Ocular surface disease in moderate-to-severe atopic dermatitis patients and the effect of biological therapy.

Atopic dermatitis (AD) is a chronic inflammatory skin disease for which new targeted therapies are currently available. Due to the increased rates of ocular surface disease (OSD) reported during treatment with these new targeted treatments, more insight into the occurrence and pathomechanism of OSD in moderate-to-severe AD patients is needed. Therefore, this review's first part highlights that most patients with moderate-to-severe AD already have characteristics of OSD before starting targeted treatment. Remarkably, not all AD patients with OSD report ocular symptoms. OSD in AD is associated with less conjunctival goblet cells (GC) compared to healthy controls. In addition, OSD severity in AD patients is associated with high AD activity, the presence of eyelid and/or facial eczema, and high levels of AD-related severity biomarkers in tear fluid. The second part of this review highlights that pre-existing ocular pathology (e.g. in combination with the use of ophthalmic medication or eyelid eczema) may be associated with the development of dupilumab-associated ocular surface disease (DAOSD). During dupilumab treatment, DAOSD (which can be new-onset OSD or worsening of pre-existing OSD) is observed in approximately one-third of the dupilumab-treated AD patients. Anti-inflammatory ophthalmic treatment improves DAOSD, and dose reduction of dupilumab may also be an effective treatment option. The pathomechanism of DAOSD is still not fully elucidated. In a prospective study low, but stable conjunctival GC numbers were observed in moderate-to-severe AD patients, before and during dupilumab treatment. However, the Mucin 5 AC (MUC5AC) expression of GCs decreased during dupilumab treatment, suggesting an impairment of the GC function by dupilumab treatment. In addition, higher dupilumab tear fluid levels were found in dupilumab-treated AD patients with moderate-to-severe OSD compared to patients with no or mild OSD, whereas the dupilumab serum levels are similar. Clinicians should be aware of the frequent occurrence of OSD in moderate-to-severe AD patients, and a low-threshold referral to an ophthalmologist is recommended.

Social networking and fear of missing out (FOMO) among medical students at University of Khartoum, Sudan 2021.

BACKGROUND: With students becoming more involved in the internet and social networking sites, they become more prone to their consequences. This study focuses on measuring the social networking intensity and the fear of missing out among the medical students of University of Khartoum, then examining the association between them. METHODS: Facility-based, descriptive, cross-sectional study was conducted at Faculty of Medicine, Khartoum University between January and March 2021. A total of 333 students were selected by simple random sampling. Data was collected from the participants using a structured self-administered questionnaire that involved the social networking intensity (SNI) scale and fear of missing out (FOMO) scale. The data was analyzed by the Statistical Package for Social Science (SPSS) software version 26. RESULTS: Moderate positive correlation between social networking intensity and fear of missing out was found (p-value < 0.01). Of the total participants; 51 participants (15.4%) experienced low SNI and low FOMO. Another 78 participants (23.6%) had moderate SNI and moderate FOMO and only 16 Participants (4.8%) showed high SNI and high FOMO. There were no significant differences in SNI or FOMO scores among the different socio-demographic variables, except for the SNI score which was positively correlated to the monthly income. CONCLUSION: An association between SNI and FOMO was found. SNI was not affected by socio-demographic factors except for the monthly income.

Early Hepatoduodenal Ligament Occlusion Versus Classic Technique During Recipient Hepatectomy for Living Donor Liver Transplant.

OBJECTIVES: Intraoperative bleeding is commonly encountered during living donor liver transplant procedures and is associated with greater need for blood transfusion, which increases morbidity. Herein, we hypothesized that early and continuous occlusion ofthe hepatic inflow would have a beneficial effect on the living donor liver transplant procedure regarding intraoperative blood loss and operative time. MATERIALS AND METHODS: This comparative study prospectively included 23 consecutive patients (the experimental group) who had early inflow occlusion during recipient hepatectomy for living donor liver transplant and compared the outcomes versus 29 consecutive patients who had previously received (immediately before the start of our study) living donor liver transplant by the classic technique. Blood loss and time for hepatic mobilization and dissection were compared between the 2 groups. RESULTS: Patient criteria and indication for living donor liver transplant showed no significant difference between the 2 groups. There was a significant decrease in blood loss during hepatectomy in the study group versus the control group (2912 vs 3826 mL, respectively; P = .017). Packed red blood cell transfusion was less in the study group versus the control group (1550 vs 2350 cells, respectively; P < .001). The skin-to-hepatectomy time was not different between the 2 groups. CONCLUSIONS: Early hepatic inflow occlusion is a simple and effective technique to reduce intraoperative blood loss and reduce the need for blood transfusion products during living donor liver transplant.

Outflow Reconstruction in Right Lobe Living Donor Liver Transplant: Middle Hepatic Vein Reconstruction Versus Separate Tributaries to Inferior Vena Cava Anastomosis.

OBJECTIVES: In right lobe living donor liver transplant, proper reconstruction of the segment 5 vein and segment 8 vein is essential. Herein, we compared 2 different techniques for segment 5 vein reconstruction. MATERIALS AND METHODS: This prospective nonrandomized study included all recipients of modified right lobe living donor liver transplant who had reconstruction of the segment 5 vein, with or without segment 8 veins, from October 2018 to October 2021. Patients were grouped into group A (classical technique) and group B (modified technique). For group A, the segment 5 (and segment 8, if present) vein was anastomosed in an end-to-side fashion to a polytetrafluoroethylene synthetic graft positioned parallel to the cut surface of the liver graft; then, during implant, its proximal end was anastomosed to recipient's middle hepatic or middle-left hepatic veins unified orifice. In group B (modified technique), the stumps of segment 5 (and segment 8 if present) were anastomosed in an end-to-end fashion to 2 different polytetrafluoroethylene grafts; then during implant, the other ends of the segment 5 grafts were anastomosed directly to the inferior vena cava. Postoperative segment 5 vein patency and graft recovery were compared. RESULTS: Forty patients were included: 22 in group A and 18 group B. There were no significant differences in the demographic data or characteristics of donors, grafts, and recipients between the groups. There was better patency in segment 5 synthetic grafts in group A at all time points compared with group B, but this difference was statistically significant only at 1 month (18 [81.8%] vs 9 [50%, respectively; P = .046).There was no statistically significant difference in the markers of graft recovery in both groups. CONCLUSIONS: Reconstruction of the segment 5 vein by polytetrafluoroethylene synthetic graft in a fashion to resemble the native middle hepatic vein in modified right lobe living donor liver transplant has better patency than anastomosis of the segment 5 vein in an end-to-end fashion to the synthetic graft and then to the inferior vena cava. Both techniques did not affect graft recovery.

A BET Protein Inhibitor Targeting Mononuclear Myeloid Cells Affects Specific Inflammatory Mediators and Pathways in Crohn's Disease.

BACKGROUND: Myeloid cells are critical determinants of the sustained inflammation in Crohn's Disease (CD). Targeting such cells may be an effective therapeutic approach for refractory CD patients. Bromodomain and extra-terminal domain protein inhibitors (iBET) are potent anti-inflammatory agents; however, they also possess wide-ranging toxicities. In the current study, we make use of a BET inhibitor containing an esterase sensitive motif (ESM-iBET), which is cleaved by carboxylesterase-1 (CES1), a highly expressed esterase in mononuclear myeloid cells. METHODS: We profiled CES1 protein expression in the intestinal biopsies, peripheral blood, and CD fistula tract (fCD) cells of CD patients using mass cytometry. The anti-inflammatory effect of ESM-iBET or its control (iBET) were evaluated in healthy donor CD14+ monocytes and fCD cells, using cytometric beads assay or RNA-sequencing. RESULTS: CES1 was specifically expressed in monocyte, macrophage, and dendritic cell populations in the intestinal tissue, peripheral blood, and fCD cells of CD patients. ESM-iBET inhibited IL1ß, IL6, and TNFα secretion from healthy donor CD14+ monocytes and fCD immune cells, with 10- to 26-fold more potency over iBET in isolated CD14+ monocytes. Transcriptomic analysis revealed that ESM-iBET inhibited multiple inflammatory pathways, including TNF, JAK-STAT, NF-kB, NOD2, and AKT signaling, with superior potency over iBET. CONCLUSIONS: We demonstrate specific CES1 expression in mononuclear myeloid cell subsets in peripheral blood and inflamed tissues of CD patients. We report that low dose ESM-iBET accumulates in CES1-expressing cells and exerts robust anti-inflammatory effects, which could be beneficial in refractory CD patients.

Pancreaticoduodenectomy for pancreatic adenocarcinoma in a patient with situs inversus abdomenalis, a case report.

INTRODUCTION AND IMPORTANCE: Situs Inversus (SI) is a rare congenital condition in which the abdominal and thoracic organs are located in a mirror image of the normal position in the sagittal plane. Although this condition does not affect normal health or longevity, its recognition is very important for treating many diseases, particularly those requiring surgical intervention. The relationship between situs inversus and cancer remain inconspicuous. CASE PRESENTATION: We report a 64-year old male with Situs Iinversus Abdominalis with Pancreatic Adenocarcinoma. Radiographic modalities were very important in preoperative assessment of the patient. The patient was managed by pyloric preserving pancreaticoduodenectomy. The patient received adjuvant chemotherapy and free of recurrence for one year after operation. CONCLUSION: Surgeons must recognize the complexity of operative intervention with respect to aberrant anatomy. The occurrence of Situs Inversus in a patient with pancreatic cancer must not deter the surgeon from sound oncologic principles of pancreatic surgery. Referral to these cases to tertiary level center is of utmost importance.

Carboxylesterase-1 Assisted Targeting of HDAC Inhibitors to Mononuclear Myeloid Cells in Inflammatory Bowel Disease.

BACKGROUND AND AIMS: Histone deacetylase inhibitors [HDACi] exert potent anti-inflammatory effects. Because of the ubiquitous expression of HDACs, clinical utility of HDACi is limited by off-target effects. Esterase-sensitive motif [ESM] technology aims to deliver ESM-conjugated compounds to human mononuclear myeloid cells, based on their expression of carboxylesterase 1 [CES1]. This study aims to investigate utility of an ESM-tagged HDACi in inflammatory bowel disease [IBD]. METHODS: CES1 expression was assessed in human blood, in vitro differentiated macrophage and dendritic cells, and Crohn's disease [CD] colon mucosa, by mass cytometry, quantitative polymerase chain reaction [PCR], and immunofluorescence staining, respectively. ESM-HDAC528 intracellular retention was evaluated by mass spectrometry. Clinical efficacy of ESM-HDAC528 was tested in dextran sulphate sodium [DSS]-induced colitis and T cell transfer colitis models using transgenic mice expressing human CES1 under the CD68 promoter. RESULTS: CES1 mRNA was highly expressed in human blood CD14+ monocytes, in vitro differentiated and lipopolysaccharide [LPS]-stimulated macrophages, and dendritic cells. Specific hydrolysis and intracellular retention of ESM-HDAC528 in CES1+ cells was demonstrated. ESM-HDAC528 inhibited LPS-stimulated IL-6 and TNF-α production 1000 times more potently than its control, HDAC800, in CES1high monocytes. In healthy donor peripheral blood, CES1 expression was significantly higher in CD14++CD16- monocytes compared with CD14+CD16++ monocytes. In CD-inflamed colon, a higher number of mucosal CD68+ macrophages expressed CES1 compared with non-inflamed mucosa. In vivo, ESM-HDAC528 reduced monocyte differentiation in the colon and significantly improved colitis in a T cell transfer model, while having limited potential in ameliorating DSS-induced colitis. CONCLUSIONS: We demonstrate that monocytes and inflammatory macrophages specifically express CES1, and can be preferentially targeted by ESM-HDAC528 to achieve therapeutic benefit in IBD.

Selective Targeting of Epigenetic Readers and Histone Deacetylases in Autoimmune and Inflammatory Diseases: Recent Advances and Future Perspectives.

Histone deacetylases (HDACs) and bromodomain-containing proteins (BCPs) play a key role in chromatin remodeling. Based on their ability to regulate inducible gene expression in the context of inflammation and cancer, HDACs and BCPs have been the focus of drug discovery efforts, and numerous small-molecule inhibitors have been developed. However, dose-limiting toxicities of the first generation of inhibitors, which typically target multiple HDACs or BCPs, have limited translation to the clinic. Over the last decade, an increasing effort has been dedicated to designing class-, isoform-, or domain-specific HDAC or BCP inhibitors, as well as developing strategies for cell-specific targeted drug delivery. Selective inhibition of the epigenetic modulators is helping to elucidate the functions of individual epigenetic proteins and has the potential to yield better and safer therapeutic strategies. In accordance with this idea, several in vitro and in vivo studies have reported the ability of more selective HDAC/BCP inhibitors to recapitulate the beneficial effects of pan-inhibitors with less unwanted adverse events. In this review, we summarize the most recent advances with these strategies, discussing advantages and limitations of these approaches as well as some therapeutic perspectives, focusing on autoimmune and inflammatory diseases.

Optimization, Purification and Antitumor Activity of Kodamaea ohmeri ANOMY L-Asparaginase Isolated from Banana Peel.

OBJECTIVE: L-Asparaginase is an important enzyme that converts L-asparagine to L-aspartate and ammonia. Microbial L-asparaginase has important applications as anticancer and food processing agents. METHODS: This study reported the isolation, screening of a local yeast isolate from banana peel for L-asparaginase production using submerged fermentation, optimization of the production, purification, and anticancer assay of L-asparaginase. The yeast isolate was identified as Kodamaea ohmeri ANOMY based on the analysis of nuclear large subunit (26S) rDNA partial sequences. It was a promising L-asparaginase producer with a specific activity of 3059±193 U/mg in a non-optimized medium. The classical one-variable-at-a-time method was used to optimize the production medium components, and it was found that the elimination of K2HPO4 from the medium increased L-asparaginase specific activity (3100.90±180 U/mg). RESULTS: Statistical optimization of L-asparaginase production was done using Plackett-Burman and Box-Behnken designs. The production medium for the maximum L-asparaginase specific activity (8500±578U/mg) was as follows (g/L): L-asparagine (7.50), NaNO3 (0.50), MgSO4.7H2O (0.80), KCl (0.80) associated with an incubation period of 5 days, inoculum size of 5.60 %, and pH (7.0). The optimization process increased L-asparaginase production by 2.78-fold compared to the non-optimized medium. L-Asparaginase was purified using ammonium sulphate precipitation followed by gel filtration on a Sephadex G-100 column. Its molecular weight was 66 KDa by SDS-PAGE analysis. CONCLUSION: The cell morphology technique was used to evaluate the anticancer activity of L-asparaginase against three different cell lines. L-Asparaginase inhibited the growth of HepG-2, MCF-7, and HCT-116 cells at a concentration of 20, 50, and 60 µL, respectively.

Osteosynthesis in Neglected Femoral Neck Fracture in an Adolescent by Internal Fixation Alone - A Case Report.

INTRODUCTION: Femoral neck fractures are less frequent in adolescents. A neglected femoral neck fracture is one in which there has been a delay of more than 30 days from seeking medical attention from the time of injury [1]. The main complications are non-union and avascular necrosis (AVN) of femoral head. Various methods have been tried to successfully manage neglected femoral fractures. CASE REPORT: A 16-year-old boy presented with complains of pain over the right hip and inability to walk for the past 3 months, following a history of fall from a height of around 6 ft. He underwent native splinting from an indigenous native bone setter for 3 months. The splint was removed after 3 months, but the symptoms did not subside. He was diagnosed to have neglected femoral neck fracture and underwent open reduction and internal fixation with three 6.5 mm cannulated cancellous screws with washers. There were no post-operative complications. The patient recovered well. At 15 months follow-up, no clinical or radiological signs of AVN were observed with excellent functional outcome. CONCLUSION: The incidence of neglected femoral neck fractures is declining with improving health-care facilities in developing countries like India. Accurate anatomical reduction and internal fixation are important to reduce the incidence of AVN and non-union after a femoral neck fracture. Internal fixation of the fracture following valgus osteotomy is the most quoted technique in the literature.

Subarachnoid block with continuous TAP catheter analgesia produces less chronic pain and better functional outcome after inguinal hernioplasty: a randomized controlled observer-blinded study.

BACKGROUND AND OBJECTIVES: The major concern after inguinal hernioplasty is chronic postsurgical pain and impaired quality of life due to central sensitization. Preoperative, intraoperative, and postoperative pre-emptive analgesia using regional techniques may help prevent the development of central sensitization. This study evaluated the effect of regional anesthesia followed by continuous regional analgesia on postoperative pain and functional outcome following inguinal hernioplasty. METHODS: Seventy-two consecutive patients scheduled to undergo open mesh inguinal hernioplasty were randomly allocated to one of three groups: subarachnoid block alone (group SAB), general anesthesia alone (group GA), or subarachnoid block combined with a continuous transverse abdominis plane block (group TAP). Pain and functional outcome was assessed before and 6 months following the surgery using the Core Outcome Measures Index score adapted for patients with hernia (COMI-hernia). During the first 72 hours postoperatively, pain was assessed at rest and during five different activities using the numerical rating scale. RESULTS: Six months following the surgery, the COMI-hernia score was lower in group TAP than in group GA or group SAB (0.54±0.41 vs 0.88±0.43 and 1.00±0.54, respectively; p<0.02). Pain at rest (p<0.02) and during activities (p<0.001) was lowest in group TAP during the first 72 hours postoperatively. CONCLUSIONS: A subarachnoid block combined with continuous postoperative analgesia via a transverse abdominis plane catheter provided better pain control and functional outcome 6 months following inguinal hernioplasty as well as better postoperative analgesia. CLINICAL TRIAL REGISTRATION: CTRI/2016/09/007238.

Transcatheter Aortic Valve Implantation (TAVI): First Case in Bangladesh.

We came across an 81 years old male with symptomatic severe aortic stenosis. He was hypertensive and had history of CABG 9 years back. Due to his advanced age and co morbidities, he was at high surgical risk. He underwent transcatheter aortic valve implantation in our centre (United Hospital Ltd) in July 2017 and no complications occurred during or in the peri-procedural period. He had good functional and haemodynamic results at 3 months follow-up.

Comparison of Dexamethasone and Buprenorphine as Adjuvant in Ultrasound-guided Brachial Plexus Blocks: A Randomized Controlled Trial.

INTRODUCTION: Effective postoperative analgesia is imperative for orthopedic surgeries to enhance recovery and facilitate early ambulation. Various additives have been used as adjuvants with local anesthetics in peripheral nerve blocks to provide postoperative analgesia. The aim of this study is to compare the duration of postoperative analgesia with buprenorphine and dexamethasone when administered as an adjuvant during ultrasound-guided brachial plexus blocks. METHODOLOGY: Sixty adult patients undergoing various upper arm surgeries were recruited for the study after acquiring ethics committee clearance. They were randomized into two groups of thirty; Group B was given ultrasound-guided supraclavicular block with 10 ml 2% lignocaine with adrenaline and 15 ml 0.5% bupivacaine and 4 mg dexamethasone as adjuvant. Group B was given the same amount of local anesthetics with 0.3 mg buprenorphine as the adjuvant. The duration of postoperative analgesia and incidence of adverse events if any were noted. RESULTS: Both groups were comparable in demographics, time for onset of sensory, and motor block. The duration of postoperative analgesia was 17.4 ± 3.4 h in the buprenorphine group and 18 ± 3.49 h in the dexamethasone group. None of the patients had significant adverse effects. A single dose of buprenorphine and dexamethasone administered perineurally can provide significant postoperative analgesia for upper limb surgeries.

A Mesopore-Dependent Catalytic Cracking of n-Hexane Over Mesoporous Nanostructured ZSM-5.

Herein, pore size, crystalinity, and Si/Al ratio of mesoporous ZSM-5 (MFI) nanocrystals was controlled by synthesis parameters, such as surfactant concentration ([3-(trimethoxysilyl)propyl] hexa-decyl dimethyl ammonium chloride), sodium hydroxide concentrations, synthesis temperature and time. The morphology, surface structure and composition of the MFI particles was systematically investigated. More notably, the mesopore-dependent catalytic activity of ZSM-5 was evaluated by studying the cracking of n-hexane. The findings suggest the porosity has pronounced impact on the catalytic activity, selectivity and stability of ZSM-5 nanocrystals. Critical surface attributes such as nature of acid sites (Brønsted and Lewis), concentration, and strength are obtained by the infrared study of adsorbed probe molecules (pyridine) and the temperature programmed desorption. In spite of being weaker in Si/Al ratio or acidic strength, mesoporous catalysts showed more stable and efficient cracking of n-hexane suggesting that acidity seems not the predominant factor operative in the activity, selectivity and stability.

A novel fabrication methodology for sulfur-doped ZnO nanorods as an active photoanode for improved water oxidation in visible-light regime.

Incorporation of foreign moiety in the lattice of semiconductors significantly alters their optoelectronic behavior and opens a plethora of new applications. In this paper, we report the synthesis of sulfur-doped zinc oxide (S-doped ZnO) nanorods by reacting ZnO nanorods with diammonium sulfide in vapor phase. Microscopic investigation revealed that the morphological features, such as, the length (2-4 µm) and width (100-250 nm) of the original hexagonal ZnO nanorods remained intact post-sulfidation. X-ray photoelectron spectroscopy analysis of the sulfide sample confirmed the incorporation of sulfur into ZnO lattice. The optical measurements suggested the extension of absorption threshold into visible region upon sulfidation. Photoelectrochemical (PEC) activities of pure and S-doped ZnO nanorods were compared for water oxidation in visible light (λ > 420 nm), which showed several-fold increment in the performance of S-doped ZnO sample; the observed amelioration in the PEC activity was rationalized in terms of preferred visible light absorption and low resistance of sulfide sample, as evidenced by optical and electrochemical impedance spectroscopy.

Single-Pot Synthesis of ⟨001⟩-Faceted N-Doped Nb2O5/Reduced Graphene Oxide Nanocomposite for Efficient Photoelectrochemical Water Splitting.

Due to exciting catalytic activity and selectivity, tailoring of nanocatalysts consisting of preferred crystal facets and desired structural properties remains at the forefront of materials engineering. A facile one-step nonhydrolytic solvothermal synthesis of a nanocomposite of reduced graphene oxide and one-dimensional nitrogen-doped Nb2O5 (N-NbOx) with exposed ⟨001⟩ facet is described. Triethylamine performed the dual role as nitrogen source and capping agent to control the size and unidirectional growth of Nb2O5 nanocrystallites. The nanocomposite showed efficient visible-light-mediated (λ > 420 nm) water splitting in a photoelectrochemical cell. A plausible mechanism for the formation of N-NbOx nanorods and improved photoelectrochemical efficacy in terms of their oriented growth is proposed.

Evolution of treatment options for vein of Galen malformations.

OBJECT: Vein of Galen aneurysmal malformations (VGAMs) continue to account for high morbidity and mortality rates in the pediatric population. Whereas in the past, mortality rates were nearly 100%, recent developments in endovascular embolization and improvements in neonatal care have improved prognoses. It is now possible that some patients can achieve normal neurological development following embolization of the VGAM. Access to the lesion can be gained via transarterial or transvenous routes. In this paper the authors review the pathophysiological characteristics of VGAM and discuss the evolution of treatment options. METHODS: A PubMed literature search was performed for vein of Galen malformation treatment options, beginning in the 1970s. A total of 22 papers were reviewed in full, and outcome data for 615 patients from 1983 to 2010 were compiled. Articles were reviewed if they focused primarily on the treatment of VGAM and reported outcomes for at least 5 treated patients. RESULTS: Of the 265 patient outcomes reported between 1983 and 2000, 200 received endovascular therapy. Of these patients 72% had a favorable outcome, and a 15% mortality rate was found. Microsurgery was found to have an 84.6% mortality rate. Furthermore, 76.7% of untreated patients died. More recently, endovascular embolization has become the mainstay of VGAM treatment. Of the 350 patients assessed between 2001 and 2010, 337 were treated endovascularly, mostly via the transarterial approach. Of these patients, 84.3% were found to have good or fair outcomes, and a 15.7% mortality rate was found. Neonates had the worst clinical outcomes following endovascular treatment, with a 35.6% mortality rate, whereas infants and children had significantly better outcomes, with mortality rates of 6.5% and 3.2%, respectively. CONCLUSIONS: Endovascular embolization has considerably improved outcomes in patients with VGAM. In the past, the prognosis for patients with VGAM was dismal, and successful procedures were considered to be those that partially or completely obliterated the lesion, but did not necessarily improve the patient's symptoms. More recently, with the continued development and improvement of endovascular techniques, many patients are found to be neurologically normal on follow-up, and mortality rates have dropped substantially when compared with microsurgical treatment.

Detection of pancreatic adenocarcinoma using circulating fragments of fibrinogen.

BACKGROUND: There is an urgent need for biomarkers to detect pancreatic cancer in the early, potentially curable, stages. METHODS: We have used SELDI profiling to analyze serum from 75 patients with pancreatic cancer and 61 patients with nonmalignant pancreaticobiliary diseases. RESULTS: A peak in the SELDI spectra corresponding to a 53 residue fragment of the α-chain of fibrinogen is remarkably elevated in approximately 50% of the cancer patients. In addition, fibrinogen degradation products were measured using the DR-70 assay. The areas under the receiver operating characteristic curves for the SELDI-detected fibrinogen fragment, DR-70 and CA19-9 were 0.65, 0.75 and 0.86, respectively. Class prediction models using combinations of these markers did not increase the area under the receiver operating characteristic curve compared with CA19-9. The novel fibrinogen fragment was not elevated to the same extent in other malignancies but was elevated in some patients with benign pancreatic disease. CONCLUSION: Both the SELDI-detected fragment of fibrinogen and DR-70 are significantly elevated in the serum of pancreatic cancer patients. However, they do not seem to improve pancreatic cancer detection over CA19-9 alone.

Tissue responses of Clarias gariepinus (Catfish) to experimental Eimeria subepithelialis infection.

Coccidial infection is a common feature in most African fishes. As a result of the chronic nature of the disease in fish, mortality is gradual (Kim and Paperna, 1993a) and is often overlooked in most farms, with losses becoming evident only at the end of the production cycle. This study evaluates the tissue responses of Clarias gariepinus (Catfish) in an experimental infection with Eimeria subepithelialis using 200 laboratory-bred Juveniles. Four groups (A, B, C and D) of 50 Juveniles each were preconditioned for 2 weeks. Groups A and B were infected per os with 200 E. subepithelialis sporocysts per juvenile, while groups C and D served as uninfected controls. At the onset of demonstrable oocysts in liver and spleen tissues, groups B and C were treated for a week in Amprolium(R) dip (0.6 mg/L) at the rate of 1 h a day. Five fish from each group were culled at intervals of 3 days to study the tissue responses to infection. At gross pathological level, intestinal and testicular congestion, splenomegaly and hepatomegaly were the common features of the infection. Histological lesions in the infected and treated group (group B) were confined to the small intestine while extra-intestinal lesions were seen in the infected and untreated fish (group A). The presence of pathological lesions in tissues, following experimental infection of C. gariepinus with E. subepithelialis sporocysts, indicated that the parasite is pathogenic to the catfish. Contrary to coccidiosis of terrestrial animals, sporulation of oocysts in piscine coccidiosis appeared to occur endogenously within the host. The use of Amprolium in the control of piscine coccidiosis is effective only when used early in the course of the infection, prior to onset of clinical signs. Proper certification of brooder and replacement stock, improved plane of nutrition and adequate stocking density are recommended aquacultural practices that may minimize the incidence of visceral coccidiosis in cultured fish.

Naltrexone treatment in clomiphene resistant women with polycystic ovary syndrome.

BACKGROUND: Endogenous opiates may affect various aspects of reproductive and metabolic function in patients with polycystic ovary syndrome (PCOS). This study evaluated long-term inhibition of the opioid system using naltrexone in clomiphene citrate (CC)-resistant women with PCOS. METHODS: A group of 30 infertile females with PCOS were evaluated; all subjects were obese, hyperandrogenic and hyperinsulinemic; 16 patients were amenorrhic and 14 were oligomenorrhic. All subjects received natrexone (50 mg p.o. daily) for 6 months. Patients who did not ovulate after 12 weeks of naltrexone monotherapy, also received CC (starting at 50 mg/day for 5 days and, for non-responders, increasing it up to 150 mg/day). RESULTS: Of the 30 women, 3 ovulated during naltrexone monotherapy and 19 of the remaining 27 ovulated during naltrexone + CC therapy. There were no conceptions during naltrexone monotherapy, but 9 of 27 women (33.3%) conceived during naltrexone + CC; there was one missed abortion at 9 weeks, one preterm delivery at 34 weeks and seven term live births. Naltrexone therapy was also followed by significant reductions in BMI, fasting serum insulin, luteinizing hormone (LH), LH/follicle-stimulating hormone ratio and testosterone. CONCLUSIONS: In this preliminary trial, naltrexone improved endocrine and metabolic function in women with CC-resistant PCOS. Furthermore, naltrexone restored CC sensitivity in the majority of subjects, resulting in a significant number of pregnancies.