Resonant multiphoton processes and excitation limits to structural dynamics.

Understanding the chemical reactions that give rise to functional biological systems is at the core of structural biology. As techniques are developed to study the chemical reactions that drive biological processes, it must be ensured that the reaction occurring is indeed a biologically relevant pathway. There is mounting evidence indicating that there has been a propagation of systematic error in the study of photoactive biological processes; the optical methods used to probe the structural dynamics of light activated protein functions have failed to ensure that the photoexcitation prepares a well-defined initial state relevant to the biological process of interest. Photoexcitation in nature occurs in the linear (one-photon per chromophore) regime; however, the extreme excitation conditions used experimentally give rise to biologically irrelevant multiphoton absorption. To evaluate and ensure the biological relevance of past and future experiments, a theoretical framework has been developed to determine the excitation conditions, which lead to resonant multiphoton absorption (RMPA) and thus define the excitation limit in general for the study of structural dynamics within the 1-photon excitation regime. Here, we apply the theoretical model to bacteriorhodopsin (bR) and show that RMPA occurs when excitation conditions exceed the linear saturation threshold, well below typical excitation conditions used in this class of experiments. This work provides the guidelines to ensure excitation in the linear 1-photon regime is relevant to biological and chemical processes.

Updated reference intervals for urine normetanephrine have no effect on test sensitivity but fewer false positives.

OBJECTIVE: We previously highlighted the problem of frequent false positives in 24 h urine normetanephrine(UNM) measurements owing to reference intervals that are inappropriately low for the population being screened for pheochromocytoma. Using a large population database, we devised new age-stratified reference intervals for the 24 h UNM test that were higher compared to previous. However, it was uncertain as to whether this would compromise test sensitivity for true pheochromocytoma cases. DESIGN AND METHODS: Retrospective analysis of all pheochromocytoma cases from a recently constructed provincial registry. All confirmed cases had their diagnostic UNM results retrospectively re-analysed according to the newly proposed UNM reference intervals to determine the percentage and phenotype of cases that might have been theoretically missed with the new reference range. RESULTS: After excluding pediatric and non-secretory head and neck paragangliomas, there were 60 confirmed pheochromocytoma cases. Using prior reference intervals, 51/60 (85%) had an abnormally high UNM. Of the 9 with normal UNM, 4 had a high urine metanephrine(UMN), 5 had normal levels of both UNM and UMN such that 55/60 had abnormal test results, representing the historical combined test sensitivity of 92%. Using the proposed reference interval, 43/60 (72%) had high UNM results. Of the 17 with normal UNM, 12 had high UMN, 5 had normal levels of both UNM and UMN. Therefore, 55/60 patients had had elevations in either UNM or UMN, corresponding to an identical combined test sensitivity of 92%. CONCLUSIONS: Reference intervals for UNM derived from actual clinical population screening data are higher than in traditional healthy volunteers. Use of these more appropriate reference intervals can significantly reduce the false positive rate without compromising test sensitivity for true pheochromocytoma.

Barriers and Facilitators to Using Statins: A Qualitative Study With Patients and Family Physicians.

BACKGROUND: Despite their proven efficacy to reduce cardiovascular disease, statin medication use remains low in individuals at high risk of cardiovascular disease considering their widespread availability and safety. Our objective was to explore the perspectives of patients and family physicians with regard to the barriers and facilitators of statin use in primary care. METHODS: In this qualitative descriptive study, we conducted 2 focus groups with patients (number, n = 8/6) and individual semistructured interviews with family physicians (n = 17) from community settings. Interviewers asked participants about barriers to and facilitators of statin use. Focus groups and interviews were digitally recorded, transcribed, and analyzed in duplicate using conventional content analysis. RESULTS: Patients were averse to taking statins for a variety of reasons: medication avoidance and burden; inadequate buy-in for statin therapy; and difficulty remembering to take statins regularly. Family physicians perceived similar barriers and reported other barriers: lack of resources such as inadequate tracking systems; specialist-primary care provider guideline discordance; and lack of continuity and relationship. Patients expressed that key facilitators were patient education and support; splitting tablets to increase cost-effectiveness; and changing to a different statin or lower dose in those with side effects. Family physicians described several similar strategies to facilitate therapy as well as shared decision making and clinical decision support tools as enablers for improvement. CONCLUSIONS: We identified several important barriers to and facilitators of statin use at the patient and prescriber level. This information offers insight into strategies to improve statin use and the development of innovative programs and interventions.

INTRODUCTION: En dépit de leur efficacité prouvée pour réduire les maladies cardiovasculaires, l'utilisation des statines reste faible chez les individus exposés à un risque élevé de maladies cardiovasculaires si l'on considère leur grande disponibilité et leur innocuité. Notre objectif était d'examiner les perspectives des patients et des médecins de famille en ce qui concerne les obstacles et les facilitateurs de l'utilisation des statines en soins primaires. MÉTHODES: Dans la présente étude qualitative descriptive, nous avons mené 2 groupes de discussion composés de patients (nombre, n = 8/6) et des entrevues semi-structurées individuelles avec des médecins de famille (n = 17) en milieu communautaire. Les intervieweurs ont demandé aux participants quels étaient les obstacles et les facilitateurs de l'utilisation des statines. Les groupes de discussion et les entrevues étaient enregistrés numériquement, transcrits et analysés en duplicata à l'aide de l'analyse de contenu traditionnelle. RÉSULTATS: Les patients se sont opposés à la prise de statines pour plusieurs raisons : l'évitement et le fardeau des médicaments, l'adhésion insuffisante au traitement par statines et la difficulté à se souvenir de prendre régulièrement les statines. Les médecins de famille ont perçu des obstacles similaires et ont rapporté d'autres obstacles dont le manque de ressources telles que les systèmes de suivi inadéquats, la divergence entre les orientations des spécialistes et des prestataires de soins primaires, et le manque de continuité et de relation. Les patients ont exprimé que les principaux facilitateurs étaient l'éducation et le soutien offerts aux patients; le fractionnement des comprimés pour améliorer l'efficience; le changement vers une statine différente ou une dose plus faible chez ceux qui présentent des effets secondaires. Les médecins de famille ont décrit plusieurs stratégies semblables pour faciliter le traitement ainsi que la prise de décision partagée et les outils d'aide à la décision clinique qui facilitent l'amélioration. CONCLUSIONS: Nous avons déterminé plusieurs obstacles et facilitateurs importants de l'utilisation des statines au point de vue du patient et du prescripteur. Ces informations offrent un aperçu des stratégies pour améliorer l'utilisation des statines et l'élaboration d'interventions et de programmes innovateurs.

How does climate variability affect water quality dynamics in Canada's oil sands region?

In Canada's oil sands region, classic boreal hydrology (i.e., winter low flow followed by peaks during spring freshet and then summer flow recession) combined with erosion of both natural and anthropogenically-exposed bitumen results in seasonal and inter-annual variability in stream water chemistry. Using data collected from all seasons over three years (2012-2015), we investigated the mechanisms driving spatial and temporal change in the concentration of 26 water quality parameters for six rivers draining Canada's oil sands region. Mantel tests showed a strong spatial aggregation of climatic drivers (average daily precipitation, accumulated precipitation, snow water equivalent) associated with west versus east discharge patterns. Wavelet analysis highlighted unique watershed attributes, in particular the importance of developed area in lowering responsiveness to seasonal precipitation. Concentrations of most chemical parameters (20 of 23) showed distinct temporal patterns that were correlated with seasonal changes in hydrology which, in turn, were related to changes in weather. Comparison of concentrations observed in this study with those reported in the scientific literature for the same watersheds showed 81% of comparisons differed significantly. This was likely due to the short duration of previous field campaigns and thus the sampling of a very narrow window of the annual streamflow regime.

Effects of oil sands process water mixtures on the mayfly Hexagenia and field-collected aquatic macroinvertebrate communities.

Extraction of Canada's oil sands has created 1 billion m3 of tailings, which are stored in on-site tailings ponds. Due to limited storage capacity, the planned release of tailings into the surrounding environment may be required. This represents an environmental management challenge, as the tailings contain contaminants that are known toxins to aquatic communities. Of particular concern are naphthenic acids and their metallic counterparts, as they are the principal toxic components of tailings, are relatively soluble, and are persistent in aquatic environments. This study examines the acute toxicity of environmentally relevant 10:1 mixtures of two process water components: naphthenic acid and sodium naphthenate. We assess the effects of these simplified oil sands process water (OSPW) mixtures under planned and unplanned tailings release scenarios, using traditional and cutting-edge bioindicators for aquatic invertebrate taxa. We found that safe concentrations for mayflies and other aquatic macroinvertebrates were less than 1 mg/l, as no mayfly taxa survived repeated exposure to this dose in either the 48-h or 72-h acute toxicity test. In the 72-h test, no mayflies survived treatment levels greater than 0.5 mg sodium naphthenate/l. In the mesocosm study, even a 90% dilution of the OSPW mixture was not sufficient to protect sensitive macroinvertebrate communities. The results of this study highlight the potential environmental damage that will occur if OSPW is not carefully managed. This information will aid with the development of a management plan for oil sands tailings ponds, which will provide insight into the potential for process water release into the surrounding environment while conserving unique ecosystems downstream of development in the oil sands region.

Evaluation and management of the child with hypothyroidism.

BACKGROUND: Thyroid hormones are critical for early neurocognitive development as well as growth and development throughout childhood. Prompt recognition and treatment of hypothyroidism is, therefore, of utmost importance to optimize physical and neurodevelopmental outcomes. DATA SOURCES: A PubMed search was completed in Clinical Queries using the key terms "hypothyroidism". RESULTS: Hypothyroidism may be present at birth (congenital hypothyroidism) or develop later in life (acquired hypothyroidism). Thyroid dysgenesis and dyshormonogenesis account for approximately 85% and 15% of permanent cases of congenital primary hypothyroidism, respectively. More than 95% of infants with congenital hypothyroidism have few, if any, clinical manifestations of hypothyroidism. Newborn screening programs allow early detection of congenital hypothyroidism. In developed countries, Hashimoto thyroiditis is the most common cause of goiter and acquired hypothyroidism in children and adolescents. Globally, iodine deficiency associated with goiter is the most common cause of hypothyroidism. Central hypothyroidism is uncommon and may be associated with other congenital syndromes and deficiencies of other pituitary hormones. Familiarity of the clinical features would allow prompt diagnosis and institution of treatment. CONCLUSIONS: To optimize neurocognitive outcome in infants with congenital hypothyroidism, treatment with levothyroxine should be started as soon as possible, preferably within the first 2 weeks of life. Children with acquired hypothyroidism should also be treated early to ensure normal growth and development as well as cognitive outcome. The target is to keep serum TSH < 5 mIU/L and to maintain serum free T4 or total T4 within the upper half of the age-specific reference range, with elimination of all symptoms and signs of hypothyroidism.

Episodic acidification of 5 rivers in Canada's oil sands during snowmelt: A 25-year record.

Episodic acidification during snowmelt is a natural phenomenon that can be intensified by acidic deposition from heavy industry. In Canada's oil sands region, acid deposition is estimated to be as much as 5% of the Canadian total and large tracks of northeastern Alberta are considered acid-sensitive because of extensive peatland habitats with poorly weathered soils. To identify the frequency, duration and severity of acidification episodes during snowmelt (the predominant hydrological period for delivery of priority pollutants from atmospheric oil sands emissions to surface waters), a 25-year record (1989 to 2014) of automated water quality data (pH, temperature, conductivity) was assembled for 3 rivers along with a shorter record (2012-2014) for another 2 rivers. Acidic episodes (pH<7, ANC<0) were recorded during 39% of all 83 snowmelt events. The severity (duration x magnitude) of episodic acidification increased exponentially over the study period (r2=0.56, P<0.01) and was strongly correlated (P<0.01) with increasing maximum air temperature and weakly correlated with regional land development (P=0.06). Concentrations of aluminum and 11 priority pollutants (Sb, As, Be, Cd, Cr, Cu, Pb, Se, Ag, Tl and Zn) were greatest (P<0.01) during low (<6.5) pH episodes, particularly when coincident with high discharge, such that aluminum and copper concentrations were at times high enough to pose a risk to juvenile rainbow trout (Oncorhynchus mykiss). Although low pH (pH<6.5) was observed during only 8% of 32 acidification episodes, when present, low pH typically lasted 10days. Episodic surface water acidification during snowmelt, and its potential effects on aquatic biota, is therefore an important consideration in the design of long-term monitoring of these typically alkaline (pH=7.72±0.05) rivers.

Gynecomastia in Infants, Children, and Adolescents.

BACKGROUND: Gynecomastia may occur physiologically in the neonatal period, during puberty, and in old age. It may also develop in association with various pathologic states. The challenge for the physician is to distinguish physiological gynecomastia from those with an underlying pathology. OBJECTIVE: To review in depth the pathophysiology, clinical manifestations, and treatment of gynecomastia. METHOD: A PubMed search was completed in Clinical Queries using the key term "gynecomastia". Patents were searched using the key term "gynecomastia" from www.google.com/patents, www.uspto.gov, and www.freepatentsonline.com. RESULTS: Gynecomastia is caused by an imbalance between the stimulatory effect of estrogen and the inhibitory effect of androgen at the breast tissue level. Clinically, gynecomastia is characterized by the presence of a firm or rubbery, discrete, subareolar ridge of glandular tissue that is symmetrical in shape, freely movable, and nonadherent to skin or underlying tissue. Since most cases of physiological gynecomastia regress spontaneously with time, reassurance is all that is necessary. For pathological gynecomastia, treatment should be directed at the underlying cause, if possible. If gynecomastia persists in spite of the above measures, pharmacologic therapy and reduction mammoplasty may be considered. Recent patents related to the management of gynecomastia are discussed. CONCLUSION: The majority of cases are physiological and do not require treatment other than reassurance. For pathological cases, the underlying cause should be treated if possible. If gynecomastia persists in spite of the above measures and treatment becomes necessary, tamoxifen is the treatment of choice. Reduction mammoplasty may be considered for resistant cases.

Evaluation and Management of Children with Thyrotoxicosis.

BACKGROUND: Uncontrolled thyrotoxicosis, especially in early infancy, may cause irreversible damage to the central nervous system as well as profound effects on the function of many organs. Thyrotoxicosis has multiple etiologies and treatment depends on the underlying etiology. An accurate diagnosis is essential so that appropriate treatment can be initiated without undue delay. OBJECTIVE: To review in depth the evaluation, diagnosis, and treatment of children with thyrotoxicosis. METHODS: A PubMed search was completed in Clinical Queries using the key terms "thyrotoxicosis" and "hyperthyroidism". The search strategy included meta-analysis, randomized controlled trials, clinical trials, observational studies, and reviews. Patents were searched using the key terms "thyrotoxicosis" and "hyperthyroidism" from www.freepatentsonline.com and www.google.com/patents. RESULTS: Graves' disease accounts for approximately 96% of pediatric cases of thyrotoxicosis. Other causes include Hashitoxicosis, toxic adenoma, toxic multinodular goiter, subacute granulomatous thyroiditis, acute suppurative thyroiditis, pituitary thyroid-stimulating hormone-secreting adenoma, pituitary thyroid hormone resistance, iodine-induced thyrotoxicosis, and drug-induced thyrotoxicosis. Familiarity of the clinical features would allow prompt diagnosis and institution of treatment. The underlying cause of thyrotoxicosis should be treated if possible. Treatment options for Graves' disease include antithyroid medications, radioiodine therapy, and surgery. Recent patents related to the management of thyrotoxicosis are discussed. CONCLUSION: Currently, antithyroid medications are considered to be the initial treatment of choice for Graves' disease in the pediatric age group. Radioactive iodine treatment is generally used for children with poor compliance with antithyroid medications, children not in remission after 1 to 2 years of antithyroid medications, and children with a major adverse effect while receiving an antithyroid medication. Total or near-total thyroidectomy should be considered in children younger than 5 years of age who do not respond to or experience a major adverse effect to antithyroid medications. Surgery should also be considered in those with very large goiter, severe ophthalmopathy, pregnancy, persistent hyperthyroidism in spite of treatment with antithyroid medications and radioactive iodine, and personal preference.

The allure of the waterpipe: a narrative review of factors affecting the epidemic rise in waterpipe smoking among young persons globally.

OBJECTIVE: The objective of this narrative review is to highlight the determinants of the epidemic rise in waterpipe tobacco smoking (WTS) among youth globally. The Ecological Model of Health Promotion (EMHP) was the guiding framework for the review. DATA SOURCES: The following electronic databases were searched: Cochrane library, MEDLINE, EMBASE, PsycINFO, Web of Science and CINAHL Plus with Full Text. Search terms included waterpipe and its many variant terms. STUDY SELECTION: Articles were included if they were published between 1990 and 2014, were in English, were available in full text and included the age group 10-29 years. DATA EXTRACTION: Articles which analysed determinants of WTS at any of the levels of the EMHP were retained regardless of methodological rigour: 131 articles are included. Articles were coded in a standard template that abstracted methods as well as results. DATA SYNTHESIS: The review found that methodologies used to assess determinants of WTS among youth were often conventional and lacked rigor: 3/4 of the studies were cross-sectional surveys and most enrolled non-representative samples. Within the framework, the review identified determinants of WTS at the intrapersonal, interpersonal, organisational, community and policy levels. CONCLUSIONS: The review suggests potential interventions to control WTS among youth, with emphasis on creative utilisation of social media, and tobacco control policies that include the specificities of WTS. The review further suggests the need for rigorous qualitative work to better contextualise determinants, and prospective observational and experimental studies that track and manipulate them to assess their viability as intervention targets.

A Case of Dilated Cardiomyopathy Associated with 3-Hydroxy-3-Methylglutaryl-Coenzyme A (HMG CoA) Lyase Deficiency.

3-hydroxy-3-methylglutaryl-coenzyme A (HMG CoA) lyase deficiency is an inborn error of metabolism characterized by impairment of ketogenesis and leucine catabolism resulting in an organic acidopathy. In 1994, a case of dilated cardiomyopathy and fatal arrhythmia was reported in a 7-month-old infant. We report a case of dilated cardiomyopathy in association with HMG CoA lyase deficiency in a 23-year-old man with the acute presentation of heart failure. To our knowledge, this is the first case reported in an adult.

Structural and functional responses of benthic invertebrates to imidacloprid in outdoor stream mesocosms.

Structural and functional responses of a benthic macroinvertebrate assemblage to pulses of the insecticide imidacloprid were assessed in outdoor stream mesocosms. Imidacloprid pulses reduced invertebrate abundance and community diversity in imidacloprid-dosed streams compared to control streams. These results correlated well with effects of imidacloprid on leaf litter decomposition and feeding rates of Pteronarcys comstocki, a stonefly, in artificial streams. Reductions in oxygen consumption of stoneflies exposed to imidacloprid were also observed in laboratory experiments. Our findings suggest that leaf litter degradation and single species responses can be sensitive ecotoxicological endpoints that can be used as early warning indicators and biomonitoring tools for pesticide contamination. The data generated illustrates the value of mesocosm experiments in environmental assessment and how the consideration of functional and structural endpoints of natural communities together with in situ single species bioassays can improve the evaluation and prediction of pesticide effects on stream ecosystems.

Persistent Mongolian spots in Chinese adults.

Four Chinese females aged 21-35 years with Mongolian spots are reported. Two patients had the spots on their arms while the other two had the spots on their shoulders. The persistence of Mongolian spots in Chinese adults has not been previously reported.

Specificity of synapse formation between Lymnaea heart motor neuron and muscle fiber is maintained in vitro in a soma-muscle configuration.

Precise neuronal connectivity during development is subservient to all nervous system functions in adult animals. However, the cellular mechanisms that mastermind this neuronal connectivity remain largely unknown. This lack of fundamental knowledge regarding nervous system development is due in part to the immense complexity of mammalian brain, as cell-cell interactions between defined sets of pre- and postsynaptic partners are often difficult to investigate directly. In this study, we developed a novel model system which has allowed us to reconstruct synapses between identified motor neurons and their target heart muscle cell in a soma-muscle configuration. Utilizing this soma-myocardial cell synapse model, we demonstrate that synapses between somata and heart muscle cells can be reconstructed in cell culture. The soma-myocardial cell synapses required 12-24 h to develop and thus differed temporally from conventional neuromuscular synapses (seconds to a few minutes). We also demonstrate that the synapses are target cell-type-specific and are most likely independent of transmitter phenotypic characteristics of presynaptic neurons.

Disposition of foscarnet during peritoneal dialysis.

OBJECTIVE: To report the disposition of foscarnet in a patient undergoing peritoneal dialysis. CASE SUMMARY: A 34-year-old man with AIDS received foscarnet for the treatment of esophageal cytomegalovirus. We characterized the clearance of foscarnet in this patient during continuous cyclic peritoneal dialysis (CCPD) and continuous ambulatory peritoneal dialysis (CAPD). DISCUSSION: The foscarnet half-lives during CCPD and CAPD were 41.4 and 45.8 hours, respectively. These values are significantly greater than the half-life of 4.5 hours observed in patients with normal renal function and about half that reported in anuric patients undergoing hemodialysis during the interdialytic period. The CCPD and CAPD clearances of foscarnet were 5.8 and 4.5 mL/min, respectively; the CAPD clearances of creatinine and urea nitrogen were 4.1 and 6.0 mL/min, respectively. The patient's estimated total body clearance values of foscarnet during CCPD and CAPD were 9.8 and 8.8 mL/min, respectively. Thus, CCPD and CAPD augmented the patient's residual clearance of foscarnet by 145% and 105%, respectively. CONCLUSIONS: Since incremental increases in residual clearance of 30% or more generally will result in clinically significant changes in a drug's serum concentration, foscarnet dosage needs to be individualized for patients receiving peritoneal dialysis.

The effect of renal insufficiency and hemodialysis on the pharmacokinetics of nalmefene.

The disposition of nalmefene, an opioid antagonist intended for the reversal of opioid-induced respiratory depression, and its primary metabolite nalmefene glucuronide, were characterized in adult volunteers with normal renal function and in patients with end-stage renal disease (ESRD). The effect of hemodialysis on the elimination of nalmefene and nalmefene glucuronide also was assessed. Participants with normal renal function received a single intravenous dose of 2 mg, and patients with ESRD received two separate doses of 1 mg nalmefene hydrochloride. Terminal elimination half-life (t1/2) of both nalmefene and nalmefene glucuronide was prolonged in patients with ESRD compared with that in participants with normal renal function. The steady-state volume of distribution (Vdss) of nalmefene was significantly higher and total body clearance lower in patients with ESRD than in participants with normal renal function. Hemodialysis clearance of nalmefene was approximately 3.3% of total body clearance. Although the hemodialysis clearance of nalmefene glucuronide was 179.3 +/- 24.1 mL/min and its t1/2 was significantly reduced during dialysis to 5.2 +/- 2.3 hours, a dramatic rebound of nalmefene glucuronide concentrations of 75.7% was observed 7.7 +/- 5.4 hours after the end of hemodialysis. Thus, hemodialysis does not result in clinically significant alterations in the disposition of nalmefene or its primary metabolite, nalmefene glucuronide. These data suggest that there is no pharmacokinetic basis for modification of the initial dosage, but maintenance doses, if needed, should be administered less frequently due to the prolonged elimination of the active moiety, nalmefene.

Medication knowledge and compliance among patients receiving long-term dialysis.

The extent to which patients receiving longterm dialysis understood and complied with their drug therapy regimens was studied. Patients undergoing long-term hemodialysis or continuous ambulatory peritoneal dialysis (CAPD) in a university-affiliated outpatient dialysis center were surveyed to determine their knowledge about and compliance with prescribed regimens for antihypertensives, phosphate binders, and calcitriol. They were asked to list their prescribed medications and state the medications' indications, the frequency with which they missed doses, and the actions they took after missing a dose. The patients were also asked where they obtained their medications and who their primary source of drug information was. Seventy-two patients (51 receiving hemodialysis and 21 receiving CAPD) were surveyed. Although 80% of the patients could recall the three target medications, only 39% of the hemodialysis patients and 57% of CAPD patients could recall all of their medications. Significantly more patients knew the indication for their antihypertensive medication and calcitriol than for their phosphate binder. The hemodialysis and CAPD patients reported they missed an average of 13.0 and 4.7 phosphate binder doses, 2.6 and 5.6 antihypertensive doses, and 6.7 and 7.0 calcitriol doses, respectively, per month. Despite the fact that 70% of the patients received their medications from a community pharmacy, less than 15% identified the pharmacist as their primary source of drug information. Patients receiving long-term hemodialysis or CAPD were more knowledgeable about and compliant with their antihypertensive and calcitriol regimens than their phosphate binder regimens.

Accumulation and pepsin solubility of collagens in the bowel of patients with Crohn's disease.

The collagen content of resected strictured intestine, with and without fistulas, from patients with Crohn's disease has been compared with that in macroscopically normal intestine removed from the same patients and from others without inflammatory bowel disease. Collagen content per unit wet or dry weight of tissue was significantly increased in all grossly diseased tissue whether fistulated or not. Although there was a significant increase in collagen types I, III, and V in diseased tissue, the relative proportions of major collagen types extracted by limited pepsin digestion were similar for both Crohn's and non-Crohn's intestine (type I, 65 to 70 percent; type III, 25 to 30 percent; type IV, 2 to 3 percent; and type V, 2.5 to 3 percent). CNBr digestion of pepsin insoluble material showed a similar relative abundance of types I and III, indicating no major change in collagen type distribution between older (insoluble) and more newly synthesized collagen. There was no evidence of the presence of type I trimer collagen. Type VI collagen, although not quantitated, was observed in 70 percent of intestinal specimens. The proportion of total collagen solubilized by pepsin treatment was significantly greater in both grossly diseased and macroscopically normal Crohn's bowel compared with non-inflammatory bowel disease bowel. These findings suggest that there are disturbances of collagen metabolism in Crohn's intestine, which account for the stricturing process and which may predate gross pathologic changes.