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Biomedical subjects

J T Roberts

Publications and source records attributed to J T Roberts.

At least 91 records · Page 5Linked to original sources
PubMed1986

Microbial examination of kidney lithotripter tub water and epidural anesthesia catheters.

Kidney lithotripsy patients frequently receive epidural anesthesia via indwelling epidural catheters. In our hospital, patients are immersed in a tub of warm, continuously-flowing tap water. The epidural catheter-entry site is covered by a transparent occlusive dressing. To determine the risk of microbial colonization of the epidural catheter during lithotripsy, we performed quantitative cultures of tub water and semiquantitative cultures of catheters in 63 lithotripsy procedures. Most of the tub water organisms were typical tap water and skin flora isolates. Total colony counts were generally low with no significant progression during the course of serial procedures. Forty-two epidural catheters were cultured; 34 (81%) were sterile, 8 (19%) were colonized with small numbers of flavobacteria or coagulase-negative staphylococci. Only four catheters had organisms present on catheter segments covered by the transparent occlusive dressing (in each case there was a single colony forming unit per semiquantitative plate) and these organisms were probable contaminants. We conclude that with our current lithotripsy procedures, the risk for the development of epidural catheter-associated infection seems to be low.

Anesthesia, Epidural↗
PubMed1986

A clinical phase I toxicity study of Ro 03-8799: plasma, urine, tumour and normal brain pharmacokinetics.

Ro 03-8799 is a lipophilic, basic 2-nitroimidazole of greater potency than misonidazole, which we have administered to 52 patients. The dose-limiting toxicity is an acute central nervous system toxicity with symptoms which include nausea, disorientation, sweating, a feeling of heat and, in one extreme case, coma. Pharmacokinetic analysis was carried out in 31 patients. The mean distribution phase half-life was 44 min and the mean elimination half-life was 6.1 h. Peak concentration was linearly related to dose over the range 0.25 g/m2 to 3 g/m2 with a mean at 1 g/m2 of 15.7 micrograms/ml. Area under the curve was also linearly related to dose and the average whole body clearance was 20.1 l/h. Urinary recovery at 24 h was 31% for the parent compound and 28% for the N-oxide metabolite. The drug is concentrated in normal brain, brain tumour and non-brain tumour to a similar extent, the respective mean tissue/plasma ratios being 381%, 329% and 355%. For a dose of 1 g/m2, tumour concentrations were 1.5 times as high as for misonidazole, and the available in vivo and in vitro sensitisation data predict as improvement of 1.8 and 3.3 times respectively.

Astrocytoma↗
PubMed1986

Hibernoma: a patient examined by CT.

We describe the computed tomographic (CT) findings in a patient with a hibernoma of the thigh, a rare tumor of brown fat. There are no specific features to allow differentiation from the more common low grade liposarcoma. This is in agreement with the only other published report of the CT features of hibernoma. Although preoperative diagnosis requires biopsy, CT is of value in detecting fatty tumors and in preoperative planning.

Adipose Tissue, Brown↗
PubMed1986

Magnetic resonance spectroscopy of the musculoskeletal system.

Magnetic resonance spectroscopy can be used to characterize the bioenergetic state of the musculoskeletal system, and several marker compounds related to the tissue's biochemistry have been found to exist. Potential new techniques involving better spatial localization, spectral editing, and examination of nuclei other than phosphorus are in the developmental stage. Their development over the next few years will determine the extent to which MRS will become a universally used medical tool. However, the results with 31P alone guarantee a continued role in the study of muscular disease, peripheral vascular disease, and hypoxia and ischemia of the neonatal brain.

Adolescent↗
PubMed1985

Severe constrictive pericarditis after single 16 MeV anterior mantle irradiation for Hodgkin's disease.

Severe constrictive pericarditis developed in 4 of 73 patients after single anterior 16 MeV mantle field irradiation for Hodgkin's disease. 3 patients (4.1%) died; the other had successful pericardectomy. Use of a single anterior mantle field of high-energy X-rays is clearly more hazardous than conventional opposed-field techniques, and the resulting radiation pericarditis is difficult to treat.

Adolescent↗
PubMed1985

Clinical pharmacokinetics of oral CCNU (lomustine).

The plasma pharmacokinetics of orally administered CCNU (130 mg/m2) were studied in four patients using reversed-phase high-performance liquid chromatography (HPLC) analysis. Parent CCNU was not detected in the plasma of any of the patients, probably due to complete conversion to monohydroxylated metabolites during the 'first pass' through liver and gut. However, two monohydroxylated metabolites, trans-4-hydroxy CCNU and cis-4-hydroxy CCNU, were found at high concentrations, the relative amounts being about 6:4. Peak concentrations of the metabolites were reached 2-4 h after administration and were remarkably similar for all four patients, the total being 0.8-0.9 micrograms/ml. The metabolites were also detected in a tumour biopsy. Plasma clearance half-lives of the two metabolites were similar in each patient but showed a two-fold variation between patients, from 1.3 to 2.9 h. These results suggest that the antitumour activity and systemic toxicity of CCNU when given orally are due mainly to its monohydroxylated metabolites. Finally, comparison with data obtained in vitro and in mice showed that the nitrosourea exposures in these patients were at the lower limit of those required for significant antineoplastic activity.

Administration, Oral↗
PubMed1985

Benznidazole with CCNU: a clinical phase I toxicity study.

It has been shown in a variety of model systems that benznidazole (BENZO) is capable of enhancing the cytotoxicity of a number of drugs, including nitrosoureas. We report an escalating dose toxicity study of the combination of BENZO and CCNU on 34 patients in whom the usual clinical dose of CCNU (130 mg/m2) was given together with escalating doses of BENZO (up to a maximum dose of 40 mg/kg). We have observed no BENZO-related toxicity and no evidence that, in the dose range studied, BENZO enhances the gastrointestinal or hematological toxicity of CCNU. It is possible to administer the usual dose of CCNU together with doses of BENZO that can be shown to have a clear effect on the pharmacokinetics of CCNU and which might be expected, from the results of animal experiments, to produce enhancement of its cytotoxicity. A Phase III study of the combination is in progress.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1985

Dangerous rises in blood pressure upon heating of trigeminal rootlets; increased bleeding times in patients with trigeminal neuralgia.

During radiofrequency (RF) heating of trigeminal rootlets, we regularly measured blood pressure rises to 250 to 300 mm Hg, confirming two previous reports. We also found abnormally increased bleeding times in 12% of 127 patients awaiting operation for trigeminal neuralgia. These two facts probably explain 6 fatalities and 2 lasting hemiplegias from intracranial bleeding unrelated to vascular puncture by the needle electrode during RF procedures for trigeminal neuralgia. We recommend correction of the abnormal bleeding time and control of the blood pressure rises by i.v. sodium nitroprusside.

Arrhythmias, Cardiac↗
PubMed1984

A phase I study of the combination of benznidazole and CCNU in man.

The 2-nitroimidazole benznidazole (BENZO) has previously been shown to be an effective potentiator of the cytotoxicity of CCNU in mice, at levels which are achievable in man. This enhancement is greater than that for normal tissues, resulting in a therapeutic gain. In this study BENZO has been given to 46 patients in oral doses of 4 mg/kg to 30 mg/kg, and drug concentrations measured in plasma, urine, tumor and normal brain by HPLC. The mean plasma t 1/2 was 12.8 +/- 0.5 h and plasma peak concentration and AUC0-infinity were linearly related to dose over the whole range. Approximately 60% of the drug was bound to plasma proteins and 6% excreted unchanged in urine. Mean tumor/plasma ratios of 88% (range 54 to 122%) for 11 gliomas and 72% (range 46 to 103%) for 6 superficially accessible non-brain tumors were obtained while that for normal brain was 69% (range 53 to 75%). Doses of more than 17 mg/kg BENZO produce changes in the plasma pharmacokinetics of CCNU (130 mg/m2 p.o.), increasing the half life of active hydroxylated metabolites. In addition, CCNU parent compound is present. This is not seen when CCNU is given alone. Such changes may result in improved response rates as it is possible to achieve in man, plasma and tumor levels of BENZO, which in the mouse model produce effective enhancement of the response to CCNU. No evidence was seen that BENZO enhanced wither the acute gastrointestinal toxicity or the hematological toxicity of CCNU over the dose range studied.

Drug Evaluation↗
PubMed1984

A phase I study of the hypoxic cell radiosensitizer Ro-03-8799.

The 2-nitroimidazole hypoxic cell radiosensitizer Ro-03-8799 has been suggested to have possible advantages over misonidazole with regard both to radiosensitization and toxicity on the basis of reported experimental work. The present work reports a Phase I escalating dose toxicity study of the drug. This has shown severe acute central neurotoxicity at high dose levels (greater than 1 g/m2). Initial results of a multiple-dose toxicity study indicate that 1 g/m2 is likely to be the maximum dose which may be given repeatedly. The plasma and tumor pharmacokinetics of the drug have been measured. The mean t 1/2 for 9 patients was 5.8 +/- 1.5 hr. Peak plasma concentration is linearly related to dose and at 1 g/m2 is 12.1 +/- 2.3 micrograms/ml (n = 6). Human tumor drug concentrations have been measured after single doses of 1 g/m2 given to 8 patients with a variety of tumors. Peak tumor concentrations of drug of 11.7-81.6 micrograms/g were found. Because of acute, dose-limiting toxicity related to individual doses it may not be possible to achieve, in human tumors, concentrations of drug that offer significant advantage over misonidazole in terms of radiosensitizing efficiency. No evidence of chronic cumulative toxicity was observed at the doses employed.

Drug Evaluation↗
PubMed1983

Total skin electron irradiation for mycosis fungoides: failure analysis and prognostic factors.

From 1970 to 1980, 106 patients with mycosis fungoides received total skin electron irradiation to full tolerance. The majority received 30 Gy of 3 MeV electrons in 12 treatments over three weeks. Eighty-eight patients had received prior therapy. Fifty patients had cutaneous plaques only (T1-2N0), and 56 had more advanced disease. At five years, actuarial survival is 66.7% and disease-free survival 21.4%. The median time to relapse is 12 months; prolonged survival is seen only with complete response. Compared with more advanced stages, T1-2N0 patients have more frequent complete response (96% vs 71%) and better relapse-free survival at five years (32 vs 7%). Of 14 patients with T2 disease in continuous complete remission for from 45-113 months, only one has relapsed. This suggests that cure is possible in up to 26% of patients with T2 disease who achieve complete response. In advanced stages, complete response is more likely with doses over 25 Gy (80 vs 50%). First recurrences were predominently in sites of previous involvement. Death resulted mainly from extracutaneous dissemination or failure to induce remission.

Aged↗
PubMed1983

The penetration of misonidazole and desmethylmisonidazole into brain tumours and other central nervous system tissues in man.

The concentration of drug after oral administration of 1 g misonidazole to patients undergoing neurosurgery has been studied in samples taken from intracerebral tumours, normal brain, cerebrospinal fluid and brain tumour cyst fluid. A total of 31 patients yielded samples at various times 2-8 h after drug administration. Results show a considerable range of tumour/plasma percentages but from about 2-5 h after drug administration this averaged between 65-80%. Normal brain and CSF showed similar good penetration but drug entry into cyst fluid was lower (30-50%). A further study with desmethylmisonidazole given to 11 additional patients showed a similar range of tumour penetration but lower concentrations in CSF and cyst fluid (10-20%). Low values were also seen in some but not all of the normal brain tissue samples. Necrotic tumour also had much lower concentrations than macroscopically viable tissue. These results are discussed in terms of their clinical relevance to sensitiser studies on patients with brain tumours with drugs of different lipophilicities.

Adolescent↗
PubMed1981

A human coenurus infection in Canada.

This is the first description of human coenurus infection in Canada. The patient, a 38-year-old Caucasian woman, suffered severe and incapacitating symptoms, including recurrent rash, pyrexia, night sweats and lymphadenopathy, that were suspicious of a lymphoma, possibly Hodgkin's disease. She received several trials of chemotherapy over a 3-year period which controlled her symptoms, but only during the treatment periods. The appearance of a hemorrhagic mass in the left breast led to the surgical removal of bladder-like cysts. The patient's symptoms have not recurred since the cysts were exercised. These have been identified as larvae of Taenia serialis.

Adult↗
PubMed1981

Familial variant of dermatofibroma with malignancy in the proband.

Multiple fibrous histiocytomas of the dermis (dermatofibromas) were found in six males of one family. A number of the tumors fell within the histologic patterns commonly encountered in dermatofibromas, but some were unusually large and others were cytologically atypical. In addition, the proband died of a malignant fibrous histiocytoma of the lung. We believe that this is a syndrome and a familial variant of a common dermal entity.

Fibroma↗
PubMed1978

Cutaneous vasculitis.

In this paper the current concepts of cutaneous vasculitis are reviewed, with emphasis on clinical patterns, strict pathologic criteria and mechanisms of injury. A plea is made to classify vasculitis not as syndromes but (a) according to organ involvement (limited cutaneous or complicated multisystem), (b) by cause, (c) by pathologic description and (d) by anatomic depth and type of vessel involvement.

Adult↗
PubMed1978

Selection of tumors with a poor prognosis in operable carcinoma of the endometrium.

A retrospective review of 405 patients with operable cancer of the endometrium tested the hypothesis that histological grading might serve to select patients with a poor prognosis for additional external radiation. Deaths from disease by the fifth anniversary were 10 times higher (28/109 - 26%) among patients in the poorly differentiated group - who made up 27% of those assessed. There were 7/288 deaths (2.5%) in the well-differentiated group. A sample of 114 curettage specimens from the above cases, graded without knowledge of the clinical findings, gave a similar result. The FIGO grading system has the advantage of having well-defined dividing lines between grades 1, 2 and 3. However, its value in clinical practice is limited, since the prognostic watershed between well-differentiated and poorly differentiated cases falls well within grade 2. The separation between grade 1 and hyperplasia is also poorly defined and may affect the interpretation of oestrogen studies in relation to endometrial cancer incidence.

Female↗