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N Z Mikhael

Publications and source records attributed to N Z Mikhael.

At least 19 recordsLinked to original sources
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↗
PubMed1991

Evaluation of a simple line width test involving magnetic resonance spectroscopy of plasma in carcinoma of the ovary.

Magnetic resonance spectroscopic (MRS) measurement of human plasma has been reported as a generally applicable marker for malignancy: patients with malignancy had a MRS line width significantly different from patients with benign diseases or healthy controls. The authors investigated the value of this test in 213 women with ovarian carcinoma, benign pelvic masses, benign nongynecologic diseases, and healthy controls. The MRS measurements were performed on plasma samples at 21 degrees C or 27 degrees C. The line width parameters were obtained by averaging the width at half the height of the methyl and methylene peaks on the resonance spectra. At 27 degrees C using 33 Hz as the threshold for an abnormal result, there was a significant correlation between the result of the test and the presence or absence of malignancy. However, the study demonstrates that the specificity (0.44) and positive predictive value (0.42) are too low for the test to be useful in the management of patients with carcinoma of the ovary. At 21 degrees C no correlation between the results of the test and the clinical status of women with carcinoma of the ovary were observed. In 47 patients the test did not predict preoperatively the benign or malignant nature of a pelvic mass.

Carcinoma↗
PubMed1991

The clinicopathological significance of cytomegalovirus inclusions demonstrated by endocervical biopsy.

A healthy 20 yr old woman presented for evaluation following a cervical smear which showed viral effects typical of human papilloma virus. Colposcopy showed changes of cervicitis with the main finding on histologic examination of biopsy material being an acute and chronic cervicitis associated with typical features of cytomegalovirus (CMV) infection. Viral identification was confirmed by immunoperoxidase staining, in situ hybridization and electron microscopy. The patient was lost to follow up for 18 mths. Following this, a repeat colposcopy again showed inflammation, with cervicitis, mild dysplasia and CMV inclusions on biopsy. Full immunological work-up, including human immunodeficiency virus (HIV) study, was performed and was normal. Only 11 other cases of endocervical biopsies with histological evidence of CMV inclusions were found in the literature, although the reported rate of detection of genital CMV in women on culture is 4-12%. In the 9 cases where information was available, endocervical inflammation was present. One patient was on immunosuppressive medication for systemic lupus erythematosus and another was found to have Acquired Immune Deficiency Syndrome (17% of total). These cases demonstrate that although histologic examination is an insensitive marker for CMV within the cervix, its presence may signify immunodeficiency and so immunological assessment of a patient with this finding is advisable.

Adolescent↗
PubMed1988

Relationship between urine beta-2-microglobulin and platinum levels during cisplatin treatment.

We evaluated whether urine beta 2-microglobulin (beta 2M) excretion as a function of nephrotoxicity correlated with plasma and urine platinum levels in patients receiving cisplatin. Thirty-one patients had urine platinum measurements in urine samples collected at 0 to 6 and 6 to 24 h after cisplatin administration, 25 of these patients had serial plasma platinum measurements. Sixteen of the 31 patients had an increase in urine beta 2M. A significant correlation was obtained between urine platinum and beta 2M in the 6- to 24-h samples (r = 0.61, p less than 0.02). The mean plasma platinum levels were higher (12.6 +/- 6.1 mumol/L) in the patients with an increase in urine beta 2M compared to those patients with no change in beta 2M (6.8 +/- 4.1 mumol/L) (p less than 0.02). Our study indicates that tubular damage occurs within 24 h after cisplatin administration and that the damage correlates with urine platinum levels.

Adult↗
PubMed1988

Platinum concentrations in human autopsy tumor samples.

Platinum concentrations were determined in autopsy tumor samples obtained from 27 patients who had received cisplatin 40-1,029 mg/m2 from 0 to 240 days antemortem. Liver metastases had significantly higher platinum concentrations than did tumors in other sites (p less than 0.005). Platinum concentrations in liver metastases were similar to platinum concentrations in normal liver. Platinum concentrations in gliomas and brain metastases were similar to platinum concentrations in other extrahepatic tumors. Platinum concentration generally decreased with increasing distance into brain from tumor. By multiple stepwise linear regression analysis, the factors that were independently most closely associated with tumor platinum concentration were time from last cisplatin treatment, cumulative lifetime dose of cisplatin, route of cisplatin administration (intraarterial vs. other), and site of tumor deposit (liver vs. other) (r = 0.69, p less than 0.001). Patients whose tumors had responded to cisplatin-containing regimens had mean tumor platinum concentrations that were higher than the mean tumor platinum concentrations in patients whose tumors had not responded to cisplatin (p less than 0.05).

Autopsy↗
PubMed1987

Use of skin surface sampling and ion mobility spectrometry as a preliminary screening method for drug detection in an emergency room.

We have evaluated the use of a novel method for detecting drug residues on the hands of emergency patients suspected of drug overdose. The residues are collected by means of a suction probe and subsequently analyzed by thermal desorption directly into an ion mobility spectrometer. All patients admitted to the Emergency Room had their palms, fingers and nostrils sampled. Of the 101 drug related ingestions, 50 were related to tablets, 47 to film or sugar-coated tablets and 4 to cocaine powder. Positive identification was possible in 42% of tablet related ingestions, 29% of coated tablet or capsule ingestions and in all patients using cocaine. In 53% of the cases where positive drug identification was made, sampling had been carried out within 30 minutes of the patient's arrival at the Emergency Room.

Adult↗
PubMed1986

Hyperuricemia and hypoalbuminemia predispose to cisplatin-induced nephrotoxicity.

The usefulness of pretreatment biochemical parameters in the prediction of nephrotoxicity associated with cisplatin treatment was studied. Twenty-two patients, who received 29 cycles of cisplatin, were evaluated. Cisplatin was given every 3-4 weeks with saline and mannitol. Azotemia occurred in almost all patients and was transient, peaking 1-2 weeks after therapy. The change in serum creatinine from baseline to peak correlated inversely with pretreatment serum albumin (r = -0.73; P less than 0.01) and with pretreatment uric acid (r = 0.76; P less than 0.01). Ten patients with uric acid levels of less than 6 mg/dl were receiving allopurinol. The competition between organic anions and cisplatin for excretion may, in part, explain the protective effects of hypouricemia. Hypoalbuminemia affects peritubular oncotic pressure and may in turn affect platinum excretion. Hypoalbuminemia also reduces the half-life of cisplatin, exposing the kidney to more of the unbound filterable drug.

Cisplatin↗
PubMed1986

Hypoalbuminemia in patients receiving cisplatin: correlation between liver platinum and decrease in serum albumin.

We evaluated changes in serum albumin concentrations in 15 patients with advanced malignancy who were also receiving cisplatin. All 15 patients had serial measurements of serum albumin. The decrease in serum albumin from the time of the first dose of cisplatin to death correlated with liver platinum levels at autopsy (r = 0.46, p less than 0.05). The decrease in serum albumin concentration associated with liver platinum concentration of less than or equal to 1.5 micrograms/g was 0.16 +/- 0.23 g/dl (range 0-0.6). The decrease associated with liver platinum concentrations of greater than 1.5 micrograms/g was 1.0 +/- 0.45 g/dl (range 0.5-1.9; p less than 0.02). The decrease in serum albumin may be secondary to a hepatotoxic effect of cisplatin.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1986

Digoxin concentrations in postmortem human tissues.

An extraction procedure is described that allows the application of a commercially available enzyme-multiplied immunoassay technique to the measurement of digoxin in whole blood, liver, and kidney. The concentrations of digoxin were measured in tissues obtained at autopsy from five patients who had been taking therapeutic doses of digoxin prior to death. Blood concentrations at autopsy were found to be higher than the therapeutic range, perhaps due to postmortem redistribution. Liver concentrations of digoxin showed a positive correlation with blood concentrations; this was not found for kidney concentrations of the drug.

Cadaver↗
PubMed1986

Human autopsy tissue concentrations of mitoxantrone.

A sensitive high-performance liquid chromatography method was used to measure mitoxantrone in autopsy tissue samples of 11 patients who had received the drug iv 10-272 days antemortem. Mitoxantrone was readily detectable in tissues from all patients. Tissue concentrations were proportional to lifetime cumulative dose of mitoxantrone, and decreased very slowly with time. The thyroid and the liver had the highest mitoxantrone concentrations, followed by the heart. These high cardiac concentrations of mitoxantrone could be partially responsible for the occasional case of cardiotoxicity seen with mitoxantrone. The brain had the lowest mitoxantrone concentrations. Organ mitoxantrone concentrations did not conform to a flow-limited model. Tumor mitoxantrone concentrations varied quite markedly from one site to another in the same patient. Tumors generally had lower mitoxantrone concentrations than did surrounding normal tissues. Mitoxantrone concentrations were consistently highest in intrahepatic tumors and lowest in intracerebral tumors. It is unclear whether the low concentrations in brain tumors were due to a partially intact blood-brain barrier or to the fact that most brain tumors had been irradiated prior to mitoxantrone administration. Further studies are warranted to more fully explore the relationship between human tissue mitoxantrone concentrations and efficacy and toxicity.

Autopsy↗
PubMed1985

Adverse tissue reactions to drugs: a five-year surveillance study.

Over a 5-year duration a total number of 57 881 tissue specimens from hospitalized patients were evaluated clinicopathologically for evidence of adverse tissue reactions to drugs. The incidence of alleged adverse tissue reactions was 3.7% of which 1.5% were definitely shown to be caused by a specific pharmacological agent. Regardless of the category of the adverse tissue reaction, the frequency of drug-related responses occurred most often in females, especially between the ages of 41 and 60 years. The target tissue affected adversely most often was endometrium where hyperplasia was the predominant response noted. An oestrogenic preparation was found most frequently to be implicated in the observed adverse tissue reaction. Evaluation of adverse drug reactions with the use of morphologic technique provides a rigorous and reliable mechanism to monitor deleterious effects in hospitalized patients.

Adolescent↗
PubMed1985

Renal and hepatic concentrations of platinum: relationship to cisplatin time, dose, and nephrotoxicity.

Autopsy tissues were obtained from 30 patients who had received cisplatin antemortem; the tissues were assayed for platinum by flameless atomic absorption spectrometry. Patients with antemortem evidence of renal toxicity had higher renal cortical platinum concentrations than did patients without evidence of kidney damage. In addition, patients with nephrotoxicity were more likely than patients without toxicity to have renal cortical platinum concentrations that were higher than renal medullary platinum concentrations. Overall, the two variables most closely associated with an increase in serum creatinine with treatment were renal cortical platinum concentration (P less than .02) and cumulative dose of cisplatin (P less than .05). These two variables were important independently of one another. Renal cortex platinum concentrations correlated inversely with time from last treatment until death, whereas hepatic platinum concentrations did not. In contrast, hepatic platinum concentrations correlated with dose of cisplatin while renal platinum concentrations did not. Our results suggest the following: (1) cisplatin-induced renal toxicity is tissue-platinum-concentration dependent and cisplatin-dose dependent; and (2) cisplatin may be handled differently at the molecular level in liver and kidney.

Adult↗
PubMed1985

Increase in serum uric acid level associated with cisplatin therapy. Correlation with liver but not kidney platinum concentrations.

Hyperuricemia associated with cisplatin therapy is considered to be a consequence of cisplatin-induced nephrotoxic reactions. We correlated changes in serum uric acid levels in patients with malignant neoplasms with tissue levels of platinum and the total dose of cisplatin. In 15 patients, the serum uric acid level increased from 6.1 +/- 1.0 mg/dL to 8.3 +/- 1.3 mg/dL during the time they were receiving cisplatin therapy. The change in uric acid level from baseline to peak correlated with both the total dose of cisplatin and the liver platinum concentration. There was no correlation with platinum concentration in the renal cortex and medulla.

Cisplatin↗
PubMed1984

Monitoring of adverse drug reactions by means of autopsy tissue examination.

Morphologic examination of autopsy tissue specimens was undertaken to establish the incidence of adverse drug reactions in a population of hospitalised patients. By removal of subjective bias recording of adverse reactions, the incidence of toxic tissue manifestations was 33%. In those reactions classified as definitely linked to a specific causative agent males between the ages of 41 and 60 displayed the highest frequency of adverse effects. In the probable and possible categories the incidence of toxic manifestations was equal amongst both sexes and highest in patients over 40 y. Regardless of the type of adverse reaction the most common causative agent identified was alcohol and hepatic tissue was primarily altered morphologically. Unlike the conventional mechanism used to monitor adverse drug reactions, autopsy tissue examination provides a system of measurement of toxic manifestations to both prescription as well as non-prescription compounds.

Adult↗
PubMed1984

Detection of drugs in saliva of impaired drivers.

This study examined the feasibility of detecting drugs using saliva samples obtained from impaired drivers. Screening procedures on 1- to 2-mL samples were for cannabinoids, volatiles, benzodiazepines, and other acidic/neutral/basic drugs. Methodology consisted of enzyme multiple immunoassay technique (EMIT) and temperature programmed gas chromatography with confirmation by gas chromatography/mass spectrometry (GC/MS). Fifty-six samples were obtained from drivers arrested for suspicion of impaired driving. Other than alcohol, the major drugs detected were cannabinoids and diazepam. Cocaine was found in one case.

Automobile Driving↗
PubMed1980

Necrotizing vasculitis in gynecological surgery.

Extensive clinical investigation of asymptomatic vasculitis found in routine histopathological studies following gynecological surgery may often be unnecessary. In 11 patients necrotizing angiitis was an incidental finding in surgically removed uterine and uterine adnexal tissues. Following irradiation for urinary bladder carcinoma, one patient died during radical surgery: vasculitis was found in surgically resected pelvic organs, colon and kidneys. In other patients, vasculitis may have been attributable to drugs, e.g. penicillin, or to local arthus-like reaction following cone biopsy of cervix. Available from 6 of these cases, follow-up data presented no evidence of progressive systemic vascular disease, supporting the view that incidentally encountered necrotizing angiitis of uterus and uterine adnexa, like that of the appendix, may be innocuous.

Adult↗