A convenient way to do valgus osteotomy for neglected fracture neck of femur.

BACKGROUND: Neglected fracture of neck of femur in young adults is a major problem in developing countries. Existing treatment options varies from osteotomy to various graft techniques (muscle pedicle, vascularized and nonvascularized fibula etc.). There is paucity of literature regarding the use of double angle barrel plate and hip screw in such cases. We conducted a prospective longitudinal observational study with displaced, neglected fracture neck of femur in young adults and compared the results with literature. OBJECTIVES: The aim of this study was to determine feasibility and effectiveness of 120° double angle barrel plate and hip screw fixation in neglected fracture neck of femur. Effectiveness of fixed 30 degree closed wedge osteotomy in neglected fracture neck of femur. METHODS: Thirty cases of neglected (more than three weeks) femoral neck fracture (Pauwel II and III) of age 20-60 years were included in the study conducted at Postgraduate Institute Of Medical Education and Research, Dr. Ram Manohar Lohia Hospital, New Delhi, India in year 2004-06. Average age of the patient was 35.4 years (range, 22yrs-55yrs). In all cases internal fixation was done by 120° double angle barrel plate and hip Screw. At the end of follow-up, results were evaluated according to Askin Bryan Criteria and Harris-hip score. RESULTS: Union was achieved in 28 of 30 patients. Two patients that went into nonunion were later treated with hemireplacement arthroplasty. According to Askin Bryan Criteria at the end of study, 35% patients had excellent results, 50% patients had good results. Minimum follow-up in our study was 12 months and maximum was five years. CONCLUSION: This study validates the use of double angled screw plate configuration for successful outcome in patients with neglected fracture neck of femur. Valgus osteotomy is also technically easy operation in hands of average trauma surgeon with the use of a fixed angle plate and hip screw.

AZD9668: pharmacological characterization of a novel oral inhibitor of neutrophil elastase.

N-{[5-(methanesulfonyl)pyridin-2-yl]methyl}-6-methyl-5-(1-methyl-1H-pyrazol-5-yl)-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2-dihydropyridine-3-carboxamide (AZD9668) is a novel, oral inhibitor of neutrophil elastase (NE), an enzyme implicated in the signs, symptoms, and disease progression in NE-driven respiratory diseases such as bronchiectasis and chronic obstructive pulmonary disease via its role in the inflammatory process, mucus overproduction, and lung tissue damage. In vitro and in vivo experiments were done to evaluate the binding kinetics, potency, and selectivity of AZD9668, its effects in whole-blood and cell-based assays, and its efficacy in models of lung inflammation and damage. In contrast to earlier NE inhibitors, the interaction between AZD9668 and NE was rapidly reversible. AZD9668 was also highly selective for NE over other neutrophil-derived serine proteases. In cell-based assays, AZD9668 inhibited plasma NE activity in zymosan-stimulated whole blood. In isolated human polymorphonuclear cells, AZD9668 inhibited NE activity on the surface of stimulated cells and in the supernatant of primed, stimulated cells. AZD9668 showed good crossover potency to NE from other species. Oral administration of AZD9668 to mice or rats prevented human NE-induced lung injury, measured by lung hemorrhage, and an increase in matrix protein degradation products in bronchoalveolar lavage (BAL) fluid. In an acute smoke model, AZD9668 reduced the inflammatory response to cigarette smoke as indicated by a reduction in BAL neutrophils and interleukin-1ß. Finally, AZD9668 prevented airspace enlargement and small airway wall remodeling in guinea pigs in response to chronic tobacco smoke exposure whether dosed therapeutically or prophylactically. In summary, AZD9668 has the potential to reduce lung inflammation and the associated structural and functional changes in human diseases.

Impact of COVID-19 on Clinical Practices during Lockdown: A pan India Survey of Orthopaedic Surgeons.

INTRODUCTION: The social lockdown measures imposed to contain the COVID-19 pandemic, have had profound effects on the healthcare systems across the world and India has been no exception to it. The study was aimed to evaluate the impact of COVID-19 on orthopaedic practice in India during the lockdown period and assess the preparedness of orthopaedic surgeons for resuming clinical practice after the initial lockdown was lifted. MATERIALS AND METHODS: An online survey of 35 questions was conducted to evaluate impact on (i) general orthopaedic practice (ii) hospital protocols (iii) out-patient practice (iv) surgical practice (v) personal protective equipment (PPE) use and (vi) post-lockdown preparedness. RESULTS: A total number of 588 practising orthopaedic surgeons from India completed the survey. Majority (88.3%) found severe impact (>50%) on trauma surgery and non-trauma surgery with significant reduction in out -patient attendance compared to corresponding time in 2019. There were significant changes made in individual hospital protocols (91.7 %). Appropriate required PPE was available in majority of the hospitals (74.3%). No remodelling or upgrading of the existing operating theatre infrastructure was done by most surgeons (89.5%). CONCLUSION: This pan India survey of orthopaedic surgeons has indicated that COVID-19 has had a profound impact on their outpatient and surgical trauma and non-trauma practice, due to the lockdown and resulted in significant changes to hospital protocols. Preparedness to resume clinical and surgical practice was associated with anxiety in two-thirds of the respondents. Majority of the orthopaedic practitioners felt that they would continue to conduct pre-operative COVID-19 screening and use PPE even after the lockdown is over.

Treatment of neglected elbow dislocations with combination of speed V-Y muscleplasty and intra-articular injection of hydrocorticosone.

Neglected dislocations of the elbow are not uncommon in developing countries. We report case series of 3 cases of neglected dislocations of elbow. All the three cases were treated by combination of Speeds procedure and intraarticular injection of 25mg of hydrocorticosone acetate in 5 ml of distilled water. Mean time from injury was 5 months and mean follow-up was 10 months. According to Mayo Elbow Performance Index, 2 outcomes were excellent and 1 outcome was good.

Clinical profile and outcomes of De novo posttransplant thrombotic microangiopathy.

Thrombotic microangiopathy (TMA) after kidney transplant is rather uncommon but an important reversible cause of graft loss. This retrospective study of biopsy-proven posttransplant TMA was done to identify the important etiological factors, clinical features, and outcomes of post transplant TMA in a tertiary care referral hospital in northern India. This retrospective study was conducted among all renal transplant recipients who presented with graft dysfunction between 1989 and 2015. All the cases were looked for their etiology, clinical course, treatment modalities, and renal outcomes. The study was conducted in accord with prevailing ethical principles and reviewed by our own institutional review board. Seventeen patients out of 2000 (0.008%) transplants done during the study period had posttransplant TMA, out of which all the patients had de novo TMA, and the median time of presentation after transplantation was four months. Systemic TMA was noted in only four patients. Biopsy revealed associated rejection in five patients and associated calcineurin inhibitor (CNI) toxicity in 12 patients. Patients with TMA due to CNI toxicity were managed with CNI reduction or switching to alternate CNI or mammalian target of rapamycin inhibitors. In addition, antithymocyte globulin and plasma exchange were used in rejection-associated TMA. While four out of 12 patients (33%) in CNI-related TMA developed end-stage renal disease (ESRD), all patients in rejection-associated TMA developed ESRD. The overall one-year graft survival was 47%, whereas five- and 10-year survival was 35%. There was no significant difference in graft survival between localized and systemic TMAs (P = 0.4). Posttransplant TMA should be suspected even if there are no systemic features of hemolysis and early graft biopsy and prompt action is needed. The occurrence of TMA in the setting of rejection is associated with grave prognosis.

Influence of diabetes on liver injury induced by antitubercular drugs and on silymarin hepatoprotection in rats.

Isoniazid, rifampicin and pyrazinamide during short-course chemotherapy for tuberculosis can result in liver injury. The coexistence of tuberculosis and diabetes is common in patients who receive inadequate treatment. The risk of hepatotoxicity from many toxicants is increased in diabetic rats. Silymarin provides protection against liver injury caused by many hepatotoxicants, including antitubercular drugs (ATDs). In the wake of increased severity of ATD-induced hepatotoxicity in diabetes we report here the results of a study on the influence of diabetes on silymarin hepatoprotection in rats. Rats with diabetes induced via intraperitoneally injected streptozotocin (50 mg/kg), nondiabetic rats and insulin-treated diabetic rats received isoniazid (7.5 mg/kg/day), rifampicin (10 mg/kg/day) and pyrazinamide (35 mg/kg/day) orally (p.o.) with or without silymarin (100 mg/kg/day p.o.) treatment for 45 days. Compared to nondiabetic rats, liver function tests and histological changes of liver revealed exaggerated liver injury in diabetic rats caused by ATDs which was evident by 5- to 8-fold increases in serum levels of marker enzymes (aspartate and alanine aminotransferase, alkaline phosphatase and gamma-glutamyltranspeptidase) and 1- to 2-fold increases in bilirubin accompanied by a 2-fold decrease in total serum proteins, intense fatty and inflammatory infiltrations, necrosis and fibrosis. Coadministration of silymarin provided protection against ATD hepatotoxicity in all animals. However, insulin-treated diabetic animals showed greater silymarin-induced hepatoprotection against ATD-induced liver injury, which was characterized by near normal levels of marker enzymes, an increase in total proteins and normal hepatic structure. These results thus indicate that diabetes exaggerates ATD-induced liver injury and attenuates silymarin-induced hepatoprotection. However, insulin treatment for diabetes offers greater silymarin-induced hepatoprotection against ATD-induced liver injury.

Late Posttransplant Lymphoproliferative Disease: Report of a Rare Case and Role of Positron Emission Tomography-computed Tomography.

Posttransplant lymphoproliferative disease (PTLD) is an uncommon complication of immunosuppression after solid organ transplantation. Early PTLD (<1 year after transplantation) is frequently found around the allograft, whereas late PTLD (>1 year after transplantation) does not have such a preference. 18-Fluorodeoxyglucose positron emission tomography-computed tomography (18FDG PET-CT) has clinical significance in the evaluation of PTLD. 18FDG PET-CT scan allows precise anatomic localization of FDG-avid lesions, hence helpful in staging of disease and evaluation of response to therapy. It can better characterize persistent lesions and differentiate residual tumor from fibrosis or necrosis. We present a rare case report of a perigraft PTLD developing 12 years after renal transplantation sparing the graft, in an Epstein-Barr virus-negative patient.

Role of Preoperative Duplex Ultrasonography to Predict Functional Maturation of Wrist Radiocephalic Arteriovenous Fistula: A Study on Indian Population.

Radiocephalic arteriovenous fistula (RCAVF) is the first choice for native arteriovenous fistula (AVF). Preoperative vessel assessment with ultrasonography (USG) has been reported to enhance the outcome of native AVF, but data regarding its predictive value for functional maturation of RCAVF are scanty. We aimed to determine the role of preoperative duplex USG (DUS) for prediction of functional maturity of radiocephalic fistula in the wrist. The data from 173 patients were analyzed prospectively. The estimated duplex variable included size, patency, and continuity of cephalic vein and size, peak systolic velocity, and wall calcifications in radial artery at the wrist. The subjects underwent RCAVF creation and were reviewed 6-8 weeks post procedure for adequacy of maturation. Doppler variables between successful and failed maturation groups were compared. Successful functional fistula maturation was noted in 138 (80.9%) patients. Values of radial artery diameter, cephalic vein diameter, and peak systolic velocity were >2 mm, 2.2 mm, and 32.8 cm/s, respectively, for successful maturation of RCAVF in more than 90% of cases. Vascular calcifications were detected preoperatively in 15 diabetic patients and 9 (60%) of them had fistula failure. Preoperative DUS can provide a good prediction on functional maturation of RCAVF. Vascular calcifications were associated with high risk of maturation failure in diabetics.

Postrenal Transplant Metastatic Colonic Neoplasm: Posttransplant Lymphoproliferative Disorder or Adenocarcinoma?

Transplant recipients are vulnerable to a horde of infections and neoplastic conditions due to immunosuppression. Posttransplant lymphoproliferative disorder (PTLD) is a condition unique to the transplant recipient occurring due to monoclonal lymphocytic proliferation. It may affect any organ system with reportedly highest incidence in the gastrointestinal tract. The incidence of adenocarcinoma of the colon, however, has not been shown to be uniformly higher in transplant recipients. We report here an unusual case of adenocarcinoma of the ascending colon presenting with liver, lymph node and skin metastasis in a transplant recipient, which simulated PTLD both clinically and radiologically. For any gastrointestinal lesion in transplant recipient, the possibility of carcinoma must be considered. However, a high index of suspicion for PTLD facilitates early diagnosis since the treatment of the two conditions is starkly different.

Impact of COVID-19 on Clinical Practices during Lockdown: A pan India Survey of Orthopaedic Surgeons

@#Introduction: The social lockdown measures imposed to contain the COVID-19 pandemic, have had profound effects on the healthcare systems across the world and India has been no exception to it. The study was aimed to evaluate the impact of COVID-19 on orthopaedic practice in India during the lockdown period and assess the preparedness of orthopaedic surgeons for resuming clinical practice after the initial lockdown was lifted. Materials and Methods: An online survey of 35 questions was conducted to evaluate impact on (i) general orthopaedic practice (ii) hospital protocols (iii) out-patient practice (iv) surgical practice (v) personal protective equipment (PPE) use and (vi) post-lockdown preparedness. Results: A total number of 588 practising orthopaedic surgeons from India completed the survey. Majority (88.3%) found severe impact (>50%) on trauma surgery and nontrauma surgery with significant reduction in out -patient attendance compared to corresponding time in 2019. There were significant changes made in individual hospital protocols (91.7 %). Appropriate required PPE was available in majority of the hospitals (74.3%). No remodelling or upgrading of the existing operating theatre infrastructure was done by most surgeons (89.5%). Conclusion: This pan India survey of orthopaedic surgeons has indicated that COVID-19 has had a profound impact on their outpatient and surgical trauma and non-trauma practice, due to the lockdown and resulted in significant changes to hospital protocols. Preparedness to resume clinical and surgical practice was associated with anxiety in two-thirds of the respondents. Majority of the orthopaedic practitioners felt that they would continue to conduct pre-operative COVID-19 screening and use PPE even after the lockdown is over.

Diazepam-induced changes in tardive dyskinesia: suggestions for a new conceptual model.

Using an ABA' research design, the effects of a benzodiazepine gamma-aminobutyric acid (GABA)-ergic agent, diazepam, on various aspects of tardive dyskinesia (TD) were investigated in 21 patients. Videotaped recordings of the examinations were rated blind on the Abnormal Involuntary Movements Scale. In nonsedating amounts, diazepam had a significant anti-TD effect, especially in terms of limb dyskinesia. A significant portion of the therapeutic effect persisted after the medication was withdrawn. The results suggest that diazepam has a specific anti-TD action and that in some cases it may be able to produce a somewhat lasting correction of the deranged neurobiological mechanisms in TD. Since the main sites of action of benzodiazepines and the highest concentrations of benzodiazepine-linked GABA receptors are in the limbic and cortical structures that provide principal sources of inputs to the basal ganglia, it is suggested that the supra-striato-pallidal mechanisms of voluntary movement control should be considered in understanding the pathogenesis and treatment of TD.

Autoimmunity and age-associated cognitive decline.

It is suggested that the immune system may play a role in the etiology of age-associated cognitive decline and/or Alzheimer's disease. The relationship between brain-reactive antibodies (BRA) and age-associated cognitive dysfunction is reviewed and discussed. A parallel relationship between BRA increases with age and decline of avoidance learning capacity is described in mouse models. Transfer of immunity from old to young mice was found to accelerate both age-related formation of brain-reactive antibodies and age-related decline of avoidance learning capacity. Short-lived mouse genotypes with accelerated autoimmunity were found to show accelerated age-related declines in their ability to acquire an avoidance response when compared with nonautoimmune mice. Overall, these findings suggest that the immune system could be an important target for development of intervention strategies aimed at extending the intellectually competent period of life. Mice in which autoimmunity is accelerated may be useful as models for the development of such interventions.

Estimating age-related changes in psychomotor function: influence of practice and of level of caloric intake in different genotypes.

This article presents a discussion of some key considerations in the measurement of age-related changes in psychomotor function of mice. We illustrate that "standard" measures of psychomotor performance, such as running speed on a rotorod task, are highly sensitive to practice effects. Examples are cited in which failure to assess practice effects can influence conclusions regarding the magnitude and rate of change in psychomotor capacity as a function of age. A second set of examples is focused on estimating the effect of an experimental intervention, caloric restriction, on age-related changes in psychomotor performance. These examples show that psychomotor performance at a given age may vary directly, and reversibly, with the level of caloric intake. Independent of such reversible effects, the level of caloric intake can also modulate the rate of change in capacity as a function of age. It is concluded that reversible, short-term effects must be considered in estimating the effect of an experimental intervention on the rate of age-associated change in psychomotor function.

Exercise does not modify spatial memory, brain autoimmunity, or antibody response in aged F-344 rats.

Old F-344 rats were given endurance training over a 10-week period on a motorized treadmill. This treatment resulted in substantial heart-to-body weight ratio increases, indicative of effective training. To determine whether endurance training might alter some of the known immune system and cognitive changes observed during aging, exercised old rats were compared to nonexercised old and young controls on three variables: in vivo antigen-specific immune activity, brain-reactive antibody formation, and spatial memory. The exercise training did not influence any of these measures in the old rats. Both groups of old rats showed poorer antibody response to a specific antigen, more brain-reactive antibody formation, and poorer spatial memory than the young controls. There was, however, a significant relationship between brain-reactive antibody formation and spatial memory performance, regardless of training condition.

Pathogenesis of Alzheimer's disease: current status on apolipoprotein E4 gene research.

Alzheimer's disease (AD) affects millions of people throughout the world. The financial and emotional costs that are inflicted by this devastating disease are enormous. Genes responsible for the early-onset familial AD have been cloned and found to be membrane associated transport proteins. Evidence suggests that apolipoprotein E4 may be the risk factor for the late-onset form of the disease. Beta-amyloid and potassium channel dysfunction have also been implicated in the development of AD. Hyperphosphorylation of "tau" has been indicated for the generation of neurofibrillary tangles in the brains of Alzheimer's patients. Since apoE4 does not bind to "tau", apoE4 may contribute to the hyperphosphorylation of "tau" which may cause the formation of neurofibrillary tangles in AD patients. Molecular biology research on AD should help in the development of drugs for the prevention and treatment of the disease.

Effect of age and caloric restriction on DNA oxidative damage in different tissues of C57BL/6 mice.

The objective of this study was to explore the role of molecular oxidative damage and caloric intake in the aging process. The concentration of 8-hydroxydeoxyguanosine (8-OHdG), a product of DNA oxidation, was compared in five different tissues of mice (skeletal muscle, brain, heart, liver and kidney) as a function of age and in response to dietary restriction. A comparison of 8- and 27-month-old mice indicated that the age-related increase in 8-OHdG concentration was greater in skeletal muscle, brain and heart, which are primarily composed of long-lived, post-mitotic cells, than in liver and kidney, which consist of slow-dividing cells. Dietary restricted (DR) mice kept on 60% caloric intake as compared to the ad libitum-fed (AL) mice showed a lower concentration in 8-OHdG content in all the tissues compared to AL mice. The DR-related amelioration of DNA oxidative damage was greater in the post-mitotic tissues compared to those undergoing slow mitoses. Results support the hypothesis that oxidative damage to long-lived post-mitotic cells may be a key factor in the aging process.

Oxidative damage, mitochondrial oxidant generation and antioxidant defenses during aging and in response to food restriction in the mouse.

This study was conducted in order to test the concept that oxidative damage is associated with aging and may be a factor in the modulation of life span in response to variations in caloric intake. Mice fed a diet that was 40% lower in calories (DR) than the ad libitum fed (AL) animals exhibited a 43% extension in average life span and a 61% prolongation in mortality rate doubling time. A comparison of AL and DR mice at 9, 17 and 23 months of age indicated that the protein carbonyl content in the brain, heart and kidney increased with age and was significantly greater in the AL than DR group in each organ at each of the three ages. Mitochondrial state 4 or resting respiratory rate increased with age in the AL, but not the DR group, and was also relatively higher in the former. The rates of mitochondrial superoxide and hydrogen peroxide generation increased with age and were higher in the AL than DR mice in all the three organs at each age. In contrast, there was no clear-cut overall pattern of age-related or dietary-related changes in antioxidant defenses provided by superoxide dismutase, catalase and glutathione peroxidase. Results suggest that mechanisms of aging and life span shortening by enhanced caloric intake are associated with oxidative damage arising from corresponding changes in mitochondrial oxidant production. Protein carbonyl content, and mitochondrial O2.- and H2O2 generation may act as indices of aging.

Protracted withdrawal: sensitization of the anxiogenic response to cocaine in rats concurrently treated with ethanol.

Rats were trained to respond on one lever following an injection of saline and the alternate lever after the anxiogenic drug pentylenetetrazol (PTZ 20 mg/kg), according to a fixed ratio (FR10) schedule of food reinforcement. The trained animals were then administered dependence-producing regimens of either cocaine (20 mg/kg, [IP], three times daily for 7 days) or ethanol (mixed 4.5% w/v with sweetened liquid diet given for 5 days). Separate groups of trained rats were given either subthreshold regimens of cocaine (20 mg/kg, IP, three times daily for 5 days), ethanol (2.25% w/v of the diet given for 5 days), or both. Additional groups were matched for control groups. After discontinuation of these regimens, rats were administered test injections of either saline or cocaine, and tested for elicitation of the PTZ-stimulus at selected intervals of withdrawal. After a saline injection, maximum elicitation of the PTZ-stimulus was observed 12 hours following chronic treatment with the higher dose of ethanol, and 120 hours following longer treatment with cocaine. During those periods of withdrawal when a saline injection failed to produce a PTZ-like stimulus, a test injection of cocaine (10 mg/kg) elicited the PTZ-stimulus in the ethanol withdrawn rats, although only partially eliciting the PTZ-stimulus in the cocaine withdrawn group. In the pair-fed controls, or rats withdrawn from the smaller dosage of either ethanol or cocaine, the test dose of saline or cocaine did not elicit the PTZ-stimulus; only 30% of rats selected the PTZ-appropriate level at the highest dose of cocaine tested (10 mg/kg).(ABSTRACT TRUNCATED AT 250 WORDS)

The pentylenetetrazol-like interoceptive stimulus produced by ethanol withdrawal is potentiated by bicuculline and picrotoxinin.

We investigated whether the interoceptive discriminative stimulus (IDS) arising from ethanol withdrawal was related to decreased activity of the gamma-aminobutyric acid (GABA) system by determining whether the sensitivity of rats to the GABA antagonists was altered by chronic treatment with ethanol. Rats were trained to obtain food reward by responding on one lever following pentylenetetrazol (PTZ) and the other lever following saline. Whereas all of the trained rats selected the PTZ-appropriate lever after PTZ, no more than 50% of them selected this lever following an optimum dose of bicuculline or picrotoxinin. After either saline or diazepam (5 mg/kg), all of the rats selected the saline-appropriate lever. Ethanol (0.24 mol/kg/day) was then administered to the rats for 4 days via a nutritionally balanced liquid diet. Between 48 and 96 hours postethanol, 30% of the rats selected the PTZ-appropriate lever following saline, whereas selection of this lever was increased to 80% following either bicuculline or picrotoxinin. Thus, further antagonism of GABAergic activity increased the subjective effect of ethanol withdrawal. These data support the hypothesis that the PTZ-like IDS produced during withdrawal from ethanol is related to an ethanol-induced deficit in the activity of the GABA-benzodiazepine receptor-coupled chloride channel.

Genes implicated in the pathogenesis of Alzheimer's disease.

Both the early and late-onset Alzheimer's disease affect millions of people throughout the world. A number of molecules have been implicated in the pathogenesis of Alzheimer's disease. These include presenilin 1 and 2 (PS1 and PS2), a beta-amyloid peptide, and tau protein. Presenilin 1 and 2 genes implicated in the early-onset familial Alzheimer's disease have been cloned. Both PS1 and PS2 are integral membrane proteins and may function as receptors or channel proteins. Missense mutations in PS1 and PS2 genes have been found in families that cosegregate with early-onset Alzheimer's disease. Overexpression of the mutated PS1 gene produced amyloid plaques in the brain of transgenic mice. Secreted beta-amyloid protein similar to that in the senile plaques of Alzheimer's disease was found to be elevated in fibroblast media from subjects with PS1 or PS2 mutations. Transgenic mice which carried the mutant form of the beta-amyloid precursor protein gene expressed high concentrations of mutant copy of the gene and exhibited abundant amyloid plaques in the brain and memory loss. The mutated PS2 gene enhanced apoptotic activity. This enhanced apoptotic activity may accelerate the process of neurodegeneration leading to an earlier age in the onset of the disease. Identification of lesions in the molecules that are important in the Alzheimer's disease should allow developing therapeutic approaches for its treatment.