Development of normal ocular alignment

Ocular alignment was examined in a large population of normal infants to determine the prevalence of various motility findings at ages ranging from birth to 10 months. Exodeviations were frequently seen up to the age of 6 months. Esodeviations were occasionally seen in infants who did not go on to develop congenital esotropia, but not after 2 months of age. It is unclear whether precursors of pathologic strabismus, such as congenital esotropia, can be distinguished from these transient ocular deviations seen in normal infants. However, any strabismus persisting after the ages listed above should be considered abnormal and receive ophthalmologic evaluation.     

Long-term effects of early kwashiorkor compared with marasmus. II. Intellectual performance

Intellectual performance including IQ (Wechsler Intelligence Scale for Children-Revised) and conservation was measured at ages 11-18 years in a follow-up study of Barbadian girls and boys who had histories of kwashiorkor (n = 53) or marasmus (n = 55) in their first year of life. They were compared with healthy neighborhood children matched by sex and age who had normal patterns of growth in early childhood (n = 58). On both IQ and conservation tests, children with previous kwashiorkor or marasmus had similar scores, which were significantly lower than scores of healthy comparison children. These findings were examined in relationship to current environmental conditions, which were similar in children with histories of kwashiorkor or marasmus and somewhat less advantaged than those of the comparison children. The effect of early malnutrition and related conditions at the time of episode still emerged as significant even when the current environmental factors were controlled for.     

Etiology of recurrent pregnancy losses and outcome of subsequent pregnancies

Prospective evaluation of 155 couples with two or more consecutive pregnancy losses disclosed uterine morphologic abnormalities in 27%, chromosomal abnormalities in 21 individuals (7.7%, or 15.4% of the couples), and at least one abnormal diagnostic test suggestive of a cause for recurrent pregnancy losses in 106 (68%). A positive test for antinuclear antibody was found in 7.5% of the women, whereas the expected rate in a population of this age is less than 2%. Cervical cultures for Ureaplasma urealyticum (T-strain mycoplasma) were positive in 48% of the women, and 28% of these women had a genetic or uterine abnormality to explain their pregnancy losses. Thyroid function profiles and cervical cultures for Mycoplasma hominis provided no significant information in the evaluation in these couples. With the exception of women with a positive antinuclear antibody, the overall prognosis for later pregnancies was quite good whether the diagnostic evaluation of the couple was normal (77% subsequent live births) or abnormal (71% subsequent live births). The significance of the positive antinuclear antibody in these women is unclear, but further studies and long-term evaluation are necessary to determine the relationship between recurrent pregnancy losses and later development of collagen-vascular diseases.     

Increased cholesterol levels during paroxetine administration in healthy men

BACKGROUND: Despite the frequent use of selective serotonin reuptake inhibitors in patients with coronary heart disease (CHD), their effects on plasma lipid levels have not been systematically investigated. Our objective was to assess the effects of 8 weeks of paroxetine administration on plasma cholesterol and triglyceride levels. METHOD: Blood samples were collected at baseline, after 8 weeks of paroxetine administration, and post-discontinuation in 18 healthy male volunteers. RESULTS: In the 16 of 18 patients whose plasma levels of paroxetine indicated an unequivocal compliance to treatment, paroxetine administration induced an 11.5% increase in low-density lipoprotein cholesterol (LDL-C), which normalized after paroxetine discontinuation. CONCLUSION: The magnitude of the paroxetine-induced increase in LDL-C would lead to a minor increase in CHD risk in a minority of healthy male volunteers without associated CHD risk factors but might increase LDL-C sufficiently to warrant therapeutic intervention in patients with established CHD, based on the National Cholesterol Education Program guidelines.     

Intensity-modulated radiation therapy: First reported treatment in Australasia

Intensity-modulated radiation therapy (IMRT) is an exciting new advance in the practice of radiation oncology. It is the use of non-uniform radiation beams to achieve conformal dose distributions. As a result of the high initial capital costs and the time and complexity of planning, IMRT is not yet a widely available clinical treatment option. We describe the process involved in applying this new technology to a case of locally advanced nasopharyngeal cancer.     

Noscapine alters microtubule dynamics in living cells and inhibits the progression of melanoma

Cellular microtubules, polymers of tubulin, alternate relentlessly between phases of growth and shortening. We now show that noscapine, a tubulin-binding agent, increases the time that cellular microtubules spend idle in a paused state. As a result, most mammalian cell types observed arrest in mitosis in the presence of noscapine. We demonstrate that noscapine-treated murine melanoma B16LS9 cells do not arrest in mitosis but rather become polyploid followed by cell death, whereas primary melanocytes reversibly arrest in mitosis and resume a normal cell cycle after noscapine removal. Furthermore, in a syngeneic murine model of established s.c. melanoma, noscapine treatment resulted in an 85% inhibition of tumor volume on day 17 when delivered by gavage compared with untreated animals (P 相似文献   

Resistance of Copenhagen rats to chemical induction of glutathione S- transferase 7-7-positive liver foci

Copenhagen (Cop) rats are completely resistant to the chemical induction of mammary adenocarcinomas, but their susceptibility to hepatocarcinogenesis is virtually unknown. Rat liver is a well- characterized and easily manipulated tissue in which to study carcinogenesis. Therefore, if Cop rats are resistant to hepatocarcinogenesis, studies into resistance mechanisms may be feasible. Male Cop and F344 rats, 7-8 weeks old, were initiated using either N-nitrosodiethylamine (DEN) (200 mg/kg, i.p.) or a two-thirds partial hepatectomy (PH) followed by N-methyl-N-nitrosourea (MNU) (60 mg/kg, i.p.). The rats were then promoted using a modified resistant hepatocyte (RH) protocol (a combination of four doses of 2- acetylaminofluorene (2-AAF) and a single dose of CCl4 that provides a selective mitotic stimulus for initiated cells). Six weeks after initiation the rats were killed and liver sections were stained for glutathione S-transferase 7-7 (GST 7-7), a marker for putative preneoplastic hepatocytes. Cop rats were found to be highly resistant, having a approximately 9- and approximately 27-fold smaller percentage of liver area occupied by GST 7-7-positive foci than susceptible F344 rats following initiation by DEN and MNU respectively. Furthermore, gross liver nodules did not form in any of the Cop rats, whereas all F344 rat livers contained nodules. Hepatic necrosis caused by DEN during initiation, and CCl4 during promotion is necessary to stimulate compensatory hepatocyte division. We demonstrated that these agents do indeed increase serum transaminase levels and produce histologic evidence of necrosis in Cop rats. In order for liver foci to grow rapidly in the RH protocol, the surrounding normal hepatocytes must be mito-inhibited by 2-AAF. We found that the degree of mito-inhibition of normal hepatocytes by 2-AAF is the same in Cop and F344 rats. These results show that the Cop rat is highly resistant to the chemical induction of putative preneoplastic liver foci and nodules.      

The role of hepatocyte heterogeneity in the initiation of hepatocarcinogenesis

N-Nitrosodimethylamine (NDMA) is a carcinogen in rat liver whileN-nitrosomethylbenzylamine (NMBzA) produces no liver tumorsbut is a potent esophageal carcinogen in the rat. Both nitrosamines,however, are metabolically activated in the liver and methylatehepatic DNA. The reasons for their different carcinogenic propertiesin rat liver are unclear. Here we show that as expected, NDMAproduces large numbers of putative initiated hepatocytes thatoverexpress the placental form of glutathione S-transferase(GST-P⁺ hepatocytes). Hepatocyte division induced by the hepatotoxiceffect of NDMA occurs principally in the periportal region ofthe liver lobule, while O⁶-methylguanine formation is principallyin the DNA of perivenous cells. These two effects lead to theproduction of GST-P⁺ hepatocytes in roughly equal numbers throughoutthe liver lobule. NMBzA also induces the formation of a small,but significant number of GST-P⁺ hepatocytes. The NMBzA-inducedGST-P⁺ hepatocytes are localized within the perivenous zoneof the liver lobule. Since, unlike NDMA, NMBzA produces no hepatocellularnecrosis and hence does not induce regenerative cell division,these results suggest that NMBzA initiates only those hepatocytesadjacent to the hepatic vein that are spontaneously dividingat the time their DNA becomes methylated by the nitrosamine.We used partial hepatectomy to stimulate cell division in specificregions of the liver lobule. When the peak of DNA methylationproduced by NMBzA in the perivenous cells coincided with a peakof cell division in that region, an increased number of GST-P⁺hepatocytes was induced. Our results suggest that the potencyof initiating agents in the liver depends both on their abilityto form mutagenic lesions in DNA and to induce division in thespecific hepatocytes that contain the modified DNA.