Cardiopulmonary and cerebrovascular acclimatization in children and adults at 3800 m.

Maturational differences exist in cardiopulmonary and cerebrovascular function at sea-level, but the impact of maturation on acclimatization responses to high altitude is unknown. Ten children (9.8 ± 2.5 years) and 10 adults (34.7 ± 7.1 years) were assessed at sea-level (BL), 3000 m and twice over 4 days at 3800 m (B1, B4). Measurements included minute ventilation ( V ̇ E ${\dot{V}}_{\rm{E}}$ ), end-tidal partial pressures of oxygen ( P ETO 2 ${P}_{{\rm{ETO}}_{\rm{2}}}$ ) and carbon dioxide, echocardiographic assessment of pulmonary artery systolic pressure (PASP) and stroke volume (SV) and ultrasound assessment of blood flow through the internal carotid and vertebral arteries was performed to calculate global cerebral blood flow (gCBF). At 3000 m, V ̇ E ${\dot{V}}_{\rm{E}}$ was increased from BL by 19.6 ± 19.1% (P = 0.031) in children, but not in adults (P = 0.835); SV was reduced in children (-11 ± 13%, P = 0.020) but not adults (P = 0.827), which was compensated for by a larger increase in heart rate in children (+26 beats min-1 vs. +13 beats min-1 , P = 0.019). Between B1 and B4, adults increased V ̇ E ${\dot{V}}_{\rm{E}}$ by 38.5 ± 34.7% (P = 0.006), while V ̇ E ${\dot{V}}_{\rm{E}}$ did not increase further in children. The rise in PASP was not different between groups; however, ∆PASP from BL was related to ∆ P ETO 2 ${P}_{{\rm{ETO}}_{\rm{2}}}$ in adults (R2  = 0.288, P = 0.022), but not children. At BL, gCBF was 43% higher in children than adults (P = 0.017), and this difference was maintained at high altitude, with a similar pattern and magnitude of change in gCBF between groups (P = 0.845). Despite V ̇ E ${\dot{V}}_{\rm{E}}$ increasing in children but not adults at a lower altitude, the pulmonary vascular and cerebrovascular responses to prolonged hypoxia are similar between children and adults. KEY POINTS: Children have different ventilatory and metabolic requirements from adults, which may present differently in the pulmonary and cerebral vasculature upon ascent to high altitude. Children (ages 7-14) and adults (ages 23-44) were brought from sea level to high altitude (3000 to 3800 m) and changes in ventilation, pulmonary artery systolic pressure (PASP) and cerebral blood flow (CBF) were assessed over 1 week. Significant increases in ventilation and decreases in left ventricle stroke volume were observed at a lower altitude in children than adults. PASP and CBF increased by a similar relative amount between children and adults at 3800 m. These results help us better understand age-related differences in compensatory responses to prolonged hypoxia in children, despite similar changes in pulmonary artery pressure and CBF between children and adults.

Cryptococcus meningitis and skin lesions in an HIV negative child.

Disseminated cryptococcosis is an uncommon occurrence in immunocompetent populations and occurs mainly in immunocompromised patients. The first case of cryptococcus meningitis and skin lesions in a 4-year-old confirmed HIV negative boy who presented with fever, meningism and skin lesions is reported. On examination the child was confused, uncooperative, and had neck stiffness and raised skin lesions. A septic screen, including skin scraping, was performed; the child was treated with penicillin and ceftriaxone for suspected meningococcal meningitis. The cerebrospinal fluid (CSF) had normal protein, glucose and chloride levels; yeasts were observed on Gram stain from the CSF and skin scraping. The India ink stain and Cryptococcus neoformans latex agglutination test on the CSF were both positive. Bacterial culture of the skin biopsy, CSF and blood culture specimens was negative. The child was treated with amphotericin B based on preliminary results, and had a gradual recovery with no neurological sequelae. The child continued oral fluconazole.

The dipsomania of great distance: water intoxication in an Ironman triathlete.

Of 371 athletes (62% of all finishers) whose weights were measured before and after the 226 km South African Ironman Triathlon, the athlete who gained the most weight (3.6 kg) during the race was the only competitor to develop symptomatic hyponatraemia. During recovery, he excreted an excess of 4.6 litres of urine. This case report again confirms that symptomatic hyponatraemia is caused by considerable fluid overload independent of appreciable NaCl losses. Hence prevention of the condition requires that athletes be warned not to drink excessively large volumes of fluid (dipsomania) during very prolonged exercise. This case report also shows that there is a delayed diuresis in this condition and that it is not caused by renal failure.

Twice weekly vs. daily chemotherapy for childhood tuberculosis.

BACKGROUND: Treating childhood tuberculosis places a large burden on health services, and ways of lessening this were sought. METHODS: A randomized controlled trial was conducted to determine the effectiveness of fully intermittent twice weekly treatment for intrathoracic childhood tuberculosis and its effect on adherence to treatment, in comparison with daily (weekday) treatment. The setting was a district of Cape Town, South Africa, an area of high incident tuberculosis. We randomized 206 children with confirmed (4%), probable (94%) and suspected (2%) intrathoracic tuberculosis: 89 (median age, 25 months) received intermittent treatment; and 117 (median age, 28 months) received daily treatment. Intermittent treatment (twice weekly for 6 months) was isoniazid 15 mg/kg/dose, rifampin 15 mg/kg/dose and pyrazinamide 55 mg/kg/dose for 2 months, followed by isoniazid and rifampin only for 4 months. Daily treatment was isoniazid 10 mg/kg/day, rifampin 10 mg/kg/day and pyrazinamide 25 mg/kg/day on weekdays for 6 months. RESULTS: At 6 months 97% of subjects were discharged, with treatment outcomes in the two groups equivalent at that time (P = 0.90) and at the 18- to 30-month follow-up. One relapse occurred in the twice weekly group (P = 0.25). Adherence was equivalent; 70 children (79%) on intermittent and 90 (77%) on daily treatment took 75% or more of the prescribed doses (P = 0.90). Nonadherence over the full course of therapy was significantly associated with nonadherence during the first month of treatment (P = 0.0002) and household crowding (P = 0.002). CONCLUSIONS: Six month fully intermittent antituberculosis treatment is an effective and acceptable alternative to daily treatment.

Elastin gene expression is upregulated during pulmonary fibrosis.

Elastin is a chief component of lung interstitium, and it is central to lung morphology and function. Efforts to understand the pathogenesis of pulmonary fibrosis have focused primarily upon collagen turnover in the lung; few studies have focused on elastin. In this study, we examined steady-state elastin mRNA levels after lung injury in the mouse induced by (1) butylated hydroxytoluene (BHT) which causes acute lung injury with recovery, (2) BHT + 70% O2 (fibrosis), or (3) 70% O2. Total lung elastin mRNA increased 70-80-fold on d10-14 after BHT/O2, but was unchanged after BHT or O2 alone. In situ hybridization studies localized elastin mRNA to cells in the muscularis of conducting airways and to scattered interstitial cells in fibrotic foci. Elastic fiber morphology was markedly distorted after BHT/O2. Thus, marked upregulation of elastin gene expression is correlated with the histopathology of fibrotic lung disease.

Novel sites for expression of an Escherichia coli heat-stable enterotoxin receptor in the developing rat.

Escherichia coli heat-stable enterotoxin (STa) mediates diarrheal disease by binding to and activating an intestinal transmembrane receptor, guanylate cyclase C (GC-C). To test the hypotheses that there was 1) increased perinatal expression of GC-C in rat intestine and 2) GC-C expression and STa binding in extraintestinal tissues of immature rat, we prepared whole cell membranes and total RNA from jejunum, ileum, colon, liver, kidney, heart, lung, brain, testis, and placenta of rats ranging in age from 12 days gestation to adult. Northern analysis demonstrated the presence of a unique 3.8-kb mRNA transcript at all ages in the jejunum, ileum, colon, and, to a lesser degree, in the testis. GC-C was also detected by Northern analysis in liver (from gestational age 18 days through 14 days postnatal) and in placenta. Steady-state mRNA encoding GC-C was not detected by Northern analysis in the other organs examined. GC-C-specific mRNA expression was greatest in the perinatal period in the jejunum, ileum, and liver. Specific binding of 125I-labeled STa was found in each of the tissue membranes in which GC-C mRNA was present; binding was not present in those tissues that had no detectable GC-C mRNA. The existence of GC-C in extraintestinal organs in the rat, and the development changes in GC-C expression support our hypothesis that GC-C, apart from its role as an STa receptor in mediating diarrheal disease, also serves as a receptor for an endogenous ligand.

DNA sequence and analysis of a cryptic 4.2-kb plasmid from the filamentous cyanobacterium, Plectonema sp. strain PCC 6402.

The 4194-bp plasmid, pRF1, from Plectonema sp. Strain PCC 6402 was completely sequenced and analyzed. Seven potential open reading frames were identified. The predicted amino acid sequence of open reading frame C (ORF C) had identities of 34, 29, and 25% with Rep B from the Staphylococcus aureus plasmid, pUB110; Rep from the Bacillus amyloliquefaciens plasmid, pFTB14; and protein A from the S. aureus plasmid, pC194, respectively. A 75-amino-acid region conserved in these proteins (Rep B, Rep, and protein A) also was highly conserved in ORF C with identities of 45, 37, and 40%, respectively. Significantly, 16 of the 21 amino acids conserved in Rep B, Rep, and protein A were found at the same positions in ORF C. This ORF may encode a replication protein that includes a region conserved in some eubacteria. Additional structural features include a 425-bp region that contains palindromes, tandem repeats, and short direct repeats which may correspond to the origin of replication. An 18-bp inverted repeat was located between two open reading frames, A and G.