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Biomedical subjects

J Graham

Publications and source records attributed to J Graham.

At least 37 records · Page 2Linked to original sources
PubMed1988

Cochlear implants in children: physiological considerations.

Cochlear implants now play a standard role in the management of adults with acquired profound sensorineural deafness. Their role in children is more controversial. However, as demonstrated by a 1979 report on childhood deafness in the European Communities, there is no reason for complacency in the present management of profoundly deaf children. Transtympanic electrocochleography has been used as a method of estimating neural survival in deafened adults being assessed for the U.C.H./R.N.I.D. single channel extracochlear implant and also in a parallel group of profoundly deaf children referred by a paediatric hearing assessment clinic. In adults the effectiveness of electrocochleography in judging neural survival was monitored by electrical stimulation of the cochlea and found to be significantly effective. This result was extrapolated to the paediatric group to estimate the proportion of congenitally deaf children who might benefit from a cochlear implant. It is suggested that in a programme designed to implant such children at 2 years of age, techniques should be chosen that neither damage the cochlea nor the middle ear sound conducting mechanism.

Adult↗
PubMed1988

Results of treatment of non seminomatous germ cell tumours; 122 consecutive cases in the West of Scotland, 1981-1985.

Between January 1981 and December 1985, 122 patients with non-seminomatous germ cell tumours (NSGT) were seen at a regional referral centre. Of these, a total of 98 patients received chemotherapy for metastatic disease. Treatment was given within collaborative EORTC Urology group studies, all of which involved cis-platin-containing schedules. Ninety patients had tumours of testicular origin, and their 2 year actuarial survival rate is 91%; 8 had tumours of extragonadal origin and their 2 year actuarial survival is 25%. Patients with testicular tumours were subdivided by volume of metastatic disease using the recommendations of the Testicular Cancer Subgroup of the MRC Urological Cancer Working Party and survival was significantly worse in the group with very large volume metastatic disease (VLVM, 57%) compared with the groups with large volume metastases (LVM, 100%) and small volume metastases (SVM, 98%). There were 31 patients with Stage I disease at presentation; of these 6 were treated by prophylactic abdominal radiotherapy and 25 were managed by a policy of surveillance only. Seven of these Stage I patients (23%) relapsed with metastatic disease (median 8 months); all have been successfully treated with chemotherapy. These data confirm that the majority of patients now presenting with metastatic NSGCT are curable with chemotherapy, but that a small proportion with very large volume metastases or extragonadal tumours require alternative chemotherapy schedules.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

The impact of preoperative skin disinfection on preventing intraoperative wound contamination.

The efficacy of total body showering and incision site scrub with disinfectant agents was evaluated in a randomized, prospective study of 575 patients undergoing selected surgical procedures. Patients who showered twice with 4% chlorhexidine gluconate had lower mean colony counts of skin bacteria at the surgical incision site in the operating room prior to the final scrub than patients who showered twice with povidone-iodine solution or medicated bar soap. Patients in the chlorhexidine group had no growth on 43% of the incision site skin cultures compared with 16% in the povidone-iodine group and 6% in the soap and water group. Patients who showered and who were scrubbed with chlorhexidine also had lower rates of intraoperative wound contamination. Bacteria were recovered from the wounds of 4% of patients using this regimen compared with 9% for patients who used povidone-iodine and 15% for patients who showered with medicated soap and water and were scrubbed with povidone-iodine. We noted no difference in surgery-specific infection rates among patients in the three treatment groups; however, our sample sizes were too small to evaluate this outcome parameter adequately. These data suggest that preoperative showering and scrubbing with chlorhexidine is an effective regimen to reduce extrinsic intraoperative contamination of the surgical wound from skin bacteria. The efficacy of this regimen to prevent postoperative wound infection needs to be evaluated in a well-designed, carefully controlled prospective trial with adequate numbers of patients to achieve statistically valid conclusions.

Baths↗
PubMed1987

Receptor-mediated endocytosis of enterokinase by rat liver. Preliminary characterisation of low-density endosomes.

The endocytosis of enterokinase by rat hepatocytes has been studied both in a perfused liver system and in the intact, anaesthetised animal. 10 min after administration of the enzyme, only 70% of the activity was cleared by the perfused liver, whereas clearance was total in the intact animal. In both cases, about 85% of the internalised enzyme co-purified with the smooth microsomes and virtually all (more than 90%) of the catalytic activity was latent and could only be detected in the presence of detergent. After 10 min, 22.5% of the activity remained with the sinusoidal plasma membrane in the case of the perfused liver, while for the intact animal this figure was only 10%, confirming the more efficient clearance of enterokinase in the intact animal. Further subcellular fractionation showed that in the anaesthetised animal 8% of the internalised enzyme was associated with a low-density Golgi-like endosomal compartment (prepared from the mitochondrial pellet), whereas the corresponding value for the perfused liver was only 2.5%. Enterokinase specific activity was also up to 50-times greater in the low-density endosomes prepared from the intact animal. A second low-density Golgi-like compartment (purified from the smooth microsomes) also contained latent enterokinase, which together with the endosomes derived from the mitochondria accounted for 20% of the total enterokinase internalised by the liver 10 min after its administration to the intact animal. The passage of enterokinase through these two low-density compartments was shown not to be synchronous with its passage through the peripheral (sinusoidal membrane) and internal endosomes (smooth microsomes). There were qualitative differences in marker enzymes and polypeptide composition between the mitochondria and microsome-derived low-density endosomes. The sub-fractionation of low-density fractions on shallow sucrose gradients revealed a complex enzyme and polypeptide heterogeneity both between and within fractions. There was an apparent density-dependent separation of enterokinase from galactosyltransferase and the asialoglycoprotein receptor which was coincident with marked changes in the polypeptide composition of the endosomal membranes, particularly in the 30-45 kDa range.

Animals↗
PubMed1987

Compliance with oral drug therapy in patients with hematologic malignancy.

Compliance with oral self-administered allopurinol (daily medication) and prednisone (intermittent medication) as well as compliance with monthly scheduled clinic appointments, were examined in 108 patients with newly diagnosed hematologic malignancy. Baseline levels of compliance (control group) were compared to results obtained after implementation of three intervention packages, whose aim was to increase compliance. The packages included combinations of education, home psychologic support and restructuring, and training in pill taking. A 24-hour profile of the two drugs and their metabolites was first determined. Serum samples were then obtained monthly over 6 months and analyzed for presence of the drugs. Control patients were fully compliant with allopurinol only 16.8% of the time. This rate increased significantly (44% to 48% of the time) for those who received any one of the intervention programs. With respect to prednisone, control patients were compliant 26.8% of the time, with no real improvement after interventions. Finally, self reports overestimated compliance by a factor of two when compared to drug analysis. The results indicated that full compliance with oral medications was remarkably low among our patients who have treatable and in some cases curable hematologic malignancy. However, compliance can be significantly improved by the use of various intervention packages.

Administration, Oral↗
PubMed1987

Automation of routine clinical chromosome analysis. I. Karyotyping by machine.

An automated karyotyping system suitable for widespread use in clinical laboratories is described. The software is implemented on a general-purpose, commercially available image analyzer (Magiscan 2) using TV input from a conventional research microscope with minimal modification. The analysis is automatic, but operator interaction is used to resolve difficulties. Extensive experience with a routine clinical workload shows that the system is robust and easy to use and that its use results in a substantially increased laboratory throughput.

Chromosomes↗
PubMed1987

Automation of routine clinical chromosome analysis. II. Metaphase finding.

Metaphase finding is an essential activity in chromosome analysis, and there is much to gain from its automation. This paper describes software for automatic metaphase finding developed for use as part of a routine clinical chromosome analysis system, principally for samples from blood and amniotic fluid. Since the metaphase finding and analysis programs were intended to be used widely in clinical laboratories, cost and portability were important design features. The metaphase finder has been implemented on a moderately priced, general-purpose image analyzer (Magiscan 2), which controls a standard research microscope with motorized stage and focus. Metaphases are detected using fast gray-level processing on whole fields of view, followed by binary processing to produce a figure of merit for each detected object. Clinical experience has shown that this ability to rank detected objects on the basis of their suitability for analysis is a critical feature in determining the usefulness of an automatic metaphase finder.

Amniotic Fluid↗
PubMed1986

The effect of verapamil on the pharmacokinetics of adriamycin.

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

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↗