Total parenteral nutrition-associated intrahepatic cholestasis in infants: 25 years' experience

BACKGROUND/PURPOSE: There are few long-term chronological reviews examining the incidence of total parenteral nutrition (TPN)-associated intrahepatic cholestasis (TPNAC) in infants. The authors therefore reviewed TPNAC in their 25-year series, and also looked at the current problems associated with TPN in infants. METHODS: Two hundred seventy-three surgical neonates who received TPN for more than 2 weeks were divided into 3 groups chronologically: group A (1971 through 1982, n = 77), group B (1983 through 1987, n = 72), and group C (1992 through 1996, n = 124). TPNAC was defined as serum direct bilirubin (DB) level greater than 2.0 mg/dL during the neonatal period. RESULTS: The incidence of TPNAC in groups A, B and C was 57%, 31%, and 25% (P< .01), respectively, and the mortality rate from TPN-associated complications was 13%, 3%, and 3% (P< .05), respectively. Over the last 5 years, severe TPNAC developed in 20 patients (16%). Four of 20 died of TPN-associated sepsis with hepatic failure; 2 had hypoganglionosis with intractable stagnant enteritis and subsequent sepsis, and 2 had fatal respiratory or cardiac disease. CONCLUSIONS: The incidence of TPNAC in surgical neonates and TPN-associated mortality rates have decreased significantly. The mortality rate, however, still remains at 3%. Two of 4 fatal cases had hypoganglionosis, which were totally dependent on TPN. In patients who require long-term TPN, TPN still has unsolved problems, and small bowel transplantation may be indicated.     

Effects of corticosteroid on porcine retinal pigment epithelial cells in culture--2. Effects on phagocytosis and lysosomal activity

PURPOSE: The effects of a corticosteoid on the phagocytosis and lysosomal activity of cultured porcine retinal pigment epithelium (RPE) cells were investigated. METHODS: After exposing cultured RPE cells to various concentrations (10, 50, 100, 500, 1,000 nM) of betamethasone sodium phosphate (betamethasone), the cells were incubated with latex microspheres for 6 hours. RESULTS: The number of latex microspheres phagocytized by the cultured RPE cells was inhibited by 50 nM betamethasone within 24 hours. Ten-nM betamethasone did not inhibit the proliferation of cultured RPE cells, but ingestion of latex microspheres by the cells was inhibited after 3 days. Lysosomal activity (acid phosphatase, beta-glucuronidase) of RPE cells was inhibited by a high concentration (500 nM) of betametasone. CONCLUSION: These results suggest that corticosteroid inhibits the phagocytosis and lysosomal activity of cultured RPE cells.     

Age-specific effects of noradrenergic alpha-2 agonist clonidine on the development of amygdaloid kindling in developing rats

The effects of clonidine on the development of amygdaloid kindling were studied in rats of various ages (14, 21, 28 and 70 postnatal days). Administration of clonidine (0.2, 0.5 mg/kg i.p.) caused a significant retardation of kindling development in the 28-day-old rats as well as in the adult rats, whereas, in the 14-day-old rats, the development of kindling was significantly facilitated by clonidine. No significant effect of clonidine was observed in the 21-day-old rats. These results indicate that in rats the effects of clonidine on the development of amygdaloid kindling vary during development.     

Natural history of elderly patients with asymptomatic meningiomas

OBJECTIVE: For the treatment of elderly patients with asymptomatic meningiomas, it is important to determine their natural history. Based on results of follow up examinations, the natural history of such patients was clarified and prognostic factors concerning the potential of tumour growth in the aged were identified. METHODS: The clinical records and imaging studies of 40 elderly (over 70 years) patients with asymptomatic meningiomas were analysed. The patients were followed up with repeated imaging studies, and changes in tumour size, clinical signs, and outcomes were evaluated. RESULTS: There were 32 women and eight men with a mean age of 76.1 years. The mean follow up period was 38.4 months, ranging from 6 to 97 months. Six patients died during the follow up period from disorders other than the tumours, and one patient died as a result of the tumour. Twenty six patients (mean follow up period 41.8 months, range 10-97 months) showed no tumour growth. Fourteen patients showed tumour growth (mean follow up period 32.1 months, range 6-88 months). Five (four men and one woman) of these patients became symptomatic. Based on imaging analysis (1) calcification of the tumour was associated with no tumour growth (p=0.036), and (2) the tumour size at the initial diagnosis was related to subsequent tumour growth (p=0.016). Other possible factors related to tumour growth included sex and hyperintensity on MRI T2 weighted images. CONCLUSION: In elderly patients with asymptomatic meningiomas, careful clinical follow up with imaging studies is important. The imaging features mentioned may contribute to prediction of tumour growth.     

Evaluation of the Malignant Grade of Thymic Epithelial Tumors According to the Epithelial Subclassification

(Received for publication on June 15, 1998; accepted on May 27, 1999)     

A randomized study of cisplatin versus cisplatin plus vindesine for non-small cell lung carcinoma.

Between August 1983 and March 1985, a randomized study was conducted that compared cisplatin (CDDP) (80 mg/m2 on day 1) alone with CDDP plus vindesine (VDS) (3 mg/m2 on days 1, 8, and 15) in 160 consecutive patients with inoperable non-small cell lung cancer (NSCLC). There were no complete responses. The response rate for CDDP plus VDS (22 of 77 patients, 29%) was significantly higher than that for CDDP alone (9 of 78 patients, 12%) (P less than 0.05). However, no difference existed in the median duration of response (20 weeks for CDDP plus VDS versus 20 weeks for CDDP alone) or the median survival time (45 weeks for CDDP plus VDS versus 39 weeks for CDDP alone). No significant differences in toxicity were detected between the two arms; myelosuppression, alopecia, and peripheral neuropathy occurred more frequently with CDDP plus VDS and there was one lethal episode of hepatorenal syndrome in the CDDP plus VDS arm. Among the variables Eastern Cooperative Oncology Group (ECOG) performance status (PS), age, sex, stage, weight loss, serum lactate dehydrogenase (LDH) level, albumin level, histologic cell type, and chemotherapy arm, only chemotherapy arm was a significant factor leading to a major response (P = 0.019, multiple logistic regression analysis). The significant predictors of survival were PS (P = 0.000), sex (P = 0.000), and stage (P = 0.002) (Cox's proportional hazards model), with a PS of 0 or 1, female sex, and lower stage yielding the best survival. Although a significantly higher response rate was obtained in the combination arm than in the single agent arm, the survival benefit to patients receiving such combination chemotherapy was not determined and more effective chemotherapy regimens are required.     

Solubilization and characterization of putative alpha-2 adrenergic isoceptors from the human platelet and the rat cerebral cortex

Alpha-2 adrenergic receptor isotypes have been proposed to explain several pharmacologic differences between rodent and nonrodent species. In support of this hypothesis, we found that the differences in the pharmacologic properties of rat cerebral cortex and human platelet alpha-2 adrenergic receptors were not due to 1) differential proteolysis of the receptor, 2) degradation of the ligand, 3) the detection of different affinity states or 4) the presence of different quantities of various affinity modulators. In an effort to test the hypothesis further we have characterized these prototype isoceptors in soluble form. Soluble receptors from both species showed the appropriate rank order of potencies for various adrenergic agonists and antagonists expected for an alpha-2 adrenergic receptor. The KD values for soluble human platelet and rat cerebral cortical alpha-2 receptors were 4.2 and 5.9 nM, respectively. The species differences in the affinities of prazosin and oxymetazoline were retained upon solubilization. Both soluble receptors were insensitive to modulation by guanine nucleotides, indicating uncoupling from the inhibitory regulatory subunit Ni. Sucrose density gradient centrifugation of soluble receptors did not indicate any significant molecular size differences.     

Decreased expression of aquaporin 2 in the collecting duct of mice lacking the vasopressin V1a receptor

Background

Vasopressin V1a receptor null (V1aR^?/?) mice recently showed incomplete urinary concentration due to higher urine volume during control and water diuresis (euhydration), but showed normal response during dehydration (Aoyagi et al., Am J Physiol 295: F100–7, 2008).

Methods

Water balance, plasma vasopressin, plasma and urine osmolality, and aquaporin 2 (AQP2) expression in the kidney of wild-type (WT) and V1aR^?/? mice were therefore further examined using improved methods of urine collection (urinary bladder urine).

Results

V1aR^?/? mice demonstrated a lower urine osmolality (3,360 ± 138 vs. 3,610 ± 47 mOsm/kgH₂O) and a higher plasma osmolality (354.3 ± 1.3 vs. 342.5 ± 1.5 mOsm/kgH₂O) after dehydration for 24 h compared to WT mice (P < 0.05). In contrast, the plasma vasopressin concentration was significantly (P < 0.001) higher in the V1aR^?/? mice (48.8 ± 4.8 vs. 22.1 ± 2.4 pg/ml). On the other hand, although the AQP2 protein expression in the kidney was increased after dehydration, the basal (control) and dehydration-induced AQP2 protein levels were significantly lower in V1aR^?/? mice compared to WT mice (by Western blotting). Staining by an anti-AQP2 antibody in the luminal membrane of the collecting ducts was increased in both V1aR^?/? and WT mice after dehydration, but was relatively weaker in the V1aR^?/? mice (by immunohistochemistry). Moreover, urinary excretion of AQP2 protein, an index of the luminal AQP2 expression, was significantly (P < 0.05) lower in the V1aR^?/? mice.

Conclusion

V1aR signaling may be fundamentally important for the expression of AQP2 in the collecting ducts during control conditions and dehydration.     

Multicenter Experience of Hematopoietic Stem Cell Transplantation in WHIM Syndrome

Journal of Clinical Immunology - WHIM (warts, hypogammaglobulinemia, infections, and myelokathexis) syndrome is a rare disease, caused by CXCR4 gene mutations, which incorporates features of...