Alveolar capillary dysplasia. Report of a case of prolonged life without extracorporeal membrane oxygenation (ECMO) and review of the literature

We describe an unusual infant with the diagnosis of alveolar capillary dysplasia who had a relatively prolonged life without extracorporeal membrane oxygenation (ECMO). We have used this case as a springboard for a thorough review of the literature. This was a full-term female infant who presented with a picture of persistent pulmonary hypertension of the newborn. She was treated as such, with various ventilatory modes, alkalinizing agents, surfactant therapy, tolazoline, prostacyclin and nitric oxide. Because of the prolonged clinical course the possibility of alveolar capillary dysplasia was raised. The parents refused ECMO. Despite all efforts she progressively deteriorated and died at 22 days of age. Macro- and microscopic examination of the lung at autopsy were diagnostic of alveolar capillary dysplasia. A detailed review of 39 cases published in the literature with comments regarding incidence, etiology, pathophysiology, clinical picture, diagnosis and treatment is presented.     

Efficacy of antimicrobial treatment in non-dysenteric persistent diarrhoea in a community setting

Objectives : To determine the efficacy of antimicrobial treatment in non-dysenteric persistent diarrhoea in a community setting. Methods : In this double-blind field trial, 156 children aged 4 36 months with persistent diarrhoea not associated with Giardia lamblia infestation seeking treatment in a community outpatient clinic, were randomized to receive a combination of nalidixic acid and metronidazole, metronidazole alone, or placebo for 7 days. Results : In comparison with placebo, metronidazole treatment did not result in a significant reduction in the mean post-enrolment diarrhoeal duration and stool frequency, increase in the proportion of patients recovered by days 3, 5 and 7 of treatment, and increase in weight gain at days 7 and 14. Comparing the combination of nalidixic acid and metronidazole with metronidazole alone, 17.5% more children treated with the combination recovered by day 3 of treatment ( p = 0.08) and the mean stool frequency ascertained on day 7 for the previous 24 h was 26.8% less in them ( p = 0.05). The weight gains at days 7 and 14 were similar in the two groups. Conclusions : These findings indicate that metronidazole offers no therapeutic benefit in persistent diarrhoea not associated with Giardia lamblia and nalidixic acid has only a modest clinical benefit, which is not substantial enough to warrant its routine use.     

Risk factors for development of dehydration in young children with acute watery diarrhoea: a case-control study

In a case-control study to understand the risk factors for development of life-threatening dehydration, a total of 379 children comprising 243 cases (moderate or severe dehydration) and 136 controls (non or mild dehydration) up to 2 years of age suffering from acute watery diarrhoea were studied. By univariate analysis, the presence of vibrios in stool, withdrawal of breast feeding during diarrhoea, not giving fluids, including oral rehydration solution (ORS), during diarrhoea, frequent purging (> 8/ day), vomiting (> 2/day) and undernutrition were identified as risk factors. However, by multivariate analysis after controlling for confounders, withdrawal of breast feeding during diarrhoea (odds ratio (OR) = 6.8, p < 0.00001) and not giving ORS during diarrhoea (OR = 2.1, p < 0.006) were identified as significant risk factors. The confounding variables which also contributed significantly to increasing the risk were age (≤ 12 months; OR = 2.7, p = 0.001), frequent purging (> 8/day; OR = 4.1, p < 0.00001), vomiting (> 2/day; OR = 2.4, p = 0.001) and severe undernutrition (%median <60 weight-for-age of Indian Academy of Paediatrics classification; OR = 3.1, p = 0.001). We feel that these findings will be useful for Global and National Diarrhoeal Diseases Control Programmes for formulating intervention strategies for preventing death due to diarrhoeal dehydration.     

The Methylazoxymethanol Acetate (MAM-E17) Rat Model: Molecular and Functional Effects in the Hippocampus

Administration of the DNA-alkylating agent methylazoxymethanol acetate (MAM) on embryonic day 17 (E17) produces behavioral and anatomical brain abnormalities, which model some aspects of schizophrenia. This has lead to the premise that MAM rats are a neurodevelopmental model for schizophrenia. However, the underlying molecular pathways affected in this model have not been elucidated. In this study, we investigated the molecular phenotype of adult MAM rats by focusing on the frontal cortex and hippocampal areas, as these are known to be affected in schizophrenia. Proteomic and metabonomic analyses showed that the MAM treatment on E17 resulted primarily in deficits in hippocampal glutamatergic neurotransmission, as seen in some schizophrenia patients. Most importantly, these results were consistent with our finding of functional deficits in glutamatergic neurotransmission, as identified using electrophysiological recordings. Thus, this study provides the first molecular evidence, combined with functional validation, that the MAM-E17 rat model reproduces hippocampal deficits relevant to the pathology of schizophrenia.     

Identification and characterisation of SB-366791, a potent and selective vanilloid receptor (VR1/TRPV1) antagonist

Vanilloid receptor-1 (TRPV1) is a non-selective cation channel, predominantly expressed by peripheral sensory neurones, which is known to play a key role in the detection of noxious painful stimuli, such as capsaicin, acid and heat. To date, a number of antagonists have been used to study the physiological role of TRPV1; however, antagonists such as capsazepine are somewhat compromised by non-selective actions at other receptors and apparent modality-specific properties. SB-366791 is a novel, potent, and selective, cinnamide TRPV1 antagonist isolated via high-throughput screening of a large chemical library. In a FLIPR-based Ca(2+)-assay, SB-366791 produced a concentration-dependent inhibition of the response to capsaicin with an apparent pK(b) of 7.74 +/- 0.08. Schild analysis indicated a competitive mechanism of action with a pA2 of 7.71. In electrophysiological experiments, SB-366791 was demonstrated to be an effective antagonist of hTRPV1 when activated by different modalities, such as capsaicin, acid or noxious heat (50 degrees C). Unlike capsazepine, SB-366791 was also an effective antagonist vs. the acid-mediated activation of rTRPV1. With the aim of defining a useful tool compound, we also profiled SB-366791 in a wide range of selectivity assays. SB-366791 had a good selectivity profile exhibiting little or no effect in a panel of 47 binding assays (containing a wide range of G-protein-coupled receptors and ion channels) and a number of electrophysiological assays including hippocampal synaptic transmission and action potential firing of locus coeruleus or dorsal raphe neurones. Furthermore, unlike capsazepine, SB-366791 had no effect on either the hyperpolarisation-activated current (I(h)) or Voltage-gated Ca(2+)-channels (VGCC) in cultured rodent sensory neurones. In summary, SB-366791 is a new TRPV1 antagonist with high potency and an improved selectivity profile with respect to other commonly used TRPV1 antagonists. SB-366791 may therefore prove to be a useful tool to further study the biology of TRPV1.     

Indium-111 labeled platelet deposition following transfemoral angiography

The incidence of thromboembolitic events in patients undergoing transfemoral angiography was examined using indium-111 labeled platelets. Twenty-seven patients received approximately 300 muCi of autologous labeled platelets at least 3 hours before angiography and were scanned with a gamma camera immediately before and after angiography. All patients were free of clinically obvious complications in the 1-2 day period after angiography. Our results showed evidence of platelet deposition at 21 sites other than the puncture site in 12 (44%) patients. Most platelet deposition (54%) occurred along the region between the puncture site and the aortic bifurcation; 24% occurred at sites not traversed by the catheter. At the puncture site itself, there was substantial platelet uptake in 44% of patients. This study indicates the need for further work in determining the most suitable catheter material and in assessing the efficacy of other measures such as anticoagulant or antiplatelet therapy.     

Long-term use of antecubital veins for plasma exchange. The Canadian Cooperative Multiple Sclerosis Study Group

True or sham plasma exchange was done weekly for 20 weeks in patients in two of the randomization groups in a prospective, blind clinical trial of experimental treatments for multiple sclerosis. Because patients could be randomized to receive sham plasma exchange and placebo medications, it was decided when the trial was designed that the use of fistulae, arteriovenous shunts, venous cutdowns, or other aggressive forms of venous access would not be permitted for any patient. Accordingly, patients judged to have inadequate superficial antecubital veins were ineligible for the trial. To date, only 13 (4.4%) of 294 patients considered for entry into the trial have been rejected on these grounds. In only 4 of the 93 patients undergoing exchange was it necessary to discontinue plasma exchange because of inadequate venous access. In 79.3 percent of the 1207 exchanges done in these patients, there were no problems of any kind with venous access. In 5.4 percent of these 1207 exchanges, it was necessary to terminate the procedure prematurely because of difficulties with patients' veins. Thus, the great majority of patients free of serious systemic illness (other than chronic progressive multiple sclerosis) can undergo weekly plasma exchange for up to 20 weeks using superficial antecubital veins without the need to resort to more invasive methods of venous access.