Faculty Bibliography

PURPOSE OF REVIEW/OBJECTIVE:Bronchiectasis is an under-appreciated cause of chronic lung disease in the USA. We highlight developments in diagnosis and treatment of this debilitating disease. RECENT FINDINGS/RESULTS:A possible link between gastroesophageal reflux and development of nontuberculous mycobacterial lung disease was highlighted. Reflux is more common in patients with nontuberculous mycobacterial lung disease, and among those with established bronchiectasis more extensive disease was observed in those patients who also had reflux. Long-term mortality in bronchiectasis was significantly associated with age, lower body mass index, dyspnea, lack of vaccination, hypoxemia, hypercapnia, and other functional parameters. In a large, randomized clinical trial, addition of inhaled tobramycin to ciprofloxacin for acute exacerbations of Pseudomonas infection produced microbiologic improvement correlating with clinical outcomes but not overall improvement. A review noted that five macrolide trials reported reduced sputum volume, improved lung function, and better symptom control. Finally, articles suggested benefit from inhaled hyperosmolar agents (e.g. hypertonic saline and inhaled mannitol). SUMMARY/CONCLUSIONS:The possible link between gastroesophageal reflux and nontuberculous mycobacterial lung disease, and the microbiology and resistance patterns of bacteria observed in these patients were clarified. A large study of inhaled tobramycin for exacerbations was inconclusive, but macrolide therapy and hyperosmolar agents hold promise.

BACKGROUND: Parenteral nutrition-associated cholestasis (PNAC) has historically been a significant cause of morbidity and mortality in neonates undergoing parenteral feeding. Studies examining the causes of cholestasis in the PN-dependent neonate have produced a wide range of data, with some conflicting results. Increased protein/nonprotein calorie ratios, increased glucose concentrations, and increased lipid concentrations have all been implicated as possible causes of PNAC. However, these studies were done in the pre-TrophAmine (neonatal-specific amino acid parenteral nutrition [PN] formulation) era. With the introduction of TrophAmine, infants are now receiving higher concentrations of protein, often being advanced rapidly even when nonprotein calories may not be sufficiently advanced to meet the infants' caloric needs. To the best of our knowledge, no studies have been conducted to evaluate the protein/nonprotein calorie ratio as a cause of PNAC in the TrophAmine era. METHODS: A retrospective chart review of 25 cholestatic and 25 noncholestatic PN-dependent premature neonates was conducted. All neonates weighed between 600 and 1000 g. Cholestasis was defined as a serum total bilirubin (TB) >or=2.0 mg/dL, with a serum direct bilirubin (DB) >or=20% of the TB. Neonates with major congenital anomalies or who underwent major surgery were excluded. PN macronutrient compositions were analyzed to examine if the different amounts of protein concentrations and protein/nonprotein calorie ratios played a role in the development of PNAC. Statistical analysis was performed using Student's t-tests. p Values < .05 were considered statistically significant. RESULTS: All measured nutrition parameters did not differ significantly between the cholestatic and noncholestatic groups. Protein intake, the protein/nonprotein calorie ratio, and renal function as evaluated by blood urea nitrogen (BUN) and creatinine did not differ between the 2 study groups. The only parameters that differed significantly between the groups were the duration of PN therapy and length of hospital stay. CONCLUSIONS: Protein to nonprotein calorie ratio was not an etiology in the development of cholestasis in infants (600-1000 g) receiving PN. Renal function elicited not to have an impact on cholestasis status of these infants. Therefore, providing adequate protein calories should not be limited in this patient population, as suggested by previous studies in the pre-TrophAmine era. We found that increased duration of PN therapy and increased length of hospital stay were associated with PNAC

Necrotizing enterocolitis (NEC) is the most common gastrointestinal emergency in the neonatal period. NEC causes ulceration of the intestinal mucosa and may lead to perforation or a stricture. To the best of the authors' knowledge intestinal inflammatory polyps after NEC have not been described previously. The authors report on a 17-week-old boy with pseudopolyps at the site of a colonic stricture after NEC

Hepatotoxity associated with amoxicillin/clavulanic acid is usually a self-limited disease with complete recovery. We report a rapidly progressing liver disease with ductopenia and portal fibrosis in a 3-year-old boy treated with Augmentin

BACKGROUND: Poor linear growth frequently complicates chronic inflammatory bowel disease in children. Circulating inflammatory mediators may play a role in this growth delay. We evaluated the effect of experimental colitis on bone growth in a nutritionally controlled rat model. METHODS: Experimental colitis was induced in male Sprague-Dawley rats (125-150 g) by enema with trinitrobenzene sulfonic acid in 50% ethanol on day 1 and 11 of a 14-day protocol. Control animals were pair-fed and all animals received a liquid rat diet (1 kcal/ml). Twenty-four-hour urine, collected on days 2 and 12 and serum samples, collected at death, were analyzed for calcium, zinc, and magnesium. Serum samples from a separate set of animals were studied for serial interleukin-6 levels. Right proximal tibias were processed for growth-plate histomorphometry, in which linear growth is proportional to the heights of the proliferative zone, and terminal hypertrophic chondrocyte, but inversely proportional to the height of the resting zone. RESULTS: Histology confirmed active inflammation in the animals given trinitrobenzene sulfonic acid. Weight gain and both urinary excretion and serum levels of zinc, calcium, and magnesium did not differ between treatment and nontreatment groups. Histologically, there was impaired linear bone growth. The resting zone was greater in the colitis group (94.5 +/- 32.6 microns versus 3.9 +/- 5.4 microns; p < 0.05); the proliferative zone was smaller in the colitis group (123.7 +/- 18.2 microns versus 78.9 +/- 11.2; p < 0.05 micron); the terminal hypertrophic chondrocyte was reduced in the colitis group (19.5 +/- 1.4 microns versus 28.8 +/- 3.6 microns; p < 0.05). At 6 and 24 hours after induction, the level of interleukin-6 was elevated in the colitis group. CONCLUSIONS: Experimental colitis results in a decreased linear bone growth, independent of nutritional intake. Circulating cytokines derived from intestinal inflammation may contribute to the suppression of bone growth

Increasing intracellular bicarbonate concentration ([HCO3-]i) inhibits calcium-mediated Cl- secretion in rat distal colon and T84 cells. We investigated the effect of [HCO3-]i on Cl- secretion in rat ileum. Segments of intact ileum from Sprague-Dawley rats were studied in Ussing chambers and villus and crypt intracellular pH and [HCO3-]i were determined using BCECF. A range of crypt and villus [HCO3-]i from 0 to 31 mM was obtained by varying Ringer's composition. Basal serosal-to-mucosal Cl- flux (JsmCl) averaged 8.5 +/- 0.2 mu eq.h-1.cm-2 and was unaffected by changing [HCO3-]i or serosal bumetanide. Carbachol increased JsmCl by 3.9 +/- 0.5 mu eq.h-1.cm-2 at [HCO3-]i = 0 mM but only by 1.0 +/- 0.3 mu eq.h-1.cm-2 at high crypt and villus [HCO3-]i. Dibutyryl-cAMP increased JsmCl by 2.5 +/- 0.2 mu eq.h-1.cm-2 at all [HCO3-]i. Carbachol and db-cAMP showed mutual antagonism at low [HCO3-]i and near-additivity at high [HCO3-]i. We conclude that like rat colon and T84 cells, calcium-mediated but not cAMP-mediated Cl- secretion in the ileum is inhibited by increasing [HCO3-]i. Mutual antagonism between carbachol and db-cAMP at low [HCO3-]i was present in ileum and distal colon but not in T84 cells

Human immunodeficiency virus-associated nephropathy (HIVAN), characterized by heavy proteinuria, rapidly progressive renal failure, 'collapsing' glomerulopathy, and tubulointerstitial abnormalities, is the most common finding in HIV-infected patients undergoing a renal biopsy and predominantly affects blacks. We describe the clinical features and renal pathologic findings of 12 intravenous drug users (IVDUs) coinfected with HIV and hepatitis C virus (HCV) who were selected for renal biopsy because they presented with features different from typical HIVAN, including hypertension, microscopic hematuria, and cryoglobulinemia. There were seven black and five Hispanic patients. Eleven patients had immune complex glomerulonephritis (ICGN); one had glomerulosclerosis with immune complex deposits. Ten individuals had evidence of past hepatitis B viral infection, but none had persistent hepatitis B surface antigenemia. No other underlying cause for immune complex glomerulonephritis was identified. Renal biopsy showed membranoproliferative glomerulonephritis in five patients, mesangial proliferative glomerulonephritis in five, membranous nephropathy in one, and 'collapsing' glomerulopathy with immune complex deposits in one. Hepatitis C virus RNA was detected by reverse transcription-polymerase chain reaction (RT-PCR) in the renal tissue and/or serum of nine of the 11 patients tested, and also in the renal biopsy tissue of four of eight patients with clinical and pathologic features of typical HIVAN without immunofluorescence evidence of immune complex deposits. One patient presented with renal failure, five patients developed end-stage renal disease (ESRD) requiring hemodialysis (mean time, 6.5 months), and six had stable renal function after a mean follow-up of 29.1 months (range, 2 to 72 months). Liver function abnormalities were present in seven of the 12 individuals, including four of the six patients who developed renal failure. These findings indicate that in some patients coinfected with HIV and HCV, the development of ICGN may dominate the clinical course of the disease. The occurrence of ICGN among black patients at risk for HIVAN may be related to the relatively high prevalence of HCV infection among IVDUs in this group