Clinical and immunological relevance of antibodies in solid organ transplantation.

The two important issues affecting recipients of solid organ transplants and of importance to immunologists are (i) sensitization of the recipient to HLA antigens and the resultant humoral immune response leading to the development of anti-HLA antibodies; and ii) development of robust assays for early detection of humoral rejection post-transplant. Evidence from several studies clearly indicates that presence of circulating anti-HLA antibodies especially donor specific leads to early graft loss and high titres of DSA may even lead to hyperacute or accelerated acute rejection. Long-term graft survival too is adversely affected by the presence of either pre- or post-transplant DSA. HLA matching status of the recipient - donor pair - is an important factor in the modulation of humoral response following transplantation and in a way affects de novo development of DSA. Data collected over the past decade clearly indicate significantly lower level of DSAs in optimally matched donor-recipient pairs. HLA mismatches especially those on HLA-DR and HLA-C loci have wider implications on post-transplant graft survival. The presence of circulating anti-HLA antibodies leads to endothelial damage in the newly grafted organ through complement dependent or independent pathways. Although detection of C4d deposition in renal biopsies serves as an important indicator of humoral rejection, its absence does not preclude the presence of DSAs and humoral rejection, and hence, it cannot be relied upon in every case. The emergence of epitope-based screening for anti-HLA antibodies on Luminex platform with high degree of sensitivity has revolutionized the screening for anti-HLA antibodies and DSAs. Studies indicate that humoral response to non-HLA antigens might also have a detrimental effect on allograft survival. High titres of such circulating antibodies may even lead to hyperacute rejection. Pre-emptive testing of solid organ recipients, especially kidney transplant recipients for anti-HLA and non-HLA antibodies and aggressive post-transplant monitoring of allograft function to detect DSAs using Luminex-based tests, is highly recommended.

Potential risk of hypoxaemia in patients with severe pneumonia but no hypoxaemia on initial assessment: a prospective pilot trial.

BACKGROUND: The World Health Organization recommends oxygen therapy for children under 5 years of age with pneumonia and lower chest indrawing. In patients with severe pneumonia who are initially normoxaemic, there is little information on the risk of subsequently developing hypoxaemia and the benefit of routine oxygen therapy. OBJECTIVES: To study the incidence of subsequent hypoxaemia in initially normoxaemic children with pneumonia and lower chest indrawing. METHODS: Children (n = 58, 3-59 mths) with pneumonia, lower chest indrawing and normoxaemia (SpO(2) >90%) were randomly assigned to receive supplemental oxygen (nasal prongs, 1-2 L/min flow) (n = 29) or room air (n = 29). Vital signs and SpO(2) were monitored continuously and recorded every 6 hours. Outcome variables were incidence of hypoxaemia, length of tachypnoea and lower chest indrawing. RESULTS: The two groups had similar demographic and clinical profiles. Thirty-one patients (53%) developed hypoxaemia later, without significant differences between the two arms (RR 0·61, 95% CI 0·36-1·04). Patients who developed hypoxaemia later were similar to those who did not, except for a lower SpO(2) on enrolment. However, they took more time to recover from tachypnoea (P<0·05), chest indrawing (P<0·05) and fever, indicating that they had more severe disease. Early oxygen therapy did not alter the course of disease. CONCLUSIONS: About half of the normoxaemic patients with severe pneumonia developed hypoxaemia after enrolment, indicating a significant potential risk. Children hospitaled with severe pneumonia might benefit from routine oxygen therapy. Alternatively, oxygen might be provided to those who develop hypoxaemia identified by a pulse oximeter.

Empyema thoracis: a 10-year comparative review of hospitalised children from south Asia.

AIMS: To study the clinical and microbial profile of childhood empyema in South Asia and to identify the changes over the past three decades. METHODS: A total of 265 children (aged 1 month to 12 years) with empyema admitted to the Advanced Pediatric Center, PGIMER, Chandigarh, India in 1989-98, were reviewed retrospectively. RESULTS AND CONCLUSIONS: One third of children were under 5. Culture positivity had decreased significantly (48% v 75%) over the years. Staphylococcus aureus continues to be the commonest (77%) aetiological agent; clustering was seen during hot and humid months (46%). Culture positive Streptococcus pneumoniae cases also decreased (9% v 27%); all were seen during the winter and spring season. Gram negative rods grew in more patients (11% v 7%). Community acquired methicillin resistant S aureus (MRSA) was isolated in three patients. Most children (93%) were treated with parenteral cloxacillin and an aminoglycoside. Tube drainage (TD) was used in 92% of fibropurulent cases, and was successful in 79%. Of 48 patients with failed TD, 12 needed decortication; limited thoracotomy was sufficient in the remaining 36. Surgery was mainly required by children with persistent pleural sepsis after 10 days of TD. Delaying surgery until 14 days had a significantly higher potential of requiring decortication. Early change to oral antibiotics (after 1-2 weeks of parenteral therapy) reduced the hospital stay significantly (17+7 v 23+7 days) without compromising long term outcome. Twenty two patients presenting late in the chronic stage underwent decortication at admission.

Morphometry of single small enhancing computed tomographic lesions: outcome and effect of albendazole therapy.

Single small enhancing computerized tomographic (CT) lesions (SSECTLs) are common in children with focal seizures. However, there is a paucity of systematic information regarding their morphometry, effect of albendazole therapy and long-term outcome. The objectives were to study the pattern of SSECTL on radiological follow up, alterations made by albendazole therapy, and correlation with seizure recurrence. A randomized, placebo controlled, double blind trial was carried out at the Advanced Pediatric Center, PGIMER, an urban tertiary-care teaching hospital. Sixty-three children between 2 and 12 years of age with focal seizures for < 3 months and SSECTLs were included in the study. All children were randomly assigned to receive either albendazole (15 mg/kg/day) or placebo for 28 days. CT scan was done at 1 and 3 months after beginning treatment. Codes opened after 6 months of recruitment in the study showed that 31 had received albendazole and 32 had received placebo. Over a period of 3 months, natural resolution of SSECTL passed through many stages. Albendazole was seen to accelerate this natural process as evident by the progression of various morphometric markers. An increase in the size of the lesion was associated with early seizure recurrence.

Single small enhancing computed tomographic lesions in indian children--II. Clinical features, pathology, radiology and management.

Single small enhancing computed tomographic lesions (SSECTL) are commonly seen in Indian children presenting with focal or at times generalized seizures. One-third of the subjects have raised intracranial pressure; focal deficit may occasionally occur depending on the localization of the lesion. SSECTLs mostly represent neurocysticercosis granulomas; visualization of scolex on MRI confirms the diagnosis. As most lesions resolve spontaneously, the use of anthehminthics has been controversial. Albendazole has been shown to cause faster resolution with decreased calcification of lesions. Short duration anticonvulsants may suffice in cases where the lesion disappears and EEG is normal. An approach to the diagnosis and management of SSECTL is presented.

Bacterial meningitis in children: critical care needs.

Acute bacterial meningitis (ABM) in children is associated with a high rate of acute complications and mortality, particularly in the developing countries. Most of the deaths occur during first 48 hours of hospitalization. Coma, raised intracranial pressure (ICP), seizures, shock have been identified as significant predictors of death and morbidity. This article reviews issues in critical care with reference to our experience of managing 88 children with ABM in PICU. Attention should first be directed toward basic ABCs of life-support. Children with Glasgow Coma Scale (GSC) score < 8 need intubation and supplemental oxygen. Antibiotics should be started, even without LP (contraindicated if focal neuro-deficit, papilledema, or signs of raised ICP). Raised ICP is present in most of patients; GCS < 8 and high blood pressure are good guides. Mannitol (0.25 gm/Kg) should be used in such patients. If there are signs of (impending) herniation short-term hyperventilation is recommended; prolonged hyperventilation (> 1 hour) must be avoided. Any evidence of poor perfusion, hypovolemia and/or hypotension needs aggressive treatment with normal saline boluses and inotropes, if necessary, to maintain normal blood pressure. Empiric fluid restriction is not justified. Seizures may be controlled with intravenous diazepam or lorazepam. Refractory status epilepticus may be treated with continuous diazepam (0.01-0.06) mg/kg/min) or midazolam infusion. Ventilatory support may be needed early for associated pneumonia, poor respiratory effort and/or coma, and occasionally to reduce work of breathing in shock. Provision of critical care to children with ABM may reduce the mortality significantly as experienced by us.

Single small enhancing computed tomographic lesion in Indian children--I: Evolution of current concepts.

Single, small (<20 mm) enhancing CT lesions are the commonest cause of focal seizures in Indian children and are also frequently reported from other tropical countries. They often resolve spontaneously on follow-up and have therefore led to controversies regarding their etiology and appropriate management. Initially, these lesions were often considered to be tuberculomas. However, as research progressed over the last two decades, solitary cysticercus granuloma has been found to be the most likely cause for these lesions. In this article we discuss the evolution of current etiological concepts regarding single, small enhancing CT lesions among Indian children, and an approach towards management.

Seizure recurrence in children with focal seizures and single small enhancing computed tomographic lesions: prognostic factors on long-term follow-up.

Single small enhancing computed tomographic (CT) lesions are common in children with focal seizures. There is a paucity of information regarding their long-term outcome and prognostic factors for seizure recurrence. The objective of this work was to study the frequency of seizure recurrence in children with single small enhancing computed tomographic lesions and to identify prognostic factors, if any, for seizure recurrence. A prospective long-term follow-up was conducted at the Advanced Pediatric Center, Postgraduate Institute of Medical Education and Research, an urban tertiary care teaching hospital. Sixty-three children between 2 and 12 years of age with focal seizures for less than 3 months and single small enhancing computed tomographic lesions were enrolled in a randomized, double-blind, placebo-controlled trial of albendazole therapy and followed up for 4 years. On long-term follow-up, the albendazole and placebo groups were left with 29 and 28 children, respectively. After several months of seizure-free period, antiepileptic drug was tapered off. Children with relapse underwent magnetic resonance imaging examination. All children were followed up for at least 18 months after stopping of the antiepileptic drug. Seizure recurrence was seen in three children each in both groups, after a mean interval of 6.4 weeks after stopping the antiepileptic drug. Magnetic resonance imaging revealed persistent chronic granuloma in 2 and calcified granuloma in 4 children. Residual lesions were significantly correlated with seizure recurrence. In children whose lesions completely disappeared, no seizure recurrence was seen even during shorter periods of antiepileptic drug treatment. Seizure recurrence was seen in a small number of children with focal seizures and single small enhancing computed tomographic lesions. It appears to be related to either a persistent or a calcified lesion.

Aldosterone-producing adrenocortical adenoma in childhood: a case report.

Aldosterone-producing adrenal tumor is an exceptional cause of hypertension in childhood. The authors describe an 11-year-old girl with hypertension and lower limb weakness who had hyperaldosteronism and left adrenocortical adenoma.

Albendazole therapy in children with focal seizures and single small enhancing computerized tomographic lesions: a randomized, placebo-controlled, double blind trial.

BACKGROUND: Single small enhancing computerized tomographic (CT) lesions (SSECTLs) are common in children with focal seizures. These are considered to represent solitary cysticercus granulomas. Controversy exists regarding their treatment. OBJECTIVE: To evaluate the efficacy of albendazole in cases of focal seizures with SSECTLs. DESIGN: Randomized, placebo-controlled, double blind trial. SETTING: Pediatric service of Nehru Hospital, PGIMER, an urban tertiary care teaching hospital. SUBJECTS: 63 children between 2 and 12 years of age with focal seizures for <3 months and SSECTLs. INTERVENTION: All children were randomly assigned to receive either albendazole (15 mg/kg/ day) or placebo for 28 days. CT scan was done at 1 and 3 months after beginning treatment. Codes opened after 6 months of inclusion in the study showed that 31 had received albendazole and 32 had received placebo. All children were followed up for at least 15 months. RESULTS: Disappearance of lesions on CT scan was noted in 41% of albendazole vs. 16.2% of placebo patients after 1 month of follow-up (P < 0.05) and 64.5% of albendazole- vs. 37.5% of placebo-treated patients after 3 months of follow-up (P < 0.05). During the first 4 weeks of therapy seizure recurrence was seen in 9.7% of albendazole vs. 3.2% of placebo-treated children (odds ratio, 3.32; 95% confidence interval, 0.33 to 33.8). After 4 weeks seizure recurrence was seen in 31.3% of placebo-treated children vs. 12.9% of albendazole-treated children (odds ratio, 3.07; 95% confidence interval, 1.18 to 11.15). CONCLUSIONS: Albendazole therapy results in significantly faster and increased resolution of solitary cysticercus lesions (SSECTLs) and appears to reduce the risk of late seizure recurrences.