Nand Kishore Dubey

AA amyloidosis associated with hepatitis B

We report a 13-year-old Indian boy with nephrotic syndrome caused by renal AA amyloidosis. Workup of the AA amyloidosis revealed chronic hepatitis B. Laser microdissection of the Congo-red-positive glomeruli and vessels followed by liquid chromatography and tandem mass spectrometry confirmed the presence of serum amyloid A (SAA) protein and ruled out hereditary and familial amyloidosis. Furthermore, mass spectrometry also detected a variant of SAA protein (SAA W71R).

Do Interventions in an Icu Affect the Predictive Ability of Pediatric Index of Mortality and Pediatric Index of Mortality-2 Scores in a Tertiary Care Hospital?

Objective: Our objective was to evaluate the effect of interventions in the initial period of stabilization (i.e., at 4 hrs) on the predictive ability of Pediatric Index of Mortality and Pediatric Index of Mortality-2 scores and to evaluate their performance in our ICU. Design: Prospective observational study. Setting: PICU of a tertiary care teaching hospital. Patients: Consecutive children aged 2 months to 17 yr admitted to our ICU from June 2010 to July 2011 were included. Interventions: None. Measurements and Main Results: We prospectively recorded the baseline characteristics, variables of Pediatric Index of Mortality and Pediatric Index of Mortality-2 at 1 and 4 hrs after admission, and the outcome data in a predesigned proforma. We compared the performance of the scores at these two time points by calculating their discriminative ability and calibration as measured by the area under curve of the receiver operating characteristic curves and the Hosmer-Lemeshow goodness-of-fit test, respectively. Of the 282 children enrolled, 93 (32.9%) died. The median (interquartile) age of the study patients was 3.5 yr (0.8, 10). The major reasons for ICU admission as well as mortality were sepsis/severe sepsis and cardiac and neurological illnesses. The area under curves for Pediatric Index of Mortality at 4 and 1 hrs were 0.73 (95% confidence interval 0.66–0.79) and 0.70 (0.63–0.77), respectively. The corresponding values for Pediatric Index of Mortality-2 were 0.72 (0.66–0.79) and 0.71 (0.64–0.78), respectively. The goodness-of-fit test showed a good calibration across deciles of risk for the two scores at both the time points (p > 0.1 for all). The calibration across different age and diagnostic subgroups was also good. Conclusion: Interventions in the first 4 hrs did not affect the predictive ability of Pediatric Index of Mortality and Pediatric Index of Mortality-2 scores. The 4-hr scores may be used in place of the 1-hr score, particularly in units where scoring is not possible with in the 1-hr time frame.

Electrical injuries in urban children in New Delhi

Aim The objective of this study was to analyze the epidemiology, presentation, management, and complications of electrical burn injuries in urban children. Methods Data from records and clinical data were collected retrospectively and prospectively during 2008 to 2010. Results Of 41 children enrolled, the mean age of children enrolled was 8.1 ± 4.5 years. Low-voltage injury was seen in 28 (68.2%), and 13 (31.8%) had high-voltage injuries. Low-voltage injuries were most commonly (52.45%) secondary to direct contact with live wire, whereas high-voltage injuries in 70% were due to direct contact with broken wires lying in fields/rooftops. Fourteen children of the 41 enrolled had associated injuries. Low-voltage injuries were associated with minor burns, seizures, tibial fracture, eyelid burn, scalp hematoma, and speech and visual impairment, whereas high-voltage injuries were associated with cardiac arrest, extradural hematoma, visceral burns, pulmonary hemorrhage and hypoxic encephalopathy, and postelectrocution acute respiratory distress syndrome. Surgical interventions done included split-thickness skin grafting, fasciotomy, and amputation procedures. The mean duration of hospital stay of all the children enrolled was 9.02 days with 35 children discharged, 71.4% of them having low-voltage injuries. Four children died, 75% of them having high-voltage injury, whereas 2 children left without medical advice, both having low-voltage injuries. Conclusions Children are a major group susceptible to electrical injuries in our country. Most of the mechanisms leading to them are easily preventable, but occur because of lack or awareness among the children and their guardians. Burn prevention program should be implemented incorporating these epidemiological data.

Death in an Adolescent Girl with Methemoglobinemia and Malaria

A 16-year-old girl working in a paint and dye-casting factory of aniline dyes presented to the emergency with cyanosis, fever and altered sensorium. She had been diagnosed as a case of malaria and treated with chloroquine elsewhere. At admission, her saturation was 79%, which did not improve despite mechanical ventilation with 100% oxygen. Her PaO2 levels, however, remained high-140 mmHg. The observed difference in PaO2 and SpO2 prompted us to investigate her for methemoglobinemia, which was confirmatory. Despite symptomatic and specific treatment, she succumbed to her illness possibly due to late presentation and prolonged cerebral anoxia. Though the girls raised methemoglobin levels may be explained by her history of exposure to aniline dyes, the temporal association of her methemoglobinemia related symptoms with chloroquine administration cannot be ignored. We believe that this rare complication of chloroquine therapy should be kept in mind before prescribing it to any child with malaria.

Infantile status epilepticus and no evident history of exposure - can it still be organophosphate poisoning?

To the Editor : Organophosphate poisoning (OPP) is rare during infancy and difficult to suspect when present with atypical presentation. A 4-mo-old, previously healthy baby girl was referred to us gasping in status epilepticus [multifocal seizures (first episode)] after receiving midazolam, phenytoin and mannitol from outside. There was no history of fever or abnormal birth events. She had hypotonia, depressed deep tendon reflexes, bilateral pinpoint pupils, normal anterior fontanelle and poor response to pain. She was treated as sepsis and ventilated. Her blood investigation, cranial imaging and CSF were normal. During monitoring, profuse oral, endotracheal secretions and sweating were noted. This along with miosis fitted into OPP. Atropine and Pralidoxime were started empirically. She improved with antidote therapy and was extubated on 6th day. Later OPP was confirmed with low pseudocholinesterase levels <1 kU/L (3.93–10.80). Possibility of OPP in this infant was remote due to 1) its uncommonness in this age group; 2) it rarely causes seizures (Moreover with excessive secretions and respiratory insufficiency hypoxia may be a cause of seizures) and most important; 3) absent history of exposure to the toxin. Younger children are prone to poisoning accidently due to their active and curious nature [1]. In new born, OPP can be explained by trans-placental acquisition of the chemical if mother ingests the compound during delivery [2]. During infancy homicidal attempt can be thought of, as female infanticide is common in north India. But such a history was unavailable. Moreover the secretion of these chemicals in breast milk is not known and future studies would be required to know if this can be the source of the chemical during infancy. Possible source of OPP may have been dermal contact with adult skin/clothes, floor as the father was a gardener and used to keep OP compounds at home. The presence of toxidrome of OPP like excessive secretions was disregarded initially as excessive salivation can be associated with seizure. This later on along with miosis and low heart rate made the basis of our suspicion. Further, absence of fever propelled us to think noninfectious causes of seizures. Though rarely, seizure can occur in OPP [3]. It is also possible that patient had muscle fasciculation and those were recorded as multifocal seizures but then these will not subside with antiepileptics. We recommend that full consideration should be given to the symptom constellation of OPP even in the absence of history of exposure as this is not uncommon and is fully treatable.

Warfarin-induced raised international normalized ratio is further prolonged by pantoprazole.

Sir, n nDrug–drug interactions are important to know so that any complication arising can be avoided, especially when it is life-endangering. We present a case where pantoprazole further increased the warfarin-induced raised International normalized ratio (INR) by potentiating warfarin effect. This increase in INR attenuated after stopping the pantoprazole, and a stable INR target was achieved. n nPantoprazole is commonly used in Pediatric Intensive Care Unit (ICU) for prophylaxis of stress-induced ulcers. It probably can interact with warfarin and further prolong INR, which can result in life-threatening bleeding. A 14-year-old patient was admitted in our ICU in view of sepsis with pneumonia and later developed deep vein thrombosis of circumflex vein, common femoral vein, superficial vein, and popliteal vein. Heparin was started, later followed by warfarin in a dose of 0.2 mg/kg (8 mg/day) to maintain a target INR of 2.5. On day 3, her INR rose to 6, but the patient was stable, and there was no bleeding. Hence, we decreased the warfarin dose by 20%. After 2 days, INR was still raised at 5.0. We again decreased the dose and monitored INR. High INR led to a reduction of warfarin to a total dose of 1 mg/day. This usually does not happen in our practice, so we looked for drug interactions which can cause raised INR in patients on warfarin therapy and checked that our patient was not receiving any such drugs or dietary items such as garlic, mango, papaya, or fish. Our patient was receiving ceftriaxone, vancomycin, and pantoprazole. We could not change/stop antibiotics and so decided to stop pantoprazole. After 3 days, INR decreased to 1.4. We had to increase the warfarin dose to increase INR to 2.5. Final dose of warfarin now was 8 mg/day. We observed a 87.5% reduction in dose of warfarin when given concomitantly. n nWarfarin is a racemic mixture of stereoisomers where S-warfarin is 3–5 times more potent inhibitor of the Vitamin K epoxide reductase complex than R-warfarin. It undergoes extensive metabolism by the cytochrome P450 (CYP) isoforms. n nCYP2C9is responsible for the metabolism of S-warfarin, while R-warfarin is metabolized by CYP1A2, CYP2C19, and CYP3A4.[1] Any drug which can inhibit these cytochrome isoenzymes can lead to decreased metabolism of warfarin and thus prolonged effect of the drug.[2] In a study from Sweden, pantoprazole was shown to strongly inhibit CYP2C9 activity in vitro.[3] This may form the basis for the interaction between these two drugs. As warfarin has a low therapeutic index such interaction may lead to life-threatening bleeding. This interaction has also been reported in postmarketing period. However, one study clearly showed a lack of interaction between pantoprazole and warfarin.[4] On application of DIPS scale for drug–drug interaction, this case scored 5 points which shows that interaction between pantoprazole and warfarin is probable and caused a rise in INR.[5] We did not rechallenge/made alterations in the dose of pantoprazole. CYP2C9 polymorphism is unlikely as on stopping the pantoprazole INR again decreased to nontherapeutic range. In conclusion, in spite of a good rationale, there is small evidence for interaction between pantoprazole and warfarin; it would be pragmatic to monitor INR when pantoprazole and warfarin are used concomitantly to avert any serious bleeding. n n nFinancial support and sponsorship nNil. n n nConflicts of interest nThere are no conflicts of interest.

Congenital vivax malaria: rare or underdiagnosed infection.

Congenital malaria is a rare disease both in endemic and non-endemic areas. It is seldom suspected due to its rarity and the fact that its signs and symptoms may be similar to those with neonatal sepsis. Furthermore, clues such as a history of maternal travel to an endemic area during pregnancy or any malaria symptoms may not always be revealed. The situation is further complicated by subjective smear tests and an expensive rapid diagnostic test, especially in developing countries where affordability is an issue. We call attention to the need to consider the diagnosis of malaria in neonates who present with signs and symptoms often confused with sepsis, to enable a quick diagnosis and treatment in order to reduce mortality.