Relevant risk of carboplatin underdosing in cancer patients with normal renal function using estimated GFR: lessons from a stage I seminoma cohort.

BACKGROUND: Seminoma stage I is the most frequent testis cancer and single-dose carboplatin (AUC7) is an effective and widely used adjuvant treatment. Underdosing of carboplatin by 10% has been shown to almost double the rate of relapse and hence correct dosing based on accurate GFR measurement is crucial. The gold standard of GFR measurement with a radiolabelled isotope is expensive and not readily available. In many institutions, it is replaced by GFR estimation with the Cockcroft-Gault formula, which might lead to significant carboplatin underdosing and potentially inferior clinical outcome. METHODS: Retrospective analysis of all patients with stage I seminoma treated with adjuvant carboplatin between 1999 and 2012. All patients had serum creatinine measured and underwent GFR measurement with a radioisotope ((51)Cr EDTA or (99m)Tc DTPA), which was compared with seven standard GFR estimation formulae (Cockcroft-Gault, CKD-EPI, Jelliffe, Martin, Mayo, MDRD, Wright) and a flat dosing strategy. Bias, precision, rates of under- and overdosing of GFR estimates were compared with measured GFR. Bland-Altman plots were done. RESULTS: A total of 426 consecutive Caucasian male patients were included: median age 39 years (range 19-60 years), median measured GFR 118 ml/min (51-209), median administered carboplatin dose 1000 mg (532-1638). In comparison to isotopic GFR measurement, a relevant proportion of patients would have received ≤ 90% of carboplatin dose through the use of GFR estimation formulae: 4% using Mayo, 9% Martin, 18% Cockcroft-Gault, 24% Wright, 63% Jelliffe, 49% MDRD and 41% using CKD-EPI. The flat dosing strategy, Wright and Cockcroft-Gault formulae, showed the smallest bias with mean percentage error of +1.9, +0.4 and +2.1, respectively. CONCLUSIONS: Using Cockcroft-Gault or any other formula for GFR estimation leads to underdosing of adjuvant carboplatin in a relevant number of patients with Seminoma stage I and should not be regarded as standard of care.

Reduction of hexachlorocyclohexane-induced oxidative stress and cytotoxicity in rat liver by Emblica officinalis gaertn.

The effect of prefeeding of dehydrated E. officinalis (amla) powder at 5 and 10% levels on hexachlorocyclohexane (HCH)-induced changes in multicomponent antioxidant system and lipid peroxides in rat liver was studied. HCH induced significant elevation in hepatic malondialdehyde, conjugated dienes and hydroperoxides. The prefeeding of amla at 10% level could decrease the formation of these lipid peroxides significantly. The HCH abuse resulted in a significant reduction in hepatic glutathione S-transferase (GST), glucose-6-phosphate dehydrogenase (G-6-PDH) and superoxide dismutase (SOD) activities with an elevation in the activities of glutathione peroxidase and gamma-glutamyl transpeptidase (GGT). On the other hand, the HCH-induced impairment in hepatic catalase, G-6-PDH and SOD activities were modulated by amla at the 10% level of intake. Prefeeding of amla at 5 and 10% levels appeared to reduce the HCH-induced raise in renal GGT activity. The results show the elevation of hepatic antioxidant system and reduction of cytotoxic products as a result of prefeeding of amla, which were otherwise affected by the HCH administration.

A study of acute kidney injury in hospitalized preterm neonates in NICU.

OBJECTIVES: This study was carried out to determine the incidence, clinical features, etiology and outcome of functional and intrinsic acute kidney injury (AKI) in preterm neonates. METHODS: This is a prospective observational study on premature infants admitted to the neonatal intensive care unit (NICU) over an eight month period. All biochemical parameters of renal function tests were monitored and statically analyzed. RESULTS: The study included 450 infants; of them 300 were inborn and 150 infants were outborn and transported to the NICU. Mean gestational age, weight, and age at the time of AKI diagnosis were 32.3 weeks, 1.66 kg and 3.23 days respectively. The male: female ratio was 1.84:1. Incidence of AKI was higher in low birth weight babies. Sluggishness and refusal for feed were most common symptoms. Birth asphyxia and septicemia were the most common early and late cause of AKI. Hyponatremia was the most common electrolyte disturbance. The incidences of AKI, functional renal failure, and intrinsic renal failure were 12%, 48.14%, and 51.85% respectively. CONCLUSIONS: AKI is not uncommon in preterm infants. The early recognition and aggressive management of episodes of shock which often precede AKI could be life-saving.

Pachydermoperiostosis: technetium-99m-methylene diphosphonate scintigraphic pattern.

We present two cases of pachydermoperiostosis. Both patients presented with joint pains and swelling. Bone scan revealed marked pericortical uptake involving the distal end of long bones. The distribution pattern and differential diagnosis of the scan abnormalities are discussed.

Neonatal hypothyroid disease: absent salivary gland evident on technetium-99m pertechnetate scan.

PURPOSE: Technetium-99m pertechnetate scintigraphy is a well-established technique for diagnosing congenital hypothyroid disease. However, the biodistribution of pertechnetate (TcO4-) in neonates and young infants is not well documented. The purpose of this study was to analyze and document the biodistribution of TcO4- in young infants. MATERIALS AND METHODS: Scintigraphic studies of 31 patients being examined for hypothyroid disease were analyzed. All patients had elevated levels of thyroid-stimulating hormone. Dyshormonogenesis was diagnosed in 7 patients, ectopic thyroid glands in 19, and agenesis in 5. RESULTS: Images of the neck, chest, and abdomen taken in the anterior and left lateral positions using a low-energy, all-purpose collimator were reviewed. Twenty-six of the patients had no accumulation of the isotope in the salivary glands and 11 had no gastric uptake on either view. CONCLUSIONS: Based on the absence of salivary gland activity in the patients examined, this study suggests that this is a normal finding in infants younger than 3 months. A lateral view of the neck with markers is sufficient to localize the thyroid gland, because any activity in the neck region would belong to the thyroid. Furthermore, poor and variable uptake of the isotope in the stomach may lead to false-negative results, so caution is urged in the use of this tracer in Meckel's scintigraphy in young infants, particularly if the study findings are within normal limits.

Heterotopic ossification mimicking infection. Scintigraphic evaluation.

Heterotopic ossification is a disorder of unknown etiology characterized by bone formation in the mesenchymal tissues. It occurs most commonly in patients who have had traumatic brain injury, spinal cord injury, or joint trauma or surgery.

I-123 MIBG scintigraphy in adults. A report of clinical experience.

Thirty-one adult patients with clinical findings suggestive of pheochromocytoma were studied with I-123 MIBG. All patients had images obtained at 24 and 48 hours. Five patients had abnormal uptake proved to be because of I-123 MIBG avid tumors. The remaining 26 patients had no proven tumors and showed physiologic uptake in various organs. The 24-hour images were of high quality. In all cases, the 48-hour images contributed no significant additional information. Only in 1 patient did the 48-hour image add some certainty. Physiologic uptake was seen in the salivary glands, liver, G.I. tract, and urinary bladder in all patients (100%). Uptake was also observed in the lung and heart (90%), normal adrenal glands (32%), thyroid (29%), spleen (23%) uterus (13%), and neck muscles (6%). The authors' experience indicates that I-123 MIBG gives superior images compared to the previously used I-131 MIBG, that the optimum imaging time for adults is 18-24 hours, and that normal distribution patterns including uterine and neck muscle uptake should be familiar to physicians interpreting the studies.

Evaluation of dosage forms. VI. Studies of commercial oxyphenbutazone tablet dosage forms.

Dissolution-dialysis studies of commercial tablets of oxyphenbutazone were carried out to establish the applicability of this technique for the in vitro evaluation of oxyphenbutazone dosage form. While disintegration time and dissolution rate studies did not give a true indication of bioavailability, an excellent correlation was obtained between the dialysis rate constant K and the pharmacokinetic parameters AUC and Cmax.

Acoustic field assisted demixing of aqueous two-phase polymer systems.

Acoustic field assisted demixing was employed to decrease the demixing time in polymer-polymer (polyethylene glycol-maltodextrin) two-phase system. Application of acoustic field has decreased the demixing time in these systems up to 2-fold. Ultrasonication has induced mild circulation currents in the phase dispersion, which has enhanced the rate of droplet coalescence, eventually resulting in decreased demixing time. In polymer-polymer systems, phase demixing was found to depend greatly on which of the phases is continuous and viscosity of the continuous phase was observed to have a strong influence on the movement of the droplets and hence the phase demixing. Addition of NaCl increased the demixing time and presence of E. coli cells did not seem to have any influence on phase demixing.

Diformylhydrazine as analytical reagent for spectrophotometric determination of iron(II) and iron(III).

The bidentate ligand diformylhydrazine (OHC-HN-NH-CHO), DFH, combines with iron(II) and iron(III) in alkaline media in the pH range 7.3-9.3 to form an intensely colored red-purple iron(III) complex with an absorption maximum at 470 nm. Beer's law is obeyed for iron concentrations from 0.25 to 13 microg mL(-1). The molar absorptivity was in the range 0.3258x10(4)-0.3351x10(4) L mol(-1) cm(-1) and Sandell's sensitivity was found to be 0.0168 microg cm(-2). The method has been applied to the determination of iron in industrial waste, ground water, and pharmaceutical samples.