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Biomedical subjects

A Davis

Publications and source records attributed to A Davis.

At least 379 records · Page 21Linked to original sources

Multicentre trials of praziquantel in human schistosomiasis: design and techniques.

This paper outlines the experimental design and techniques used in the initial multicentre clinical experiences with praziquantel in the treatment of human infections due to Schistosoma haematobium, S. mansoni, and S. japonicum. Trials were conducted in Brazil, Japan, the Philippines, and Zambia.Close professional cooperation between informed representatives of the manufacturers of the drug and WHO led to the use of a standard clinical trial design and agreed technical protocols, although parasitological methods of therapeutic assessment varied with the species of infecting parasite. Double-blind studies of tolerance were conducted at three different dose levels and subsequently, in Brazil and Zambia, single-blind trials of parasiticidal efficacy were carried out. The results of the various trials are reported separately.This type of close professional cooperation is a useful model for initial clinicopharmacological studies of parasiticidal drugs-an area beset with difficulties for both industry and international agencies.

Clinical Trials as Topic↗

Initial experiences with praziquantel in the treatment of human infections due to Schistosoma haematobium.

Initial studies of the tolerance and efficacy of praziquantel in the treatment of human infections due to Schistosoma haematobium were conducted at the WHO Tropical Diseases Research Centre, Ndola, Zambia. The first stage of the trial was a double-blind assessment against placebo of the tolerance and efficacy of oral doses of 1x20, 2x20, or 3x20 mg/kg in patients with a minimum schistosome egg excretion of 50 per random 10-ml sample of urine. Later a single-blind trial was carried out of the efficacy of three oral doses, each of 20 mg/kg, given at 4-hour intervals, or of a single oral dose of 50 mg/kg.In 79 young Zambians with S. haematobium infections (and often other parasitic infections), patient tolerance to the drug was very good, only minor post-treatment symptoms of intermittent epigastric pain, anorexia, and headache being noted, all of short duration.No changes of clinical relevance were detected in the results of a battery of haematological and biochemical tests. Post-treatment eosinophilia occurred in 42% of drug-treated patients but also in 30% of those given placebo. Serial electrocardiograms revealed no changes of significance.At six months after treatment, of 73 patients followed up, only 1 case of parasitological failure was detected. At one year, 66 (83.5%) of 79 patients with S. haematobium infection were followed up and 2 (2.5%) parasitological failures were detected.Two years after treatment, 45 (57%) of 79 patients with S. haematobium showed negative urines, 7 (9%) had positive hatching tests, and 27 (34%) were absent.

Adolescent↗

Absence of mutagenicity of praziquantel, a new, effective, anti-schistosomal drug, in bacteria, yeasts, insects and mammalian cells.

Praziquantel (Embay 8440, Droncit) a new, effective anti-schistosomal drug, was tested in various short-term assays that have shown a predictive value for the detection of potential carcinogens. Indicator organisms S. typhimurium strains, S. pombe, S. cerevisiae, cultured V79 Chinese hamster cells or human heteroploid cells and Drosophila melanogaster were treated with Praziquantel. The induction of reverse and forward mutations, mitotic gene conversions, X-linked recessive lethals, sister-chromatid exchanges and unscheduled DNA-repair synthesis was scored; rodent-liver microsome-, cell- and host-mediated assays were also performed. Hycanthone, another schistosomicide was included as a positive control. The absence of a genetic activity of Praziquantel uniformly observed in such a battery of tests (i) confirms the assumption that the anti-schistosomal effectiveness of this drug is not related to the mutagenic activity and (ii) should encourage the implementation of extended clinical and field trials.

Animals↗

A new dosemeter for the measurement of natural ultraviolet radiation in the study of photodermatoses and drug photosensitivity.

The production and optical properties of a dosemeter for natural ultraviolet radiation are descirbed. The physical form of the dosemeter is a thin polymer film which incorporates 8-methoxypsoralen as the chromophore. The dosemeter responds to ultraviolet radiation at wavelengths up to 380 nm and is suitable for quantifying the UV exposure of patients suffering from some idiopathic photodermatoses or drug photosensitivity.

Film Dosimetry↗

The uptake and release of [3-H]-2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthlane (ADTN) by striatal nerve terminals.

A study has been made of the uptake and release of [G-3H]-2-amino 6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene (ADTN) by crude striatal synaptosomes of the rat. 2 Uptake was rapid, temperature-dependent and could be suppressed by a variety of metabolic inhibitors. 3 The Michaelis-Menten kinetincs indicated the presence of two distinct transport systems in the striatum which were of much higher capacity than those found in the cerebellum, which lacks dopaminergic innervation. 4 Uptake of [3-H]ADTN was strongly inhibited by dopamine and the two potent dopamine-uptake inhibitors, benztropine and nomifensine, but only weakly by imipramine and amphetamine (the latter in non-reserpine-treated animals). 5 Accumulated [3-H]ADTN could be released from striatal slices by elevated K+. A similar release was evoked upon the addition of the ionophore, A23187. 6 The most potent releaser of [3-H]ADTN was (+)-amphetamine. This effect occurred at concentrations inactive against ADTN uptake. The neuroleptic cis-flupenthixol produced an inhibition of the spontaneous release. 7 It is concluded that [3-H]ADTN is accumulated preferentially into areas of the rat brain rich in dopamine. The pharmacological specificity of the uptake suggests that it is a good substrate for the dopamine carrier. Following uptake, [3-H]-ADTN may be released by K+ and a calcium ioniphore, which raises the possibility that ADTN might act as a false transmitter.

Amphetamines↗

Description and application of a personal ultraviolet dosimeter: a review of preliminary studies.

Preliminary work on a dosimeter suitable for measuring UVR exposure on individual persons is described. It is based on the use of polysulfone film which, on exposure, shows a change in absorbance that is determined spectrophotometrically. The results of studies of groups of persons with vastly different degrees of solar exposure, e.g., outdoor and indoor workers and geriatric patients, and psychiatric patients with photosensitivity from phenothiazine drugs are presented. We consider the dosimeter may also be suitable for epidemiologic studies in sunlight-induced skin cancer.

Antipsychotic Agents↗

Nuclease B. A possible precursor of nuclease A, an extracellular nuclease of Staphylococcus aureus.

During purification of nuclease (redisignated as nuclease A in the present studies) from the culture media of Staphylococcus aureus strain Foggi, three enzymacally active second species (nucleases B1, B2, and B3) were isolated as a mixture by ion exchange chromatography. Examination of the amino acid sequence of these second species indicates that nucleases B1, B2, and B3 apparently contain the same sequence as that of nuclease A with an extra sequence Ser-Gln-Thr-Asp-Asx-Gly-Val-Asx-Arg-Ser-Gly-Ser-Glu-Asp-Pro-Thr-Val-Tyr-Ser linked through a peptide bond to the NH2 terminus of the nuclease A portion. In nuclease B1 the 2 residues indicated by Asx are aspartic acid, in nuclease B2 the first and the second Asx from the NH2 terminus are aspartic acid and asparagine, respectively, and in nuclease B3 both Asx are asparagine. These second species do not contain a significant amount of carbohydrate. The extra amino acid sequence appears to be flexible and does not interfere with the ordered structure and function of the nuclease A portion. The nuclease A portion was recovered, in part, from a mixture of these nuclease B species after digestion with staphylococcal protease in the presence of ligands, deoxythymidine 3',5'-diphosphate, and calcium ion. Thus, these nuclease B species may be closely related to, if not identical with, a precursor of nuclease A. Similar second species of nuclease have been found in strain V8.

Amino Acid Sequence↗

A comparison of aphasic and normal adults in a sentence-verification task.

This study showed that in certain sentence-processing tasks, aphasics fail to perform correctly because they fail to execute particular mental operations. A straightforward information-processing model describes the mental processes that are used in deciding whether a sentence is true or false of an accompanying picture. The aphasics' performance, interpreted in light of the model, indicates what step in their processing is not operating properly in this task.

Aphasia↗

Hepatitis B in ward and clinical laboratory employees of a general hospital.

After a sharp increase in viral hepatitis cases, mostly type B, among the 2000 employees of a general hospital during three years, we conducted an investigation which consisted of obtaining data on employee cases and surveying many current employees. Of the 38 cases, 22 occurred in non-physician, ward employees. Of 189 current ward employees, 8% had antibody to hepatitis B surface antigen (anti-HBS) and 1% had hepatitis B surface antigen (HBSAg). Hepatitis B virus (HBV) seropositivity was highest for employees who worked closely with hemodialysis and renal transplant patients and for those who claimed that their ward was understaffed. Nine of the 38 cases occurred in clinical lab workers. Of 70 current lab employees, 17% were positive for anti-HBS and none for HBSAg. HBV seropositivity was highest for those working in the chemistry section (highest there among those performing blood-gas determinations and those working with the multi-channel autoanalyzers) and those who routinely got blood on their skin and clothes at work. All seropositive employees worked routinely with blood. These data support the hypotheses that many hospital employees contract hepatitis B from exposure to HBSAg-positive patients and many clinical laboratory employees contract it from exposure to HBV-contaminated blood.

Carrier State↗

The anatomical distribution of sunlight.

The relative distribution of natural ultraviolet radiation has been measured at ten sites on the surface of an unclothed manikin for 2 h around solar noon on 19 different days during late summer in Canterbury, U.K. The dosimeter used was polysulphone film. The results obtained indicate that vertical surfaces of the body receive about one half of the dose relative to the vertex and that the relative doses at different sites are independent of weather conditions.

Body Surface Area↗

A dosimeter for long wave ultraviolet radiation.

A polymer film, which incorporates phenothiazine as the chromophore, has been developed as a personnel dosimeter for long wave ultraviolet radiation. It is stable, reproducible and is particularly suited to monitoring the doses received by patients undergoing photochemotherapy for psoriasis.

Dose-Response Relationship, Radiation↗