12(S)-Hydroxyeicosatetraenoic acid (12-HETE) is one of the metabolites of arachidonic acid involved in pathological conditions associated with mitochondria and oxidative stress. The present study tested effects of 12-HETE on mitochondrial functions. In isolated rat heart mitochondria, 12-HETE increases intramitochondrial ionized calcium concentration that stimulates mitochondrial nitric oxide (NO) synthase (mtNOS) activity. mtNOS-derived NO causes mitochondrial dysfunctions by decreasing mitochondrial respiration and transmembrane potential. mtNOS-derived NO also produces peroxynitrite that induces release of cytochrome c and stimulates aggregation of mitochondria. Similarly, in HL-1 cardiac myocytes, 12-HETE increases intramitochondrial calcium and mitochondrial NO, and induces apoptosis. The present study suggests a novel mechanism for 12-HETE toxicity.
12-HETE; intramitochondrial ionized calcium; mtNOS; mitochondrial respiration; mitochondrial transmembrane potential; peroxynitrite; cytochrome c release; apoptosis
In BALB/c mice, susceptibility to infection with the intracellular parasite Leishmania major is driven largely by the development of T helper 2 (Th2) responses and the production of interleukin (IL)-4 and IL-13, which share a common receptor subunit, the IL-4 receptor alpha chain (IL-4Rα). While IL-4 is the main inducer of Th2 responses, paradoxically, it has been shown that exogenously administered IL-4 can promote dendritic cell (DC) IL-12 production and enhance Th1 development if given early during infection. To further investigate the relevance of biological quantities of IL-4 acting on DCs during in vivo infection, DC specific IL-4Rα deficient (CD11ccreIL-4Rα-/lox) BALB/c mice were generated by gene targeting and site-specific recombination using the cre/loxP system under control of the cd11c locus. DNA, protein, and functional characterization showed abrogated IL-4Rα expression on dendritic cells and alveolar macrophages in CD11ccreIL-4Rα-/lox mice. Following infection with L. major, CD11ccreIL-4Rα-/lox mice became hypersusceptible to disease, presenting earlier and increased footpad swelling, necrosis and parasite burdens, upregulated Th2 cytokine responses and increased type 2 antibody production as well as impaired classical activation of macrophages. Hypersusceptibility in CD11ccreIL-4Rα-/lox mice was accompanied by a striking increase in parasite burdens in peripheral organs such as the spleen, liver, and even the brain. DCs showed increased parasite loads in CD11ccreIL-4Rα-/lox mice and reduced iNOS production. IL-4Rα-deficient DCs produced reduced IL-12 but increased IL-10 due to impaired DC instruction, with increased mRNA expression of IL-23p19 and activin A, cytokines previously implicated in promoting Th2 responses. Together, these data demonstrate that abrogation of IL-4Rα signaling on DCs is severely detrimental to the host, leading to rapid disease progression, and increased survival of parasites in infected DCs due to reduced killing effector functions.
Leishmaniasis is a parasitic infection caused by protozoan parasites of Leishmania species and is transmitted by the sandfly. Disease in humans ranges from localized cutaneous lesions to disseminated visceral Leishmaniasis. Mouse models of Leishmania major infection have demonstrated that a “healing” response in C57BL/6 mice requires the secretion of protective T helper (Th) 1 cytokines, including IFN-γ, which mediates parasite killing by inducing nitric oxide production. Conversely, “non-healer” BALB/c mice are unable to control infection and develop a Th2 immune response characterized by the production of IL-4 and IL-13 cytokines. Although IL-4 is the main inducer of Th2 responses, it has been shown that IL-4 can instruct dendritic cell (DC)-derived IL-12 production and Th1 development if administered during DC activation. To further investigate the role of DCs, a DC specific IL-4Rα-deficient mouse model was established. L. major studies demonstrated hypersusceptibility to infection and strikingly increased parasite loads in peripheral organs of mice lacking IL-4Rα on DCs. Moreover, increased parasite burdens were observed in host cells, including DCs, which showed reduced killing effector functions. In summary, this study demonstrates that IL-4Rα-mediated instruction of DCs occurs in vivo and is necessary to avoid rapid progression of disease in the host.
Statins are well-known cholesterol lowering drugs targeting HMG-CoA-reductase, reducing the risk of coronary disorders and hypercholesterolemia. Statins are also involved in immunomodulation, which might influence the outcome of bacterial infection. Hence, a possible effect of statin treatment on Listeriosis was explored in mice. Statin treatment prior to subsequent L. monocytogenes infection strikingly reduced bacterial burden in liver and spleen (up to 100-fold) and reduced histopathological lesions. Statin-treatment in infected macrophages resulted in increased IL-12p40 and TNF-α and up to 4-fold reduced bacterial burden within 6 hours post infection, demonstrating a direct effect of statins on limiting bacterial growth in macrophages. Bacterial uptake was normal investigated in microbeads and GFP-expressing Listeria experiments by confocal microscopy. However, intracellular membrane-bound cholesterol level was decreased, as analyzed by cholesterol-dependent filipin staining and cellular lipid extraction. Mevalonate supplementation restored statin-inhibited cholesterol biosynthesis and reverted bacterial growth in Listeria monocytogenes but not in listeriolysin O (LLO)-deficient Listeria. Together, these results suggest that statin pretreatment increases protection against L. monocytogenes infection by reducing membrane cholesterol in macrophages and thereby preventing effectivity of the cholesterol-dependent LLO-mediated phagosomal escape of bacteria.
Acute and chronic inflammation is characterized by increased reactive oxygen species (ROS) production, dysregulation of mitochondrial metabolism and abnormal immune function contributing to cardiovascular diseases and sepsis. Clinical and epidemiological studies suggest potential beneficial effects of dietary interventions in inflammatory diseases but understanding of how nutrients work remains insufficient. In the present study, we evaluated the effects of apigenin, an anti-inflammatory flavonoid abundantly found in our diet, in endothelial cells during inflammation. Here, we show that apigenin reduced lipopolysaccharide (LPS)-induced apoptosis by decreasing ROS production and the activity of caspase-3 in endothelial cells. Apigenin conferred protection against LPS-induced mitochondrial dysfunction and reestablished normal mitochondrial complex I activity, a major site of electron leakage and superoxide production, suggesting its ability to modulate endothelial cell metabolic function during inflammation. Collectively, these findings indicate that the dietary compound apigenin stabilizes mitochondrial function during inflammation preventing endothelial cell damage and thus provide new translational opportunities for the use of dietary components in the prevention and treatment of inflammatory diseases.
inflammation; flavonoids; metabolism; mitochondrial dysfunction
Nematode secreted haemoglobins have unusually high affinity for oxygen and possess nitric oxide deoxygenase, and catalase activity thought to be important in protection against host immune responses to infection. In this study, we generated a monoclonal antibody (48Eg) against haemoglobin of the nematode Anisakis pegreffii, and aimed to characterize cross-reactivity of 4E8g against haemoglobins of different nematodes and its potential to mediate protective immunity against a murine hookworm infection.
Immunoprecipitation was used to isolate the 4E8g-binding antigen in Anisakis and Ascaris extracts, which were identified as haemoglobins by peptide mass fingerprinting and MS/MS. Immunological cross-reactivity was also demonstrated with haemoglobin of the rodent hookworm N. brasiliensis. Immunogenicity of nematode haemoglobin in mice and humans was tested by immunoblotting. Anisakis haemoglobin was recognized by IgG and IgE antibodies of Anisakis-infected mice, while Ascaris haemoglobin was recognized by IgG but not IgE antibodies in mouse and human sera. Sequencing of Anisakis haemoglobin revealed high similarity to haemoglobin of a related marine nematode, Psuedoterranova decipiens, which lacks the four –HKEE repeats of Ascaris haemoglobin important in octamer assembly. The localization of haemoglobin in the different parasites was examined by immunohistochemistry and associated with the excretory-secretary ducts in Anisakis, Ascaris and N. brasiliensis. Anisakis haemoglobin was strongly expressed in the L3 stage, unlike Ascaris haemoglobin, which is reportedly mainly expressed in adult worms. Passive immunization of mice with 4E8g prior to infection with N. brasiliensis enhanced protective Th2 immunity and led to a significant decrease in worm burdens.
The monoclonal antibody 4E8g targets haemoglobin in broadly equivalent anatomical locations in parasitic nematodes and enhances host immunity to a hookworm infection.
Nematode haemoglobins are fascinating molecules with unusually high affinity for oxygen. This is one example of many unique adaptations that nematodes have acquired to survive in their hosts, as nematode haemoglobin is thought to sequester oxygen to maintain an anaerobic environment, and can break down nitric oxide (NO) and hydrogen peroxide produced by host defences. This study describes the characterization of nematode haemoglobins using a novel monoclonal antibody (anti-Hb) generated against Anisakis haemoglobin, which was found to be highly expressed in stage 3 larvae and associated with the excretory-secretary ducts. Anisakis haemoglobin is an IgE-binding molecule in infected mice, while Ascaris haemoglobin was recognized by IgG but not IgE in human sera. Finally, passive immunization of mice with anti-Hb provided protection against Nippostrongylus brasiliens (rodent hookworm), with mice showing reduced worm burden and enhanced Th2 responses, showing that haemoglobin may be a good vaccine target in some nematodes. The monoclonal antibody generated in this study will be useful in further studies to examine the biology of nematode haemoglobins.
Chromosomal abnormalities are seen in nearly 1% of live born infants. We report a 5-year-old boy with the clinical features of Down syndrome, which is the most common human aneuploidy. Cytogenetic analysis showed a mosaicism for a double aneuploidy, Down syndrome and XYY. The karyotype was 47, XY,+21/48, XYY,+21. ish XYY (DXZ1 × 1, DYZ1 × 2). Mosaic double aneuploidies are very rare and features of only one of the aneuploidies may predominate in childhood. Cytogenetic analysis is recommended even if the typical features of a recognized aneuploidy are present so that any associated abnormality may be detected. This will enable early intervention to provide the adequate supportive care and management.
Disorder of sexual development; double aneuploidy; Down syndrome with XYY; meiotic non-disjunction; mosaic
Left ventricular noncompaction (LVNC) is a rare disease caused by intrauterine failure of the myocardium to compact. The major clinical manifestations of LVNC include heart failure, ventricular tachyarrhythmia, thromboembolic event, and sudden deaths. Atrial arrhythmia usually seen is atrial fibrillation. We report a rare case of focal left atrial tachycardia in an 18-year-old patient who presented for evaluation of persistent tachycardia. Transthoracic echocardiogram showed severe systolic dysfunction and evidence of noncompaction of the left ventricle. A detailed review of ECG revealed the possibility of ectopic atrial tachycardia, most likely originating from the left side. Electrophysiology study showed sustained atrial tachycardia originating on the ridge anterior to the left sided pulmonary veins. A successful radiofrequency catheter ablation was performed at this site without any complications.
Primary non-Hodgkin's lymphoma (NHL) is a rare entity. When it does occur, mandibular NHL typically manifests similar to an odontogenic pathology. This results in delayed diagnosis and treatment. We present a 50-year-old female who was erroneously treated for a pyogenic granuloma several months before the correct diagnosis of extranodal primary NHL of the oral cavity was made. Fortunately, the solitary bony lymphoma had not disseminated and management by chemo-radiation allowed for disease eradication and new post-treatment bone formation. The purpose of this report is to describe a rare case of primary NHL of the mandible, explore the diagnosis and work-up and discuss treatment strategies. This case illustrates the need for co-operative diagnostic referrals between physicians and dentists.
Cyclophosphamide hydroxydaunorubicin oncovin prednisolone-rituximab therapy; extranodal; mandibular swelling; non-Hodgkin's lymphoma
The antitumor effects of therapeutic mAbs may depend on immune effector cells that express FcRs for IgG. IL-12 is a cytokine that stimulates IFN-γ production from NK cells and T cells. We hypothesized that coadministration of IL-12 with a murine anti-HER2/neu mAb (4D5) would enhance the FcR-dependent immune mechanisms that contribute to its antitumor activity. Thrice-weekly therapy with IL-12 (1 μg) and 4D5 (1 mg/kg) significantly suppressed the growth of a murine colon adenocarcinoma that was engineered to express human HER2 (CT-26HER2/neu) in BALB/c mice compared with the result of therapy with IL-12, 4D5, or PBS alone. Combination therapy was associated with increased circulating levels of IFN-γ, monokine induced by IFN-γ, and RANTES. Experiments with IFN-γ–deficient mice demonstrated that this cytokine was necessary for the observed antitumor effects of therapy with IL-12 plus 4D5. Immune cell depletion experiments showed that NK cells (but not CD4+ or CD8+ T cells) mediated the antitumor effects of this treatment combination. Therapy of HER2/neu-positive tumors with trastuzumab plus IL-12 induced tumor necrosis but did not affect tumor proliferation, apoptosis, vascularity, or lymphocyte infiltration. In vitro experiments with CT-26HER2/neu tumor cells revealed that IFN-γ induced an intracellular signal but did not inhibit cellular proliferation or induce apoptosis. Taken together, these data suggest that tumor regression in response to trastuzumab plus IL-12 is mediated through NK cell IFN-γ production and provide a rationale for the coadministration of NK cell-activating cytokines with therapeutic mAbs.
To compare the efficacy and tolerability of Ivabradine (IVA) and Ranolazine (RAN) in chronic angina patients.
Materials and Methods:
This was a follow-on, open-label trial conducted in a tertiary care hospital of Uttarakhand. Thirty patients each taking IVA 5 mg twice daily or RAN 500 mg twice daily were distributed to the respective groups. Patients were asked to fill a pretested questionnaire on frequency of anginal attacks and adverse reactions before and 2, 4 and 8 weeks after taking the respective medicines. Their blood pressure, heart rate and routine hematological and biochemical estimations were performed at baseline and after intervention. Results were statistically analyzed using different statistical tests, with P < 0.05 considered as significant.
There was no significant difference in the frequency of anginal attacks per week between the groups. The adverse drug reactions (ADRs) reported in the IVA group were dizziness (30%), headache (16.6%), backache (16.6%), vertigo (13.3%), blurred vision (13.3%), muscle cramps (10%), arthralgia (10%), cough and dyspnea (6.6%), hypersensitivity rash (6.6%), fever (3.3%) and nausea (3.3%). The ADRs in the RAN group were nausea (26.6%), dizziness (23.3%), vomiting (3.3%), constipation (3.3%) and vertigo (3.3%). The blood pressure, heart rate and routine hematological and biochemical evaluations did not show any significant difference in the pre–post values. IVA significantly decreased the resting heart rate after eight weeks of intervention.
Both antianginal agents appeared equiactive. However, RAN had a better safety and tolerability profile than IVA. Serum sickness-like reaction was an adverse event noticed with IVA, which needs causality establishment.
Antianginals; dizziness; equiefficacious; nausea; serum sickness-like reaction
To estimate the prevalence of metabolic syndrome among adolescents attending school in the Jammu region, India.
Materials and Methods:
This is a cross-sectional study conducted between November 2009 and December 2010, among a total of 1160 school-going adolescents of both sexes aged 10-18 years. Relevant metabolic and anthropometric variables were analyzed and criteria suggested by National Cholesterol Education Program Adult Treatment Panel Third (NCEP-ATP III) modified forage was used to define metabolic syndrome.
The overall prevalence of metabolic syndrome was 2.6%. Prevalence of metabolic syndrome was higher in males (3.84%) than in females (1.6%) and slightly higher in urban area (2.80%) than in rural area (2.52%), whereas prevalence of metabolic syndrome among centrally obese subjects was as high as 33.33%. High density lipoprotein cholesterol was the most common and high blood pressure was the least common constituent of metabolic syndrome. Metabolic syndrome was most prevalent in 16-18 years age group (4.79%).
This study demonstrates that metabolic syndrome phenotype exists in substantial number (up to 3%) of adolescent population in the Jammu region, India, and particularly 33% of obese adolescents are at risk to develop metabolic syndrome. These findings pose a serious threat to the current and future health of these young people.
Adolescents; metabolic syndrome; obesity; prevalence
Imaging plays an important role in detection, diagnosis as well as pre and post operative management of patients with soft tissue sarcomas. Soft tissue sarcomas are generally a diagnostic dilemma needing the complimentary use of both radiology and pathology for their accurate diagnosis. In this review article, we have tried to highlight the important facts about the various imaging modalities available as well as the recent advances in the field of radiology.
Soft tissue sarcoma; Imaging; Ultrasound; CT; MRI; PET-CT
Eosinophilic granuloma is a rare disease which is difficult to diagnose clinically and radiographically. Localized Langerhans’ cell histiocytosis, previously known as eosinophilic granuloma, mainly affects the skull, mandible, vertebrae, pelvis and ribs in children and the long bones of adults. We present a case report of a female who developed pain and swelling over the left mandibular region, and was later diagnosed as eosinophilic granuloma, which after administration of intralesional corticosteroid with surgical enucleation showed positive response. This disease is of importance to dental professionals because early clinical signs can occur in the jaw and can cause extensive destruction of the periodontal tissues and bone. The purpose of this case report is to describe a case of eosinophilic granuloma with emphasis on conservative approach for the treatment and the radiographic changes observed during and after the treatment.
Adrenal cortex hormones; eosinophilic granuloma; Langerhans’ cell histiocytosis
Configuration and size of the foramen magnum and posterior fossa plays an important role in the pathophysiology of the posterior fossa and craniovertebral junction disorders. This study is aimed to find out various dimensions of the foramen magnum and posterior fossa.
Materials and Methods:
This is a prospective study of 100 consecutive normal computerized tomography (CT) scans of posterior fossa and 100 dry adult skulls without any bony abnormality. The posterior fossa volume was calculated by abc/2 in method 1 and by advanced work station of CT scan in method 2. Various dimensions of posterior fossa and foramen magnum were also studied.
Age ranged from 16 to 89 years with a mean of 51.3 years. Mean height of posterior fossa were 3.01 cm (±0.22) and 3.52 (±0.43) cm in dry skull and CT scan group, respectively (P < 0.0001). Mean volume of posterior fossa were 157.88 (±27.94) cm3 and 159.58 (±25.73) cm3 by method 1 and method 2, respectively (P > 0.05). All the dimensions of posterior fossa and foramen magnum were larger in male as compared to female. Mean anteroposterior (AP), transverse diameter and surface area of the foramen magnum were 3.31 (±0.35) cm, 2.76 (±0.31) cm, and 729.15 (±124.87) mm2, respectively, in CT scan group as compared to 3.41 (±0.29) cm, 2.75 (±0.25) cm, and 747.67 (±108.60) mm2, respectively, in dry skull group.
Normal values of posterior fossa and foramen magnum could serve as a future reference. Dry skull dimensions could be different from CT scan measurement. More studies are needed as there could be variations in dimensions in different regions in India
Foramen magnum; posterior cranial fossa; skull
Endoscopic endonasal trans-sphenoid surgery (EETS) is increasingly used for pituitary lesions. Pre-operative CT and MRI scans and peroperative endoscopic visualization can provide useful anatomical information. EETS is indicated in sellar, suprasellar, intraventricular, retro-infundibular, and invasive tumors. Recurrent and residual lesions, pituitary apoplexy and empty sella syndrome can be managed by EETS. Modern neuronavigation techniques, ultrasonic aspirators, ultrasonic bone curette can add to the safety. The binostril approach provides a wider working area. High definition camera is much superior to three-chip camera. Most of the recent reports favor EETS in terms of safety, quality of life and tumor resection, hospital stay, better endocrinological, and visual outcome as compared to the microscopic technique. Nasal symptoms, blood loss, operating time are less in EETS. Various naso-septal flaps and other techniques of CSF leak repair could help reduce complications. Complications can be further reduced after achieving the learning curve, good understanding of limitations with proper patient selection. Use of neuronavigation, proper post-operative care of endocrine function, establishing pituitary center of excellence and more focused residency and endoscopic fellowship training could improve results. The faster and safe transition from microscopic to EETS can be done by the team concept of neurosurgeon/otolaryngologist, attending hands on cadaveric dissection, practice on models, and observation of live surgeries. Conversion to a microscopic or endoscopic-assisted approach may be required in selected patients. Multi-modality treatment could be required in giant and invasive tumors. EETS appears to be a better surgical option in most pituitary adenoma.
Neuroendoscopy; nasal cavity surgery; pituitary neoplasm; pituitary adenoma; sphenoid sinus; sphenoid bone surgery
Orbital tuberculosis is an extremely rare, potentially devastating state, when not effectively treated, can lead to grave sequelae. Proptosis can be the result of primary orbital pathology or systemic disease processes. (1, 2) Thyroid ophthalmopathy being commonest cause of proptosis .It can also be a manifestation of, diseases involving various structures of orbit and of superior orbital fissure or cavernous sinus. A case of orbital tubercular abscess presenting with proptosis and blindness in a young male 27 years is reported. Clinicians should suspect rare causes in an immuno- compromised host .(2, 3) The failure to diagnose these conditions can lead to unintended sequelae.
Key Message: The patient who presents with proptosis must be evaluated to ascertain the causation. Preservation of vision is of paramount importance. On follow-up patients should be monitored for complications and remedied.
Orbital tuberculosis; proptosis; orbital apex syndrome; HIV
Spontaneous pathological fractures of the cervical spine due to tuberculosis are rare. But with escalating incidences of atypical presentations of tubercular disease, clinicians should exercise a high index of suspicion for early diagnosis of such cases.
We present a case of a 50-year-old Hindu man from northern India, who complained of pain and stiffness in his neck. His radiographs showed a fracture in his second cervical vertebral body. But further investigations raised the suspicion of an infective pathology, which was corroborated by magnetic resonance imaging and fine needle aspiration cytology. His symptoms improved and the fracture healed following antitubercular chemotherapy and immobilization.
In endemic regions like India, clinicians should be on the lookout for atypical presentations of tuberculosis. Any suspicious lesion should be evaluated with care for clinical, radiological and laboratory evidences of the infection. The affected spine should be protected and appropriate chemotherapy should be instituted at the earliest opportunity.
Endoscopic third ventriculostomy (ETV) is considered as a treatment of choice for obstructive hydrocephalus. It is indicated in hydrocephalus secondary to congenital aqueductal stenosis, posterior third ventricle tumor, cerebellar infarct, Dandy-Walker malformation, vein of Galen aneurism, syringomyelia with or without Chiari malformation type I, intraventricular hematoma, post infective, normal pressure hydrocephalus, myelomeningocele, multiloculated hydrocephalus, encephalocele, posterior fossa tumor and craniosynostosis. It is also indicated in block shunt or slit ventricle syndrome. Proper Pre-operative imaging for detailed assessment of the posterior communicating arteries distance from mid line, presence or absence of Liliequist membrane or other membranes, located in the prepontine cistern is useful. Measurement of lumbar elastance and resistance can predict patency of cranial subarachnoid space and complex hydrocephalus, which decides an ultimate outcome. Water jet dissection is an effective technique of ETV in thick floor. Ultrasonic contact probe can be useful in selected patients. Intra-operative ventriculo-stomography could help in confirming the adequacy of endoscopic procedure, thereby facilitating the need for shunt. Intraoperative observations of the patent aqueduct and prepontine cistern scarring are predictors of the risk of ETV failure. Such patients may be considered for shunt surgery. Magnetic resonance ventriculography and cine phase contrast magnetic resonance imaging are effective in assessing subarachnoid space and stoma patency after ETV. Proper case selection, post-operative care including monitoring of ICP and need for external ventricular drain, repeated lumbar puncture and CSF drainage, Ommaya reservoir in selected patients could help to increase success rate and reduce complications. Most of the complications develop in an early post-operative, but fatal complications can develop late which indicate an importance of long term follow up.
Cerebrospinal fluid shunt; endoscopy; endoscopic third ventriculostomy; hydrocephalus; neuroendoscpy; ventriculostomy
Differences in CD8+CD57− and CD8+CD57+ lymphocyte lifespan have been documented. Lower numbers and shorter lifespan are characteristic of CD8+CD57+ in normal individuals. However, CD8+CD57+ are expanded in certain disease states including T cell large granular leukemia and other hematologic malignancies. The mechanisms responsible for the differences in CD8+CD57− and CD8+CD57+ lifespan remain elusive. In this study, we demonstrate that the small heat shock protein (Hsp) 27 is a key regulator of CD8+CD57+ lymphocyte lifespan. We found that Hsp27 expression is significantly lower in CD8+CD57+ than in CD8+CD57− lymphocytes. In contrast, Hsp60 and Hsp70 are expressed at comparable levels. Unlike other antiapoptotic Bcl-2–like molecules, the expression of Hsp27 tightly correlates with CD8+CD57+ and CD8+CD57−lifespan. We demonstrate that Hsp27 overexpression in CD8+CD57+ lymphocytes to levels found normally in CD8+CD57− lymphocytes decreased apoptosis. Accordingly, silencing of Hsp27 in CD8+CD57− lymphocytes increased apoptosis. Collectively these results demonstrate that Hsp27 is a critical regulator of normal CD8+CD57+ lifespan supporting its use as a marker of lifespan in this lineage, and suggest a mechanism responsible for the decreased apoptosis and clonal expansion characteristic of certain disease states.
Congenital double lip is a rare developmental anomaly which usually involves the upper lip. It may occur in isolation or as a part of Ascher's syndrome. The occurrence of double lip may result in facial deformity especially when patient attempts to talk, smile, or even try to show the teeth. It affects esthetics and also interferes with speech and mastication. Although surgery may be undertaken to facilitate speech and mastication, majority of cases are operated for cosmetic reasons. A case of congenital double upper lip which was surgically treated for cosmetic reason is reported.
Acute seizure (AS) activity in old age has an increased predisposition for evolving into temporal lobe epilepsy (TLE). Furthermore, spontaneous seizures and cognitive dysfunction after AS activity are often intense in the aged population than in young adults. This could be due to an increased vulnerability of inhibitory interneurons in the aged hippocampus to AS activity. We investigated this issue by comparing the survival of hippocampal GABA-ergic interneurons that contain the neuropeptide Y (NPY) or the calcium binding protein parvalbumin (PV) between young adult (5-months old) and aged (22-months old) F344 rats at 12 days after three-hours of AS activity. Graded intraperitoneal injections of the kainic acid (KA) induced AS activity and a diazepam injection at 3 hours after the onset terminated AS-activity. Measurement of interneuron numbers in different hippocampal subfields revealed that NPY+ interneurons were relatively resistant to AS activity in the aged hippocampus in comparison to the young adult hippocampus. Whereas, PV+ interneurons were highly susceptible to AS activity in both age groups. However, as aging alone substantially depleted these populations, the aged hippocampus after three-hours of AS activity exhibited 48% reductions in NPY+ interneurons and 70% reductions in PV+ interneurons, in comparison to the young hippocampus after similar AS activity. Thus, AS activity-induced TLE in old age is associated with far fewer hippocampal NPY+ and PV+ interneuron numbers than AS-induced TLE in the young adult age. This discrepancy likely underlies the severe spontaneous seizures and cognitive dysfunction observed in the aged people after AS activity.
The objective of this prospective audit was to compare two methods of anticoagulation reversal in the pre-oper-ative period for hip fracture patients.
PATIENTS AND METHODS
In the first part of the audit, our current practice was analysed. Data relating to the number of days from admission to surgery and the reasons for delay to surgery were collected. Also, data concerning common reasons for which the patients were started on warfarin and the time required for INR to drop to 1.5 or below were collected. In the second part of the audit, 45 patients with INR above 1.5 were given a single dose of vitamin K (1 mg i.v.) in addition to stopping warfarin.
The mean difference in the time for INR < 1.5 in the two groups was 2 days (52 h; P < 0.05). The mean difference in wait for surgery since admission between the two groups was 4 days (91 h; P < 0.05). There was no significant difference between the two groups as regards the average number of co-morbidities in the patient groups.
A single 1 mg intravenous dose of vitamin K significantly reduces the time for the reversal of INR and the pre-operative delay to surgery, in patients on long-term warfarin. We conclude that 1 mg of intravenous vitamin K on admission is a safe and effective treatment to avoid delay in the treatment in this group of patients.
Hip fracture; Vitamin K; INR