The impact of musculoskeletal ill health on quality of life and function after critical care: a multicentre prospective cohort study.

Physical disability is a common component of post-intensive care syndrome, but the importance of musculoskeletal health in this population is currently unknown. We aimed to determine the musculoskeletal health state of intensive care unit survivors and assess its relationship with health-related quality of life; employment; and psychological and physical function. We conducted a multicentre prospective cohort study of adults admitted to intensive care for > 48 h without musculoskeletal trauma or neurological insult. Patients were followed up 6 months after admission where musculoskeletal health state was measured using the validated Musculoskeletal Health Questionnaire score. Of the 254 participants, 150 (59%) had a musculoskeletal problem and only 60 (24%) had received physiotherapy after discharge. Functional Comorbidity Index, Clinical Frailty Scale, duration of intensive care unit stay and prone positioning were all independently associated with worse musculoskeletal health. Musculoskeletal health state moderately correlated with quality of life, rs = 0.499 (95%CI 0.392-0.589); anxiety, rs = -0.433 (95%CI -0.538 to -0.315); and depression, rs = -0.537 (95%CI -0.631 to -0.434) (all p < 0.001). Patients with a musculoskeletal problem were less physically active than those without a problem (median (IQR [range]) number of 30 min physical activity sessions per week 1 (0-3.25 [0-7]) vs. 4 (1-7 [0-7]), p < 0.001, respectively). This study found that musculoskeletal health problems were common after intensive care unit stay. However, we observed that < 25% of patients received physical rehabilitation after discharge home. Our work has identified potential high-risk groups to target in future interventional studies.

Incidence and morphology of the incisive suture in CT scanning of young children and human fetuses.

PURPOSE: Incisive suture is a suture classically described on the oral face of the palate in fetuses and young children. The aim of our study was to describe the evolution of the incisive suture in human fetuses and to evaluate the incidence of this suture in a population of young children under 4 years, to determine if there is a possibility of improving the anterior growth of the maxilla, by stimulation of this suture. METHODS: One hundred and thirty CT scan images of patients aged from birth to 48 months have been studied and nine fetal palates aged from 18 to 26 weeks of development, have been scanned using high-resolution X-ray micro-computed tomography RESULTS: The CT scan images of patients showed that an incisive suture was present in 33/130 cases (25,4%). All the patients with a suture were under 2 years old. The fetal palate study showed that the suture was present in the inferior aspect of the palate (oral cavity) in all cases. The incisive suture increased from 18 to 24 weeks. At 26 weeks it stopped growing although the intercanine length increased. Considering the closure of the suture in a vertical plane, our study on fetuses has shown that the incisive suture is closing from its superior side (nasal side) to its inferior side. CONCLUSIONS: Considering all these results it appears to us that the incisive suture is partially ossified after birth, it cannot be stimulated by orthodontic appliances.

Surgical implications of the anatomic situation of the mandibular canal for mandibular osteotomies: a cone beam computed tomographic study.

PURPOSE: In bilateral sagittal split osteotomy (BSSO), the risk of lesion of the inferior alveolar nerve (IAN) is important. The aim of this study was to investigate the situation of the IAN in the area of the BSSO in preoperative 158 CBCT. METHODS: The situation of the mandibular canal (MC) has been studied in six coronal sections (one section each 4 mm) from the proximal root of the second mandibular molar. The height of the MC related to the height of the mandible, and the horizontal distance between the MC and the lateral cortical plate related to the mandibular width have been determined in each section. The cancellous bone width has been measured allowing to determine a cancellous bone ratio. RESULTS: The variability of the MC was high, depending mainly on the cancellous bone ratio which was higher when the IAN was deep. When a third molar was present, the MC was lower in the area of the third molar. CONCLUSIONS: To decrease the risk of injuring the IAN in BSSO, the evaluation of the cancellous bone ratio by a preoperative CBCT may be proposed to adapt the surgical technique to the anatomy.

Anatomic study of the arterial territories of the face depending on the external carotid artery branches.

AIM OF THE STUDY: Blood supply of the skin of the face is mainly provided by 3 branches of the external carotid artery: facial artery (FA), superficial temporal artery (STA) and transverse facial artery (TFA) which is a branch of the STA. The aim of the study was to describe the arterial territories of the skin of the face depending on the external carotid branches. MATERIAL AND METHODS: After dissection of the first two centimeters of these arteries on one side, we performed an injection of India ink of different colors in the arteries in order to describe the arterial territories (angiosomes) of the face on 24 embalmed cadavers. RESULTS: The lips and the tip of the nose were vascularized in most cases by the FA. The STA vascularizes the temporal and frontal areas and a part of the auricle. The buccal area blood supply is coming from the FA with a participation of the TFA which is variable (10/24 cases), and the zygomatic area blood supply is coming from the STA with a participation of the TFA (9/24 cases). CONCLUSIONS: Variations in the angiosomes of the face have to be considered in reconstructive surgery, and in face transplantation.

[Acyclovir-resistant perineal HSV infection revealing chronic lymphoid leukaemia]. / Herpès chronique périnéal résistant à l'aciclovir révélateur d'une leucémie lymphoïde chronique.

BACKGROUND: Chronic HSV infection is a cause of chronic perineal ulcerations. We report a case of a chronic and refractory HSV infection revealing chronic lymphoid leukaemia. PATIENTS AND METHODS: An 85-year-old woman with an 8-month history of chronic perineal ulcerations was referred to our dermatology department. She had no previous medical history of herpes infection. Skin biopsies ruled out carcinoma but were consistent with HSV infection. A local swab was positive for HSV2. Treatment with valaciclovir and intravenous acyclovir (ACV) at the recommended doses was ineffective. Laboratory tests revealed type-B chronic lymphoid leukaemia. Molecular biology studies confirmed the presence of ACV-resistant HSV via decreased thymidine kinase activity (stop codon: M183stop). Foscarnet was administered for a period of 3 weeks with almost complete healing of the ulcerations. Treatment was stopped prematurely due to acute renal insufficiency and the remaining lesions were treated using imiquimod cream. Valaciclovir was prescribed to prevent further episodes. The condition recurred a mere 11 months later. DISCUSSION: The prevalence of ACV-resistant HSV is 0.32 % in immunocompetent patients and 3.5 % in immunocompromised patients. Insufficient dosing regimens or prolonged treatment with TK inhibitors result in the local selection of pre-existing mutant HSV viruses. Foscarnet, a DNA polymerase inhibitor, is the treatment of choice in HSV-resistant infections. ACV-resistant HSV is less virulent and replicates less, with reactivations being mainly due to wild-type HSV latent in the neural ganglia. Valaciclovir can be used as a preventive treatment. To our knowledge, this is the first case of ACV-resistant HSV infection revealing chronic lymphoid leukaemia. CONCLUSION: Chronic perineal ulcerations can be the first manifestation of immunodeficiency seen for example with haematological diseases. In the event of clinical resistance of an HSV infection to recommended thymidine kinase inhibitor regimens, the use of foscarnet should be considered.

Erosive pustular dermatosis of the leg: A prospective, multicentre, observational study of 36 cases.

BACKGROUND: Erosive pustular dermatosis of the leg (EPDL) is a poorly understood entity first described by Lanigan and Cotteril in 1987. Its clinical diagnosis is based on exclusion since the physiopathology is unknown. The primary objective of this investigation was to specify the clinical aspects and outcomes in a prospective study. The secondary objectives were to describe associated diseases, the circumstances of occurrence, and the laboratory tests used. PATIENTS AND METHODS: This was a prospective study that included 45 patients selected by members of the Angiology-Dermatology Group of the SFD (French Dermatology Society) at 13 centres between 01/09/2013 and 31/10/2014. There was a 180-day monitoring period. The records of 36 patients were analysed. Clinical and laboratory data were collected. RESULTS: Mean patient age was 79.6±9.9 years with a M/F sex ratio of 0.2. Among the patients, 16.7% had skin cancer and 91.7% had venous insufficiency. The proportion of patients wearing venous compression hose was constant between inclusion and D180. Lesions were bilateral (53%), affected the middle third of the leg, and were on the anterior aspect. Complete healing was achieved in 77.8% of cases with time to healing of 2.4±1.2 months, and under topical corticosteroids in 97.3% of cases. During follow-up, relapse occurred in 38.9% of cases after a mean time of 2.4±1.2 months. CONCLUSION: EPDL appears to be an idiopathic inflammatory dermatosis with a particular topographic expression. The physiopathology could be related to chronic inflammation associated with venous insufficiency and with certain trigger factors. Currently, there are few therapeutic alternatives to topical corticosteroids.

[Retrospective study of hypertensive leg ulcers at Reims University Hospital: Epidemiological, clinical, disease progression data, effects of vitamin K antagonists]. / Étude rétrospective des angiodermites nécrotiques au CHU de Reims : données épidémiologiques, cliniques, évolutives et rôle des antivitamine K.

BACKGROUND: Hypertensive leg ulcers (HLU) are a form of necrotic leg ulcer. Their physiopathology is not well known and in these patients, no venous or arterial insufficiency is detected. The primary objective of this study was to evaluate the association between HLU severity and the presence or absence of concomitant vitamin K antagonist (VKA) medication. We furthermore aimed to describe the epidemiology of this entity and the prevalence of thrombophilia factors in this population. PATIENTS AND METHODS: This was a retrospective study in 54 patients hospitalized in the dermatology department of Reims University Hospital between 01/01/2007 and 31/12/2013: 23 patients were included in the "without VKA" group, and 30 were included in the "with VKA" group. Clinical and laboratory data were collected. RESULTS: The average HLU surface was higher in the "with VKA" group i.e. 35.00cm2 (min: 3.0; max: 220.0) versus 23.00cm2 (min: 5.0; max: 300.0) (P=0.05). No significant difference was found in terms of time to healing, mean hospitalization duration, HLU treatment by skin grafting, or time to recurrence after healing. Mean patient age was 74.2±9.3 years; 100% of patients had arterial hypertension, 50.9% had diabetes, and 20.8% were active smokers. Abnormal but non-significant values for thrombophilia factors were observed. CONCLUSION: Our study shows no obvious differences between patients with HLU with or without VKA medication. A prospective, comparative study is necessary to further evaluate this hypothesis, with particular emphasis on routine thrombophilia factor analysis.

The role of sub-retinal fluid in determining treatment outcomes in patients with neovascular age-related macular degeneration--a phase IV randomised clinical trial with ranibizumab: the FLUID study.

BACKGROUND: With increasing experience using anti-VEGF therapy for the treatment of neovascular age-related macular degeneration (nAMD), ophthalmologists have shifted away from a "one size fits all" to an "individualised" approach based on disease activity with the aim of achieving a fluid-free retina. The FLUID study investigates the non-inferiority of a Treat and Extend (T&E) protocol of 0.5 mg ranibizumab, which allows treatment extension in the presence of incomplete resolution of sub-retinal fluid (SRF) ≤200 µm at the foveal centre relative to a T&E protocol that requires complete resolution of all retinal fluid (i.e., both SRF and intra-retinal fluid [IRF]) in patients with nAMD. METHODS/DESIGN: This 24 month, randomised, phase IV trial has completed recruitment of treatment-naïve patients randomised 1:1 to ranibizumab "intensive" treatment (complete resolution of IRF and SRF) or ranibizumab "relaxed" treatment (resolution of IRF or >200 µm SRF only at foveal centre). Patients in both arms follow a T&E regimen where extension decisions are based upon assessment of lesion activity: loss of ≥5 letters of visual acuity, new haemorrhage, presence of IRF and SRF on an optical coherence tomography (OCT) scan. The determination of SRF is conducted at a reading centre while the assessment of IRF is physician-determined. The primary endpoint is the mean change in best-corrected visual acuity (BCVA) from baseline to 24 months. Secondary endpoints include the mean change in central retinal thickness (CRT) from baseline to 12 and 24 months, the number of ranibizumab injections administered at 12 and 24 months, and the pharmacogenomic assessment of AMD Gene Consortium-identified single-nucleotide polymorphisms (SNPs) and their association with treatment response. Three hundred and forty seven (347) patients have been recruited by 16 Australian sites within approximately 16 months. A protocol to adjudicate on SRF has been established by the central reading centre and is demonstrating good concordance with investigator assessment. DISCUSSION: This study will provide important insights into retreatment criteria for managing nAMD using a T&E regimen. The current paper describes the clinical rationale for using a less intensive treatment approach using ranibizumab and details of the treatment protocol. TRIAL REGISTRATION NUMBER: NCT01972789. Date of registration: 24th October 2013.

Creating leadership collectives for sustainability transformations.

Enduring sustainability challenges requires a new model of collective leadership that embraces critical reflection, inclusivity and care. Leadership collectives can support a move in academia from metrics to merits, from a focus on career to care, and enact a shift from disciplinary to inter- and trans-disciplinary research. Academic organisations need to reorient their training programs, work ethics and reward systems to encourage collective excellence and to allow space for future leaders to develop and enact a radically re-imagined vision of how to lead as a collective with care for people and the planet. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11625-021-00909-y.

The transverse facial artery and the mandibular condylar process: An anatomic and radiologic study.

INTRODUCTION: In surgical approaches to condylar fractures, there is a risk of damage to the transverse facial artery (TFA) which may in turn account for impaired blood supply to the temporomandibular joint (TMJ). In order to investigate the risk of damage to the TFA, and prevent lesions to this artery resulting from TMJ surgical procedures, we studied the distance between the TFA and the head of the condylar process. METHODOLOGY: A dissection study was conducted on 10 fresh cadavers (20 condylar specimens dissected), involving fifty CT scans of the face with intravenous contrast. Vertical distance from the TFA to the top of the mandibular condyle head and distance from the TFA to the lateral aspect of the mandibular condyle were measured. RESULTS: The lateral aspect of the mandibular condyle is vascularized by branches emanating from the superficial temporal artery (STA) and the TFA. The TFA was located 1.84 ± 0.6 cm below the condylar process of the mandible and ran 1.09 ± 0.54 mm lateral to the head of the mandibular condyle. DISCUSSION: In order to spare the TFA in fractures involving the condylar neck, surgical approaches to the condyle should preserve the uppermost 2 cm of the lateral surface of the condyle during dissection. Due to the necessity for periosteal elevation of the lateral surface of the condyle in condylar head fractures, it is possible to spare the TFA, running lateral to the condylar neck, and the medial condylar surface in order to leave the branches that derive from the maxillary artery (MA) intact.

Post-thrombotic syndrome, recurrence, and death 10 years after the first episode of venous thromboembolism treated with warfarin for 6 weeks or 6 months.

BACKGROUND: The influence of the duration of anticoagulant therapy after venous thromboembolism (VTE) on the long-term morbidity and mortality is unclear. AIM: To investigate the long-term sequelae of VTE in patients randomized to different duration of secondary prophylaxis. METHODS: In a multicenter trial comparing secondary prophylaxis with vitamin K antagonists for 6 weeks or 6 months, we extended the originally planned 2 years follow-up to 10 years. The patients had annual visits and at the last visit clinical assessment of the post-thrombotic syndrome (PTS) was performed. Recurrent thromboembolism was adjudicated by a radiologist, blinded to treatment allocation. Causes of death were obtained from the Swedish Death Registry. RESULTS: Of the 897 patients randomized, 545 could be evaluated at the 10 years follow-up. The probability of developing severe PTS was 6% and any sign of PTS was seen in 56.3% of the evaluated patients. In multivariate analysis, old age and signs of impaired circulation at discharge from the hospital were independent risk factors at baseline for development of PTS after 10 years. Recurrent thromboembolism occurred in 29.1% of the patients with a higher rate among males, older patients, those with permanent triggering risk factor - especially with venous insufficiency at baseline - signs of impaired venous circulation at discharge, proximal deep vein thrombosis, or pulmonary embolism. Death occurred in 28.5%, which was a higher mortality than expected with a standardized incidence ratio (SIR) of 1.43 (95% CI 1.28-1.58), mainly because of a higher mortality than expected from cancer (SIR 1.83; 95% CI 1.44-2.23) or from myocardial infarction or stroke (SIR 1.28; 95% CI 1.00-1.56). The duration of anticoagulation did not have a statistically significant effect on any of the long-term outcomes. CONCLUSION: The morbidity and mortality during 10 years after the first episode of VTE is high and not reduced by extension of secondary prophylaxis from 6 weeks to 6 months. A strategy to reduce recurrence of VTE as well as mortality from arterial disease is needed.

Impact of nurse-mediated management on achieving blood pressure goal levels in primary care: Insights from the Valsartan Intensified Primary carE Reduction of Blood Pressure Study.

BACKGROUND: Blood pressure targets in individuals treated for hypertension in primary care remain difficult to attain. AIMS: To assess the role of practice nurses in facilitating intensive and structured management to achieve ideal BP levels. METHODS: We analysed outcome data from the Valsartan Intensified Primary carE Reduction of Blood Pressure Study. Patients were randomly allocated (2:1) to the study intervention or usual care. Within both groups, a practice nurse mediated the management of blood pressure for 439 patients with endpoint blood pressure data (n=1492). Patient management was categorised as: standard usual care (n=348, 23.3%); practice nurse-mediated usual care (n=156, 10.5%); standard intervention (n=705, 47.3%) and practice nurse-mediated intervention (n=283, 19.0%). Blood pressure goal attainment at 26-week follow-up was then compared. RESULTS: Mean age was 59.3±12.0 years and 62% were men. Baseline blood pressure was similar in practice nurse-mediated (usual care or intervention) and standard care management patients (150 ± 16/88 ± 11 vs. 150 ± 17/89 ± 11 mmHg, respectively). Practice nurse-mediated patients had a stricter blood pressure goal of ⩽125/75 mmHg (33.7% vs. 27.3%, p=0.026). Practice nurse-mediated intervention patients achieved the greatest blood pressure falls and the highest level of blood pressure goal attainment (39.2%) compared with standard intervention (35.0%), practice nurse-mediated usual care (32.1%) and standard usual care (25.3%; p<0.001). Practice nurse-mediated intervention patients were almost two-fold more likely to achieve their blood pressure goal compared with standard usual care patients (adjusted odds ratio 1.92, 95% confidence interval 1.32 to 2.78; p=0.001). CONCLUSION: There is greater potential to achieve blood pressure targets in primary care with practice nurse-mediated hypertension management.

Randomized trial of insulin-glucose infusion followed by subcutaneous insulin treatment in diabetic patients with acute myocardial infarction (DIGAMI study): effects on mortality at 1 year.

OBJECTIVES: We tested how insulin-glucose infusion followed by multidose insulin treatment in diabetic patients with acute myocardial infarction affected mortality during the subsequent 12 months of follow-up. BACKGROUND: Despite significant improvements in acute coronary care, diabetic patients with acute myocardial infarction still have a high mortality rate. METHODS: A total of 620 patients were studied: 306 randomized to treatment with insulin-glucose infusion followed by multidose subcutaneous insulin for > or = 3 months and 314 to conventional therapy. RESULTS: The two groups were well matched for baseline characteristics. Blood glucose decreased from 15.4 +/- 4.1 to 9.6 +/- 3.3 mmol/liter (mean +/- SD) in the infusion group during the 1st 24 h, and from 15.7 +/- 4.2 to 11.7 +/- 4.1 among control patients (p < 0.0001). After 1 year 57 subjects (18.6%) in the infusion group and 82 (26.1%) in the control group had died (relative mortality reduction 29%, p = 0.027). The mortality reduction was particularly evident in patients who had a low cardiovascular risk profile and no previous insulin treatment (3-month mortality rate 6.5% in the infusion group vs. 13.5% in the control group [relative reduction 52%, p = 0.046]; 1-year mortality rate 8.6% in the infusion group vs. 18.0% in the control group [relative reduction 52%, p = 0.020]). CONCLUSIONS: Insulin-glucose infusion followed by a multidose insulin regimen improved long-term prognosis in diabetic patients with acute myocardial infarction.

Reduced sympathetic innervation underlies adjacent noninfarcted region dysfunction during left ventricular remodeling.

OBJECTIVES: We examined the association of sympathetic denervation and reduced blood flow with mechanical dysfunction in adjacent noninfarcted regions late after myocardial infarction (MI). BACKGROUND: Using a well characterized ovine model of left ventricular (LV) remodeling after transmural anteroapical MI, we previously showed that histologically normal adjacent noninfarcted regions demonstrate mechanical dysfunction. METHODS: Ten sheep underwent coronary ligation. Magnetic resonance imaging was performed before and 8 weeks after infarction for measurement of LV mass, volumes, ejection fraction and regional intramyocardial circumferential shortening (%S). Iodine-123 metaiodobenzylguanidine (I-123 MIBG) and fluorescent microspheres before and after administration of adenosine were infused before death for measurement of sympathetic innervation, blood flow and blood flow reserve from matched postmortem regions. RESULTS: From baseline to 8 weeks after infarction, LV end-diastolic volume increased from (mean +/- SD) 1.5 +/- 0.3 to 2.6 +/- 0.5 ml/kg (p < 0.001), and LV mass increased from 2.0 +/- 0.3 to 2.6 +/- 0.5 g/kg (p = 0.001). Regionally, the decline in subendocardial %S was greater in adjacent (19 +/- 5% to 8 +/- 5%) than in remote noninfarcted regions (20 +/- 6% to 19 +/- 6%, p < 0.002). No difference in regional blood flow or blood flow reserve was found between adjacent and remote regions, whereas I-123 MIBG uptake was lower in adjacent than in remote myocardium (1.09 +/- 0.30 vs. 1.31 +/- 0.40 nmol/g, p < 0.003). Topographically, from apex to base at 8 weeks after infarction, %S correlated closely with I-123 MIBG uptake (r = 0.93, p = 0.003). CONCLUSIONS: In mechanically dysfunctional noninfarcted regions adjacent to chronic transmural myocardial infarction in the remodeled left ventricle, blood flow and blood flow reserve are preserved, yet sympathetic innervation is reduced. Chronic sympathetic denervation in adjacent noninfarcted regions, in association with regional mechanical dysfunction, may contribute to LV remodeling after infarction.

Sicca syndrome and dementia in a patient with hepatitis C infection: a case report with unusual bifocal extrahepatic manifestations.

INTRODUCTION: Hepatitis C virus (HCV) infections are associated with extrahepatic manifestations in 40-75 % of cases. Sialitis and secondary Sjögren syndrome are well characterized complications of chronic HCV infections but the mechanisms (primary or secondary) leading to xerostomia are not understood. Similarly, brain lesions due to HCV can be primary or secondary but the pathology of primary HCV-related brain lesions is not well described. CASE REPORT: We report the postmortem case of a 60-year old patient initially presenting with sicca syndrome and dementia. HCV was identified in the brain but not in the salivary glands using transcription-mediated amplification (TMA). Focal sialitis was found in submandibular glands. Neuropathological examination revealed the presence of multiple dot-sized demyelination foci. CONCLUSION: Sicca syndrome is a common concern in chronic HCV infections and may be due to secondary immune mechanisms (we could not isolate HCV in salivary gland tissues). TMA had never been applied to the detection of viruses in salivary glands and neural tissues and proves to be a promising technique. Neuropathological reports in HCV infections are rare and the lesions we report may be the first characterization of the direct effect of HCV on brain cells. More cases are needed to define the full spectrum of lesions potentially caused by the direct action of the HCV on salivary glands and neural tissues.

Caries burden and efficacy of a referral pathway in a cohort of preschool refugee children.

BACKGROUND: This study aimed to assess the early caries experience and the efficacy of a community based dental referral pathway in preschool refugees in Western Australia. METHODS: Preschool refugee children referred to the Western Australian paediatric hospital Refugee Health Clinic were prospectively screened for caries by a paediatric dentist before being referred to community dental clinics. Dental forms and medical records were audited to assess decayed, missing and filled teeth (dmft), medical data and dental services engagement. Poisson regression analysis determined the contribution of count variables to the final model. RESULTS: Among the 105 screened children (54% male, median age 3.2 years, 41% Burmese), community dental clinic engagement was low (46%, n=48). Of the 62% with caries (n=65/105, mean dmft 5.2, SD 4.1), 45% were recommended for specialist dental services and 48% were treated. After adjustment for age, gender and total number of teeth, caries incidence was significantly associated with BMI-for-age Z score (p=0.02). CONCLUSIONS: Preschool refugee caries burden was high. The community dental referral pathway was ineffective compared to co-located intersectorial dental screening. Specialist dental service needs are high in this cohort and require a targeted approach.

Urinary hydroxypyridinium crosslinks of collagen in population-based screening for overt vertebral osteoporosis: results of a pilot study.

The urinary pyridinium crosslinks pyridinoline (PYD) and deoxypyridinoline (DPD) have been shown to provide valid indices of bone resorption. At present, both crosslink components are determined by reversed-phase HPLC, a time-consuming method precluding the use of these markers for routine purposes. Therefore, efforts have been made to develop simple immunoassays for the rapid measurement of urinary crosslinks, and their application to large-scale osteoporosis screening has been proposed. To evaluate the applicability and diagnostic validity of pyridinium crosslink measurements for screening purposes, urinary concentrations of total and free PYD and DPD were determined by HPLC and immunoassay technique (ELISA) in a sample of 269 individuals (male to female ratio = 130:139; age 50-81 years) recruited at random within a population survey of vertebral osteoporosis. On a molar basis, ELISA measures of crosslink-related epitopes were highly correlated with both total and free PYD and DPD as determined by HPLC (r > 0.82, p < 0.001). Age-specific means for creatinine-corrected total and free pyridinium crosslinks were significantly higher in females than in males (p < 0.001). In both sexes, neither age nor anthropometric variables (weight, height, and body mass index) showed a linear effect on the urinary crosslink/creatinine ratio. On average, 50% of the total amount of urinary crosslinks were present in free form. For both PYD and DPD, this proportion was significantly higher in women than in men (p < 0.05), but no change was observed with age or anthropometric measures. The excretion of pyridinium crosslinks was higher in osteoporotic (n = 18) than in nonosteoporotic individuals (n = 208) from the same population.(ABSTRACT TRUNCATED AT 250 WORDS)

Sorbin in the porcine gastrointestinal tract and pancreas: an immunocytochemical analysis.

Sorbin is a 153-amino acid peptide that was initially discovered in the porcine duodenum. We have reported previously that this peptide regulates intestinal electrolyte transport and have described accumulation sites in the rat digestive tract. In the present study, we investigated the anatomical distribution and the site(s) of sorbin production in the porcine digestive tract using immunocytochemistry. The use of polyclonal antisera, which by cross-reaction studies were shown to be specific for different regions of the molecule, revealed a diversified distribution. Sorbin predominated in endocrine cells preferentially localized in the pyloric glands, duodenal crypts of Lieberkühn, and pancreatic islets; in the gastrointestinal tract, sorbin coexisted with Met-enkephalin or with substance P in a small fraction of serotonin-storing [enterochromaffin (ED)] cells, i.e. EC2 cells and EC1 cells, respectively; in the pancreas, sorbin coexisted with insulin in the beta-cells, also considered as serotonin-storing cells in the pig, and with EC cells in the exocrine pancreas. An enteric neuronal system containing sorbin was also reported. Our results demonstrate that sorbin is a component of the serotonin-storing cell type in the porcine gastrointestinal tract and pancreas, and suggest potential directions to investigate the functions of this new regulatory peptide.