Hyaline membrane disease, alkali, and intraventricular haemorrhage

The relation between intraventricular haemorrhage (IVH) and hyaline membrane disease (HMD) was studied in singletons that came to necropsy at Hammersmith Hospital over the years 1966-73. The incidence of IVH in singleton live births was 3-22/1000 and of HMD 4-44/1000. Although the high figures were partily due to the large number of low birthweight infants born at this hospital, the incidence of IVH in babies weighing 1001-1500 g was three times as great as that reported in the 1658 British Perinatal Mortality Survey. Most IVH deaths were in babies with HMD, but the higher frequency of IVH was not associated with any prolongation of survival time of babies who died with HMD as compared with the 1958 survey. IVH was seen frequently at gestations of up to 36 weeks in babies with HMD but was rare above 30 weeks' gestation in babies without HMD. This indicated that factors associated with HMD must cause most cases of IVH seen at gestations above 30 weeks. Comparison of clinical details in infants with HMD who died with or without IVH (at gestations of 30-37 weeks) showed no significant differences between the groups other than a high incidence of fits and greater use of alkali therapy in the babies with IVH. During the 12 hours when most alkali therapy was given, babies dying with IVD received a mean total alkali dosage of 10-21 mmol/kg and those dying without IVH 6-34 mmol/kg (P less than 0-001). There was no difference in severity of hypoxia or of metabolic acidosis between the 2 groups. Babies who died with HMD and germinal layer haemorrhage (GLH) without IVH had received significantly more alkali than those who died with HMD alone, whereas survivors of severe respiratory distress syndrome had received lower alkali doses than other groups. It is suggested that the greatly increased death rate from IVH in babies with HMD indicates some alteration of management of HMD (since 1958) as a causative factor. Liberal use of hypertonic alkali solutions is the common factor which distinguishes babies dying with GLH and IVH from other groups of babies with HMD. Although the causal nature of this association remains unproved, it seems justifiable to lrge caution in alkali usage.     

Chordoma of the thoracic spine--case report

A 44-year-old woman presented with a thoracic chordoma with intrathoracic extension manifesting as complaints of lower extremity weakness, hypesthesia below the levels of T5-6, and sphincter incontinence. Almost total resection combined with anterior interbody fusion and stabilization was possible through a left transpleural transthoracic approach. She suffered recurrence after 2 years and was considered inoperable. Biopsy revealed a malignant chordoma with no sarcomatous differentiation. Chordoma is an uncommon malignant bone tumor originating from remnants of the embryonal notochord, occurring mostly along the axial skeleton, at the extremity of the vertebral spine, and is least common in the thoracic region. Differential diagnosis is problematic and biopsy is helpful particularly if considered inoperable. Thoracic chordomas of the malignant type manifest as cord or root compression. Classical malignant chordomas must be distinguished from chondroid, benign, or other types of chordomas, since the biological behavior and clinical features are distinct. However, the differential diagnosis cannot be based on histological examination, but long-term follow up is required. Most patients have extradural and intraspinal tissue extension at the time of diagnosis, which makes complete resection impossible. Aggressive surgery without violation of surgical borders is the best choice in the treatment of thoracic chordoma. Thoracic chordoma is a recurring neoplasm and is prone to dissemination and sarcomatous differentiation despite its slow-growing nature.     

Safety and pharmacokinetics of multiple doses of recombinant human CuZn superoxide dismutase administered intratracheally to premature neonates with respiratory distress syndrome

OBJECTIVES: To examine the safety and pharmacokinetics of multiple intratracheal (IT) doses of recombinant human CuZn superoxide dismutase (rhSOD) in premature infants with respiratory distress syndrome who are at risk for developing bronchopulmonary dysplasia (BPD). Methods. Thirty-three infants (700 to 1300 g) were randomized and blindly received saline, 2.5 mg/kg or 5 mg/kg rhSOD IT within 2 hours of surfactant administration. Infants were treated every 48 hours (as long as endotracheal intubation was required) up to 7 doses. Serial blood and urine studies, chest radiographs, neurosonograms, SOD concentration and activity measurements, and tracheal aspirate (TA) inflammatory markers were assessed throughout the 28-day study. RESULTS: SOD concentrations in serum (0.1 [0.05/0.15] microg/mL-geometric mean with lower/upper confidence intervals), tracheal aspirates (TA) (0.2 [0.1/0.3] microg/mL) and urine (0.3 [0.2/0.4] microg/mL) were similar at baseline in all 3 groups and did not change significantly in the placebo group. In the rhSOD treatment groups, SOD concentrations were increased on day 3 and did not change significantly thereafter over the 14-day dosing period (also measured on days 5, 7, and 13). SOD concentrations averaged 0.4 [0.3/0.5] microg/mL in serum, 0.8 [0.6/1.2] microg/mL in TA and 1.1 [1.0/1.3] microg/mL in urine for the low-dose group and 0.6 [0.5/0.7] microg/mL in serum, 1.1 [0.9/1.5] microg/mL in TA, and 2.2 [1.6/2.9] microg/mL in urine for the high-dose group over the 14-day dosing period. Enzyme activity directly correlated with SOD concentration and rhSOD was active even when excreted in urine. TA markers of acute lung injury (neutrophil chemotactic activity, albumin concentration) were lower in the rhSOD agroups compared with placebo. No significant differences in any clinical outcome variable were noted between groups. CONCLUSIONS: These data indicate that multiple IT doses of rhSOD increase the concentration and activity of the enzyme in serum, TA and urine, reduce TA lung injury markers and are well-tolerated. Further clinical trials examining the efficacy of rhSOD in the prevention of BPD are warranted.     

Chorionic gonadotropin inhibits rat mammary carcinogenesis through activation of programmed cell death

Human chorionic gonadotropin (hCG) inhibits the progression of 7,12- dimethylbenz[a]anthracene (DMBA) induced mammary carcinomas. In order to determine whether this phenomenon was mediated by induction of programmed cell death or apoptosis, 45-day-old virgin Sprague-Dawley rats received 8 mg DMBA/100 g body weight; 20 days later they were injected daily with 100 IU hCG for 40 days (DMBA + hCG group). Age- matched untreated, hCG- and DMBA + saline treated rats were used as controls. Tissues were collected at the time of DMBA administration and at 5, 10, 20 and 40 days of hCG injection. RNA from mammary glands, adenocarcinomas and ovaries was probed for transforming growth factors (TGF) alpha and beta, and the apoptotic genes TRPM2, ICE, bcl2, bcl-XL, bcl-XS, p53 and c-myc. The mammary glands of hCG-treated animals with or without DMBA exhibited elevated expression of TRPM2, ICE, bcl-XS, c- myc and p53; and elevation in the apoptotic index. Mammary adenocarcinomas developed in those animals treated with hCG showed an elevation in the expression of p53, c-myc and ICE genes in comparison with the levels detected in the adenocarcinomas developed by the animals treated with DMBA alone. No significant alterations in the expression of any of the genes tested was observed in ovarian RNAs. These results led us to conclude that hCG induces programmed cell death in the mammary gland initiated in the carcinogenic process, that this process is p53 dependent, and is modulated by c-myc expression. Our data also indicate the possibility that a cell death program dependent on the bcl2 family exists, because of the potential involvement of p53, bcl-XS and Bax in apoptosis. This additional mechanism of tumor inhibition makes hCG treatment a useful approach for the prevention and therapy of breast cancer.      

Cloning and characterization of DXS6673E, a candidate gene for X-linked mental retardation in Xq13.1

In several families with non-specific X-linked mental retardation (XLMR) linkage analyses have assigned the underlying gene defect to the pericentromeric region of the X chromosome, but none of these genes have been isolated so far. Here, we report on the cloning and characterization of a novel gene, DXS6673E, that maps to Xq13.1, is subject to X-inactivation and is disrupted in the 5' untranslated region by a balanced X;13 translocation in a mentally retarded female. The DXS6673E gene is highly conserved among vertebrates and its expression is most abundant in brain. It encodes a hydrophilic protein of 1358 amino acids (aa) that does not show sequence homology to other known proteins. A segment of this protein consisting of neutral and hydrophobic aa with a proline residue in every second position may represent a transmembrane domain. Almost complete sequence identity was found between the 3' end of the DXS6673E gene and two expressed sequence tags (ESTs) and between the 5' end of the DXS6673E gene and a third EST. Moreover, weaker sequence similarity was observed between coding regions and two other ESTs.      

Molecular basis of choroideremia (CHM): Mutations involving the rab escort protein-1 (REP-1) gene

Choroideremia (CHM) is an X-linked recessive eye disease that results from mutations involving the Rab escort protein-1 (REP-1) gene. In 18 patients deletions of different sizes have been found. Two females suffering from CHM were reported to have translocations that disrupt the REP-1 gene. In 22 patients, small mutations have been identified. Interestingly, these are all nonsense, frameshift or splice-site mutations; with one possible exception, missense mutations have not been found. This comprises all the known mutations in the disease. Hum Mutat 9:110–117, 1997. © 1997 Wiley-Liss, Inc.     

Chemoprevention of fibroid tumors by [−]-epigallocatechin-3-gallate in quail

Spontaneous leiomyomas of the oviduct are common tumors of the Japanese quail (Coturnix coturnix japonica), and fibroid tumors in the laying hen are similar to human fibroid tumors with respect to estrogen and progesterone receptors. This makes the quail a good animal model for screening potential agents for that aid in the prevention and treatment of human myoma uteri. We have previously reported a decreased incidence of leiomyomas in the oviduct of Japanese quail with antioxidant supplementation, for example, lycopene and soy isoflavones. Most of the health benefits associated with green tea consumption is attributed to EGCG, one of 4 major catechins found in green tea. This study investigated the effects of epigallocatechin-3-gallate supplementation on the development of leiomyomas in the oviduct of Japanese quail. We also measured serum and tissue levels of malondialdehyde and TNF-α. One hundred eighty quail (8 months old) were assigned to 3 treatment groups consisting of 6 replicates of 10 quail in each group. Animals were fed either a basal diet (control group) or the basal diet supplemented with 200 or 400 mg of EGCG/kg of diet. The animals were euthanized at the end of the 12-month study period, and the tumors were characterized. Epigallocatechin gallate supplementation significantly decreased the number of leiomyomas as compared with the controls (P = .001). The tumors in the EGCG fed birds were smaller than those found in the control birds (P = .001). Serum and liver malondialdehyde and TNF-α concentrations decreased (P = .001) with EGCG supplementation. The results indicate that dietary supplementation with EGCG reduces the incidence and size of spontaneously occurring leiomyoma of the oviduct in Japanese quail. Clinical trials should be conducted to investigate the efficacy of EGCG supplementation in the prevention and treatment of uterine leiomyoma in humans.     

The effect of an angiotensin converting enzyme inhibitor on intestinal wound healing

BACKGROUND: Dehiscence of intestinal anastomosis is associated with high mortality and morbidity rates. Angiotensin II is a potent agent in the acceleration of wound repair. Angiotensin converting enzyme (ACE) inhibitors have antifibrogenic effects. AIM: This study was performed to investigate the effect of ACE inhibitors on healing of intestinal anastomosis. MATERIALS AND METHODS: Forty-five male Wistar albino rats were divided into three groups. Ileum was divided above 10 cm from ileocecal valve after laparotomy and a single-layer ileoileal anastomosis was performed. While no treatment was given to rats in group 1, Lisinopril (an ACE inhibitor) was given to rats in group 2 and group 3 for post-operative 7 days in drinking water at 50 and 5 mg/l concentrations, respectively. Estimated amounts of supplied lisinopril were 6.5 and 0.65 mg/kg/day in groups. On post-operative 8th day, relaparotomy was performed and anastomosis-bursting pressures were measured. Then blood and tissue samples were taken for serum transforming growth factor beta-1 and tissue hydroxyproline measurements and histopathological examinations. RESULTS: High dose of lisinopril impaired the all parameters of anastomotic wound healing including bursting pressure, tissue hydoxyproline level, collagen deposition and epithelization (P < 0.001, group 2 versus groups 1 and 3). But low dose of lisinopril had no effect on those parameters (P > 0.05, group 1 versus group 3). CONCLUSION: It was concluded that lisinopril has impaired intestinal wound healing in a dose dependent manner and low doses of lisinopril can be safely used on patients with intestinal anastomosis.     

有机磷解毒剂的研究2.吡啶甲醛肟碘甲烷盐(简称2-PAM)的药理作用

2-吡啶甲醛肟碘甲烷盐(2-PAM)为有效的有机磷解毒剂,本文对其药理作用作了初步的观察.证明对乌拉坦麻醉猫在接近临床用量时已能产生拟肾上腺素作用.连续应用多次后出现快速耐受现象.在应用抗肾上腺素药、利血平或切除两侧肾上腺后,2-PAM作用即减弱.C₆即使用至50毫克/公斤,亦不能阻断其作用,而5毫克/公斤的阿托品几能完全取消之.对离体及在位蟾蜍心脏也表现兴奋,此作用可部分地被C₆所阻断.2-PAM对离体豚鼠肠的兴奋作用,亦可被阿托品所取消.文内对其作用机制作了初步分析.     

Primary Ewing's sarcoma of the occipital bone--case report

A 17-year-old female presented with a very rare case of primary Ewing's sarcoma of the skull involving the occipitotemporal region. Systemic examination found no evidence of metastasis. The tumor was surgically removed, and the patient underwent radiotherapy and chemotherapy. Fourteen months after surgery there has been no recurrence of the tumor. Cranial primary Ewing's tumor has a good prognosis after radical surgery and adjuvant therapy.