Synthesis and summary of patient-reported outcome measures to inform the development of a core outcome set in colorectal cancer surgery.

AIM: Patient-reported outcome (PRO) measures (PROMs) are standard measures in the assessment of colorectal cancer (CRC) treatment, but the range and complexity of available PROMs may be hindering the synthesis of evidence. This systematic review aimed to: (i) summarize PROMs in studies of CRC surgery and (ii) categorize PRO content to inform the future development of an agreed minimum 'core' outcome set to be measured in all trials. METHOD: All PROMs were identified from a systematic review of prospective CRC surgical studies. The type and frequency of PROMs in each study were summarized, and the number of items documented. All items were extracted and independently categorized by content by two researchers into 'health domains', and discrepancies were discussed with a patient and expert. Domain popularity and the distribution of items were summarized. RESULTS: Fifty-eight different PROMs were identified from the 104 included studies. There were 23 generic, four cancer-specific, 11 disease-specific and 16 symptom-specific questionnaires, and three ad hoc measures. The most frequently used PROM was the EORTC QLQ-C30 (50 studies), and most PROMs (n = 40, 69%) were used in only one study. Detailed examination of the 50 available measures identified 917 items, which were categorized into 51 domains. The domains comprising the most items were 'anxiety' (n = 85, 9.2%), 'fatigue' (n = 67, 7.3%) and 'physical function' (n = 63, 6.9%). No domains were included in all PROMs. CONCLUSION: There is major heterogeneity of PRO measurement and a wide variation in content assessed in the PROMs available for CRC. A core outcome set will improve PRO outcome measurement and reporting in CRC trials.

Native Language Spoken as a Risk Marker for Tooth Decay.

OBJECTIVE: The purpose of this study was to assess dmft, the number of decayed, missing (due to caries), and/ or filled primary teeth, of English-speaking and non-English speaking patients of a hospital based pediatric dental clinic under the age of 72 months to determine if native language is a risk marker for tooth decay. STUDY DESIGN: Records from an outpatient dental clinic which met the inclusion criteria were reviewed. Patient demographics and dmft score were recorded, and the patients were separated into three groups by the native language spoken by their parents: English, Spanish and all other languages. RESULTS: A total of 419 charts were assessed: 253 English-speaking, 126 Spanish-speaking, and 40 other native languages. After accounting for patient characteristics, dmft was significantly higher for the other language group than for the English-speaking (p<0.001) and Spanish-speaking groups (p<0.05), however the English-speaking and Spanish-speaking groups were not different from each other (p>0.05). CONCLUSIONS: Those patients under 72 months of age whose parents' native language is not English or Spanish, have the highest risk for increased dmft when compared to English and Spanish speaking patients. Providers should consider taking additional time to educate patients and their parents, in their native language, on the importance of routine dental care and oral hygiene.

A systematic review of outcome reporting in colorectal cancer surgery.

AIM: Evaluation of surgery for colorectal cancer (CRC) is necessary to inform clinical decision-making and healthcare policy. The standards of outcome reporting after CRC surgery have not previously been considered. METHOD: Systematic literature searches identified randomized and nonrandomized prospective studies reporting clinical outcomes of CRC surgery. Outcomes were listed verbatim, categorized into broad groups (outcome domains) and examined for a definition (an appropriate textual explanation or a supporting citation). Outcome reporting was considered inconsistent if results of the outcome specified in the methods were not reported. Outcome reporting was compared between randomized and nonrandomized studies. RESULTS: Of 5644 abstracts, 194 articles (34 randomized and 160 nonrandomized studies) were included reporting 766 different clinical outcomes, categorized into seven domains. A mean of 14 ± 8 individual outcomes were reported per study. 'Anastomotic leak', 'overall survival' and 'wound infection' were the three most frequently reported outcomes in 72, 60 and 44 (37.1%, 30.9% and 22.7%) studies, respectively, and no single outcome was reported in every publication. Outcome definitions were significantly more often provided in randomized studies than in nonrandomized studies (19.0% vs 14.9%, P = 0.015). One-hundred and twenty-seven (65.5%) papers reported results of all outcomes specified in the methods (randomized studies, n = 21, 61.5%; nonrandomized studies, n = 106, 66.2%; P = 0.617). CONCLUSION: Outcome reporting in CRC surgery lacks consistency and method. Improved standards of outcome measurement are recommended to permit data synthesis and transparent cross-study comparisons.

Designing a therapeutic hepatitis B vaccine to circumvent immune tolerance.

An effective prophylactic hepatitis B virus (HBV) vaccine has long been available but is ineffective for chronic infection. The primary cause of chronic hepatitis B (CHB) and greatest impediment for a therapeutic vaccine is the direct and indirect effects of immune tolerance to HBV antigens. The resulting defective CD4+/CD8+ T cell response, poor cytokine production, insufficient neutralizing antibody (nAb) and poor response to HBsAg vaccination characterize CHB infection. The objective of this study was to develop virus-like-particles (VLPs) that elicit nAb to prevent viral spread and prime CD4+/CD8+ T cells to eradicate intracellular HBV. Eight neutralizing B cell epitopes from the envelope PreS1 region were consolidated onto a species-variant of the HBV core protein, the woodchuck hepatitis core antigen (WHcAg). PreS1-specific B cell epitopes were chosen because of preferential expression on HBV virions. Because WHcAg and HBcAg are not crossreactive at the B cell level and only partially cross-reactive at the CD4+/CD8+ T cell level, CD4+ T cells specific for WHcAg-unique T cell sites can provide cognate T-B cell help for anti-PreS1 Ab production that is not curtailed by immune tolerance. Immunization of immune tolerant HBV transgenic (Tg) mice with PreS1-WHc VLPs elicited levels of high titer anti-PreS1 nAbs equivalent to wildtype mice. Passive transfer of PreS1 nAbs into human-liver chimeric mice prevented acute infection and cleared serum HBV from mice previously infected with HBV in a model of CHB. At the T cell level, PreS1-WHc VLPs and hybrid WHcAg/HBcAg DNA immunogens elicited HBcAg-specific CD4+ Th and CD8+ CTL responses.

Development of Faecalibacterium 16S rRNA gene marker for identification of human faeces.

AIMS: The focus of this study was to identify a bacterial 16S rRNA gene sequence, unique to microbiota in the human gut, for use in development of a dependable PCR assay to detect human faecal pollution in water. METHODS AND RESULTS: Suppression subtractive hybridization (SSH) and bioinformatics were used to identify a genetic marker, within the 16S rRNA gene of Faecalibacterium, for the detection of human faeces. DNA sequencing analysis demonstrated that a majority (16) of 74 clones of the SSH library contained insertion sequences identified as Faecalibacterium 16S rRNA genes. Human faeces-specific sequences were derived and six PCR primer sets designed and tested against faecal DNA samples from human and nonhuman sources. One PCR primer set, HFB-F3 and HFB-R5, was exclusively associated with human faeces. These primers generated a human faeces-specific amplicon of 399 bp from 60.2% of human faecal samples and 100% of sewage samples. CONCLUSIONS: The subject Faecalibacterium marker is specific for sewage. SIGNIFICANCE AND IMPACT OF THE STUDY: This study represents the initial report of a Faecalibacterium marker for human faeces, which may prove useful for microbial source tracking.

Language function in childhood idiopathic epilepsy syndromes.

PURPOSE: To examine the impact of diverse syndromes of focal and generalized epilepsy on language function in children with new and recent onset epilepsy. Of special interest was the degree of shared language abnormality across epilepsy syndromes and the unique effects associated with specific epilepsy syndromes. METHODS: Participants were 136 youth with new or recent-onset (diagnosis within past 12 months) epilepsy and 107 healthy first-degree cousin controls. The participants with epilepsy included 20 with Temporal Lobe Epilepsy (TLE; M age = 12.99  years, SD = 3.11), 41 with Benign Epilepsy with Centrotemporal Spikes (BECTS; M age = 10.32, SD = 1.67), 42 with Juvenile Myoclonic Epilepsy (JME; M age = 14.85, SD = 2.75) and 33 with absence epilepsy (M age = 10.55, SD = 2.76). All children were administered a comprehensive test battery which included multiple measures of language and language-dependent abilities (i.e., verbal intelligence, vocabulary, verbal reasoning, object naming, reception word recognition, word reading, spelling, lexical and semantic fluency, verbal list learning and delayed verbal memory). Test scores were adjusted for age and gender and analyzed via MANCOVA. RESULTS: Language abnormalities were found in all epilepsy patient groups. The most broadly affected children were those with TLE and absence epilepsy, whose performance differed significantly from controls on 8 of 11 and 9 of 11 tests respectively. Although children with JME and BECTS were less affected, significant differences from controls were found on 4 of 11 tests each. While each group had a unique profile of language deficits, commonalities were apparent across both idiopathic generalized and localization-related diagnostic categories. DISCUSSION: The localization related and generalized idiopathic childhood epilepsies examined here were associated with impact on diverse language abilities early in the course of the disorder.

Use of a Bacteroides thetaiotaomicron-specific alpha-1-6, mannanase quantitative PCR to detect human faecal pollution in water.

AIMS: The aims of this work were to develop a quantitative test, based on Bacteroides thetaiotaomicron, for human faecal pollution in water and to evaluate test performance. METHODS AND RESULTS: qPCR primers, based on the complete genomic sequence of B. thetaiotaomicron VPI 5482, were designed and tested. The single-copy putative mannanase homologue, alpha-1-6 mannanase, was selected as the particular target and sequences within this gene chosen as the qPCR primers by Blast search for specificity to B. thetaiotaomicron. The average concentration of B. thetaiotaomicron in human faeces was 1.39 x 10(8) cells per gram faeces and the detection limit was 9.3 B. thetaiotaomicron copies per qPCR procedure. Comparison of B. thetaiotaomicron content in sewage vs pooled nonhuman faecal samples indicated that the current assay is specific for sewage. CONCLUSION: The subject assay is potentially useful for quantification of sewage pollution in water. SIGNIFICANCE AND IMPACT OF THE STUDY: Bacteroides-associated markers, proposed for faecal source tracking, have exclusively been based on gene sequences related to generally classified and uncultured bacteria. However, genes associated with host-microbe interaction have been suggested as more specific markers. The present assay targets such a gene of B. thetaiotaomicron which is considered to be a symbiont in the human gut.

Impact of exudate and odour from chronic venous leg ulceration.

AIMS: To explore depression in people treated for chronic venous leg ulceration, and to assess the impact of excessive exudate, leading to leakage and odour, on their daily lives, overall health and quality of life. METHODS: Completion of a questionnaire and Hospital Anxiety and Depression Scale to determine the prevalence of anxiety and depression in people with chronic leg ulceration (n = 196), and interviews with 20 people living with chronic leg ulceration. FINDINGS: Odour and excessive exudate leading to leakage had an adverse effect on patients' psychological state, leading to feelings of disgust, self-loathing and low self-esteem. CONCLUSION: Chronic leg ulcers disrupt patients' lives and restrict their social lives, leading to social isolation and depression. Healthcare professionals should better understand the impact of symptoms such as odour and exudate leakage on patients' mental health, physical health and healing.

Regulation of mouse CYP1A1 gene expression by dioxin: requirement of two cis-acting elements during induction.

The mouse cytochrome P1450 (CYP1A1) gene is responsible for the metabolism of numerous carcinogens and toxic chemicals. Induction by the environmental contaminant tetrachlorodibenzo-p-dioxin (TCDD) requires a functional aromatic hydrocarbon (Ah) receptor. We examined the 5'-flanking region of the CYP1A1 gene in mouse hepatoma Hepa-1 wild-type cells and a mutant line having a defect in chromatin binding of the TCDD-receptor complex. We identified two cis-acting elements (distal, -1071 to -901 region; proximal, -245 to -50 region) required for constitutive and TCDD-inducible CYP1A1 gene expression. Three classes of DNA-protein complexes binding to the distal element were identified: class I, found only in the presence of TCDD and a functional Ah receptor, that was heat labile and not competed against by simian virus 40 (SV40) early promoter DNA; class II, consisting of at least three constitutive complexes that were heat stable and bound to SV40 DNA; and class III, composed of at least three constitutive complexes that were thermolabile and were not competed against by SV40 DNA. Essential contacts for these proteins were centered at -993 to -990 for the class I complex, -987, -986, or both for the class II complexes, and -938 to -927 for the class III complexes. The proximal element was absolutely essential for both constitutive and TCDD-inducible CYP1A1 gene expression, and at least two constitutive complexes bound to this region. These data are consistent with the proximal element that binds proteins being necessary but not sufficient for inducible gene expression; interaction of these proteins with those at the distal element was found to be required for full CYP1A1 induction by TCDD.

Regulation of protein kinase C activity in neuronal differentiation induced by the N-ras oncogene in PC-12 cells.

Expression of the N-ras oncogene under the control of the glucocorticoid-responsive promoter in the pheochromocytoma cell line UR61, a subline of PC-12 cells, has been used to investigate the differentiation process to neuronal cells triggered by ras oncogenes (I. Guerrero, A. Pellicer, and D. E. Burstein, Biochem. Biophys. Res. Commun. 150:1185-1192, 1988). Using ras-inducible cell lines, we observed that expression of the oncogenic N-ras p21 protein interferes with the ability of phorbol esters to induce downregulation of protein kinase C. This effect was associated with the appearance of immunologically detectable protein kinase C as well as the activity of the enzyme as analyzed either by binding of [3H]phorbol-12,13-dibutyrate in intact cells or by in vitro kinase activity. These results indicate a relationship between ras p21 and protein kinase C in neuronal differentiation in this model system. Comparison to the murine fibroblast system suggests that this relationship may be functional.

Skin grafting for venous leg ulcers.

BACKGROUND: Venous leg ulceration is a recurrent, chronic, disabling condition. It affects up to one in 100 adults at some time. Standard treatments are simple dressings and compression bandages or stockings. Sometimes, despite treatment, ulcers remain open for months or years. Sometimes skin grafts are used to stimulate healing. These may be taken, or grown into a dressing, from the patient's own uninjured skin (autografts), or applied as a sheet of bioengineered skin grown from donor cells (allograft). Preserved skin from other animals, such as pigs, has also been used (xenografts). OBJECTIVES: To assess the effect of skin grafts for treating venous leg ulcers. SEARCH STRATEGY: We searched the Cochrane Wounds Group Specialised Register (February 2006) and the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 1, 2006). SELECTION CRITERIA: Randomised controlled trials (RCTs) of skin grafts in the treatment of venous leg ulcers. DATA COLLECTION AND ANALYSIS: Two reviewers independently undertook data extraction and assessment of study quality. MAIN RESULTS: We identified 15 trials - generally of poor methodological quality - involving 768 participants. In 11 trials participants also received compression bandaging. One trial (31 participants) compared a dressing with an autograft. Three trials (74 participants) compared frozen allografts with dressings, and three trials (47 participants) compared fresh allografts with dressings. Two trials (345 participants) compared tissue-engineered skin (bilayer artificial skin) with a dressing. In two trials (71 participants) a single-layer dermal replacement was compared with standard care. Four trials compared skin grafting techniques: one trial (92 participants) compared autografts with frozen allograft, a second (51 participants) compared a pinch graft (autograft) with a porcine dermis (xenograft), the third (seven participants, 12 ulcers) compared tissue-engineered skin with a split-thickness graft, the fourth (10 participants) compared a fresh allograft with a frozen allograft. The trials comparing bilayer artificial skin with a dressing reported a significantly higher proportion of ulcers healing with artificial skin. There was not enough evidence from the other trials to determine whether other types of skin grafting increased the healing of venous ulcers. AUTHORS' CONCLUSIONS: Bilayer artificial skin, used in conjunction with compression bandaging, increases the chance of healing a venous ulcer compared with compression and a simple dressing. Further research is needed to assess whether other forms of skin grafts increase ulcer healing.

High accuracy plasma density measurement using hybrid Langmuir probe and microwave interferometer method.

High spatial resolution plasma density measurements have been taken as part of an investigation into magnetic nozzle physics at the NASA/MSFC Propulsion Research Center. These measurements utilized a Langmuir triple probe scanned across the measurement chord of either of two stationary rf interferometers. By normalizing the scanned profile to the microwave interferometer line-integrated density measurement for each electrostatic probe measurement, the effect of shot-to-shot variation of the line-integrated density can be removed. In addition, by summing the voltage readings at each radial position in a transverse scan, the line density can be reconstituted, allowing the absolute density to be determined, assuming that the shape of the profile is constant from shot to shot. The spatial and temporal resolutions of this measurement technique depend on the resolutions of the scanned electrostatic probe and the interferometer. The measurement accuracy is 9%-15%, which is on the order of the accuracy of the rf interferometer. The measurement technique was compared directly with both scanning rf interferometer and standard Langmuir probe theory. The hybrid technique compares favorably with the scanning rf interferometer, and appears more accurate than probe theory alone. Additionally, our measurement technique is generally applicable even for nonaxisymmetric plasmas.

A modular route to boron doped PAHs by combining borylative cyclisation and electrophilic C-H borylation.

Heteroatom doping into polyaromatic hydrocarbons (PAHs) is a powerful approach for modifying key physical properties, however, there are extremely few modular routes that enable facile formation of B-, B2- and B,N-(specifically not containing direct B-N bonds) doped PAHs despite the growing importance of these materials. Sequential, one pot borylative cyclisation/intramolecular electrophilic C-H borylation of naphthyl-alkynes provides a simple new route to access novel B-, B,N- and B2-doped (PAHs). The initial products, dihydronaphthalene/dihydroquinoline B-mesityl PAHs, were reacted with [Ph3C][BF4]/pyridyl base to form the oxidised B-, and B,N-doped PAHs. However, for B-triisopropylphenyl (Trip) PAH congeners oxidation has to be performed prior to Trip installation due to preferential oxidation of an isopropylaryl moiety to the styrene. This alternative sequence enables access to Trip-B-PAHs and to structurally constrained B and B2-PAHs. Analysis of the solid state structures and optoelectronic properties of these PAHs confirm that frontier orbital energies, extended packing structures, Stokes shift and quantum yields all can be rationally modified using this methodology. The simplicity of this synthetic approach makes it a powerful tool for rapidly generating novel bench stable boron doped PAHs, which is important for facilitating further structure-property relationship studies and the wider utilisation of these materials in optoelectronic applications.

Parental communication deviance and affective style. Predictors of subsequent schizophrenia spectrum disorders in vulnerable adolescents.

In an attempt to assess the contributory role of family factors to the development of schizophrenia-like disorders, measures of parental communication deviance and affective styles of communication were obtained for a sample of families of disturbed but nonpsychotic adolescents. Outcome was assessed five years later. Absence of a pathologic affective style was associated with a benign outcome, but neither parental variable alone allowed precise identification of the schizophrenia-spectrum cases. However, an index using a combination of both variables was statistically predictive of subsequent psychiatric status at follow-up. Thus, adolescents whose parents had both a pathologic affective style of communication and a high level of communication deviance had schizophrenia-like disorders develop in young adulthood. Adolescents of parents who had both lower levels of communication deviance and a benign affective style had offspring with healthier outcomes.

Parental transactional style deviance as a possible indicator of risk for schizophrenia.

The presence of a pattern of parental transactional style deviance on the Thematic Apperception Test (TAT) (a significant attribute of parents of offspring with schizophrenia spectrum disorders) was used to identify a group of disturbed nonpsychotic adolescents hypothesized to be at high risk for subsequently developing schizophreniform psychopathology. High-risk male adolescents came from two symptom groups, withdrawn adolescents and adolescents in active family conflict, which are symptom patterns similar to the premorbid pictures of two schizophrenia subtypes. High-risk parents also tended to show transactional style deviance in direct interaction with their child and in a written statement describing their child's problem. The degree of risk was significantly related to the amount of therapy in which the family was subsequently engaged and, at a four-year follow-up, to the level of adjustment of the adolescents seen earlier in the project.

Human CYP1A2: sequence, gene structure, comparison with the mouse and rat orthologous gene, and differences in liver 1A2 mRNA expression.

We have sequenced the human CYP1A2 (cytochrome P(3)450) gene, 1,906 basepairs (bp) of the 5' flanking region, and 113 bp of the 3' flanking region. The gene spans almost 7.8 kilobases, comprising seven exons and six introns. The transcriptional start site was determined by both primer extension and S1 mapping. Including the first noncoding exon of 55 bp, the entire mRNA is 3,121 bp in length, and the open reading frame, starting with nucleotide 10 of exon 2, encodes 515 amino acids (mol wt = 58,294). Between the human CYP1A2 and CYP1A1 (cytochrome P(1)450) genes, exons 2, 4, 6, and especially 5 are strikingly conserved in both nucleotide similarity and total number of bases. Alignment of the upstream sequences and exon 1 of human CYP1A2 with that of mouse or rat CYP1A2 revealed two possibly significant regions of similarity: 1) 68% in the approximately 150 bases immediately 5' from the mRNA cap site and 2) 80% identify between the human -841 to -758 segment and the mouse -1,529 to -1,439 segment. The canonical 5-bp box (CACGC), found upstream of all mammalian CYP1A1 genes to date and believed to interact with the inducer.aromatic hydrocarbon receptor complex, was not found on either strand in the 1,906 bp of the 5' flanking region of human CYP1A2. In contrast, alignment of the upstream sequences, exon 1, and intron 1 of human CYP1A1 with that of mouse or rat CYP1A1 revealed large, highly conserved regions. Conserved regions were found in intron 1 of the human, mouse, and rat CYP1A2 gene. These data suggest that the regulatory elements controlling the CYP1A2 gene might differ in location from those controlling the CYP1A1 gene. Among 12 human liver samples, striking differences (greater than 15-fold) in the 3.3-kilobase 1A2 mRNA levels were seen. This result may reflect significant genetic differences in constitutive and/or inducible CYP1A2 gene expression that could play an important role in individual risk of environmental toxicity or cancer.

Skin grafting for venous leg ulcers.

BACKGROUND: Venous leg ulceration is a common and disabling condition which often recurs. It affects up to one in 100 adults at some time. The usual treatments are simple dressings and compression bandages or stockings. Unfortunately, in some cases this treatment is unsuccessful, with ulcers remaining open for months or years. Sometimes skin grafts are used to stimulate healing. These skin grafts may be taken from the patient's own uninjured skin, may be grown from the patient's skin cells into a dressing (autografts), or applied as a sheet of bioengineered skin grown from donor cells (allograft). Preserved skin from other animals, such as pigs, has also been used; these grafts are known as xerografts. OBJECTIVES: To assess the effect of skin grafts for treating venous leg ulcers. SEARCH STRATEGY: We searched the Cochrane Wounds Group Specialised Register (June 2004) and the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 2, 2004). SELECTION CRITERIA: Randomised controlled trials (RCTs) of skin grafts in the treatment of venous leg ulcers. DATA COLLECTION AND ANALYSIS: Two reviewers independently undertook data extraction and assessment of study quality. MAIN RESULTS: Nine trials of skin grafts for venous leg ulcers were identified, involving 579 participants. The trials were generally of poor methodological quality. In eight trials participants also received compression bandaging. Two trials (98 participants) evaluated split thickness autografts (one against a dressing and one against a xerograft), four trials (119 participants) evaluated cultured keratinocyte grafts (3 allografts and 1 autograft) , two compared tissue engineered skin (bilayer artificial skin) with a dressing (345 participants), and one compared it with a split thickness skin graft (7 participants, 13 ulcers). The trials comparing bilayer artificial skin with a dressing reported a significantly higher proportion of ulcers healing with artificial skin. There was not enough evidence from the other trials to determine whether other types of skin grafting increased the healing of venous ulcers. AUTHORS' CONCLUSIONS: There is evidence that a bilayer artificial skin, used in conjunction with compression bandaging, increases the chance of healing a venous ulcer compared with compression and a simple dressing. Further research is needed to assess whether other forms of skin grafts increase ulcer healing.

Human peptidylglycine alpha-amidating monooxygenase transcripts derived by alternative mRNA splicing of an unreported exon.

We are characterizing the alternatively spliced human peptidylglycine alpha-amidating monooxygenase (hPAM)-encoding mRNA transcripts expressed by human cells. Reverse transcription coupled to the polymerase chain reaction (RT-PCR) has been used to identify four alternatively spliced variants that differ in the region joining the two catalytic domains. Two of the transcripts represent previously reported splice variants differentiated by the presence (hPAM-A) or absence (hPAM-B) of a 321-nucleotide (nt) linker (optional exon A) which in the rat produce functionally distinct enzymes. Different mRNAs represent two splice variants, hPAM-C and hPAM-D, that show the presence of an exon unreported for PAM in any other species. This new exon, designated exon C, is 54 nt in length, encodes an 18-amino-acid (aa) peptide containing a conserved dibasic aa endoproteolytic processing motif, and is located 3' of exon A in human genomic DNA. We propose that cell-specific regulation of mRNA splicing would provide a mechanism for control of prohormone activation by these variants of the PAM enzyme.

Is colonoscopic cancer surveillance in ulcerative colitis essential for every patient?

Surveillance aims to diagnose precancer or cancer at a surgically curable stage. Cancer complicating ulcerative colitis affects only 1-2 per million of the general population annually. The risk is low within 10 years of disease onset, and in proctitis or left-sided colitis. It is approximately one in 120 per year for those with extensive disease after 10 years from onset. Results of surveillance programmes from regional hospitals among 423 patients led to surgery for precancer or cancer once every 123 colonoscopies; there were no cancer deaths during surveillance and all 4 cancers were Dukes' stage A or B. At referral centres, many patients have dysplasia at the first colonoscopy. Two-thirds of cancers in colitis develop in the recto-sigmoid; flexible sigmoidoscopy has a role in surveillance which is untested. Colonoscopic surveillance is not appropriate for most patients with colitis; it is worthwhile but not essential for those with long-standing extensive disease.

Tissue- and cell type-specific expression of cytochrome P450 1A1 and cytochrome P450 1A2 mRNA in the mouse localized in situ hybridization.

We used in situ hybridization to examine organ- and cell type-specific constitutive and 3-methylcholanthrene (3MC)-inducible cytochrome P450 (CYP)1A1 and CYP1A2 mRNA expression in various tissues of the C57BL/6N mouse. In situ hybridization was carried out 10 hr after the mice had received intraperitoneal 3MC, or vehicle alone. We detected levels of 3MC-induced CYP1A1 mRNA in: liver (centrilobular, more so than periportal, regions); lung (Clara Type II cells much more than Type I epithelial cells); brain, especially endothelial cells lining the vascular surface of the choroid plexus; the digestive tract (duodenum > jejunum > ileum > colon > esophagus > stomach--in particular, the villous epithelium, plus cells surrounding glands in the lamina propria); renal corpuscles of the kidney; the ovary (medulla more so than cortex); and the endothelial cells of blood vessels throughout the animal. Constitutive CYP1A1 mRNA was not detectable by in situ hybridization in any of these tissues. In contrast, constitutive CYP1A2 mRNA was measurable in liver, and 3MC-inducible CYP1A2 mRNA was observed only in liver, lung, and duodenum (having cell-type locations similar to those of CYP1A1); the other above-mentioned tissues were negative for CYP1A2 mRNA. These data demonstrate the striking differences in tissue- and cell type-specific expression between the two members of the mouse Cypla subfamily. Because of the ubiquitous nature of 3MC-inducible CYP1A1 throughout the animal rather than just "portals of entry," these results support our hypothesis that CYP1A1, induced by particular endogenous signals in various tissues and cell types, might participate in one or more critical life processes--in addition to its well-established role of metabolism of polycyclic hydrocarbons, certain drugs, and other environmental pollutants.