Spurious euglycaemia in severe diabetic ketoacidosis.
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Biomedical subjects
Publications and source records attributed to L Price.
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The pharmacokinetics and metabolism of cyclophosphamide were studied in nine paediatric patients. Plasma samples were obtained from eight subjects and urine was collected from six children during a 24-h period after drug administration. Cyclophosphamide and its major metabolites phosphoramide mustard (PM), carboxyphosphamide (CX), dechloroethylcyclophosphamide (DCCP) and 4-ketocyclophosphamide (KETO) were determined in plasma and urine using high-performance thin-layer chromatography-photographic densitometry (HPTLC-PD). Cyclophosphamide (CP) was nearly, if not completely, cleared from plasma by 24 h after its administration. The plasma half-life of CP ranged from 2.15 to 8.15 h; it decreased following higher doses and was shorter than that previously reported for adult patients. Both the apparent volume of distribution (0.49 +/- 1.4 l/kg) and the total body clearance (2.14 +/- 1.4 l m-2 h-1) increased with increasing dose. Renal clearance ranged between 0.12 and 0.58 l/h (mean, 0.43 +/- 0.19 l/h). Between 5.4% and 86.1% of the total delivered dose was recovered as unchanged drug in the urine. The major metabolites identified in plasma and urine were PM and CX. One patient appeared to be deficient in CX formation. This study suggests that there is interpatient variability in the pharmacokinetics and metabolism of CP in paediatric patients. The shorter half-life and higher clearance as compared with adult values indicate faster CP metabolism in children.
Nephrotoxicity is an important adverse effect of chemotherapy in children. Renal function after treatment with either ifosfamide or cisplatinum in children aged 5 years or less ('younger children') was compared with that in those over 5 years ('older children'). Eighteen children (six younger, 12 older) given ifosfamide were studied after completion of chemotherapy, and 28 patients (16 younger, 12 older) were evaluated after cisplatinum. Glomerular filtration rate was measured from the plasma clearance of 51chromium-labelled edetic acid. Proximal tubular function was assessed by determination of plasma and urine calcium, phosphate, magnesium and glucose concentration; calculations of their fractional excretions, and of the renal threshold for phosphate; and measurement of urinary excretion of beta 2-microglobulin. Distal tubular function was evaluated by measurement of the early morning urine osmolality. Younger children had more severe proximal tubular toxicity than older children treated with ifosfamide, with significantly lower plasma phosphate concentrations and higher fractional excretions of glucose. However, there was no evidence of any such difference in glomerular or distal tubular damage after ifosfamide, and no difference in any aspect of renal function between younger and older children treated with cisplatinum. Increased proximal tubular toxicity after ifosfamide in younger children may have serious implications for future growth and development.
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We retrospectively reviewed 443 patients who had cardiopulmonary resuscitation (CPR). The focus of the study was to discover what preexisting factors should be assessed to determine the probability of survival. There were 88 successes out of 340 cases (25.9%). The absence of a previous myocardial infarction (MI), shock, partial pressure of oxygen (PaO2) less than 60 mm Hg, blood urea nitrogen (BUN) level greater than 20 mg/dL, pneumonia, pulmonary edema, and oliguria were found to predict a successful outcome. Logistic regression was used to predict percentage of successes in the various groups of patients with various clinical characteristics. The observed and predicted numbers of successes were in close agreement in most cases. We also constructed a classification function to predict whether an individual subject would survive the event for which CPR was required. Sixty-seven of the 88 observed successes would have been predicted, for an estimated sensitivity of 76%, and 164 of the 252 failures would have been predicted, for an estimated specificity of 65%. A large percentage (24%) of cases in which the patient actually survived CPR would have been predicted to be failures. We conclude that preexisting factors before a cardiopulmonary arrest do not accurately predict survival after CPR.
We present the first case of solitary temporal bone infantile myofibromatosis. This benign entity clinically and radiologically resembles a malignant process. Diagnosis is established with biopsy and electron microscopy studies. Local resection is the recommended treatment.
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Eleven children and adolescents with previously normal renal function who received ifosfamide for the treatment of extrarenal solid tumours underwent detailed investigation of glomerular and renal tubular function to assess the incidence and extent of renal damage. None had received cisplatin. Glomerular filtration rate (measured by plasma clearance of 51Cr labelled edetic acid) was reduced in six children. All 11 patients had evidence of proximal, and six of distal, tubular damage. Proximal tubular toxicity was indicated by phosphaturia and hypophosphataemia (n = 4), glycosuria (n = 5), increased urine beta 2 microglobulin excretion (n = 11), and generalised aminoaciduria (n = 10); distal tubular damage caused a reduction of the osmolality of the urine in an early morning sample. Two children developed clinical hypophosphataemic rickets, and one of these also had severe nephrogenic diabetes insipidus. Glomerular and tubular nephrotoxicity are common and potentially serious complications of ifosfamide treatment in children.
This paper describes an acupuncture and osteopathy service offered free of charge to patients at a National Health Service general practice. The background to the setting up of this service, its organization, funding, aims and philosophy, and the ethical and legal implications for the general practitioners whose patients are treated by complementary therapists are discussed. This service provides a model of cooperation between allopathic and complementary medicine in a primary care setting and could be copied elsewhere.
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EEG studies of marihuana use dating back to 1945 were reviewed. The earlier studies depended upon visual analysis of the tracing, and while some minor frequency and amplitude variations occurred in some subjects, there was no consistent THC induced change noticeable across subjects. Quantitative EEG studies of acute exposure to THC came later and produced reliable findings of a placebo controlled dose dependent THC induced increase in relative power of alpha, combined with decreased alpha frequency and a reduction of beta activity. These findings were reported for data collected from central-occipital derivations only. In our present investigation, we report that chronic heavy THC users have EEGs characterized by (1) increased absolute power of all frequencies over all cortical areas (2) hyperfrontality of elevated relative and absolute power and coherence values of alpha activity, and (3) a decrease in relative power of all non-alpha frequencies. Methodological issues were discussed and some suggestions were made for continuing research in this area.
Midazolam is a water soluble benzodiazepine with potent sedative and amnestic properties. Sixty unpremedicated patients who were to undergo upper endoscopy for diagnostic purposes were enrolled in an open, non-randomized study to assess the efficacy of 4 increasing dosages of midazolam (0.05, 0.10, 0.15 and 0.20 mg/kg). Efficacy measures included Trieger test (psychomotor drawing), presence of anterograde amnesia, patient rating (PR) of the sedation, evidence of inflammation at the site of the injection and physician's global assessment (PGA). The 4 patient groups were similar in age, sex and ASA class. Eight of the 15 patients who received the 0.05 mg/kg and 1 patient each in the 0.10 mg/kg and 0.15 mg/kg group were considered to be treatment failures and required supplemental diazepam. PR (excellent-good) was constant for all doses throughout. Nearly all patients had anterograde amnesia. Deterioration in the Trieger test results was associated with increasing dose (ANOVA, p less than 0.05). There were no significant changes in vital signs. Signs of phlebitis were noted in two patients who received both diazepam and midazolam. PGA rating rose from 26.7% (0.05 mg/kg) to 80.0% (0.20 mg/kg) (p less than 0.01). Few adverse effects (unrelated to dosage) were noted. Midazolam is a well tolerated benzodiazepine which provides satisfactory sedation for endoscopy. If no premedication is given, there are no benefits to be gained from using a dose greater than 0.10 mg/kg.
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