Hypospadias trends in two US surveillance systems

OBJECTIVE: Hypospadias is a common congenital anomaly, the cause of which is unknown. Unexplained increases in the rates of hypospadias occurred in five European countries in the 1970s and 1980s. We examined data from two birth defects surveillance systems in the United States for evidence of similar trends. METHODOLOGY: The Metropolitan Atlanta Congenital Defects Program (MACDP) provided birth prevalence rates from 1968 to 1993. The nationwide Birth Defects Monitoring Program (BDMP) provided rates from 1970 to 1993. MACDP data are population-based and could be categorized by the severity of the hypospadias. BDMP data allowed analysis of rate trends for the four census regions of the United States. RESULTS: Data from both surveillance systems showed an approximate doubling of hypospadias rates in the 1970s and 1980s. MACDP data showed that the rate of severe cases increased while the ratio of mild to severe cases decreased. BDMP data showed that hypospadias rates increased markedly in all four regions of the United States. CONCLUSIONS: The observed increases are unlikely to be attributable to increased sensitivity of the surveillance systems or the identification of more mild cases by physicians over time, because either trend would have increased rather than decreased the ratio of mild to severe cases. If real, these trends represent the largest number of cases and the first report of an increase in hypospadias rates outside of Europe. Additional investigation of a possible increase in hypospadias rates is warranted.     

Analyses of mutation and loss of heterozygosity of coding sequences of the entire transforming growth factor beta type II receptor gene in sporadic human gastric cancer

Mutations in the transforming growth factor beta type II receptor (TGFbetaRII) gene have been detected in several human cancer types exhibiting microsatellite instability. Using intron primers previously reported for examination of the entire coding region of the TGFbetaRII gene, 29 sporadic gastric cancers were screened with non-radioactive single strand conformation polymorphism and subsequent DNA sequencing analysis. Mutations of the TGFbetaRII gene were detected in three out of 29 tumors (10%). Two cases showed deletions in a polyadenine tract in both alleles and was positively associated with replication error. One case had an insertion of GA dinucleotide sequence in one allele. Mutations of the TGFbetaRII gene were restricted to exon 3 and other coding regions were not affected. Loss of heterozygosity was detected by analyzing a polymorphic site in intron 2. Three out of nine (33%) informative cases, which were all of intestinal type and advanced cases, showed loss of heterozygosity but neither TGFbetaRII mutation nor replication error was found in these cases. Immunoreactivity of TGFbetaRII in tumor tissues was reduced to a different extent in the gastric cancer with genetically abnormal transforming growth factor. Although the numbers studied are small, homozygous (A)10 deletion or loss of heterozygosity of TGFbetaRII is involved in tumorigenesis and progression of at least some part of sporadic gastric cancer.      

Intracranial chondroma of the occipital lobe

A case report of an intracranial chondroma is discussed with emphasis on magnetic resonance imaging.     

Prospects for cardiovascular research

Cardiovascular disease is the greatest threat to human life and health. The past decade has seen remarkable progress in clinical and basic cardiovascular research, and many areas of opportunity are promising. The pace of current progress in clinical and basic research is such that remarkable improvement in the quality and length of life for those at risk for cardiovascular disease is likely.     

Breast cancer cell lines: friend or foe?

The majority of breast cancer research is conducted using established breast cancer cell lines as in vitro models. An alternative is to use cultures established from primary breast tumours. Here, we discuss the pros and cons of using both of these models in translational breast cancer research.     

Unexplained diarrhoea and failure to thrive in 2 siblings with unusual facies and abnormal scalp hair shafts: a new syndrome

A family is described in which 2 siblings born to healthy parents presented with abnormal facies, persistent diarrhoea, and early death. Exhaustive pathological and biochemical investigations failed to find a cause. The scalp hair of both babies had an abnormal amino-acid composition, and presented an appearance that was unique on scanning electron microscopical examination; this fact and the clinical picture probably represents a new syndrome.     

Surgical anatomy of the nose

It is imperative to know the details of the anatomy of the nose before understanding any surgical procedure performed on the nose. The details presented in this article should help the experienced and the novice surgeon accomplish the difficult task of a rhinoplasty.     

Where does the developing brain obtain its docosahexaenoic acid? Relative contributions of dietary alpha-linolenic acid, docosahexaenoic acid, and body stores in the developing rat

Docosahexaenoic acid (DHA), a 22-carbon, highly unsaturated, n-3 fatty acid, is important for optimal nervous system function. In this study, designed to quantify how preformed dietary DHA regulates metabolic pathways in vivo, 8-d-old rat pups were divided into four groups and fed artificial rat milk diets. One group was fed formula with deuterium-labeled LNA (d5-LNA) as the only source of n-3 fatty acids, and a second group was fed formula that contained d5-LNA and unlabeled DHA. Two additional groups were dam-reared to permit analysis of fatty acyl pool sizes at postnatal days 8 and 28. The dams were fed a diet that contained 3% unlabeled LNA. DHA in brain and liver was analyzed. Our study demonstrated that preformed DHA in the diet markedly decreased the amount of biosynthesized DHA that accumulated in the brain and the liver. Surprisingly, 40% of the DHA that was newly acquired during this period in the "LNA" group was unlabeled. Because there were no unlabeled n-3 fatty acids in this diet, this DHA must have been derived from body stores of n-3 fatty acids. Thus, body stores can be a significant source of brain DHA in animals that are fed LNA as the only source of n-3 fatty acids.     

Possibility of selection against mtDNA mutations in tumors

Several studies of tumors have revealed substantial numbers of clonally expanded somatic mutations in mitochondrial DNA (mtDNA), not observed in adjacent intact tissues. These findings were interpreted as indicating the involvement of mtDNA mutations in tumorigenesis. Such comparisons, however, ignore an important confounding factor: the monoclonal origin of tumors as opposed to the highly polyclonal nature of normal tissues. Analysis of recently published data on the incidence of somatic mutations in nontumor monoclonal cells suggests that, contrary to the prevailing view, the process of tumorigenesis may be accompanied by active selection against detrimental mtDNA mutations.