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The increased deposition of extracellular matrix proteins in the liver is a key factor in the morbidity and mortality of alcoholic liver disease (ALD). This increased fibrosis may be due to a superabundance of profibrogenic factors such as transforming growth factor-beta (TGF-beta). The original peptide is now called TGF-beta 1, and two other isoforms have been recognized in humans (TGF-beta 2 and TGF-beta 3). It was the aim of the present study to determine the expression of the TGF-beta isoforms in different stages of ALD. Thirty patients with ALD had percutaneous liver biopsies performed for diagnostic purposes. They were grouped by clinical findings and by liver histology into four groups: I, steatosis; II, fibrosis; III, hepatitis; and IV, cirrhosis. An unused portion of each biopsy sample was used to evaluate the gene expression of TGF-beta 1, TGF-beta 2, and TGF-beta 3 by reverse transcription polymerase chain reaction (RT-PCR). The expression of all isoforms from patients was significantly greater than their expression in controls. No significant correlation was determined between TGF-beta isoform expression and liver function test results. When the different isoforms were grouped by histology, increased expression with more severe disease was found; however, differences existed among the isoforms. In ALD, all TGF-beta isoforms were increased and their expression was significantly greater in patients with more active and advanced disease. RT-PCR is an effective method for evaluating gene expression in clinical samples which often provide a limited amount of tissue. [ABSTRACT FROM AUTHOR]

Background: Art. 50 of the proposal for a Regulation on the European Health Data Space (EHDS) states that "health data access bodies shall provide access to electronic health data only through a secure processing environment, with technical and organizational measures and security and interoperability requirements"., Objective: To identify specific security measures that nodes participating in health data spaces shall implement based on the results of the IMPaCT-Data project, whose goal is to facilitate the exchange of electronic health records (EHR) between public entities based in Spain and the secondary use of this information for precision medicine research in compliance with the General Data Protection Regulation (GDPR)., Data and Methods: This article presents an analysis of 24 out of a list of 72 security measures identified in the Spanish National Security Scheme (ENS) and adopted by members of the federated data infrastructure developed during the IMPaCT-Data project., Results: The IMPaCT-Data case helps clarify roles and responsibilities of entities willing to participate in the EHDS by reconciling technical system notions with the legal terminology. Most relevant security measures for Data Space Gatekeepers, Enablers and Prosumers are identified and explained., Conclusion: The EHDS can only be viable as long as the fiduciary duty of care of public health authorities is preserved; this implies that the secondary use of personal data shall contribute to the public interest and/or to protect the vital interests of the data subjects. This condition can only be met if all nodes participating in a health data space adopt the appropriate organizational and technical security measures necessary to fulfill their role., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Carlos Parra Calderon reports financial support was provided by Carlos III Health Institute. The other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Cyclic nucleotide-gated channel β1 (CNGB1) encodes the 240-kDa β subunit of the rod photoreceptor cyclic nucleotide-gated ion channel. Disease-causing sequence variants in CNGB1 lead to autosomal recessive rod-cone dystrophy/retinitis pigmentosa (RP). We herein present a comprehensive review and analysis of all previously reported CNGB1 sequence variants, and add 22 novel variants, thereby enlarging the spectrum to 84 variants in total, including 24 missense variants (two of which may also affect splicing), 21 nonsense, 19 splicing defects (7 at noncanonical positions), 10 small deletions, 1 small insertion, 1 small insertion-deletion, 7 small duplications, and 1 gross deletion. According to the American College of Medical Genetics and Genomics classification criteria, 59 variants were considered pathogenic or likely pathogenic and 25 were variants of uncertain significance. In addition, we provide further phenotypic data from 34 CNGB1-related RP cases, which, overall, are in line with previous findings suggesting that this form of RP has long-term retention of useful central vision despite the early onset of night blindness, which is valuable for patient counseling, but also has implications for it being considered a priority target for gene therapy trials., (© 2021 The Authors. Human Mutation Published by Wiley Periodicals LLC.)

Belantamab mafodotin (belamaf) demonstrated deep and durable responses in patients with heavily pretreated relapsed or refractory multiple myeloma (RRMM) in DREAMM-2 (NCT03525678). Corneal events, specifically keratopathy (including superficial punctate keratopathy and/or microcyst-like epithelial changes (MECs), eye examination findings with/without symptoms), were common, consistent with reports from other antibody-drug conjugates. Given the novel nature of corneal events in RRMM management, guidelines are required for their prompt identification and appropriate management. Eye examination findings from DREAMM-2 and insights from hematology/oncology investigators and ophthalmologists, including corneal specialists, were collated and used to develop corneal event management guidelines. The following recommendations were formulated: close collaboration among hematologist/oncologists and eye care professionals is needed, in part, to provide optimal care in relation to the belamaf benefit-risk profile. Patients receiving belamaf should undergo eye examinations before and during every treatment cycle and promptly upon worsening of symptoms. Severity of corneal events should be determined based on corneal examination findings and changes in best-corrected visual acuity. Treatment decisions, including dose modifications, should be based on the most severe finding present. These guidelines are recommended for the assessment and management of belamaf-associated ocular events to help mitigate ocular risk and enable patients to continue to experience a clinical benefit with belamaf.

Introduction: Patients with relapsed or refractory multiple myeloma (RRMM) represent an unmet clinical need. Belantamab mafodotin (belamaf; GSK2857916) is a first-in-class antibody-drug conjugate (ADC; or immunoconjugate) that delivers a cytotoxic payload, monomethyl auristatin F (MMAF), to myeloma cells. In the phase II DREAMM-2 study (NCT03525678), single-agent belamaf (2.5 mg/kg) demonstrated clinically meaningful anti-myeloma activity (overall response rate 32%) in patients with heavily pretreated disease. Microcyst-like epithelial changes (MECs) were common, consistent with reports from other MMAF-containing ADCs., Methods: Corneal examination findings from patients in DREAMM-2 were reviewed, and the clinical descriptions and accompanying images (slit lamp microscopy and in vivo confocal microscopy [IVCM]) of representative events were selected. A literature review on corneal events reported with other ADCs was performed., Results: In most patients receiving single-agent belamaf (72%; 68/95), MECs were observed by slit lamp microscopy early in treatment (69% had their first event by dose 4). However, IVCM revealed hyperreflective material. Blurred vision (25%) and dry eye (15%) were commonly reported symptoms. Management of MECs included dose delays (47%)/reductions (25%), with few patients discontinuing due to MECs (1%). The first event resolved in most patients (grade ≥2 MECs and visual acuity [each 77%], blurred vision [67%], and dry eye [86%]), with no reports of permanent vision loss to date. A literature review confirmed that similar MECs were reported with other ADCs; however, event management strategies varied. The pathophysiology of MECs is unclear, though the ADC cytotoxic payload may contribute to on- or off-target effects on corneal epithelial cells., Conclusion: Single-agent belamaf represents a new treatment option for patients with RRMM. As with other ADCs, MECs were observed and additional research is warranted to determine their pathophysiology. A multidisciplinary approach, involving close collaboration between eye care professionals and hematologist/oncologists, is needed to determine appropriate diagnosis and management of these patients., Trial Registration: ClinicalTrials.gov Identifier, NCT03525678.

Aims: To report the mean change in Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity (BCVA) and reading performance (reading acuity and maximum reading speed (MRS) using the MNREAD test) between baseline and 24 months in treatment-naïve patients with neovascular age-related macular degeneration (nAMD) treated with intravitreal aflibercept injections., Methods: A prospective, open-label, interventional non-randomised case series with 24 months' duration. Patients were recruited to the study from medical retina clinics at Moorfields Eye Hospital. Intravitreal injections of 2.0 mg aflibercept in the study eye were administered using a fixed dosing regimen during the first year and a treat-and-extend treatment regimen during the second year of treatment., Results: Fifty patients were enrolled with a mean age (SD) of 78.7 (7.6) years; a mean BCVA of 62.8 ETDRS letters; mean reading acuity of 0.52 logMAR; mean maximum reading speed (MRS) of 141.3 words per minute and a central macular thickness of 322.6 µm at baseline. The mean improvement in BCVA was 6.4 letters for the 44 patients (88%) for whom data was available at 2 years. The mean improvement in reading acuity was 0.13 logMAR with an improvement in MRS of 2.9 words per minute. The mean reduction in CRT from baseline was 104.8 µm., Conclusions: Aflibercept treatment of nAMD using fixed dosing in year 1 and treat and extend in year 2 leads to improvements in reading ability, visual acuity and retinal morphology which were maintained to 2 years of treatment., Trial Registration: ClinicalTrials.gov Identifier NCT02441816, the VITAL study.

Purpose: To assess the presence of binocular gain in macular telangiectasia type 2 (MacTel) and its correlation to paracentral scotomas., Methods: Sixty-eight patients with MacTel were consecutively recruited for a cross-sectional analysis. Best-corrected visual acuity (BCVA), reading acuity, and reading speed were tested monocularly and binocularly. Macular retinal sensitivity was examined with fundus-controlled perimetry (microperimetry). Scotomas were quantified by their size, their depth, and their proximity to the fovea., Results: Binocular reading speed and acuity were lower than monocular reading speed and acuity in the functionally better eye (142 vs. 159 words per minute and 0.43 vs. 0.28 log reading acuity determination, P < 0.001). Magnitude of binocular inhibition of reading speed was correlated to the degree of interocular functional difference (R2 = 0.61, P < 0.001). This correlation was not found for reading acuity or BCVA (R2 < 0.03). Binocular reading speed was negatively correlated to size of right and left eye scotomas, with bigger effect size for left eye scotomas. The magnitude of binocular inhibition was correlated to size of left eye scotomas, but not of right eye scotomas. When both eyes had similar scotoma characteristics, the right eye was more frequently the better reading eye., Conclusions: We provide evidence for the presence of binocular inhibition of reading performance in MacTel, likely due to binocular rivalry. This may result from the characteristic paracentral scotomas in noncorresponding retinal fields and, in particular, a disruptive projection of scotomas in reading direction arising from the left eyes. Patients may benefit from occluding one eye while reading.

The provision of oocytes plays an important role in human fertility treatments. Spain alone performs half of oocyte provision cycles in the European Union whilst all other European countries face an oocyte shortage. How do Spanish fertility clinics manage to match the increasing domestic and foreign demand for female oocytes? Adopting a weak performativity approach and drawing insights from interviews carried out with 20 fertility clinic representatives, this study suggests that Spanish clinics are successful thanks to an egg provision system designed as a (quasi) social market. In the absence of traditional market mechanisms based on price fluctuations, the combination of fixed monetary compensation for providers and altruistic framing of oocyte provision as an act of donation, are used to mobilize relatively high numbers of women. Fertility clinics optimize this supply through a set of supplementary strategies to ensure oocyte supply always meets oocyte demand. Though successful, this market design reinforces gender stereotypes and relies on manipulative notions of altruism. A clear but unacknowledged appropriation of women's bodies and reproductive labour are also operated, which reinforces and reproduces racial and social stratifications. Therefore, we ask whether alternative mechanisms to promote female solidarity across different generations, to raise awareness of the risks of advanced maternal age, and to explore alternative market designs should be considered., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Purpose: To describe the 3 distinct patterns of choroidal nevi in swept-source (SS) OCT and apply that classification to a cohort of consecutive choroidal nevi. Also, we aim to describe the findings of these lesions in near-infrared reflectance (NIR) at different wavelengths (820 and 1050 nm)., Design: Single-center, retrospective, observational study., Participants: One hundred four consecutive patients with choroidal nevi., Methods: Retrospective analysis of choroidal nevi imaged with SS OCT and NIR., Main Outcome Measures: Lesions were classified according to OCT patterns as type A (high reflectivity with optical shadowing), type B (medium reflectivity with partial visualization of the scleral boundary), and type C (hyporeflective with complete visualization of the scleral boundary)., Results: Of 104 choroidal nevi, 97 lesions (93.3%) could be classified into 1 of the SS OCT patterns. Forty-nine percent corresponded to type A, 26% corresponded to type C, and 18.3% corresponded to type B. In NIR (n = 820), 76% of lesions were hyperreflective, whereas in NIR (n = 1050), most of the lesions were hyporeflective (59.6%; inverse reflectance)., Conclusions: Choroidal nevi present distinct patterns according to SS OCT features. Clinical implications are yet to be determined. In NIR, inverse reflectance may be a consequence of the confocality of the device, rather than a property of the lesions., (Copyright © 2019 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

This article investigates the normative and procedural criteria adopted by European citizens to assess the acceptability of surveillance-oriented security technologies. It draws on qualitative data gathered at 12 citizen summits in nine European countries. The analysis identifies 10 criteria, generated by citizens themselves, for a socially informed security policy. These criteria not only reveal the conditions, purposes and operation rules that would make current European security policies and technologies more consistent with citizens' priorities. They also cast light on an interesting paradox: although people feel safe in their daily lives, they believe security could, and should, be improved.

Aim: To report the natural history of subretinal fluid (SRF) causing foveal detachment in macular telangiectasia type 2 (MacTel) and our experience of therapeutic intervention with intravitreal steroids or antivascular endothelial growth factor inhibitor (anti-VEGF) agents in some cases., Methods: Retrospective case series. Three of the MacTel study's largest registries were searched to identify eyes with foveal detachment., Results: We identified 7 eyes from 6 exclusively female patients. The prevalence of foveal detachment was low, present in 1.4% of the assessed MacTel population. Age at presentation ranged from 50 to 66 years. Follow-up ranged from 2 to 8 years. There was late-phase leakage on fluorescein angiography from what was presumed to be ectatic capillaries. The SRF fluctuated without a rapid decline in visual acuity in cases that were not treated. When they were, intravitreal anti-VEGF and steroid therapy in general reduced SRF, at least temporarily, but did not halt the gradual long-term decrease in visual acuity. In one case, optical coherence tomography angiography showed significant reduction in the extent of the predominantly deep intraretinal vascular complex 1 month after anti-VEGF therapy., Discussion and Conclusions: As the natural history of this unusual MacTel phenotype is not characterised by rapid visual decline, intervention with intravitreal anti-VEGF or steroid therapy may not be necessary., Competing Interests: Competing interests: None declared., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Background: Women with inflammatory bowel disease (IBD) are at increased risk for adverse birth outcomes such as preterm delivery and small for gestational age (SGA) infants. Most recognized cases of fetal growth restriction in singleton pregnancies have underlying placental causes. However, studies in IBD examining poor birth outcomes have focused on maternal factors. We examined whether women with IBD have a higher rate of placental inflammation than non-IBD controls., Methods: Between 2008 and 2011, the placental tissue of 7 ulcerative colitis, 5 Crohn's disease, and 2 IBD-unclassified subjects enrolled in the Pregnancy in Inflammatory Bowel Disease and Neonatal Outcome (PIANO) registry were evaluated for villitis, deciduitis, and chorioamnionitis with/without a fetal inflammatory response. The history and birth outcomes of all IBD subjects were reviewed and matched to 26 non-IBD controls by gestational age at delivery., Results: Of women with IBD, 29% delivered preterm infants and 21% delivered SGA infants. Half of the IBD patients had mild-moderate disease flares during pregnancy. Five (36%) patients required corticosteroids, 2 (14%) were maintained on an immunomodulator, and 3 (21%) others received tumor necrosis factor-alpha inhibitors during their pregnancy. Chorioamnionitis was the only identified placental pathology present in the placentas reviewed, occurring less frequently in cases compared to controls (7% vs. 27%, P=0.32)., Conclusions: Placental inflammatory activation does not appear to be responsible for the increase in adverse birth outcome in women with IBD. Further studies are necessary to validate these findings in IBD to explain poor birth outcomes.

Purpose: To evaluate the spatial distribution and total amount of macular pigment (MP) in patients with idiopathic macular telangiectasia type 2 (MacTel) compared to healthy subjects., Methods: Totals of 53 MacTel patients and 38 normal subjects underwent macular pigment optical density (MPOD) measurement using a 2-wavelength autofluorescence (2-AF) technique. The peak MPOD and total MP (sum of pixel OD values) were measured within the central 21 degrees. Data were correlated with motion photometry in a cohort of normal subjects., Results: A Bland-Altman analysis revealed minimal differences between psychophysical and 2-AF measurements of MPOD (bias = 0.025, SD = 0.06, N = 156 values). In the normal comparison group, 2-AF MPOD peak had a median value of 0.57 (range 0.21-0.93), and median eccentricity of the peak was 0.19 degrees (range 0.00-0.41). In the MacTel group, MPOD peak had a median value of 0.08 (range 0.01-0.26), and median eccentricity of the peak was 5.04 degrees (range 0.18-7.27). The median total amount of MP within the central 21 degrees was greater for normal subjects (4802, range 2362-9215) than for the patients (2938, range 142-7198), but there was marked overlap between the groups. Comparison of the total amount within the central 8, 12, or 16 degrees to that within the central 21 degrees revealed underestimation of up to 68% (median 53%), 42% (27%), and 24% (8%), respectively., Conclusions: Most MacTel patients have a normal total complement of MP with an abnormal paracentral distribution. The study highlights the limitations of MP measurement techniques that assume minimal MP at eccentricities less than 10.5 degrees.

Hepatitis B virus (HBV) during pregnancy presents unique management challenges. Varying aspects of care must be considered, including the effects of HBV on maternal and fetal health, effects of pregnancy on the course of HBV infection, treatment of HBV during and after pregnancy, and prevention of perinatal infection. Antiretroviral therapy has not been associated with increased risk of birth defects or toxicity, but despite studies designed to elucidate the drug efficacy and safety in affected individuals and the developing fetus, recommendations are inconclusive. Clinicians and patients must make individualized decisions after carefully evaluating the risks and benefits summarized in this article., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: Training in gastrointestinal (GI) disorders in pregnancy is required for all gastroenterology fellows. Nevertheless, the actual role of the gastroenterologist in the management of pregnant patients is unknown. Establishing the characteristics of GI consultations in pregnancy can help focus trainee education and prepare gastroenterologists for future practice. The purpose of this study was to determine the indications for consultations in pregnancy and the gastroenterologist's role in the evaluation and management of the pregnant patient., Methods: A chart review was performed of all consecutive outpatient GI consultations for pregnant women at a high-volume obstetrics hospital over a 3-year period. Referring source, patient characteristics, indication(s) for consultation, diagnosis(es), change in management after consultation, and need for follow-up were recorded., Results: We reviewed 370 charts. The mean age (±standard deviation [SD]) at referral was 28.7 years ± 6.5, and mean weeks of gestation (±SD) was 21.3 ± 8.8. Obstetrician/gynecologists requested most consultations (70.1%). New GI symptoms arising in pregnancy comprised 35.4% of consultations, and worsening of a preexisting GI disorder comprised 24.4%. The most common indications for consultation were viral hepatitis (20.2%), nausea and vomiting (18.9%), and nonspecific abdominal pain (13.5%). The most common diagnoses were acute or chronic viral hepatitis (17.8%), hyperemesis gravidarum (15.1%), gastroesophageal reflux disease (14.3%), and constipation (13.0%). Consultation changed the diagnosis in 25.1% of patients and changed management in 78.6%. Follow-up was required in 77.3% of cases during pregnancy and 37.8% postpartum., Conclusions: GI consultation in pregnancy is sought more frequently for the evaluation and management of GI disorders not unique to pregnancy than for pregnancy-unique disorders. Although GI consultation changed the diagnosis in a minority of cases, it changed management in the majority. Gastroenterologists should be familiar with the most common indications for consultation in pregnancy and be prepared to evaluate and manage pregnant women with GI disorders.

Background: Hyperemesis gravidarum is severe nausea and vomiting during pregnancy leading to dehydration, nutrition deficiency, and fetal morbidity and mortality. Treatment must maintain fluid and electrolyte balance and caloric intake. Parenteral nutrition is often attempted; however, complication rates are high. Nutrition via nasoenteric and percutaneous endoscopic gastrostomy tubes is limited by poor patient tolerance, tube dislodgement, and altered anatomy in pregnancy., Methods: Women with hyperemesis gravidarum who failed standard therapy were offered jejunostomy. All patients underwent surgical jejunostomy in the second trimester. Isotonic tube feeds were administered to a goal caloric factor calculated by the Harris-Benedict equation with a correction added for pregnancy. Patients were monitored until delivery., Results: Five women underwent jejunostomy placement at our institution between 1998 and 2005. One patient underwent jejunostomy placement twice for consecutive pregnancies. The mean body weight loss from prepregnancy was 7.9% (range, 4.0%-15.9%). Patients underwent jejunostomy placement between 12 and 26 weeks of gestation (median 14 weeks). Twelve to 16 Fr catheters were placed in the proximal jejunum. Maternal weight gain occured in 5 of 6 pregnancies. The mean duration of tube placement was 19 weeks (range, 8-28 weeks). All pregnancies ended with term deliveries (range, 36-40 weeks of gestation). The mean infant birth weight was 2885 g (range, 2270-4000 g). Tube-related complications were limited to dislodgement in 2 patients in the third trimester. No cases of infection, bleeding, or preterm labor occured., Conclusions: Feeding via jejunostomy is a potentially safe, effective, and well-tolerated mode of nutrition support therapy in hyperemesis gravidarum.

Authors investigated the scavenger capability of lazaroids, a new group of compounds (21-aminosteroid) that are reported in the literature to have interesting anti-lipid peroxidation properties. Authors tested the degree of scavenger activity related to the oxygen derived free radicals (ODFR) with different methods: 1) chemiluminescence; 2) production of superoxide anion from activated polymorphonuclear cells; 3) production of hydroxyl radical through a chemical procedure. Results showed a global scavenger activity of the three lazaroids (U78517F, U74389F, U74500A) in all the various tests, but differences of intensity of their action were noted among in each compound. We can thus attribute to these compounds a scavenger activity on the oxygen free radicals; this activity may facilitate their already known anti-lipid peroxidation action. Therefore, clinical use of lazaroids can be hypothesized for the diseases in which inflammation plays an important pathogenetic role via the production of oxygen free radicals and the resulting lipid peroxidation associated with tissue damage.

Hepatitis C (HCV) is an indolent and often fatal disease affecting four million Americans commonly associated with low socioeconomic status. We assessed its prevalence in a sample of 334 consecutively admitted middle class substance abusers in a private urban hospital, and ascertained risk factors for its transmission. We found that the point prevalence rate for HCV was 27.7% among all substance abusers, and 76.7% among intravenous drug users. Using logistic regression, we found risk factors associated with HCV were intravenous drug use, needle sharing, prior liver disease, opioid dependence, HIV infection, and benzodiazepine dependence. Not found to increase infective risk were lower social class, male gender, African-American race, male homosexuality, unemployment, and the absence of private health insurance. Multiple viral genotype types were identified in this sample, suggesting diverse sources of transmission in the sample. This study documents an epidemic of HCV in an American middle class sample.

An outbreak of hepatitis A is described involving thirteen cases in a town in central-northern Italy. The consumption of infected clams, caught in a polluted coastal area of the Adriatic Sea, caused hepatitis A in all five members of a family consisting of mother, father and children, two of whom attended primary school. The epidemic subsequently spread to the primary school with a secondary attack rate of 7.9%, 0 for female pupils and 18.9% for males. The epidemiological and environmental investigations showed that the critical exposure took place in the boys' toilet in the primary school (OR: 32.79, 95% CI: 6.83-157.45). To prevent the spreading of contagion, extra disinfection was carried out in the whole school and health education campaigns were mounted. The good basic hygienic conditions of the homes, together with the cooperation of school staff in surveillance and providing information, allowed the epidemic to be controlled.

Total hip arthroplasty means sacrificing the joint capsule and the mechanoreceptors contained therein. Recent neurophysiological experiences seem to redefine the sensorial and proprioceptive role of the joint capsule in favor of the activity of the muscular mechanoreceptors, particularly in the area of the coxofemoral joint. The authors have examined the sensorial lesion caused by total hip arthroplasty in a group of 20 patients. Clinical testing was conducted prior to surgery, 7 and 40 days later. The tests were aimed at exploring the perceptive and proprioceptive activity of the hip, and showed marked decrease in all of the receptorial activity one week after surgery. After 40 days perceptive function was completely recovered, as the scores for tests conducted were the same as those obtained prior to surgery: proprioceptive activity was instead considerably improved, with significant changes in most parts of the tests. The authors conclude by observing that total hip arthroplasty does not cause permanent lesion of the perception of joint movement; furthermore, renewed coxofemoral mechanics allow for a better proprioceptive response with strengthening of static and dynamic antigravitational reactions.

TA1, a novel rat oncofetal cDNA, is the predicted homolog of the human lymphocyte activation gene E16. The encoded peptides share high homology with transport-associated and uncharacterized sequences in distant species, suggesting an important and conserved function in cellular homeostasis. Moderate steady-state levels of TA1 RNA were induced following acute and chronic CCl4-mediated liver injury. TA1 expression was either greatly reduced or absent in livers of animals receiving injury-protective doses of vitamin E in conjunction with CCl4. In contrast to the in vivo data, acute in vitro exposure of hepatocytes to CCl4 did not induce TA1 RNA. Our results indicate that TA1 is spatially and temporally associated with liver injury in vivo and may play an adaptive role in the hepatic response to environmental toxicants.

The authors conducted a study to evaluate the effects of cigarette smoke on the healing of septic pseudarthrosis of the tibia treated by ilizarov external fixator. A total of 31 patients of both sexes were chosen, and the healing time in relation to the habit of smoking was examined. The results have shown that the healing time in non-smokers as compared to smokers was shorter by 33%. The difference is highly significant. This shows that abstention from smoking during treatment should be given maximum importance in prevention.

Oxidative stress, with reactive oxygen intermediate formation, may represent a common mechanism by which liver injury is induced by diverse etiologies. Oxidative stress enhances nuclear factor kappa B (NF-kappa B) activity, and NF-kappa B activity has been shown to enhance the expression of cytotoxic cytokines. Acute hepatic injury caused by reactive oxygen intermediate production was induced by an intraperitoneal injection of CCl4 in mice. This injury was significantly inhibited by intravenous pretreatment of the mice with a water-soluble emulsion of alpha-tocopherol. Alpha-tocopherol treatment of the mice given the CCl4 also reduced the NF-kappa B binding to levels approaching those found in normal mice. In vitro treatment of a monocyte/macrophage cell line with CCl4 led to enhanced NF-kappa B binding and an increase in tumor necrosis factor-alpha (TNF-alpha) messenger RNA levels. Liver specimens taken from patients with acute fulminant hepatitis had markedly increased NF-kappa B binding activity in comparison with the binding of normal livers. These data demonstrate that abolishing acute hepatic injury with alpha-tocopherol, a free radical scavenger, also eliminated increased NF-kappa B binding. It is tempting to speculate that enhanced NF-kappa B expression caused by free radical production/oxidative stress may modulate liver injury, perhaps through an effect on cytotoxic cytokine synthesis.

Background/aims: The study of Schistosoma-induced hepatic fibrosis in murine Schistosoma mansoni infection has elucidated the nature of hepatic fibrosis in humans. In the present study, fibrogenic gene expression was determined in murine S. mansoni infection during primary infection, after chemotherapy with praziquantel, and during secondary infection., Methods: Both histomorphometric analysis and Northern blot profiles were performed., Results: Histomorphometric analysis of granulomatous inflammation showed smaller hepatic fibrotic granulomata after chemotherapy and during secondary infection. Albumin gene expression remained relatively constant throughout primary infection, chemotherapy, and secondary infection. Fibronectin gene expression in primary infection was comparable with the level observed in noninfected mice and was reduced by chemotherapy. Reinfection resulted in augmented expression levels equal to primary infection levels. Osteonectin gene expression was active in primary infection, was reduced by chemotherapy, and was actively reexpressed in secondary infection. Interstitial matrix macromolecules, types I and III collagen, and basement membrane collagen showed high levels of gene expression in primary infection, were virtually terminated by chemotherapy, and were reexpressed on reinfection. The gene expression of transforming growth factor beta 1, a major, fibrogenic cytokine, paralleled collagen expression., Conclusions: Chemotherapy of schistosomiasis initiated a dramatic decrease in steady-state messenger RNA levels of major proteins associated with fibrosis; reinfection resulted in a reexpression of these genes.

The pathogenic role of lipid peroxidation in the reperfusion injury of the liver is still controversial. This study was performed to determine whether the damage caused by oxygen free radicals during reoxygenation in perfused rat hepatocytes is related to lipid peroxidation. Superoxide anion was detected by lucigenin-enhanced chemiluminescence. Lipid peroxidation and cell injury were assessed by the release of malondialdehyde and lactic dehydrogenase. Upon reoxygenation following 2.5 h of anoxia, isolated hepatocytes generated considerable amount of O2-. Following O2- formation, a significant increase in malondialdehyde release was measured. Cell injury was temporally delayed relative to O2- generation, but preceded the occurrence of a significant lipid peroxidation. Treatment with Vitamin E abolished lipid peroxidation but had no effect upon superoxide anion formation and cell injury. These results suggest that in perfused rat hepatocytes non-peroxidative mechanisms are more important than peroxidative mechanisms in the pathogenesis of the early phases of reoxygenation injury.

We present a morphologic and molecular comparison of two models of hepatic fibrosis. Immune complexes are the source of insult in one model. In the other model, CCl4 induces fibrosis. For the immune complex model, rats were immunized intraperitoneally over the course of 4 weeks with human albumin, then injected through a tail vein three times a week for at least 5 more weeks with the same albumin. Seventy-five percent of all treated animals developed fibrosis characterized by fine collagen bands. There was a mild degree of hepatocyte trapping and necrosis as well as some bile duct hyperplasia and tissue eosinophilia. However, there was no significant Kupffer cell hyperplasia or inflammatory reaction. Quantification of specific mRNA species was determined by Northern blot hybridization analysis of total RNA. In comparison with CCl4-induced fibrosis in rats, a hepatotoxin-mediated model with a much greater inflammatory response, this immune complex model showed a less pronounced increase in type I procollagen mRNA, but a relatively greater increase in types III and IV procollagen mRNA. Whereas transforming growth factor-beta 1 mRNA levels were markedly increased in CCl4-induced fibrosis, there was only a slight increase in this cytokine, known to stimulate type I collagen synthesis, in the immune complex model. A comparison of the two model systems indicates that a variety of mechanisms may be involved in the process of hepatic fibrogenesis. It appears that an inflammatory response and elevated transforming growth factor-beta 1 levels are associated with a marked increased synthesis of type I collagen in a hepatotoxin model while other, as yet undefined, mediators may be responsible for the increase in types III and IV procollagen mRNA species found in the immune complex model.

The relationship between Ito cells and hepatic fibrogenesis has been investigated in an experimental model: intraperitoneal injection of heterologous serum in rats leads to the appearance of fibrous septa within 5 weeks. Groups of rats were sacrificed at various intervals (from 2.5 to 20 weeks), saline-injected rats being used as controls. Liver fragments were prepared for light and electron microscopy and determination of hydroxyproline. Ito cells were identified by defined morphological criteria on 1 micron sections. The volume density (VD) of Ito cells and fibrous septa, and the Ito cell index were determined. Ito cells represent a very relevant component of early septa. In later stages, the VD of cells with morphological features of Ito cells falls to very low values. This might be related to modulation of Ito cells to fibroblasts. The increase of tissue hydroxyproline is delayed with respect to the peak VD of septal Ito cells, actually corresponding to the fall in the VD of septal Ito cells. The striking increase in the VD of total Ito cells cannot be related to a theoretically possible increase in the volume of single Ito cells, as VD always parallels the Ito cell index. These data suggest a hyperplastic reaction, possibly associated with a cellular migration from the lobules to early septa.