The concurrent administration of adriamycin (intravenous) and verapamil (oral) is of considerable interest because of experimental data suggesting that resistance to adriamycin may be overcome by this means. The potential for a pharmacokinetic interaction between the two drugs has therefore been investigated in five patients with small cell lung cancer treated with combination chemotherapy comprising adriamycin, VP16, vincristine and cyclophosphamide. The data indicate that a significant interaction takes place. Adriamycin peak levels, terminal half-life and the volume of distribution at steady state are higher, whereas plasma drug clearance and the volume of the central compartment are lower with co-administration of verapamil. There was no evidence of enhanced drug toxicity in this study; however, the data should be considered in the interpretation of clinical trials in which adriamycin and verapamil are used together, both in terms of toxicity and tumour response.

Administration, Oral↗

PubMed1986

The use of nylon as a denture-base material.

Explore the source record for details and available documents.

Acrylic Resins↗

PubMed1986

Small deletions of the short arm of the Y chromosome in 46,XY females.

Structural anomalies of the sex chromosomes provide a means to study the location of genes responsible for sex determination. Recently, a type of sex reversal in humans, the 46,XX male, was shown to result in some cases from translocation of Y chromosome material to the X chromosome. In the present report, another type of sex reversal, the 46,XY female, is shown to result, in two cases, from small deletions of the short arm of the Y chromosome. Prometaphase chromosome analysis showed a 46,X,Yp- karyotype. Several Y chromosome-specific DNA probes were found to be deleted in the two female patients. DNA analysis showed that the two deletions were different but included a common overlapping region likely to be essential for male determination.

Chromosome Deletion↗

PubMed1986

Postcholecystectomy wound infection. The impact of prophylactic antibiotics on the epidemiology of infections.

The clinical courses of 347 patients undergoing gallbladder surgeries were monitored to study the epidemiology of postcholecystectomy wound infection in a hospital in which high-risk patients received prophylactic antibiotics. Overall, 3.8% of patients had wound infections. Patients who had positive bile cultures taken during surgery or positive intraoperative wound cultures had higher rates of infection than patients with negative cultures. However, there was a poor correlation among the bacterial isolates that were recovered from the bile or the wound surface during surgery and from postoperative infections. Antibiotic-sensitive enteric bacteria were recovered from bile samples at surgery, gram-positive organisms and enteric gram-negative bacteria were isolated from intraoperative cultures of the wound surface, and antibiotic-resistant gram-negative bacteria or enterococci were recovered from wounds that developed postoperative infections. There was a strong association between the prior receipt of prophylactic antibiotics and infections with antibiotic-resistant bacteria. Data suggest that bactibilia is still an important epidemiologic marker that identifies patients at high risk for subsequent wound infection. However, in patients who have received prophylactic antibiotics, intraoperative cultures cannot be relied on to guide the choice of empiric therapeutic antibiotics for postoperative infections. Bacteria responsible for these infections are not identified by cultures taken at the time of surgery and are often resistant to the class of antibiotics used for prophylaxis.

Adolescent↗

PubMed1986

Evaluation of patients for cochlear implant by promontory stimulation. Psychophysical responses and electrically evoked brainstem potentials.

The protocol for assessing patients for cochlear implantation at University College Hospital and the Royal National Institute for the Deaf, London, includes a session of electrophysiological tests and electrical stimulation of the cochlea. Electrocochleography is performed with the object of excluding non-organic hearing loss and of clarifying the site of deafness. Using the same transtympanic needle, AC and DC electrical stimulation is performed to establish whether patients perceive a sensation of sound, dynamic range and ability to detect frequency shifts. Tinnitus suppression was produced by AC and DC stimulation. It is likely that AC suppression of tinnitus occurs by a masking effect. Electrically evoked auditory brainstem potentials were recorded in one patient.

Brain Stem↗

PubMed1986

Phase I and pharmacokinetic study of LM985 (flavone acetic acid ester).

We have conducted a Phase I and initial clinical pharmacological evaluation of LM985, the first of a series of compounds based on the flavone ring structure to be considered for clinical trial in malignant disease. The drug was administered i.v. to 26 patients with advanced cancer on an every-21-day schedule. Patients were treated at 14 dosage levels ranging from 10 to 1500 mg/m2. Dose limiting toxicity was identified as acute reversible hypotension occurring during drug infusion; no leukopenia, alopecia, hepatic toxicity, or renal toxicity was observed, but at the higher dose range, mild sedation was apparent. Twenty patients had measurable disease and were evaluable for response. One patient with colorectal carcinoma had stable disease after three courses of LM985; however, no other responses were seen. Pharmacokinetic and in vitro drug degradation studies imply that the ester LM985 is hydrolyzed to LM975 (flavone acetic acid) rapidly in vivo. LM975 is active in a variety of animal tumor models, but it does not have the cardiovascular side effects seen with LM985 (hypotension and bradycardia) in pithed or anesthetized rats. We would recommend that LM975 be considered for clinical trial, because it seems likely that substantially higher doses of LM975 than of LM985 can be given without dose limiting cardiovascular toxicity.

Adult↗

PubMed1985