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.      

The duration of phorbol-inducible ErbB2 tyrosine dephosphorylation parallels that of receptor endocytosis rather than threonine-686 phosphorylation: implications for the physiological role of protein kinase C in growth factor receptor signalling

Tumour cell growth may be accelerated by protein kinase C (PKC) agonists such as phorbol esters and receptor tyrosine kinases, but receptor tyrosine kinases are in turn desensitized to growth factors by PKC agonists. To clarify this apparent PKC bifunctionality, we have used phosphoantibodies to determine the relationship between PKC- dependent phosphorylation events affecting the ErbB2 oncoprotein in G8/DHFR 3T3 cells. Neither the kinetics nor the extent of phorbol- induced juxtamembrane domain (Thr686) phosphorylation vary directly with C-terminal (Tyr1222) dephosphorylation, with Tyr1222 continuing to be dephosphorylated long after Thr686 phosphorylation has also declined. Platelet-derived growth factor (PDGF) mimics the short-term effects of phorbol on Thr686 and Tyr1222 phosphorylation, and confocal microscopy reveals that both of these PKC agonists induce rapid internalization of PKC-modified ErbB2. Phorbol causes sustained cytoplasmic accumulation of PKC-phosphorylated receptors, however, whereas PDGF triggers the appearance of this ErbB2 subset only briefly. Metabolic labelling and co-precipitation studies fail to implicate heterologous molecules in either the tyrosine dephosphorylation or internalization of PKC-modified ErbB2. Taken in the context of earlier juxtamembrane domain mutagenesis studies, these findings indicate that phorbol-activated PKC may desensitize growth factor receptors to extracellular ligands solely by triggering sustained receptor internalization. We submit that PKC-dependent juxtamembrane domain phosphorylation represents a physiological mechanism for shortening the duration and enhancing the specificity of growth factor signalling by promoting internalization of liganded and unliganded receptors, respectively.      

Intracranial chondroma of the occipital lobe

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

The free radical spin trap alpha-phenyl-tert-butyl nitrone attenuates the cerebral response to deep hypothermic ischemia

OBJECTIVE: The aim of this study was to assess the role of reactive oxygen species in the impairment of cerebral recovery that follows deep hypothermic circulatory arrest. METHODS: Twelve 1-week-old piglets were randomized to placebo (control group; n = 6) or 100 mg x kg(-1) intravenous alpha-phenyl-tert -butyl nitrone, a free radical spin trap (PBN group; n = 6). All piglets underwent cardiopulmonary bypass, cooling to 18 degrees C, 60 minutes of circulatory arrest followed by 60 minutes of reperfusion, and rewarming. Cerebral blood flow and metabolism were determined at baseline before deep hypothermic circulatory arrest and after 60 minutes of reperfusion. RESULTS: In control animals, mean global cerebral blood flow (+/- 1 standard error) before circulatory arrest was 48.4 +/- 3.6 mL x 100 g(-1) x min(-1) and fell to 25.1 +/- 3.6 mL x 100 g(-1) x min(-1) after circulatory arrest (P =.001). Global cerebral metabolism fell from 3.5 +/- 0.2 mL x 100 g(-1) x min(-1) before arrest to 2.2 +/- 0.2 mL x 100 g(-1) x min(-1) after circulatory arrest (P =.0002). In the PBN group after circulatory arrest, the mean global cerebral blood flow and metabolism of 37.2 +/- 4.9 and 3.6 +/- 0.5 mL. 100 g(-1). min(-1), respectively, were significantly higher than in the control group (P <.05). Recovery of cerebral blood flow in the PBN group was 78% of pre-arrest level compared with 52% in the control group (P =.002). Global cerebral metabolism after circulatory arrest was 100% of the pre-arrest value compared with 61% in the control group (P =.01). Regional recovery of cerebral metabolism in the cerebellum, brain stem, and basal ganglia was 131%, 130%, and 115%, respectively, of pre-arrest values in the PBN group compared with 85%, 78%, and 70% in the control group (P <.04). CONCLUSIONS: Reactive oxygen species contribute to the impairment of cerebral recovery that follows deep hypothermic circulatory arrest. The use of alpha-phenyl-tert -butyl nitrone before the arrest period attenuates the normal response to ischemia and improves recovery by affording protection from free radical-mediated damage.     

Characterization of Healthcare-Associated and Community-Associated Clostridioides difficile Infections among Adults,Canada, 2015–2019

We investigated epidemiologic and molecular characteristics of healthcare-associated (HA) and community-associated (CA) Clostridioides difficile infection (CDI) among adult patients in Canadian Nosocomial Infection Surveillance Program hospitals during 2015–2019. The study encompassed 18,455 CDI cases, 13,735 (74.4%) HA and 4,720 (25.6%) CA. During 2015–2019, HA CDI rates decreased by 23.8%, whereas CA decreased by 18.8%. HA CDI was significantly associated with increased 30-day all-cause mortality as compared with CA CDI (p<0.01). Of 2,506 isolates analyzed, the most common ribotypes (RTs) were RT027, RT106, RT014, and RT020. RT027 was more often associated with CDI-attributable death than was non-RT027, regardless of acquisition type. Overall resistance C. difficile rates were similar for all drugs tested except moxifloxacin. Adult HA and CA CDI rates have declined, coinciding with changes in prevalence of RT027 and RT106. Infection prevention and control and continued national surveillance are integral to clarifying CDI epidemiology, investigation, and control.