Circulating microRNA as a Potential Biomarker for Skeletal Disease in Primary Hyperparathyroidism: A Case-control Study.

OBJECTIVE: The goal of this study was to characterize the microRNA (miRNA) expression signatures in patients with PHPT and identify miRNA biomarkers of bone homeostasis. SUMMARY BACKGROUND DATA: Primary hyperparathyroidism (PHPT) is associated with increased bone turnover and decreased bone mass. miRNA are markers of bone remodeling. METHODS: We performed a prospective case-control study of post-menopausal females with PHPT and control subjects matched for race, age, and BMD. We collected clinical and biochemical data, assessed BMD by dual-energy X-ray absorptiometry, and measured 27 serum miRNAs related to bone remodeling. We used linear regression to assess the correlation between miRNA levels, conventional biochemical markers and BMD. RESULTS: A total of 135 subjects were evaluated, including 49 with PHPT (discovery group), 47 control patients without PHPT, and an independent validation cohort of 39 PHPT patients. Of 27 miRNAs evaluated, nine (miR-335-5p, miR-130b-3p, miR-125b-5p, miR-23a-3p, miR-152-3p, miR-582-5p, miR-144-5p, miR-320a and miR-19b-3p) were differentially expressed in PHPT compared to matched control subjects. All nine differentially expressed miRNAs significantly correlated with levels of serum parathyroid hormone (PTH), and eight of the nine correlated with calcium levels. No differentially expressed miRNAs were consistently correlated with markers of BMD. Subjects with PHPT segregate from controls based on the signature of these nine miRNAs on principle component analysis. CONCLUSIONS: These data suggest that PHPT is characterized by a unique miRNA signature that is distinct from postmenopausal and idiopathic osteoporosis. Levels of specific miRNAs significantly correlate with PTH, suggesting that bone remodeling in PHPT may be mediated in part by PTH-induced changes in miRNA.

Pneumothorax as a complication of dry needling technique.

Post-dry needling pneumothorax is not extremely rare. Patients and referring doctors should be aware of this. Informed consent should mention pneumothorax as a considerable risk of dry needling procedures in the neck, shoulder or chest region. https://bit.ly/49YYNR8.

Occult solitary fibrous tumour of the pleura presenting as recurrent spontaneous pneumothorax.

A woman in her 30s, non-smoker, presented at the emergency department two times because of spontaneous pneumothorax. The first episode was treated with small bore catheter drainage, while during the second episode-occurring only 1 week later-thoracoscopic talcage was attempted. The postoperative course was characterised by slow clinical and radiological resolution, and recurrence 3 days after discharge. Eventually, multiportal video-assisted thoracoscopic exploration identified an interfissural solid mass. Resection and further work-up revealed the diagnosis of 'low-risk' solitary fibrous tumour (SFT) stage pT1N0M0. The interdisciplinary tumour board advised no adjuvant therapy. A CT thorax was scheduled in 1 year for follow-up. The patient was discharged without complications and has had no recurrences of pneumothorax at 6 months of follow-up. This report shows that SFT can easily be missed on initial presentation and should be considered in the differential diagnosis of pneumothorax, especially when frequently recurring.

ABCB5+ Limbal Epithelial Stem Cells Inhibit Developmental but Promote Inflammatory (Lymph) Angiogenesis While Preventing Corneal Inflammation.

The limbus, the vascularized junction between the cornea and conjunctiva, is thought to function as a barrier against corneal neovascularization. However, the exact mechanisms regulating this remain unknown. In this study, the limbal epithelial stem cell (LESC) marker ABCB5 was used to investigate the role of LESCs in corneal neovascularization. In an ABCB5KO model, a mild but significant increase of limbal lymphatic and blood vascular network complexity was observed in developing mice (4 weeks) but not in adult mice. Conversely, when using a cornea suture model, the WT animals exhibited a mild but significant increase in the number of lymphatic vessel sprouts compared to the ABCB5KO, suggesting a contextual anti-lymphangiogenic effect of ABCB5 on the limbal vasculature during development, but a pro-lymphangiogenic effect under inflammatory challenge in adulthood. In addition, conditioned media from ABCB5-positive cultured human limbal epithelial cells (ABCB5+) stimulated human blood and lymphatic endothelial cell proliferation and migration. Finally, a proteomic analysis demonstrated ABCB5+ cells have a pro(lymph)angiogenic as well as an anti-inflammatory profile. These data suggest a novel dual, context-dependent role of ABCB5+ LESCs, inhibiting developmental but promoting inflammatory (lymph)angiogenesis in adulthood and exerting anti-inflammatory effects. These findings are of high clinical relevance in relation to LESC therapy against blindness.

Allogeneic Hematopoietic Stem Cell Transplantation After Prior Lung Transplantation for Hereditary Pulmonary Alveolar Proteinosis: A Case Report.

Pulmonary alveolar proteinosis (PAP) is a rare, diffuse lung disorder characterized by surfactant accumulation in the small airways due to defective clearance by alveolar macrophages, resulting in impaired gas exchange. Whole lung lavage is the current standard of care treatment for PAP. Lung transplantation is an accepted treatment option when whole lung lavage or other experimental treatment options are ineffective, or in case of extensive pulmonary fibrosis secondary to PAP. A disadvantage of lung transplantation is recurrence of PAP in the transplanted lungs, especially in hereditary PAP. The hereditary form of PAP is an ultra-rare condition caused by genetic mutations in genes encoding for the granulocyte macrophage-colony stimulating factor (GM-CSF) receptor, and intrinsically affects bone marrow derived-monocytes, which differentiate into macrophages in the lung. Consequently, these macrophages typically display disrupted GM-CSF receptor-signaling, causing defective surfactant clearance. Bone marrow/hematopoietic stem cell transplantation may potentially reverse the lung disease in hereditary PAP. In patients with hereditary PAP undergoing lung transplantation, post-lung transplant recurrence of PAP may theoretically be averted by subsequent hematopoietic stem cell transplantation, which results in a graft-versus-disease (PAP) effect, and thus could improve long-term outcome. We describe the successful long-term post-transplant outcome of a unique case of end-stage respiratory failure due to hereditary PAP-induced pulmonary fibrosis, successfully treated by bilateral lung transplantation and subsequent allogeneic hematopoietic stem cell transplantation. Our report supports treatment with serial lung and hematopoietic stem cell transplantation to improve quality of life and prolong survival, without PAP recurrence, in selected patients with end-stage hereditary PAP.

The radiological interpretation of possible microbleeds after moderate or severe traumatic brain injury: a longitudinal study.

INTRODUCTION: In order to augment the certainty of the radiological interpretation of "possible microbleeds" after traumatic brain injury (TBI), we assessed their longitudinal evolution on 3-T SWI in patients with moderate/severe TBI. METHODS: Standardized 3-T SWI and T1-weighted imaging were obtained 3 and 26 weeks after TBI in 31 patients. Their microbleeds were computer-aided detected and classified by a neuroradiologist as no, possible, or definite at baseline and follow-up, separately (single-scan evaluation). Thereafter, the classifications were re-evaluated after comparison between the time-points (post-comparison evaluation). We selected the possible microbleeds at baseline at single-scan evaluation and recorded their post-comparison classification at follow-up. RESULTS: Of the 1038 microbleeds at baseline, 173 were possible microbleeds. Of these, 53.8% corresponded to no microbleed at follow-up. At follow-up, 30.6% were possible and 15.6% were definite. Of the 120 differences between baseline and follow-up, 10% showed evidence of a pathophysiological change over time. Proximity to extra-axial injury and proximity to definite microbleeds were independently predictive of becoming a definite microbleed at follow-up. The reclassification level differed between anatomical locations. CONCLUSIONS: Our findings support disregarding possible microbleeds in the absence of clinical consequences. In selected cases, however, a follow-up SWI-scan could be considered to exclude evolution into a definite microbleed.

Effect of isolation method on human corneal stromal cell behaviour.

Current research on healthy corneal stromal cells will typically use primary cells as they are the most representative of in vivo behaviour. Primary cells are normally isolated from the limbus of discarded donor peripheral corneal tissue left over from transplantation (due to its relative abundance). Therefore, the central part of the cornea is less used in research as this tissue is usually used for transplantation. In some cases, although rare, the whole cornea, can become available for research. It is important to keep in mind that these corneas often have longer storage time, but the use of the central tissue for research is even more interesting, as knowing what cells are being transplanted into recipients would be highly relevant. To this end, stromal cells were extracted from both the limbus and central button of healthy corneas donated for research. This allowed for important comparison between central and limbal cells in culture. Of interest here was the extraction method of stromal cells from the donor tissue. The two most common methods of extraction are enzyme digestion and explant migration. However, no work has been done to understand how each method relatively affects the extracted cells. The extraction method and location from which stromal cells are harvested seems to have a significant effect on the cell adherence, survival, and gene expression of the stromal cells in culture. Enzyme digested cells showed that limbal and central cells had different gene expressions prior to culture, with gene such as ALDH3A1 being much more expressed in limbal cells. Enzyme digesting the limbal ring seems to yield the hardiest populations of stromal cells, a desirable trait in the culture of primary cells.

Keratoconus at a Molecular Level: A Review.

Keratoconus is the most common ectatic disease of the cornea. The disease is usually detected between ages 15 and 25. Incidence is estimated at one out of every 2000 individuals, with some specific ethnic groups being more at risk. Keratoconus manifests itself as a progressive stromal thinning and deformation of the corneal tissue into a conical shape. The etiology of keratoconus is uncertain, although several studies have associated the disease to environmental factors, behavioral conditions and certain genetic disorders. In an effort to better understand how the corneal stroma becomes compromised, multiple experiments have been conducted over the last few years looking at the cells themselves and the factors they produce. The secretion pathways and levels of inflammatory molecules, growth factors, digestive enzymes, and apoptotic factors are all relevant to keratoconus. This review describes the current knowledge of keratoconic pathological signaling pathways within the cornea that may help future developments in disease prevention, treatment and modeling. Anat Rec, 2019. © 2019 Wiley Periodicals, Inc.

Automated Fetal Head Detection and Circumference Estimation from Free-Hand Ultrasound Sweeps Using Deep Learning in Resource-Limited Countries.

Ultrasound imaging remains out of reach for most pregnant women in developing countries because it requires a trained sonographer to acquire and interpret the images. We address this problem by presenting a system that can automatically estimate the fetal head circumference (HC) from data obtained with use of the obstetric sweep protocol (OSP). The OSP consists of multiple pre-defined sweeps with the ultrasound transducer over the abdomen of the pregnant woman. The OSP can be taught within a day to any health care worker without prior knowledge of ultrasound. An experienced sonographer acquired both the standard plane-to obtain the reference HC-and the OSP from 183 pregnant women in St. Luke's Hospital, Wolisso, Ethiopia. The OSP data, which will most likely not contain the standard plane, was used to automatically estimate HC using two fully convolutional neural networks. First, a VGG-Net-inspired network was trained to automatically detect the frames that contained the fetal head. Second, a U-net-inspired network was trained to automatically measure the HC for all frames in which the first network detected a fetal head. The HC was estimated from these frame measurements, and the curve of Hadlock was used to determine gestational age (GA). The results indicated that most automatically estimated GAs fell within the P2.5-P97.5 interval of the Hadlock curve compared with the GAs obtained from the reference HC, so it is possible to automatically estimate GA from OSP data. Our method therefore has potential application for providing maternal care in resource-constrained countries.

Comparison Study of Low-Cost Ultrasound Devices for Estimation of Gestational Age in Resource-Limited Countries.

We investigated how accurately low-cost ultrasound devices can estimate gestational age (GA) using both the standard plane and the obstetric sweep protocol (OSP). The OSP can be taught to health care workers without prior knowledge of ultrasound within one day and thus avoid the need to train dedicated sonographers. Three low-cost ultrasound devices were compared with one high-end ultrasound device. GA was estimated with the head circumference (HC), abdominal circumference (AC) and femur length (FL) using both the standard plane and the OSP. The results revealed that the HC, AC and FL can be used to estimate GA using low-cost ultrasound devices in the standard plane within the inter-observer variability presented in the literature. The OSP can be used to estimate GA by measuring the HC and the AC, but not the FL. This study shows that it is feasible to estimate GA in resource-limited countries with low-cost ultrasound devices using the OSP. This makes it possible to estimate GA and assess fetal growth for pregnant women in rural areas of resource-limited countries.

Automated measurement of fetal head circumference using 2D ultrasound images.

In this paper we present a computer aided detection (CAD) system for automated measurement of the fetal head circumference (HC) in 2D ultrasound images for all trimesters of the pregnancy. The HC can be used to estimate the gestational age and monitor growth of the fetus. Automated HC assessment could be valuable in developing countries, where there is a severe shortage of trained sonographers. The CAD system consists of two steps: First, Haar-like features were computed from the ultrasound images to train a random forest classifier to locate the fetal skull. Secondly, the HC was extracted using Hough transform, dynamic programming and an ellipse fit. The CAD system was trained on 999 images and validated on an independent test set of 335 images from all trimesters. The test set was manually annotated by an experienced sonographer and a medical researcher. The reference gestational age (GA) was estimated using the crown-rump length measurement (CRL). The mean difference between the reference GA and the GA estimated by the experienced sonographer was 0.8 ± 2.6, -0.0 ± 4.6 and 1.9 ± 11.0 days for the first, second and third trimester, respectively. The mean difference between the reference GA and the GA estimated by the medical researcher was 1.6 ± 2.7, 2.0 ± 4.8 and 3.9 ± 13.7 days. The mean difference between the reference GA and the GA estimated by the CAD system was 0.6 ± 4.3, 0.4 ± 4.7 and 2.5 ± 12.4 days. The results show that the CAD system performs comparable to an experienced sonographer. The presented system shows similar or superior results compared to systems published in literature. This is the first automated system for HC assessment evaluated on a large test set which contained data of all trimesters of the pregnancy.

Complaints about dental practitioners: an analysis of 6 years of complaints about dentists, dental prosthetists, oral health therapists, dental therapists and dental hygienists in Australia.

BACKGROUND: Previous research has found dental practitioners at elevated risk of complaint compared with other health professions. This study aimed to describe the frequency, nature and risk factors for complaints involving dental practitioners. METHODS: We assembled a national dataset of complaints about registered health practitioners in Australia between January 2011 and December 2016. We classified complaints into 23 issues across three domains: health, performance and conduct. We compared rates of complaints about dental practitioners and other health practitioners. We used negative binomial regression analysis to identify factors associated with complaints. RESULTS: Dental practitioners made up 3.5% of health practitioners, yet accounted for approximately 10% of complaints. Dental practitioners had the highest rate of complaints among fourteen health professions (42.7 per 1000 practitioners per year) with higher rates among dentists and dental prosthetists than allied dental practitioners. Male practitioners were at a higher risk of complaints. Most complaints about dentists related to treatments and procedures (59%). Around 4% of dentists received more than one complaint, accounting for 49% of complaints about dentists. In 60% of closed cases no regulatory action was required. Around 13% of complaints resulted in restrictive actions, such as conditions on practice. CONCLUSION: Improved understanding of patterns may assist regulatory boards and professional associations to ensure competent practice and protect patient safety.

Development of a Low-Cost Medical Ultrasound Scanner Using a Monostatic Synthetic Aperture.

OBJECTIVE: In this paper, we present the design of low-cost medical ultrasound scanners aimed at the detection of maternal mortality risk factors in developing countries. METHOD: Modern ultrasound scanners typically employ a high element count transducer array with multichannel transmit and receive electronics. To minimize hardware costs, we employ a single piezoelectric element, mechanically swept across the target scene, and a highly cost-engineered single channel acquisition circuit. Given this constraint, we compare the achievable image quality of a monostatic fixed focus scanner (MFFS) with a monostatic synthetic aperture scanner (MSAS) using postfocusing. Quantitative analysis of image quality was carried out using simulation and phantom experiments, which were used to compare a proof-of-concept MSAS prototype with an MFFS device currently available on the market. Finally, in vivo experiments were performed to validate the MSAS prototype in obstetric imaging. RESULTS: Simulations show that the achievable lateral resolution of the MSAS approach is superior at all ranges compared to the fixed focus approach. Phantom experiments verify the improved resolution of the MSAS prototype but reveal a lower signal to noise ratio. In vivo experiments show promising results using the MSAS for clinical diagnostics in prenatal care. CONCLUSION: The proposed MSAS achieves superior resolution but lower SNR compared to an MFFS approach, principally due to lower acoustic energy emitted. SIGNIFICANCE: The production costs of the proposed MSAS could be an order of magnitude lower than any other ultrasound system on the market today, bringing affordable obstetric imaging a step closer for developing countries.

Dental prosthesis aspiration: An uncommon cause of respiratory distress.

We present a case of a 66-year-old Caucasian man with acute respiratory distress. The patient had a history of multiple cerebrovascular accidents which resulted in left hemiplegia, swallowing problems, and aphasia. He was tentatively diagnosed with aspiration pneumonia. However, because of clinical deterioration further investigations concluded to the aspiration of a dental prosthesis. After intubation and stabilization, the prosthesis could be manually extracted. However, the patient developed a Staphylococcus epidermidis sepsis and despite adequate antibiotic therapy, he eventually died. Dental prosthesis aspiration is a medical situation associated with a higher morbidity and mortality rate compared to ingested foreign bodies. It requires a high level of suspicion to ensure a timely diagnosis and life-saving treatment. Thorough history taking is of great importance in case of tracheobronchial aspiration, which is in the adult population mostly secondary to an underlying disorder. In impaired adults with missing dental prostheses there should be extra awareness for this problem. This case report illustrates the importance of a detailed history in case of tracheobronchial aspiration and shows the limitations in the diagnostic usefulness of bedside chest radiography.

Rehabilitation in patients with radically treated respiratory cancer: A randomised controlled trial comparing two training modalities.

INTRODUCTION: The evidence on the effectiveness of rehabilitation in lung cancer patients is limited. Whole body vibration (WBV) has been proposed as an alternative to conventional resistance training (CRT). METHODS: We investigated the effect of radical treatment (RT) and of two rehabilitation programmes in lung cancer patients. The primary endpoint was a change in 6-min walking distance (6MWD) after rehabilitation. Patients were randomised after RT to either CRT, WBVT or standard follow-up (CON). Patients were evaluated before, after RT and after 12 weeks of intervention. RESULTS: Of 121 included patients, 70 were randomised to either CON (24), CRT (24) or WBVT (22). After RT, 6MWD decreased with a mean of 38m (95% CI 22-54) and increased with a mean of 95m (95% CI 58-132) in CRT (p<0.0001), 37m (95% CI -1-76) in WBVT (p=0.06) and 1m (95% CI -34-36) in CON (p=0.95), respectively. Surgical treatment, magnitude of decrease in 6MWD by RT and allocation to either CRT or WBVT were prognostic for reaching the minimally clinically important difference of 54m increase in 6MWD after intervention. CONCLUSIONS: RT of lung cancer significantly impairs patients' exercise capacity. CRT significantly improves and restores functional exercise capacity, whereas WBVT does not fully substitute for CRT.

Alcohol Related Non-traumatic Rhabdomyolysis and Compartment Syndrome.

Rhabdomyolysis is a serious and life-threatening condition in which skeletal muscle is damaged, commonly resulting in acute renal failure. The causes of this clinical entity can be traumatic and non-traumatic. In the latter group, alcohol is the commonest cause. This report describes the case of a 25 year old man who presented with rhabdomyolysis leading to acute renal failure after an alcohol binge. He presented with painful legs and lower extremity compartment syndrome. The patient recovered with surgical fasciotomy and renal support. This case illustrates the importance of early recognition and treatment of alcohol related non-traumatic rhabdomyolysis and compartment syndrome.

Octreotide induced prolongation of colonic transit increases faecal anaerobic bacteria, bile acid metabolising enzymes, and serum deoxycholic acid in patients with acromegaly.

BACKGROUND: Acromegalic patients have slow colonic transit, increased rates of deoxycholic acid formation, and an increased prevalence of cholesterol gall stones, especially during long term octreotide treatment. However, the effects of this prolonged large bowel transit time on the numbers of faecal anaerobes and the activities of the enzyme systems which biotransform conjugated cholic acid into unconjugated deoxycholic acid (cholylglycine hydrolase and 7alpha-dehydroxylase) are unknown. METHODS: Therefore, in 10 non-acromegalic controls, 11 acromegalic patients not treated with octreotide, and 11 acromegalics on long term (8-48 months) octreotide (100-200 mug three times daily subcutaneously), we measured large bowel transit time and, in freshly voided faeces, the activities of the two bile acid metabolising enzymes, and related the results to the proportion of deoxycholic acid in fasting serum. Moreover, in patients with acromegaly, we measured quantitative bacteriology in faeces. RESULTS: Mean large bowel transit time in acromegalics not treated with octreotide (35 (SEM 6.5) hours) was 66% longer than that in non-acromegalic controls (21 (3.1) hours; NS) and became further prolonged during octreotide treatment (48 (6.6) hours; p<0.001). These octreotide induced changes in transit were associated, in acromegalic patients, with more total (15.0 (2.5) v 6.3 (1.3)x10(9) colony forming units (cfu)/g; p<0.05) and Gram positive (6.3 (2.3) v 3.2 (1.0)x10(9) cfu/g; p<0.05) faecal anaerobes. Mean faecal cholylglycine hydrolase activity in the long term octreotide group (22.0 (6.0)x10(-2) U/mg protein) was 138% greater than that in non-acromegalic controls (12.0 (6.0)x10(-2); p<0.01). Similarly, mean 7alpha-dehydroxylase activity in octreotide treated acromegalics (11.1 (1.18)x10(-4) U/mg protein) was 78% greater than that in patients not receiving long term octreotide (6.3 (0.5)x10(-4); p<0.001). The mean proportion of deoxycholic acid in fasting serum also increased from 18.0 (2.88)% in the untreated group to 29.6 (2.3)% during long term octreotide (p<0.05). There were significant linear relationships between large bowel transit time and: (i) faecal 7alpha-dehydroxylase activity; and (ii) the proportion of deoxycholic acid in fasting serum and between 7alpha-dehydroxylase activity and the proportion of deoxycholic acid in serum.Summary/interpretation: These data suggest that increased deoxycholic acid formation seen in acromegalics during octreotide treatment is due not only to the greater numbers of faecal anaerobes but also to increased activity of the rate limiting enzyme pathway (7alpha-dehydroxylation) converting cholic acid to deoxycholic acid.

Objective evaluation of ERCP procedures: a simple grading scale for evaluating technical difficulty.

BACKGROUND: and objective: Endoscopic retrograde cholangiopancreatography (ERCP) is a technically demanding endoscopic procedure that varies from a simple diagnostic to a highly complex therapeutic procedure. Simple outcome measures such as success and complication rates do not reflect the competence of the operator or endoscopy unit, as case mix is not taken into account. A grading scale to assess the technical difficulty of ERCP can improve the objectivity of outcome data. METHODS: A I to IV technical difficulty grading scale was constructed and applied prospectively to all ERCPs over a 12 month period at a single centre. The procedures were performed by two senior trainees and two experienced consultants (trainers). The grading scale was validated for construct validity and inter-rater reliability at the end of the study using the chi(2) test and kappa statistics. RESULTS: There were 305 ERCPs in 259 patients over the 12 months study period (males: 112, females: 147, age range 17-97, mean 70.3 years). There was overall success in 244 (80%) procedures with complications in 13 (4%): bleeding in five (1.6%), cholangitis in one (0.3%), pancreatitis in five (1.6%), and perforation in two (0.7%). Success rate was highest for grade I, 49/55 (89%), compared with grade IV procedures, 8/11 (73%). There was a significant linear trend towards a lower success rate from grade I to IV (p=0.021) for trainees, but not for trainers. Complications were low in grade I, II, and III procedures, 12/295(4%), compared with grade IV procedures, 1/11(9%). The inter-rater reliability for the grading scale was good with a substantial agreement between the raters (kappa=0.68, p<0.001). CONCLUSION: Success and complications of ERCP by trainees are influenced by the technical difficulty of the procedure. Outcome data incorporating a grading scale can give accurate information when auditing the qualitative outcomes. This can provide a platform for structured objective evaluation.

Bile acid metabolism by fresh human colonic contents: a comparison of caecal versus faecal samples.

BACKGROUND: Deoxycholic acid (DCA), implicated in the pathogenesis of gall stones and colorectal cancer, is mainly formed by bacterial deconjugation (cholylglycine hydrolase (CGH)) and 7 alpha-dehydroxylation (7 alpha-dehydroxylase (7 alpha-DH)) of conjugated cholic acid (CA) in the caecum/proximal colon. Despite this, most previous studies of CGH and 7 alpha-DH have been in faeces rather than in caecal contents. In bacteria, CA increases 7 alpha-DH activity by substrate-enzyme induction but little is known about CA concentrations or CA/7 alpha-DH induction in the human colon. AIMS AND METHODS: Therefore, in fresh "faeces", and in caecal aspirates obtained during colonoscopy from 20 patients, we: (i) compared the activities of CGH and 7 alpha-DH, (ii) measured 7 alpha-DH in patients with "low" and "high" percentages of DCA in fasting serum (less than and greater than the median), (iii) studied CA concentrations in the right and left halves of the colon, and examined the relationships between (iv) 7 alpha-DH activity and CA concentration in caecal samples (evidence of substrate-enzyme induction), and (v) 7 alpha-DH and per cent DCA in serum. RESULTS: Although mean CGH activity in the proximal colon (18.3 (SEM 4.40) x10(-2) U/mg protein) was comparable with that in "faeces" (16.0 (4.10) x10(- 2) U/mg protein), mean 7 alpha-DH in the caecum (8.54 (1.08) x10(-4) U/mg protein) was higher (p<0.05) than that in the left colon (5.72 (0.85) x10(-4) U/mg protein). At both sites, 7 alpha-DH was significantly greater in the "high" than in the "low" serum DCA subgroups. CA concentrations in the right colon (0.94 (0.08) micromol/ml) were higher than those in the left (0.09 (0.03) micromol/ml; p<0.001) while in the caecum (but not in the faeces) there was a weak (r=0.58) but significant (p<0.005) linear relationship between 7 alpha-DH and CA concentration. At both sites, 7 alpha-DH was linearly related (p<0.005) to per cent DCA in serum. INTERPRETATION/SUMMARY: These results: (i) confirm that there are marked regional differences in bile acid metabolism between the right and left halves of the colon, (ii) suggest that caecal and faecal 7 alpha-DH influence per cent DCA in serum (and, by inference, in bile), and (iii) show that the substrate CA induces the enzyme 7 alpha-DH in the caecum.