Characterization of Acinetobacter from clinical isolates at Gandhi memorial and associated hospitals, Lucknow

The study was conducted in 4140 clinical samples sent to Microbiology department from different department of G.M. and associated hospitals. The samples included 2270 urine, 960 pus, 300 blood, 210 sputum, 180 CSF, 20 intercostal drainage tubes and 150 other swabs like vaginal and urethral, conjunctival smear 30, 10 ascitic fluids and 10 gastric aspirates. Apart from this, 30 specimens were collected from hospitals environment, like linen and trolley. From clinical samples, 43 acinetobacter strains (1.04%) were isolated. 17 strains (0.41%), were from pus, 12 (0.28%), from respiratory tract, 1, was (0.02%) from intercostal drainage secretions, urine 9 (0.22%), blood 1 (0.2%) and CSF 3 (.72%). From environmental samples, 7 strains (23.33%) were isolated. All the isolated strains were identified by routine biochemical tests. They were preserved in 1 % agar media for characterization. Characterization was done on the basis of growth at 37 degrees c, 41 degrees c and 44 degrees c, hemolysis, gelatin hydrolysis, acid from glucose, utilization of citrate, L-phenyl alanine, malonate, B-alanine, L-arginine, L-ornithine and L-aspartate. Among species identified Acinetobacter baumannii was 30 (69.67%), from clinical specimens and 5 (71.42%) from environment, Acinetobacter lwoffi was 10 (23.25%) from clinical specimen and 2 from environmental specimen, Acinetobacter hemolyticus was 3 (6.97%) and none from the environment. All the strains were resistant to penicillin. The sensitivity pattern showed gentamycin 64% sensitive, cotrimaxazole 42% cefotoxin 32% ciprofloxacine 26% and tetracycline 16%.     

Sex Differences in Atrial Fibrillation—Update on Risk Assessment,Treatment, and Long-Term Risk

Purpose of review

Atrial fibrillation (AF) is a growing health problem worldwide. While the disease plagues both men and women, this arrhythmia does not affect both sexes equally. Women are more likely to have major adverse outcomes such as stroke and its sequela; however, recent data on stroke prevention show improving outcomes. The purpose of this review of the recent literature is to summarize important updates on risk scores and management of patients with AF.

Recent findings

It has been well known that women have a higher risk of strokes than men when untreated or when treated with warfarin. Current risk scores emphasizing new risk factors such as the higher risk of strokes in women have been incorporated into clinical guidelines. However, with the use of direct oral anticoagulants, this sex disparity on stroke is no longer seen and women have less major bleeding than men. The use of cardiac glycosides is associated with increased incidence of breast cancer, and this medication is used more in women. Procedural complications for the management of AF are higher in women.

Summary

The study of the pathophysiology of AF and its management is a rapidly evolving area of cardiovascular medicine. Sex-specific data is necessary to achieve advances in the field and improve the outcomes in both men and women.

     

Treatment of non-union of humerus diaphyseal fractures: a prospective study comparing interlocking nail and locking compression plate

Background

The aim of this prospective comparative study was to compare outcomes and complications of humeral diaphyseal fracture non-unions managed with humerus interlocking nail (HIL) and locking compression plate (LCP).

Materials and methods

40 patients with non-union of humeral diaphyseal fractures were included in this study and were randomly allocated in two groups; group A had 20 cases treated with HIL and group B had 20 cases treated with LCP. Clinico-radiological assessments were done for each case up to 2-year follow-up period. Primary outcome measures (time to fracture union, union rate) and secondary outcome measures (functional outcome and complication such as infection, malunion, delayed union, implant failure, joint stiffness and iatrogenic radial nerve palsy) were compared between both the groups. Disabilities of the arm, shoulder and hand (DASH) scoring and Steward and Hundley’s scoring system were used to assess functional outcome of the fracture fixation.

Results

There was no significant difference (p = 0.12) in terms of mean fracture union time between group A (15.8 ± 4.2 weeks) and group B (17.2 ± 3.8 weeks). Group A had 95 % union rate and group B had 100 % union rate (p = 0.14). At the 2-year follow-up visit, there was no significant difference found between both the groups regarding range of motion of shoulder and elbow joint. There was no significant difference found in final functional outcomes between both the groups on comparing DASH score (p = 0.14) and Steward and Hundley’s score (p = 0.08). In terms of complications, there was insignificant difference found between both the groups.

Conclusions

This study concludes that both the implants can be used in non-union of humeral shaft fractures with good functional outcomes and acceptable rate of complications.     

Biomechanical analysis of distal femoral fracture fixation: dynamic condylar screw versus locked compression plate

Background This human cadaveric study introduces a laboratory model to establish and compare the fixation stability of the distal femoral locking plate (DFLP) and dynamic condylar screw (DCS) in distal femoral fracture fixation.Materials and methods The study was conducted on 16 fresh cadaveric femoral specimens, 8 implanted with the DCS and the other 8 with the DFLP. The construct was made unstable by removing a standard-sized medial wedge with a 1-cm base (gap osteotomy) beginning 6 cm proximal to the lateral joint line in the distal metaphyseal region with loss of the medial buttress. Each specimen underwent axial and torsional stiffness testing along with cyclic axial loading to failure. The mean DEXA value for the DFLP group was 0.82 g/cm² and in the DCS group was 0.79 g/cm².Results Axial stiffness in the DFLP group was significantly higher than in the DCS group, but no significant difference was found in torsional stiffness between the groups. A significant difference was found in the load-to-failure results between the groups. Plastic and total deformation was significantly higher in constructs in the DCS group than in those in the DFLP group. Total energy absorbed before construct failure was also significantly higher in the DFLP group than in the DCS group.Conclusions The DFLP construct proved stronger than the DCS in both axial stiffness and cyclic loading, but similar in torsional stiffness in biomechanical testing in a simulated A3 distal femoral fracture.     

Role of FNAC in palpable chest wall lesions in developing country

Palpable chest wall lesions are unusual manifestation of an underlying thoracic pathology and it is difficult to diagnose them with their diverse spectrum ranging from benign to malignant. Considering the exposure of patient to invasive biopsy/excision and the risk of local complications, FNAC is now being increasingly used in the primary assessment of these lesions. Objectives of this study were to report the spectrum of chest wall lesions in the population of a developing country and evaluating the diagnostic role of FNAC. All the patients who presented with palpable cutaneous or subcutaneous chest wall swelling during a period of January 2003 to August 2010 were reviewed retrospectively. May Grunwald Giemsa and Papanicolaou stained aspirates were examined, along with special stains. Seven hundred seventy‐three cases were subjected to chest wall FNAC, of which 726 (93.9%) cases were satisfactory. Age ranged from 1 to 93 years with M:F = 0.92:1. 358 (49.3%) were diagnosed as inflammatory and 368 (50.7%) were neoplastic lesions. Two‐hundred thirty four cases (32.2%) were diagnosed as mycobacterial abscess (likely tuberculous). Of the neoplastic lesions, 153 were malignant with carcinomas being predominant (88.2%). Malignant cases comprised of scar site recurrence in breast carcinoma (73 cases), metastatic carcinomas (62 cases), primary sarcomas (eight cases), hematological neoplasms (six cases), and miscellaneous group (four cases). Overall malignant lesions accounted for 21.1% (153/726) of satisfactory chest wall aspirates. FNAC is very useful and simple investigation for early diagnosis of chest wall abscesses, cutaneous metastases from visceral malignancies, and scar site recurrence in breast carcinoma. Diagn. Cytopathol. 2014;42:653–659. © 2014 Wiley Periodicals, Inc.     

N-nitrosodimethylamine-derived O6-methylguanine in DNA of monkey gastrointestinal and urogenital organs and enhancement by ethanol

N-nitrosodimethylamine (NDMA) is a human cancer initiator suspect. Ethanol, a cancer risk factor, may synergize with nitrosamines by suppressing hepatic clearance, to increase internal exposure. A limitation to these hypotheses is lack of activation of NDMA by many rodent tissues. However, systematic primate studies are lacking. Patas monkeys were utilized to investigate NDMA activation by primate tissues in vivo, generating the promutagenic DNA lesion O⁶-methylguanine (O⁶-meG). Adult monkeys received 0.1 mg/kg NDMA by gavage, in some cases preceded by ethanol. Four hours after NDMA only, O⁶-meG was detected in DNA from all tissues. Levels were highest in gastric mucosa and liver and were only about 50% lower in DNA from white blood cells, esophagus, ovary, pancreas, urinary bladder and uterus. With ethanol co-exposure, amounts of O⁶-meG increased at least 2-fold in all tissues except liver. The largest effect was in esophagus (17-fold increase), followed by ovary, large intestine, urinary bladder, spleen and cerebellum (9- to 13-fold increases), and uterus, cerebrum and brain stem (7- to 8-fold increases). Alkylguanine alkyltransferase activities varied over a 30-fold range and were highest in liver and stomach. Thus primate tissues, especially those of the gastrointestinal and urogenital organs, are sensitive targets for DNA adduct damage due to NDMA, and ethanol co-exposure leads to striking increases in adducts. Our data support epidemiology implicating nitrosamines in causation of cancers of stomach and other organs, and alcohol as enhancing internal exposure to nitrosamines. © 1996 Wiley-Liss, Inc.     

Kinetics and Characterization of Non-enzymatic Fragmentation of Monoclonal Antibody Therapeutics

Purpose

To understand non-enzymatic hydrolytic fragmentation of a monoclonal antibody therapeutic under temperature stressed conditions and investigating possible mechanism for the same.

Methods

The mAb therapeutic was incubated at 50°C in phosphate buffer at pH 6.5 and fragmentation was monitored at different ionic strengths under stressed conditions. The incubated mAb was sampled at regular time intervals by analytical Size Exclusion Chromatography (SEC).

Results

It was observed that 57% of the mAb product fragmented over 4 days into two fragment species – Fc-Fab and Fab with molecular weights of 97 KDa and 47 KDa, respectively, as measured by mass spectrometry (MS) and sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). The fragmentation rate was slow initially and then accelerated with time. No change in % aggregate level was observed in this duration, implying that degradation was primarily via fragmentation at high temperature. Kinetics of hydrolytic fragmentation was hypothesized and SEC data was fitted to estimate the kinetic rate constants. While degradation of the monomer into fragment species was non-Arrhenius with a negative activation energy, further degradation of Fab-Fc fragments into Fab or Fc fragments followed Arrhenius Law with an activation energy of 2.1 and 15.38 kcal/mol, respectively.

Conclusion

High temperature (50°C) causes mAb to cleave at the hinge region to form Fab-Fc and Fab/Fc, as confirmed by dynamic light scattering, SDS-PAGE, SEC, and MS. A kinetic model for hydrolytic fragmentation has been proposed. The results are expected to assist end users in formulation development as well as in monitoring stability of biotherapeutic products.

     

β-cell metabolic alterations under chronic nutrient overload in rat and human islets

The aim of this study was to assess multifactorial β-cell responses to metabolic perturbations in primary rat and human islets. Treatment of dispersed rat islet cells with elevated glucose and free fatty acids (FFAs, oleate:palmitate = 1:1 v/v) resulted in increases in the size and the number of lipid droplets in β-cells in a time- and concentration-dependent manner. Glucose and FFAs synergistically stimulated the nutrient sensor mammalian target of rapamycin complex 1 (mTORC1). A potent mTORC1 inhibitor, rapamycin (25 nM), significantly reduced triglyceride accumulation in rat islets. Importantly, lipid droplets accumulated only in β-cells but not in α-cells in an mTORC1-dependent manner. Nutrient activation of mTORC1 upregulated the expression of adipose differentiation related protein (ADRP), known to stabilize lipid droplets. Rat islet size and new DNA synthesis also increased under nutrient overload. Insulin secretion into the culture medium increased steadily over a 4-day period without any significant difference between glucose (10 mM) alone and the combination of glucose (10 mM) and FFAs (240 μM). Insulin content and insulin biosynthesis, however, were significantly reduced under the combination of nutrients compared with glucose alone. Elevated nutrients also stimulated lipid droplet formation in human islets in an mTORC1-dependent manner. Unlike rat islets, however, human islets did not increase in size under nutrient overload despite a normal response to nutrients in releasing insulin. The different responses of islet cell growth under nutrient overload appear to impact insulin biosynthesis and storage differently in rat and human islets.