 weeks showed a diminished half-maximum and maximum secretion rate. Rats treated for 12 weeks with 1.25 mg CS-A/kg b.wt. developed an impaired glucose tolerance after 8 weeks accompanied by a diminished pancreatic insulin content. Despite continued treatment the pancreatic insulin content was able to increase and the glucose tolerance to normalize, indicating an adaptation of pancreatic B-cells to CS-A. The results support the theory that a potential toxic effect of cyclosporin A can be diagnosed by functional tests (e.g. insulin secretion in response to a stepwise increase of glucose) before the irreversible (e.g. morphological) alterations occur.     

The use of albumin microspheres in the treatment of carrageenan-induced inflammation in the rat.

Free hydrocortisone, hydrocortisone incorporated into microspheres and empty microspheres have been administered orally to rats with carrageenan-induced hindpaw inflammation. Hydrocortisone administered in particles was effective at a lower dose than free steroid in reducing inflammation. Inflammatory exudates were able to release steroid from the microspheres by proteolytic degradation.     

The effects of baclofen and pertussis toxin on epileptiform activity induced in the hippocampal slice by magnesium depletion

Bathing hippocampal slices in artificial cerebrospinal fluid without magnesium elicits repetitive, long ictal-like discharges termed ictaform events. The ictaform events are separated by interictal periods that are initially silent with no interictal bursts. Interictal bursts appear in the later part of the interictal periods and intensify just before the next ictaform event. The GABAB agonist, baclofen, entirely suppressed interictal bursts during the interictal periods and produced a dose-dependent prolongation of the interictal period. Conversely, in slices pretreated with pertussis toxin to reduce the GABAB neurotransmission, interictal bursts were greatly increased, often occupying the entire interictal period, although the total duration of the interictal periods was not affected. Pertussis toxin pretreatment also lengthened the ictaform events. These opposing effects of baclofen and pertussis toxin suggest that GABAB neuro-transmission is important in regulating both the occurrence of interictal bursts in the interictal period, as well as the duration of ictaform events in the low magnesium model of epileptiform activity.