Biomedical subjects

M D Redmond

Publications and source records attributed to M D Redmond.

9 recordsLinked to original sources

PubMed1997

Association of cisplatin nephrotoxicity with patient characteristics and cisplatin administration methods.

OBJECTIVE: To assess factors that affect cisplatin nephrotoxicity. METHODS: In 425 patients treated with cisplatin, we assessed the effect of pretreatment factors and treatment conditions on the rise in serum creatinine with the first course of cisplatin, on the maximum rise in serum creatinine over the entire course of the cisplatin therapy, and on residual nephrotoxicity after the last cisplatin treatment ended. (Because of the nature of the relationship between serum creatinine and creatinine clearance, rise in serum creatinine was divided by pretreatment creatinine squared.) Patients were dichotomized into the upper quartile versus the lower three quartiles of degree of nephrotoxicity. Multivariate analyses were based on logistic regression, controlling for cisplatin dose per course. RESULTS: Controlling for cisplatin dose per course, factors most closely associated with nephrotoxicity during the first course of cisplatin were: serum albumin and potassium, body surface area, and administration of cisplatin over 2-5 days per course vs 1 day (negative associations). Controlling for cisplatin dose per course, the single factor most closely associated with maximum life-time cisplatin nephrotoxicity was concurrent use of a vinca alkaloid (negative association). Controlling for cisplatin dose per course, factors most closely associated with residual nephrotoxicity after the end of cisplatin therapy were cumulative dose of cisplatin, concurrent use of metoclopramide (positive associations), uric acid and concurrent use of phenytoin and a vinca alkaloid (negative associations). The association of nephrotoxicity with uric acid and with body surface area was felt to be an artifact resulting from its positive association with pretreatment serum creatinine. Nephrotoxicity during the first course of cisplatin also correlated significantly with autopsy kidney cortex platinum concentrations in 77 evaluable patients. CONCLUSIONS: (1) While several factors correlated with cisplatin nephrotoxicity, most of the observed nephrotoxicity was not explained by the variables identified. (2) While most patients received intravenous hydration, patients receiving high hydration volumes did not have significantly less nephrotoxicity than patients receiving lower hydration volumes: (3) Of the variables identified, serum albumin, metoclopramide and phenytoin may have affected nephrotoxicity by altering cisplatin uptake into or distribution within the kidney.

Antineoplastic Agents↗

PubMed1995

Factors affecting platinum concentrations in human surgical tumour specimens after cisplatin.

We assessed factors which affect cisplatin concentrations in human surgical tumour specimens. Cisplatin 10 mg m-2 was given i.v. to 45 consenting patients undergoing surgical resection of neoplasms, and platinum was assayed in resected tumour and in deproteinated plasma by flameless atomic absorption spectrophotometry. By multiple stepwise regression analysis of normalised data, patient characteristics that emerged as being most closely associated (P < 0.05) with tumour platinum concentrations (after correcting for associations with other variables) were tumour 'source' [primary brain lymphomas, medulloblastomas and meningiomas ('type LMM') > 'others' > lung cancer > head/neck cancer > gliomas) or tumour 'type' (LMM > brain metastases > extracerebral tumours > gliomas), serum calcium and chloride (positive correlations) and bilirubin (negative). Tumour location (intracranial vs extracranial) did not correlate with platinum concentrations. If values for a single outlier were omitted, high-grade gliomas had significantly higher platinum concentrations (P < 0.003) than low-grade gliomas. For intracranial tumours, the computerised tomographic scan feature that correlated most closely with platinum concentrations in multivariate analysis was the darkness of peritumoral oedema. Tumour source or type is a much more important correlate of human tumour cisplatin concentrations than is intracranial vs extracranial location. Serum calcium, chloride and bilirubin levels may affect tumour cisplatin uptake or retention. CT scan characteristics may help predict cisplatin concentrations in intracranial tumours.

Blood-Brain Barrier↗

PubMed1994

Factors affecting human autopsy kidney-cortex and kidney-medulla platinum concentrations after cisplatin administration.

The objective of this study was to determine factors that affect cisplatin concentrations in human kidney cortex. We used flameless atomic absorption spectrophotometry to assay platinum in autopsy specimens of kidney cortex obtained from 83 cisplatin-treated patients. Concentrations were correlated with pretreatment factors and treatment conditions using univariate nonparametric statistics. Hierarchical stepwise multiple regression analyses of transformed (to normalize) data were then used to assess which factors were most important, controlling for other factors. Kidney-cortex platinum concentrations varied from 0 to 14.8 micrograms/g (median, 2.04 micrograms/g). The cumulative lifetime dose of cisplatin ranged from 10 to 1120 mg/m2 (median, 112 mg/m2). The time from the last cisplatin dose to death was < 1-609 days (median, 38 days). According to univariate statistics, factors that correlated (P < 0.05) with kidney-cortex platinum concentrations were the cisplatin dose per course, the pretreatment serum urea level, metoclopramide use (positive correlations), the time from the last cisplatin treatment to death, and the pretreatment serum albumin value (negative correlations). Factors that approached significance (0.05 < or = P < or = 0.10) were a history of hypertension, hyperbilirubinemia (positive), the serum calcium level, and phenytoin use (negative). In the multiple regression analysis, after controlling for the cisplatin dose per course and the time from the last treatment to death, only concurrent metoclopramide and phenytoin use entered the model. The hydration volume did not affect corrected kidney-cortex or kidney-medulla platinum concentrations. The following conclusions were reached: (1) it may be feasible to use lower hydration volumes than those used routinely, (2) any effect of hydration volume on cisplatin nephrotoxicity may not be mediated via a reduction in kidney-cortex platinum concentrations, (3) higher cisplatin doses might be tolerated with new 5-hydroxytryptamine-3 (5HT-3) antiemetics than were tolerated with metoclopramide, and (4) phenytoin should be tested for its ability to reduce cisplatin nephrotoxicity.

Autopsy↗

PubMed1993

Human autopsy tissue distribution of the epipodophyllotoxins etoposide and teniposide.

Autopsy tissues were collected from ten patients who had received etoposide, 150-3480 mg, from 1 to 412 days antemortem and from five patients who had received teniposide, 234-1577 mg, from 3 to 52 days antemortem. Tissues were assayed for etoposide and teniposide using high-pressure liquid chromatography with electrochemical detection. Etoposide was detectable in tissues of three of four patients dying < 5 days after their last etoposide treatments to cumulative doses of 150-432 (median, 280) mg but was detectable in tissues of only one of six patients dying 7-412 (median, 37) days after their last etoposide treatment to a cumulative dose of 607-3600 (median, 1553) mg. The highest tissue concentrations were in the small bowel, prostate, thyroid, bladder, spleen, and testicle. Intermediate concentrations were found in the lymph node, skeletal muscle, adrenal gland, stomach, tumor, liver, lung, pancreas, and kidney, and the lowest concentrations were found in the heart, brain, diaphragm, vagina, and esophagus. Teniposide was detectable in one patient dying 3 days after a cumulative teniposide dose of 576 mg (spleen, prostate, heart > large bowel, liver, pancreas > thyroid, adrenal, stomach, small bowel, bladder, testicle, and skeletal muscle) but was not detectable in any tissue from four patients dying 5-52 (median, 8) days after their last treatment to a cumulative teniposide dose of 234-1577 (median, 520) mg. The very short tissue half-life contrasts with our previous observations for human autopsy tissue concentrations of mitoxantrone, doxorubicin, menogaril metabolites, diaziquone, and amsacrine. The short tissue half-life may help explain the schedule dependency of epipodophyllotoxin efficacy and may also help explain the lack of visceral toxicity of these compounds.

Chromatography, High Pressure Liquid↗

PubMed1990

Isolated lesion of the lateral cutaneous nerve of the forearm.

Because of its location in the antecubital fossa, the lateral cutaneous nerve of the forearm is at risk of injury when a person is carrying objects with the forearm flexed or during venipuncture. Injury to this nerve, however, is rarely reported. A case report of traumatic injury to the lateral cutaneous nerve, the use of appropriate nerve conduction studies for diagnosis, and a discussion of the available literature is presented.

Adult↗

PubMed1990

Radial motor nerve conduction studies.

The radial motor nerve fibers were studied in 30 subjects using a technique of surface stimulation in the axilla and the antecubital fossa. Surface recording over the extensor digitorum communis 8cm from the distal stimulation site was done. Mean distal latency was 2.6msec (SD = 0.44), amplitude 11.24mV (SD = 3.5), and conduction velocity 68m/sec (SD = 7.0). Side-to-side comparison using the t-test demonstrated no significant differences. Five subjects were tested 75 more times on two successive days and showed a variation in latency of 0.2msec or less in 74 of 75 trials. Amplitude was consistent during each day's trial, but it varied slightly from one day to the next. Three case reports show the usefulness of the procedure.

Adolescent↗

PubMed1988

Hypoglossal nerve conduction in normal subjects.

A nerve conduction method is demonstrated for cranial nerve XII, the hypoglossal nerve. Submandibular surface stimulation is performed while recording over the anterior surface of the tongue. There were 30 normal adult subjects and 60 hypoglossal nerves studied. Evoked response parameters are reported as follows: mean latency 2.2 +/- 0.4 msec, mean amplitude 3.8 +/- 1.6 mV (baseline to peak, best of 5 responses). This nerve conduction method is reliable and should expand the electrophysiological assessment of XII cranial nerve motor function.

Adult↗

PubMed1988

False positive electrodiagnostic tests in carpal tunnel syndrome.

Of 50 normal subjects, 23 (46%) had at least one false positive electrodiagnostic test for carpal tunnel syndrome (CTS). There were 30% of the subjects who exhibited an abnormal median to ulnar sensory amplitude ratio of less than 1.1. In 7 subjects 8 extremities (14%) revealed prolonged residual latencies, and 4 extremities in 4 subjects (8%) had a difference of 0.4 msec between the median and ulnar palmar sensory latencies. The results of this study indicate that certain reported criteria for CTS are abnormal in a high percentage of normal subjects, thereby making them of limited value in the diagnosis of CTS. Of all the criteria studied, it appears that the comparison of the median to ulnar sensory latency across the carpal tunnel is of greatest potential value. However, even here a more conservative difference of 0.5 msec between median and ulnar nerves must be used to avoid false positive tests for CTS.

Adult↗

PubMedDate not supplied

Concentrations of doxorubicin and its metabolites in human autopsy heart and other tissues.

PURPOSE: Since doxorubicin causes cardiotoxicity, we wished to assess relative concentrations of doxorubicin and its metabolites in cardiac tissues of patients who had been treated antemortem. We also wished to determine factors that correlate with human cardiac doxorubicin and doxorubicinol concentrations. PATIENTS AND METHODS: Autopsy tissues were collected from 35 patients who had received doxorubicin at any time antemortem, and were assayed by high pressure liquid chromatography. RESULTS: The major species found in human autopsy cardiac tissues were doxorubicinol (median concentration 92 ng/g, range 0 to 484 ng/g), and doxorubicin (median 58 ng/g, range 0-1665 ng/g). Other doxorubicin metabolites were detected in cardiac tissues in < half the patients. Of ten organs studied, heart ranked fifth with respect to median doxorubicin concentration and ranked fourth with respect to median doxorubicinol concentration. By multiple stepwise regression analysis, factors most closely associated with cardiac doxorubicin concentrations were time from last treatment divided by dose intensity, serum total protein, albumin, and hemoglobin (negative correlations). Factors most closely associated with cardiac doxorubicinol concentrations were cumulative doxorubicin dose, total protein, hemoglobin, and uric acid (positive associations), and respiratory rate (negative association). The physiologic significance of these associations (if any) is uncertain. By paired t-tests, cardiac doxorubicin and doxorubicinol concentrations were significantly (p < 0.05) higher than concentrations in skeletal muscle and smooth muscle organs. CONCLUSIONS: Overall, the results suggest that the much greater tendency to develop doxorubicin toxicity in heart than in other types of muscle may be due to a propensity of cardiac muscle to accumulate doxorubicin. The results also suggest that doxorubicinol may play a role in doxorubicin cardiac toxicity, and that doxorubicin may be gradually converted to doxorubicinol in human tissues.

Autopsy↗