Treatment with the TGF-b superfamily cytokine MIC-1/GDF15 reduces the adiposity and corrects the metabolic dysfunction of mice with diet-induced obesity.

OBJECTIVES: To test the potential efficacy of recombinant macrophage inhibitory cytokine-1 (MIC-1/GDF15) as an obesity therapeutic. METHODS: Male C57BL/6 J mice, either fed on normal chow or high-fat diet for 16 weeks to induce diet-induced obesity, were infused with either recombinant MIC-1/GDF15 or vehicle for 34 days by osmotic minipump. During the experimental period metabolic parameters were measured. Blood and tissue were collected for analysis of inflammatory markers. RESULTS: MIC-1/GDF15 decreased food intake and body weight of high-fat-fed and chow-fed mice compared with their vehicle-treated control mice. MIC-1/GDF15 reduced body weight, accompanied by greater reduction in fat mass in high-fat-fed mice compared to its effect on chow-fed mice. Further, whilst MIC-1/GDF15-treated chow-fed mice lost lean as well as fat mass, MIC-1/GDF15-treated high-fat-fed mice lost fat mass alone. This reduction in body weight and adiposity was due largely to reduced food intake, but MIC-1/GDF15-treated high-fat-fed mice also displayed increased energy expenditure that may be due to increased thermogenesis. MIC-1/GDF15-treated high-fat-fed mice also had higher circulating level of adiponectin and lower tissue expression, and circulating levels of leptin and inflammatory mediators associated with insulin resistance. Peripheral insulin and glucose intolerance were improved in both MIC-1/GDF15-treated high-fat-fed and chow-fed mice compared to that of their vehicle-treated control mice. CONCLUSIONS: MIC-1/GDF15 is highly effective in reducing adiposity and correcting the metabolic dysfunction of mice with high-fat fed. These studies suggest that MIC-1/GDF15 may be a candidate anti-obesity therapeutic.

Evaluation of Anterolateral Plating of Distal Third Tibial Fractures.

Background Distal one-third tibial fractures with or without articular involvement can be difficult to manage. Variety of treatment methods have been suggested for these injuries, including conservative treatment, external fixation with or without limited internal fixation, intramedullary nailing, plate fixation (medial or anterolateral) and more recently minimally invasive plate osteosynthesis (MIPO). All of these techniques have advantages and disadvantages. None of these techniques can be considered the "gold standard" for these injuries. Objective The objective of this prospective study was to evaluate the results of anterolateral plating of these fractures. Method Forty-five fractures of distal third of tibia were treated with open reduction and internal fixation with anterolateral tibial plate from December 2011 to December 2016. All the patients were followed up at least for nine months for the study. Radiological union was finally assessed in nine months. Result All the fractures united within nine months of plating without angulation in sagittal or coronal plane. One patient (2%) had limb length shortening of more than one cm. Full range of motion of ankle and knee joint was achieved compared to the normal side by nine months follow up. 17 (38%) patients developed marginal skin necrosis. Three (7%) patients developed superficial wound infection. These complications were seen more in patients in whom posterior below knee slab was used for pre-operative splintage (as compared to calcaneal traction). Conclusion Hence distal one-third tibial fractures with or without articular involvement can be treated with anterolateral tibial plate.

Markers of Autolysis in Acute ST Elevation Myocardial Infarction.

INTRODUCTION: The availability of reliable noninvasive markers for infarct-related artery (IRA) patency status are very limited, otherwise could allow early identification of patients with patent IRA, for whom repeat thrombolysis or rescue percutaneous coronary intervention (PCI) are not necessary. METHODS: We conducted a single centered retrospective study of STEMI patients undergoing primary PCI to determine how various factors such as demographic characteristics, risk markers of coronary heart disease, clinical and blood parameters present differently in patients with higher coronary flow and patent infarct related artery from patients with total occlusion at the time of initial angiography and how they affect in outcome of the disease. RESULTS: MPV level (11.96 fL vs. 10.92 fL, P < 0.001), Lp (a) level (179.57 nmol/l vs 141.16 nmol/l , p < 0.001), CK-MB (290.2 vs. 190.98, P < 0.001), total cholesterol level (4.11 mmol/L vs. 3.8 mmol/L, p < 0.02) in total occlusion group were higher than in the patent IRA group. Wall motion abnormality was 77.2% for 203 patients with total occlusion group and 54.2% for 83 patients with patent IRA group (P<0.01). Mean hospital stay days were higher in total occlusion group as compared to the patent IRA group P < 0.01. CONCLUSIONS: MVP, Lp (a), TC, and CK-MB levels and myocardial wall motion at the presentation may play the role of markers for IRA patency status that will help in early identification of patients with IRA, for whom repeat thrombolysis or rescue PCI may not be required.

A randomized study comparing intravaginal prostaglandin (PGE2) with oxytocin for induction of labour in premature rupture of membrane at term.

This is a prospective randomized study conducted in Tribhuvan University Teaching Hospital from February 2008 to January 2009. Total 72 women with Premature rupture of membranes (PROM) were included. Thirty-six women received PGE2 vaginal gel and thirty-six received iv oxytocin. Induction was successful in majority of cases in both the groups; 88.8% in PGE2 and 83.3% in oxytocin group (p value = 0.063). Time duration from induction to active stage was comparable (p value = 0.273). Induction to delivery interval was significantly low in oxytocin group (p value = 0.002) but leaking to delivery interval was similar in both the groups (p value = 0.083). PGE2 had slightly higher side effect than oxytocin. PGE2 and oxytocin were both effective and safe for induction of labour in women with PROM at term. There was no significant difference in maternal and fetal outcome, hospital stay, leaking to delivery interval, maternal and neonatal side effects, though induction to delivery interval was significantly less with oxytocin.

Open reduction and internal fixation of supracondylar fractures of the humerus: revival of the anterior approach.

INTRODUCTION: Supracondylar fractures of the humerus occur commonly in the paediatric age group. Gartland type III fractures are treated by closed manipulation and percutaneous pinning with K-wires. Open reduction is indicated in open fractures, failed closed reductions and in a dysvascular limb. There are various approaches that can be utilized to perform an open reduction. The approach of choice must be safe, surgeon and patient friendly and should provide a good access to the fracture and the important surrounding structures. The anterior approach has been described as the most versatile approach. The aim of the study was to review the advantages and drawbacks of the anterior approach and to assess the functional outcome of fractures treated via this approach. MATERIALS AND METHODS: Twenty five (15 male and 10 female) patients out of a hundred and twenty eight children with Gartland type III extension variety of supracondylar fractures of the humerus from underwent open reduction and internal fixation with K-wires via an anterior approach January 2007 to January 2011. The results were assessed at six months using Flynn's radiological and clinical criteria. RESULTS: Twenty five patients (19.53%) out of hundred and twenty eight patients underwent open reduction and internal fixation. According to Flynn's clinical and radiological criteria, 20 (80%) were found to have excellent and 5 (20%) good results. CONCLUSION: The anterior approach is safe, easy and provides direct exposure of the surrounding neurovascular structures with good to excellent results.

Functional outcome of operatively treated displaced intra-articular calcaneal fractures using two parallel contoured reconstruction plates.

INTRODUCTION: The treatment of displaced intra-articular calcaneal fracture is controversial. Conventionally, they were treated non-operatively. However, some surgeons are now operatively treating these fractures because of continuing dissatisfaction with the outcome of conservative treatment of these fractures and improvements that have occurred in surgical techniques and complication rates. OBJECTIVE: The aim of this study was to determine the functional outcome of operatively treated displaced intra-articular calcaneal fractures using two parallel contoured reconstruction plates. MATERIALS AND METHODS: 12 patients with 14 displaced intra-articular calcaneal fractures involving the subtalar joint were included in the study conducted between July 2005 and December 2008. The fracture site was exposed using extended lateral approach. Internal fixation was done by two nearly parallel 3.5mm reconstruction plates and screws contoured to form a gentle curve in all cases with the fi rst plate fixed just below the articular surface. At the end of follow up, the patients' foot function was assessed by Calcaneal Fracture Scoring System of Kerr et al. Patients were also inquired about their satisfaction with their treatment outcome. RESULTS: The patients were followed up for duration of 12 to 24 months (mean 15.64 months). The outcome score as measured by Calcaneal Fracture Scoring System ranged from 48 to 94 (mean 83.64). 11 of 12 patients (91.6 %) were satisfied with the treatment. CONCLUSION: Displaced intra-articular fractures treated by open reduction and internal fixation, using two nearly parallel, contoured reconstruction plates through an extensile lateral approach and following the principles of treatment of intraarticular fractures, have good functional results with high patient satisfaction rate.

Osteosynthesis of intercondylar humerus fracture using Bryan and Morrey approach.

BACKGROUND: The olecranon approach has been the gold standard for surgical approaches to fracture fixation of distal articular surface of humerus. Although it provides a good exposure, it also has disadvantages of delayed union, nonunion and implant related complications at the osteotomy site. OBJECTIVE: The aim of this study was to determine the functional outcome of displaced intra-articular distal humerus fracture fixation using an alternative approach: the Bryan and Morrey approach. MATERIALS AND METHODS: Twenty patients with twenty AO type C1 and C2 intercondylar fractures of the distal humerus had bicolumnar fixation of the distal humerus with two contoured reconstruction plates and screws on the dorsal surface or various combinations of a single reconstruction plate, screws and K-wires using a Bryan and Morrey approach. Twelve of the patients were male and eight were female. The average age of the patients was 44.8 years. Eleven patients had sustained the injury as result of fall and nine of the patients had sustained it in road traffic accidents. Right elbow was involved in fifteen patients and left in five. All patients were followed up for 12 months post operatively. RESULTS: All twenty fractures had united at 4 months follow-up. The mean fixed flexion deformity was 9.0º (range 0º-15º) and the mean arc of motion was 115.0 º (range 85 º- 130º). All patients had grade 4 triceps strength and stable elbows at the end of 12 months follow up. One patient had deep seated wound infection resulting in necrosis of the triceps tendon requiring a second operative procedure. CONCLUSIONS: Bryan and Morrey approach is a simpler, easier and better approach as compared to the other posterior approaches to the elbow joint, and therefore, can be used as the approach of choice for fixation of fractures of the distal articular surface of humerus.

Comparative susceptibility of two banana cultivars to Banana bunchy top virus under laboratory and field environments.

Field and laboratory experiments were carried out on the island of Oahu, HI, to compare the susceptibility of the two most commonly grown banana (Musa sp.) cultivars in the state ('Dwarf Brazilian' or Santa Catarina [locally known as dwarf apple] and 'Williams') to the aphid-borne Banana bunchy top virus (genus Babuvirus, family Nanoviridae, BBTV). Several morphological and physiological features of the two cultivars were monitored to determine whether the banana aphid, Pentalonia nigronervosa Coquerel (Hemiptera: Aphididae), transmits BBTV to both cultivars at a similar rate; and whether after successful inoculation, does each cultivar respond similarly to viral infection. Results from the laboratory experiment showed that a similar percentage of both cultivars were infected with BBTV by aphid vectors (> 90% for both cultivars). However, field results showed a significantly lower percentage of dwarf apple (39%) infected with BBTV compared with Williams (79%). We also found that all physiological and morphological features measured (i.e., plant height, leaf area, canopy, chlorophyll level, and moisture content) for both cultivars were impacted similarly by BBTV. The incubation period, or the time between plant infection and initial appearance of disease symptoms, was similar for both cultivars. Results also showed that BBTV transmission efficiency was lower in the field than in the laboratory, despite that more aphids per plant were used for field than laboratory inoculation tests. The results highlight the potential use of less susceptible cultivars to help manage BBTV and the importance of screening banana varieties in the field to determine their response to vectors and associated diseases.

Conservative treatment of nonarticular fractures of distal third tibia.

INTRODUCTION: Distal one third tibial fractures can be difficult to manage. Variety of treatment methods have been suggested for these injuries, including conservative treatment, external fixation, intramedullary nailing, and plate fixation. None of these techniques can be considered the "gold standard" for these injuries. The purpose of this prospective study is to evaluate the results of conservative treatment of these fractures. METHODS: Total 39 fractures of distal third of tibia were treated with closed reduction and long leg cast for six to eight weeks followed by PTB cast for six to eight weeks from January 2004 to October 2008. One year follow up was done with 32 patients, eight months follow up with three patients and four patients were lost to follow up. RESULTS: All the fractures united within six months of duration. Immediate post-reduction average angulation was 3.72 degree in sagital plane and 3.32 degree in coronal plane. Average final angulation was 5.04 degree in sagital plane and 4.32 degree in coronal plane. Average limb length shortening was 6.8 mm. Full range of motion of ankle and knee joint was achieved compared to the normal side by six months of follow up. Though there was displacement of fracture during conservative treatment final outcome was within acceptable limit. CONCLUSION: Hence distal one third tibial fractures can be treated conservatively with closed reduction and cast immobilization with numerous advantages over operative methods.

External and internal fixation for comminuted intra-articular fractures of distal radius.

BACKGROUND: Distal radius fractures are a common injury and without proper treatment leads to high functional impairment and frequent complications. OBJECTIVE: The aim of this study was to see the functional outcome in patients with comminuted distal radius fractures treated with combined external fixation and open reduction and volar plating. MATERIALS AND METHODS: All comminuted distal radius fractures classified as type C in AO/OTA classification were enrolled for the study from 2005 till 2008. The clinical scoring chart modified by Cooney was used to evaluate the functional outcome. RESULTS: There were twenty-two patients with the average age of 42.18 years (range 19-60) with 15 male and 7 females. The follow-up period was from 14 to 46 months. Accordingly, there were 11 (50%) excellent, 7 (31%) good, 2 (9%) fair and 2 (9%) poor results. There were very few complications in our series. In three patients additional K-wire supplementation was necessary along with external and open internal fixation. CONCLUSIONS: Comminuted intra-articular fractures of distal radius should be treated by open reduction and combined internal and external fixation to achieve a high rate of patient satisfaction and satisfactory functional outcome.

Sub-trochanteric fractures of the femur: results of ORIF at KMCTH.

Sub-trochanteric fractures of the femur are not commonly encountered as compared to trochanteric or neck of femur fractures. Relatively younger persons are injured more and a considerable violence is required for this fracture to occur. These fractures, treated conservatively by methods like traction, splints or casts, are often associated with complications like non-union, mal-union, shortening of the limb etc. Thus, we undertook this study of 10 consecutive cases of sub-trochanteric fractures of the femur treated by open reduction and internal fixation and bone grafting in Kathmandu Medical College Teaching Hospital, Sinamangal, from the year Nov. 2000 to April 2006. There were 4 females and 6 male patients. Their age on average was 46.8 years (range 15 to 86 years). Most of the patients were in Type II or III in Seinsheimer classification; Type II A, B, and C, one, two and one respectively, and in Type III A and B three patients each. Seven patients were treated with dynamic hip screw. Three patients with type III were managed with centro-medullary interlocking nail with one cerclage suture. They were followed for a period of minimum 6 months to 6 years (average 3.5 years). Union was achieved in all, on an average 4 months postoperatively. Results were excellent and complications like nonunion, malunion or breakage of the implants, were not encountered in any patient.

Percutaneous extensor tenotomy for chronic tennis elbow using an 18G needle.

INTRODUCTION: Tennis elbow is a common orthopaedic problem presenting in office orthopaedics, but its exact patho-aetiology has not been identified to date. It is treated operatively when conservative measures including multiple local steroid injections are not helpful to the patients. MATERIAL AND METHOD: This was a retrospective study to assess the outcome of tennis elbow patients on whom percutaneous release of the common extensor origin was performed using an 18 gauge hypodermic needle. 17 patients with 21 elbows were included in the study. Data was collected by going through the patients' medical records, and follow -up by questionnaire mailed to the patient's home, to assess the outcome and patient satisfaction with the procedure. RESULTS: 14 of the 21 (66.7%) elbows became completely pain free. The time taken to achieve a completely pain free elbow ranged from 1 day to 3 months (average 60.3 days). Those that did not achieve a pain free elbow had a residual pain of 1.5 to 8.5 on the VAS (average 2.64). 9 elbows (42.9%) had an excellent outcome, 7(33.3%) had good, 4(19%) had satisfactory and 1(4.8%) had poor outcomes. CONCLUSION: Tennis elbow probably results from degenerative tear of common extensor origin and a percutaneous tenotomy using an 18 gauge hypodermic needle is a simple, safe, patient friendly, effective and easily reproducible method of treating it in those who require surgery and can be done as an office procedure.

High levels of inflammatory cytokines are associated with poor clinical response to steroid treatment and recurrent episodes of type 1 reactions in leprosy.

Levels of leprosy antigen-induced interferon-gamma (IFN-gamma), tumour necrosis factor alpha (TNF-alpha) and interleukin-10 (IL-10) were measured in 96 leprosy patients with type 1 reactions (T1R) before, during and after a standard 12-week course of steroids. Peripheral blood mononuclear cells (PBMC) from leprosy patients with untreated T1R produced significantly more TNF-alpha than leprosy patients without T1R. Median levels of IFN-gamma and TNF-alpha in T1R patients fell during treatment with steroids; however, TNF-alpha levels increased as the steroid dose was reduced. Median IL-10 levels increased throughout the steroid treatment period and were associated strongly with TNF-alpha levels. Patients with high cytokine levels had a poorer recovery of sensory or voluntary muscle nerve function, a higher risk of reactivation of symptoms during steroid treatment, and a higher risk of another episode of T1R within 2 months of completing the steroid regimen. Rapid and effective reversal of the inflammatory process in T1R is critical to prevent permanent nerve damage from T1R and monitoring cytokine levels during treatment may be useful.

Application of constructed wetlands for wastewater treatment in Nepal.

Surface water pollution is one of the serious environmental problems in urban centers in Nepal due to the discharge of untreated wastewater into the river-system, turning them into open sewers. Wastewater treatment plants are almost non-existent in the country except for a few in the Kathmandu Valley and even these are not functioning well. Successful implementation of a few constructed wetland systems within the past three years has attracted attention to this promising technology. A two-staged subsurface flow constructed wetland for hospital wastewater treatment and constructed wetlands for treatment of greywater and septage is now becoming a demonstration site of constructed wetland systems in Nepal. Beside these systems, five constructed wetlands have already been designed and some are under construction for the treatment of leachate and septage in Pokhara municipality, wastewater in Kathmandu University, two hospitals and a school. This paper discusses the present condition and treatment performance of constructed wetlands that are now in operation. Furthermore, the concept of the treatment wetlands under construction is also described here. With the present experience, several recommendations are pointed out for the promotion of this technology in the developing countries.

A postgenomic approach to identification of Mycobacterium leprae-specific peptides as T-cell reagents.

To identify Mycobacterium leprae-specific human T-cell epitopes, which could be used to distinguish exposure to M. leprae from exposure to Mycobacterium tuberculosis or to environmental mycobacteria or from immune responses following Mycobacterium bovis BCG vaccination, 15-mer synthetic peptides were synthesized based on data from the M. leprae genome, each peptide containing three or more predicted HLA-DR binding motifs. Eighty-one peptides from 33 genes were tested for their ability to induce T-cell responses, using peripheral blood mononuclear cells (PBMC) from tuberculoid leprosy patients (n = 59) and healthy leprosy contacts (n = 53) from Brazil, Ethiopia, Nepal, and Pakistan and 20 United Kingdom blood bank donors. Gamma interferon (IFN-gamma) secretion proved more sensitive for detection of PBMC responses to peptides than did lymphocyte proliferation. Many of the peptides giving the strongest responses in leprosy donors compared to subjects from the United Kingdom, where leprosy is not endemic, have identical, or almost identical, sequences in M. leprae and M. tuberculosis and would not be suitable as diagnostic tools. Most of the peptides recognized by United Kingdom donors showed promiscuous recognition by subjects expressing differing HLA-DR types. The majority of the novel T-cell epitopes identified came from proteins not previously recognized as immune targets, many of which are cytosolic enzymes. Fifteen of the tested peptides had > or =5 of 15 amino acid mismatches between the equivalent M. leprae and M. tuberculosis sequences; of these, eight gave specificities of > or =90% (percentage of United Kingdom donors who were nonresponders for IFN-gamma secretion), with sensitivities (percentage of responders) ranging from 19 to 47% for tuberculoid leprosy patients and 21 to 64% for healthy leprosy contacts. A pool of such peptides, formulated as a skin test reagent, could be used to monitor exposure to leprosy or as an aid to early diagnosis.

Interferon-gamma responses to candidate leprosy skin-test reagents detect exposure to leprosy in an endemic population.

New tools for the detection of leprosy exposure in a community will be necessary for the eradication of leprosy. Candidate leprosy skin-test antigens derived from the fractionation of the leprosy bacillus into cytoplasmic and cell-wall proteins free of immuno-inhibitory mycobacterial lipoglycans and carbohydrates were used in an overnight blood test to determine whether exposure to leprosy can be detected by the production of the cytokine interferon gamma (IFN-gamma). Strong IFN-gamma responses were detected in leprosy contacts to both skin-test antigens compared with control subjects from the same endemic communities. There was little response in patients with tuberculosis. Responses were greatest in contacts with recent leprosy exposure. The implications of these findings for the application of these reagents in a field trial as skin tests to detect exposure to leprosy are discussed in light of the strong association between overnight IFN-gamma to PPD and the tuberculin skin-test responses previously reported.

Strong human immunodeficiency virus (HIV)-specific CD4+ T cell responses in a cohort of chronically infected patients are associated with interruptions in anti-HIV chemotherapy.

Virus-specific CD4+ T-helper cell function is important in controlling human immunodeficiency virus (HIV) infection but is impaired in patients with progressive HIV disease. It has been reported that after highly active antiretroviral therapy (HAART), HIV-specific lymphoproliferative responses remain absent, whereas responses to non-HIV microbial antigens are restored. However, in analyzing immune responses in a cohort of chronically infected adults on HAART, we observed strong HIV-specific CD4+ T cell responses of Th-1 phenotype in 11 of 22 patients. The magnitude and frequency of HIV-specific lymphoproliferative responses was strongly associated with previous interruptions in HAART (P=.001). In contrast, the magnitude of CD8+ T cell responses to HIV Gag, Pol, Env, and Nef was similar in patients who had and those who had not interrupted HAART. We conclude that (1) a significant proportion of chronically HIV-infected patients on HAART can generate strong HIV-specific CD4+ and CD8+ T cell immunity and (2) transient interruptions in antiviral treatment may prime or boost HIV-specific CD4+ T-helper responses.

Risk factors for erythema nodosum leprosum.

A retrospective study of new borderline lepromatous and lepromatous patients reporting for multidrug therapy (MDT) for leprosy at the Anandaban Leprosy Hospital, Kathmandu, Nepal, over an 8-year period was conducted to determine the prevalence of erythema nodosum leprosum (ENL), the time and frequency of reactions, and clinical and laboratory parameters associated with ENL. An overall prevalence of ENL in this cohort of 19% was found. One third of these reactions occurred in patients before MDT was given, one third in the first 6 months and one third after 6 months of treatment. Nearly 1 in 10 of the ENL reactions occurred in patients who had completed 2 years of MDT; 45% of patients with ENL had more than one episode. Data collected at the patients' first presentation was used to identify four major risk factors. Patients with lepromatous disease, skin infiltration or a bacterial index (BI) of > 4+ were at significantly increased risk. Patients older than 40 were at significantly decreased risk of ENL. There was a linear relationship in the risk of ENL with an increasing BI and an inverse relationship to increasing age. These observations should enable clinicians to recognize patients at first presentation who will be likely to develop ENL.

Toxoplasma antibody prevalence in Nepalese pregnant women and women with bad obstetric history.

Sera from randomly selected 345 pregnant Nepalese women aged 16-36 years and 13 women with bad obstetric history (BOH) were tested for the presence of Toxoplasma antibodies using microlatex agglutination (MLA) and ELISA methods. The overall prevalence was 55.4% (191/345). Prevalence was slightly higher (59.0%) in older age-group (27-36 years) compared with younger age-group (16-26 years) (52.2%). No significant difference in antibody prevalence in women belonging to two different ethnic-groups (Tibeto-Burmans 57.8%, Indo-Aryans 52.7%) was observed (p>0.05). MLA antibody titer ranged from 1:16 to 1:2,048. Over three-fourth of the women showed either high (1:510 or over) or low (1:16 or 1:32) antibody titer. Three percent (6/191) of MLA antibody positive subjects had Toxoplasma IgM antibodies by IgM-ELISA. All six IgM antibody positive pregnant women had MLA antibody titer of over 1:510. Of the total 13 women with BOH, 5 (38.5%) had Toxoplasma antibodies of which 2 (40.0%) were positive for Toxoplasma-IgM antibodies.