Prevention by retinoids of azoxymethane-induced tumors and aberrant crypt foci and their modulation of cell proliferation in the colon of rats

Retinoids are proposed chemopreventive agents that inhibit cell proliferation and induce differentiation. Their ability to prevent azoxymethane (AOM)-induced aberrant crypt foci (ACF) and tumors and to modulate cell proliferation was investigated in the colon of male F344 rats. Thirteen retinoids were evaluated for prevention of ACF and two of them, 9-cis-retinoic acid (RA) and 4-(hydroxyphenyl)retinamide (4- HPR), were also evaluated for prevention of colon cancer. The retinoids were administered continuously in the diet starting 1 week prior to the first of two weekly 15 mg/kg i.p. injections of AOM and for a total of either 5 or 36 weeks in order to evaluate their effect on colonic ACF and tumors. At a concentration of 1 mmol/kg diet, 2- (carboxyphenyl)retinamide caused the greatest reduction (57.7%) in the yield of ACF. 9-cis-RA was toxic at 1 mmol/kg so that it was evaluated at 0.1 mmol/kg, resulting in a 41.6% reduction in ACF. The ability of the retinoids to reduce the proliferating cell nuclear antigen (PCNA) labeling index in ACF and in non-involved crypts correlated with their ability to prevent ACF. Both 9-cis-RA (0.1 and 0.2 mmol/kg diet) and 4- HPR (1 and 2 mmol/kg diet) were highly effective in decreasing the yield of AOM-induced colon tumors. In summary, retinoids were demonstrated to reduce cell proliferation and to prevent ACF and tumors in the colon, suggesting promise as preventive agents for colon cancer.      

Adhesive capsulitis of the wrist: arthrographic diagnosis

Persistent pain and decreased range of motion are disabling complications of wrist trauma. Between 1978 and 1986, in ten patients with persistent pain following trauma, arthrography depicted changes characteristic of adhesive capsulitis. Adhesive capsulitis has been described in the shoulder, hip, and ankle, but little mention has been made of this entity in other joints. Confirmation of this diagnosis requires arthrography, since there are no characteristic findings on plain radiographs. Typical arthrographic findings include decreased capacity, small volar and styloid recesses, and adhesions preventing complete opacification of the joint. The arthrographic diagnosis allows proper institution of appropriate therapy.     

Ventricular catheter placement in children with hydrocephalus and small ventricles: the use of a frameless neuronavigation system

OBJECT: Accurate placement of ventricular catheters in children with small ventricles can be difficult. Too often, shunt catheters are misplaced with regard to optimal position and trajectory. The objective of this study was to determine whether neuronavigation-guided free-hand placement of ventricular catheters is an effective adjunct for children with hydrocephalus and small ventricles. METHODS: Nine children with hydrocephalus (ages 1-12 years) participated in this study. Four children were diagnosed as suffering from slit ventricle syndrome and 5 children had small to mildly dilated ventricles. Of the 9 shunted children, 6 underwent previous shunt placements, and 1 child previously underwent an endoscopic third ventriculostomy. In 8 children the primary procedure was insertion of ventricular catheters using a frameless neuronavigation system. In 1 child, the neuronavigation system was used after failure to insert the ventricular catheter using a standard technique. All children showed significant improvement of their symptoms and signs following the procedure and none of them required shunt revision during the follow up period (mean 8+/-5 months). CONCLUSION: The usage of a neuronavigation system is safe and may be beneficial for optimal positioning and trajectory of ventricular catheters in children with small ventricles or an abnormal ventricular anatomy.     

EFFECTS ON GROWTH HORMONE SECRETION FOLLOWING INTRAVENOUS AND SUBCUTANEOUS INJECTIONS OF GROWTH HORMONE-RELEASING FACTOR (hGRF-44 NH2): COMPARISON OF IMMUNOREACTIVE PLASMA GRF LEVELS

The effects of subcutaneous administration of three doses of human growth hormone-releasing factor (hGRF-44 NH2 or hGRF) at doses of 100, 300 and 600 micrograms were studied in six normal young men. GH responses obtained with 100 and 300 micrograms were negligible. In contrast, the 600 micrograms dose gave a profile of response comparable in timing and magnitude to that obtained with i.v. hGRF at maximal effect doses (20, 80, 100 micrograms). Plasma immunoreactive hGRF levels (IR-hGRF) were compared after s.c. and i.v. hGRF. Mean maximal plasma concentrations were comparable with s.c. 600 micrograms and i.v. 20 micrograms. Peaks occurred earlier with i.v. hGRF (5 min as opposed to 15 min): however, return to undetectable values was obtained between 90 and 120 min after s.c. or i.v. injections. These data suggest a great loss of the peptide between the subcutaneous space and blood, without delayed absorption. High variability in plasma IR-hGRF concentrations between the subjects after the same s.c. doses was observed.     

Thiol groups and reduced acidogenicity of dental plaque in the presence of metal ions in vivo

Metal ions are known to influence the cariogenicity of dental plaque. Inhibition of acid metabolism in plaque may be of importance in this respect. Metal ions inhibit the acidogenicity of dental plaque to a different extent and it has been suggested that an enzyme inhibition based on oxidation of thiol groups may explain this observation. The aim of the present study was to evaluate the significance of oxidation of thiol groups in the inhibition of acid production in plaque by silver, tin and zinc salts. Nine subjects with 3-d sucrose induced plaque received topical applications of the metal ions. Cysteine or gilutathione, which are known to reverse thiol oxidations, were then applied in one side of the mouth. Plaque pH measurements, in the presence of sucrose, were performed prior to and up to 2 h after treatment. The results showed that the acid production inhibited by the metal ions was reactivated by cysteine or glutathione. Iodoacetamide and ρ-chloromercuribenzoate were also shown to inhibit acid formation in dental plaque. The high affinity silver, tin and zinc have for SH groups, the observed inhibitory effect of these metals, the reactivation of the metabolism by monothiols and the fact that organic sulfhydryl reagents inhibit acid formation in plaque indicate that oxidation of thiol groups may be the mechanism by which these metals exert their effect.     

Metaplastic bone formation in a low grade conus glioma: case report and review of the literature

Calcifications associated with both benign and neoplastic intra-axial lesions of the central nervous system (CNS) are well recognized. Bony metaplasia in the CNS, where there is formation of mature trabecular bone, is a much more rare entity and has not been reported in the spinal cord. We present a case of bony metaplasia in the conus medullaris associated with a low grade astrocytoma. Radiological, pathological and clinical features of this unique case are discussed.     

Serum S100beta: a noninvasive marker of blood-brain barrier function and brain lesions

BACKGROUND: S100beta protein is expressed constitutively by brain astrocytes. Elevated S100beta levels in cerebrospinal fluid and serum reported after head trauma, subarachnoid hemorrhage, and stroke were correlated with the extent of brain damage. Because elevated serum S100beta also was shown to indicate blood-brain barrier (BBB) dysfunction in the absence of apparent brain injury, it remains unclear whether elevation of serum levels of S100beta reflect BBB dysfunction, parenchymal damage, or both. METHODS: The authors conducted a prospective study of serum S100beta levels in six patients who underwent hyperosmotic BBB disruption (BBBD) with intraarterial chemotherapy for primary central nervous system lymphoma. In addition, 53 serum S100beta samples were measured in 51 patients who had a variety of primary or metastatic brain lesions at the time of neuroimaging. RESULTS: S100beta was correlated directly with the degree of clinical and radiologic signs of BBBD in patients who were enrolled in the hyperosmotic study. In patients with neoplastic brain lesions, gadolinium enhancement on a magnetic resonance image was correlated with elevated S100beta levels (n = 45 patients; 0.16 +/- 0.1 microg/L; mean +/- standard error of the mean) versus nonenhancing scans (n = 8 patients; 0.069 +/- 0.04 microg/L). Primary brain tumors (n = 8 patients; 0.12 +/- 0.08) or central nervous system metastases also presented with elevated serum S100beta levels (n = 27 patients; 0.14 +/- 0.34). Tumor volume was correlated with serum S100beta levels only in patients with vestibular schwannoma (n = 6 patients; 0.13 +/- 0.10 microg/L) but not in patients with other brain lesions. CONCLUSIONS: S100beta was correlated directly with the extent and temporal sequence of hyperosmotic BBBD, further suggesting that S100beta is a marker of BBB function. Elevated S100beta levels may indicate the presence of radiologically detectable BBB leakage. Larger prospective studies may better determine the true specificity of S100beta as a marker for BBB function and as an early detection or follow-up marker of brain tumors.     

介入治疗激素性股骨头坏死的实验研究

目的：探讨介入治疗激素性股骨头坏死的作用机制。方法：将24只兔子随机分为对照组、模型组、介入组。于介入前后行血管造影检查，并于治疗后8周，分别进行血液流变学、血脂及病理学观察。结果：介入组血管中断现象改善，终末小血管数目增我。全血粘度、血浆粘度，红细胞聚集指数、总胆固醇、甘油三脂，股骨头空骨陷窝率均明显低于模型组（P＜0．05），软骨下区血管数目增多（P＜0．01）。结论：介入、静脉注射治疗股骨头坏死，可以降低血脂，改善血液循环，通过改善股骨头血供，降低骨内压，促进坏死骨修复和新骨再生。     

Repeat endoscopic third ventriculostomy: is it worth trying?

OBJECT: The goal of this study was to evaluate the safety, efficacy, and indications for repeat endoscopic third ventriculostomies (ETV). METHODS AND RESULTS: We reviewed the records of 20 patients who had undergone repeat ETV from 1987 to 1999. Their ages ranged from 8 months to 53 years (mean 17 years). The primary etiologies of hydrocephalus were: primary aqueductal stenosis (9 cases), tumor (5), Chiari malformation (2), prior infection (2), prior intraventricular hemorrhage (1), and blocked foramen of Monro (1 patient). The interval between the first and second ETVs ranged from 8 days to almost 6 years (mean 12.8 months). The intraoperative findings at repeat surgery were: occlusion of the primary orifice by scar (10 cases), virginal floor of the third ventricle (5 cases), pinhole ventriculostomy (3 cases), incompletely penetrated membrane (1 case), and blood clot occluding the orifice (1 case). The follow-up period ranged from 3 to 47 months (median 20 months). Repeat ETV was successful in 13 patients (65%). These patients did not require further shunting or other procedures during follow-up. Seven patients (35%) required placement of a shunt after repeat ETV. Several complications were observed in 1 patient (5%), including seizures, elevated ICP, bilateral pulmonary edema, and cardiac arrhythmia. This patient ultimately recovered fully; the ETV was successful, and the patient did not require a shunt. CONCLUSIONS: Based on the experience of this group of patients, repeat ETV is as effective and as safe as a primary ETV procedure, and should be attempted in selected patients.     

Murine yolk sac endoderm- and mesoderm-derived cell lines support in vitro growth and differentiation of hematopoietic cells

The mechanisms involved in the induction of yolk sac mesoderm into blood islands and the role of visceral endoderm and mesoderm cells in regulating the restricted differentiation and proliferation of hematopoietic cells in the yolk sac remain largely unexplored. To better define the role of murine yolk sac microenvironment cells in supporting hematopoiesis, we established cell lines from day-9.5 gestation murine yolk sac visceral endoderm and mesoderm layers using a recombinant retrovirus vector containing Simian virus 40 large T- antigen cDNA. Obtained immortalized cell lines expressed morphologic and biosynthetic features characteristic of endoderm and mesoderm cells from freshly isolated yolk sacs. Similar to the differentiation of blood island hematopoietic cells in situ, differentiation of hematopoietic progenitor cells in vitro into neutrophils was restricted and macrophage production increased when bone marrow (BM) progenitor cells were cultured in direct contact with immortalized yolk sac cell lines as compared with culture on adult BM stromal cell lines. Yolk sac- derived cell lines also significantly stimulated the proliferation of hematopoietic progenitor cells compared with the adult BM stromal cell lines. Thus, yolk sac endoderm- and mesoderm-derived cells, expressing many features of normal yolk sac cells, alter the growth and differentiation of hematopoietic progenitor cells. These cells will prove useful in examining the cellular interactions between yolk sac endoderm and mesoderm involved in early hematopoietic stem cell proliferation and differentiation.