Pharmacodynamic effects of dehydroemetine

The pharmacodynamics of dehydroemetine were studied in isolated preparations and in whole animals. Dehydroemetine had no effect on the guinea-pig isolated ileum but non-specifically antagonized the spasmogenic effect of histamine, acetylcholine and nicotine on this tissue. Dehydroemetine in small concentrations inhibited relaxations of the guinea-pig and rabbit ileum produced by stimulating the sympathetic nerve without inhibiting the effect of noradrenaline. Twitches of the guinea-pig ileum elicited by transmural stimulation were blocked by dehydroemetine while higher doses of the drug also inhibited the indirectly elicited contractions of the isolated rat diaphragm. In vivo, neuromuscular blocking action could not be demonstrated for dehydroemetine while toxic doses were required to demonstrate the presence of an adrenergic neuron blocking action. Dehydroemetine had no anaesthetic action when applied locally to the rabbit cornea. Concentrations of the drug which caused local anaesthesia when injected intradermally into guinea-pigs also caused skin necrosis. It is concluded that dehydroemetine lacks any specific adrenergic neuron blocking action or neuromuscular blocking action or local anaesthetic action. It is suggested that the effects demonstrated are due to non-specific action at the nerve endings.     

The effect of dehydroemetine on isolated guinea-pig atria

1. The mechanisms of the inhibitory effect of dehydroemetine on the heart was investigated using spontaneously contracting isolated guinea-pig atria.

2. In normal Locke solution, dehydroemetine caused a reduction in the rate and amplitude of contraction of the atria. The effect was antagonized by adrenaline and augmented by acetylcholine.

3. Increasing the potassium concentration of the bathing medium increased the inhibitory effect of dehydroemetine on the atria, while decreasing the potassium concentration antagonized the effect of dehydroemetine.

4. The character of the inhibitory effect of dehydroemetine on the atria altered when the sodium concentration of the bathing solution was lowered to 75·6 mmol. In the normal sodium medium arrest of beat by dehydroemetine was gradual; in the low sodium medium, it was abrupt.

5. In the low, as in the normal sodium medium, the inhibitory effect of dehydroemetine was more marked the higher the potassium concentration of the bathing medium.

6. In both standard Locke solution and Locke solution containing 75·6 mmol sodium, the effect of dehydroemetine closely mimicked that obtained by adding excess potassium to the solution.

7. On the basis of the foregoing it was suggested that dehydroemetine acts by increasing the permeability of the myocardial cell membrane to potassium thereby leading to the accumulation of potassium in the extracellular space.

     

Informed consent under the European Convention on Biomedicine and the UNESCO Declaration on Bioethics

The desirability of obtaining freely given consent is universally accepted. The point, however, is that there is no unanimity on the definition of informed consent or its application in bioethics. Whether informed consent is based on principalism or casuistry or the virtue theory, the problem is how to handle the ethically complex situation created in the interface between informed consent and social justice under international biomedical instruments. This article will proceed by offering detailed historical and critical analyses of informed consent under the European Convention on Human Rights and Biomedicine 1997 and The UNESCO Universal Declaration on Bioethics and Human Rights 2005. Three conceptions of justice will be utilised to show that the doctrine of informed consent has driven the ethos of research on human beings and shaped the physician-patient relationship; and that casuistry and virtue theory are consistent with and not rivals of a principle-based account of informed consent.     

The Dental Caries Pandemic and Disparities Problem

Understanding caries etiology and distribution is central to understanding potential opportunities for and likely impact of new biotechnologies and biomaterials to reduce the caries burden worldwide. This review asserts the appropriateness of characterizing caries as a "pandemic" and considers static and temporal trend reports of worldwide caries distribution. Oral health disparities within and between countries are related to sugar consumption, fluoride usage, dental care, and social determinants of health. Findings of international and U.S. studies are considered in promoting World Health Organization's and others' recommendations for science-based preventive and disease management interventions at the individual, clinical, public health, and public policy levels.     

Hydrocelectomy under local anaesthesia in a Nigerian adult population

Background

Hydrocele is abnormal collection of serous fluid in the tunica vaginalis or a patent processus vaginalis. It is commonly encountered in our practice and often requires surgical treatment. However in our setting and in many underdeveloped countries, availability of general anaesthetic service is poor due to lack of trained personnel and equipment.

Objectives

To ascertain the practicability and acceptability of hydrocelectomy under sedation and local anaesthesia in Nigerian adults with hydrocele

Patients and Methods

A prospective study was carried out over a two year period on patients that had hydrocelectomy at the surgery unit of the Obafemi Awolowo University Teaching Hospitals Complex, Wesley Guild Hospital, Ilesa. Consecutive patients with diagnosis of hydrocele who consented had hydrocelectomy using intramuscular diazepam sedation and spermatic-cord block with 0.5% plane xylocaine and the scrotum infiltrated with same along the line of incision.

Results

Fifty adult patients were studied: age range 15–94 years. Eighty percent of the patients had unilateral hydrocele and the commonest type was vaginal hydrocele (94%). All patients had hydrocelectomy, 96% were under local anaesthesia while 4% were converted to general anaesthesia. All patients except one prefer to have future surgery under such local anaesthesia and sedation.

Conclusion

Hydrocelectomy under local anaesthesia and sedation is practicable and was tolerated and accepted by the adults patients studied.     

67Cu-2IT-BAT-Lym-1 pharmacokinetics, radiation dosimetry, toxicity and tumor regression in patients with lymphoma.

Lym-1, a monoclonal antibody that preferentially targets malignant lymphocytes, has induced therapeutic responses and prolonged survival in patients with non-Hodgkin's lymphoma when labeled with 1311. Radiometal-labeled antibodies provide higher tumor radiation doses than corresponding 1311 antibodies. 67Cu has an exceptional combination of properties desirable for radioimmunotherapy, including gamma and beta emissions for imaging and therapy, respectively, a biocompatible half-time and absence of pathways contributing to myelotoxicity. The radioimmunoconjugate, 67Cu-21T-BAT-Lym-1, has been shown to be efficacious in nude mice bearing human Burkitt's lymphoma (Raji) xenografts. Based on these results, a clinical study of the pharmacokinetics and dosimetry of 67Cu-21T-BAT-Lym-1 in patients with lymphoma was initiated. METHODS: Eleven patients with advanced stage 3 or 4 lymphoma were given a preload dose of unmodified Lym-1, then an imaging dose of 126-533 MBq (3.4-14.4 mCi) 67Cu-21T-BAT-Lym-1. Total Lym-1 ranged from 25 to 70 mg dependent on the specific activity of the radioimmunoconjugate and was infused at a rate of 0.5-1 mg/min. Imaging, physical examination, including caliper measurement of superficial tumors, and analysis of blood, urine and fecal samples were performed for a period of 6-13 d after infusion to assess pharmacokinetics, radiation dosimetry, toxicity and tumor regression. RESULTS: In 7 patients, in whom superficial tumors had been accurately measured, tumors regressed from 18% to 75% (mean 48%) within several days of 67Cu-21T-BAT-Lym-1 infusion. The uptake and biological half-time of 67Cu-21T-BAT-Lym-1 in tumors were greater than those of normal tissues, except the mean liver half-time exceeded the mean tumor half-time. The mean tumor-to-marrow radiation ratio was 32:1, tumor-to-total body was 24:1 and tumor-to-liver was 1.5:1. Images were of very good quality; tumors and normal organs were readily identified. Mild and transient Lym-1 toxicity occurred in 6 patients; 1 patient developed a human antimouse antibody. There were no significant changes in blood counts or serum chemistries indicative of radiation toxicity. CONCLUSION: Because of the long residence time of 67Cu-21T-BAT-Lym-1 in tumors, high therapeutic ratios were achieved and, remarkably, numerous tumor regressions were observed after imaging doses. The results indicate considerable therapeutic potential for 67Cu-21T-BAT-Lym-1.