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.     

Are increasing 5-year survival rates evidence of success against cancer?

CONTEXT: Increased 5-year survival for cancer patients is generally inferred to mean that cancer treatment has improved and that fewer patients die of cancer. Increased 5-year survival, however, may also reflect changes in diagnosis: finding more people with early-stage cancer, including some who would never have become symptomatic from their cancer. OBJECTIVE: To determine the relationship over time between 5-year cancer survival and 2 other measures of cancer burden, mortality and incidence. DESIGN AND SETTING: Using population-based statistics reported by the National Cancer Institute Surveillance, Epidemiology, and End Results Program, we calculated the change in 5-year survival from 1950 to 1995 for the 20 most common solid tumor types. Using the tumor as the unit of analysis, we correlated changes in 5-year survival with changes in mortality and incidence. MAIN OUTCOME MEASURE: The association between changes in 5-year survival and changes in mortality and incidence measured using simple correlation coefficients (Pearson and Spearman). RESULTS: From 1950 to 1995, there was an increase in 5-year survival for each of the 20 tumor types. The absolute increase in 5-year survival ranged from 3% (pancreatic cancer) to 50% (prostate cancer). During the same period, mortality rates declined for 12 types of cancer and increased for the remaining 8 types. There was little correlation between the change in 5-year survival for a specific tumor and the change in tumor-related mortality (Pearson r=.00; Spearman r=-.07). On the other hand, the change in 5-year survival was positively correlated with the change in the tumor incidence rate (Pearson r=+. 49; Spearman r=+.37). CONCLUSION: Although 5-year survival is a valid measure for comparing cancer therapies in a randomized trial, our analysis shows that changes in 5-year survival over time bear little relationship to changes in cancer mortality. Instead, they appear primarily related to changing patterns of diagnosis. JAMA. 2000.     

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.     

Antipsychotic agents and QT changes

Recently, antipsychotic medications of the novel or atypical classes have received increased attention because of concerns with respect to potential lengthening of the QT interval, yet the currently available and commonly prescribed conventional antipsychotics are significantly more cardiotoxic, particularly agents in the butyrophenone and phenothiazine classes. Lengthening of the QT interval can be associated with a fatal paroxysmal ventricular arrhythmia known as torsades de pointes. The specific duration of the QT interval at which the risk of an adverse cardiac event is greatest, is not established. There is not only significant variation in the applied definition of an abnormal interval, but the maximal QT interval in healthy volunteers is greater than the currently accepted standards. The QT interval is influenced by normal physiological and pathologic factors, but the mechanisms remain unclear. Using recombinant technology, haloperidol and sertindole have been demonstrated to be high-affinity antagonists of a human cardiac potassium channel encoded by the human ether-a-go-go-related gene. Pimozide, however, has been shown to act principally through calcium channel antagonism, and chlorpromazine may affect sodium channels. Nevertheless, it is possible that these effects are significant only in the presence of predisposing factors, either genetic or acquired. Despite proven efficacy in clinical trials and subsequent supervised use in Europe, a number of recently developed antipsychotic medications are not available to patients in North America. Yet, conventional antipsychotic medications that would not be approved by current safety standards continue to be widely used.     

Analysis of protein activity data by Gaussian stochastic process models

The effects of certain chemical additives at maintaining a high level of activity in protein constructs during storage is investigated. We use a semiparametric regression technique to model the effects of the additives on protein activity. The model is extended to handle categorical explanatory variables. On the basis of the available data, the important factors are estimated to be buffer, detergent, protein concentration, and storage temperature. The relationships among protein activity and these factors appear to be moderately nonlinear with strong interaction effects. These features are revealed in a data-adaptive way by the semi parametric model, without explicit modeling of the nonlinearities or interactions. We use cross-validation to assess the fit of our model. The protein activity response appears to be extremely erratic. We recommend several sets of storage conditions and that further design points be chosen in regions around these estimated optima.     

Massive suprachoroidal hemorrhage. Follow-up and outcome of 30 cases

The authors studied the records of 30 patients who suffered a massive suprachoroidal hemorrhage during cataract surgery. Immediate development of a retinal detachment (RD) is a very bad prognostic sign. In none of 12 such cases could the retina be reattached. Retinal complications developed in five of six patients who had vitreous incarceration and who did not have vitrectomy as opposed to only one of seven who underwent vitrectomy along with drainage of the hemorrhage. If vitreous is incarcerated in the cataract incision, drainage of the hemorrhage without vitrectomy is a dangerous procedure.     

Further delineation of Weaver syndrome

Seven new cases of Weaver syndrome are described, including the first reported case in an adult. Overgrowth is usually but not always present. The combination of characteristic facies and developmental delay, with the peculiar radiographic findings of accelerated dysharmonic osseous maturation and splaying of the distal long bones, is diagnostic of Weaver syndrome.