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1.
Urologia ; 91(1): 112-116, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37421248

ABSTRACT

INTRODUCTION: Bladder stones account for 5% of all urolithiasis. Patients present with LUTS or acute urinary retention. Thus, warranting an early intervention. Minimally invasive approach with laser lithotripsy is the present gold standard to treat bladder stones. AIMS AND OBJECTIVES: To evaluate the outcomes of TFL (60 W) for bladder stones performed under local anesthesia as a day-care procedure. MATERIALS AND METHODS: This was a retrospective single-center study conducted after obtaining IRB approval. Study period was between June 2021 and June 2022 were included. All patients were operated under local anesthesia as a day care procedure. The procedure was carried out using an 18 Fr laser sheath and calculus dusted using TFL energy (15-30 W). Parameters including operative time in minutes, complications were recorded. Patients were encouraged oral and normal voiding in the immediate post-op period. RESULTS: A total of 47 patients with bladder stones presented during this period. Of these, 30 underwent laser lithotripsy (TFL) for bladder calculi. The clinical presentation of patients was LUTS in 28 (93%) and 5 (16%) patients had AUR. The average size of the stone in this series was 15 ± 2.8 mm. The mean duration of laser lithotripsy was 15 ± 5.4 min. Energy to dust the stone was variable with mean LASER energy of 18.23 ± 10 W. All patients tolerated the procedure well and none required conversion to conventional anesthesia. One patient failed to void in the post-op period. 100% clearance rate was documented in all patients. CONCLUSION: Thulium fiber laser for transurethral cystolithotripsy of bladder stones under local anesthesia is a feasible technique with minimal morbidity and good outcome.


Subject(s)
Lasers, Solid-State , Lithotripsy, Laser , Urinary Bladder Calculi , Humans , Urinary Bladder Calculi/complications , Urinary Bladder Calculi/therapy , Thulium , Anesthesia, Local , Retrospective Studies , Day Care, Medical , Lithotripsy, Laser/adverse effects , Lithotripsy, Laser/methods , Lasers , Lasers, Solid-State/therapeutic use
2.
Perspect Med Educ ; 12(1): 169-178, 2023.
Article in English | MEDLINE | ID: mdl-37252268

ABSTRACT

Introduction: Clinical observation skills are fundamental to the practice of medicine. Yet, the skill of looking carefully is rarely taught within the medical curriculum. This may be a contributory factor in diagnostic errors in healthcare. A growing number of medical schools, especially in the United States, have turned to the humanities to offer visual arts-based interventions to foster medical students' visual literacy. This research aims to map the literature on the relationship between art observation training and diagnostic skills of medical students, highlighting effective teaching methodologies. Methods: Based on the Arksey and O'Malley framework, a comprehensive scoping review was conducted. Publications were identified by searching nine databases and hand searching the published and grey literature. Two reviewers independently screened each publication using the pre-designed eligibility criteria. Results: Fifteen publications were included. Significant heterogeneity exists between the study designs and the methods employed to evaluate skill improvement. Nearly all studies (14/15) reported an increase in the number of observations made post-intervention, but none evaluated long-term retention rates. There was an overwhelmingly positive response to the programme, but only one study explored the clinical relevance of the observations made. Discussion: The review establishes improved observational acumen following the intervention, however, uncovers very limited evidence towards improved diagnostic abilities. There is a need for greater rigour and consistency within the experimental designs, through using control groups, randomisation, and a standardised evaluation rubric. Further research on the optimal intervention duration and the application of skills gained to clinical practice, should be performed.


Subject(s)
Education, Medical, Undergraduate , Students, Medical , Humans , United States , Humanities , Curriculum , Education, Medical, Undergraduate/methods , Clinical Competence
3.
J Family Med Prim Care ; 11(8): 4821-4823, 2022 Aug.
Article in English | MEDLINE | ID: mdl-36353018

ABSTRACT

Acrogeria is a rare disorder that is characterized by premature aging of the distal extremities. It was first described by Gottron in 1941. Only about 50 cases have yet been reported worldwide. It is diagnosed clinically, and patients have a normal life expectancy. The disorder is seen from birth and could have an autosomal dominant or recessive inheritance. The classic features include a characteristic pinched face, thin lips, fine hair, skeletal defects, and thin, taut parchment-like skin of the extremities. We describe a case of Acrogeria, Gottron type, who also had a borderline personality disorder. However, there is very little information on the prevalence of psychopathology in patients having syndromes of premature aging.

4.
J Glaucoma ; 31(12): 935-940, 2022 12 01.
Article in English | MEDLINE | ID: mdl-35980862

ABSTRACT

PRCIS: In this population-based, cross-sectional study of Indian and Malay adults in Singapore aged 40 years or above, intermediate or high risk of obstructive sleep apnea (OSA) was associated with 50% higher odds of having glaucoma. BACKGROUND/AIMS: The relationship between OSA and glaucoma is unclear. We assessed the association between the risk of OSA and glaucoma in an Asian population. MATERIALS AND METHODS: In this population-based, cross-sectional study, we included Indian and Malay adults aged 40 years or above recruited between 2011 and 2015. Glaucoma was assessed by trained ophthalmologists and classified into primary open angle glaucoma (POAG) and primary angle closure glaucoma (PACG). OSA risk was assessed with the Snoring, Tiredness, Observed apnea, High blood pressure, Body mass index, Age, Neck circumference, and male Gender (STOP-Bang) questionnaire and categorized as low risk (<3) or intermediate/higher risk (≥3). We used multivariable logistic regression models to evaluate the relationship between risk of OSA and glaucoma adjusted for key variables, and further stratified for subtype and ethnicity. RESULTS: Of the 3126 participants (mean age: 63.1±9.6 y; 52.5% female), 134 (4.3%) had glaucoma, comprising 86 (2.8%) POAG, 22 (0.7%) PACG and 26 (0.8%) secondary glaucomas, and 1182 (37.8%) had an intermediate/higher risk of OSA. Compared with individuals with a low risk of OSA, individuals with intermediate/higher risk had 50% greater odds of having glaucoma (odds ratio: 1.55, 95% confidence interval: 1.03-2.33; P =0.035). We observed a nonsignificant increase in likelihood of having POAG in those with intermediate/higher risk of OSA compared with those with low risk. The OSA-glaucoma relationship was modified by ethnicity, with Malays with intermediate/higher risk of OSA having a 2-fold risk of having any glaucoma (odds ratio: 2.01, 95% confidence interval: 1.12-3.59 P =0.019); while the same elevated risk was not observed for Indians. CONCLUSIONS: Intermediate or high risk of OSA is associated with 50% higher odds of having glaucoma in our Singaporean population, with a 2-fold higher risk of glaucoma observed in Malays (but not Indians); however a conformational sleep study is needed.


Subject(s)
Glaucoma, Open-Angle , Sleep Apnea, Obstructive , Adult , Male , Female , Humans , Middle Aged , Aged , Singapore/epidemiology , Cross-Sectional Studies , Glaucoma, Open-Angle/diagnosis , Glaucoma, Open-Angle/epidemiology , Glaucoma, Open-Angle/complications , Intraocular Pressure , Sleep Apnea, Obstructive/complications , Sleep Apnea, Obstructive/diagnosis , Sleep Apnea, Obstructive/epidemiology , Surveys and Questionnaires
5.
Asian J Endosc Surg ; 15(1): 90-96, 2022 Jan.
Article in English | MEDLINE | ID: mdl-34320694

ABSTRACT

INTRODUCTION: Retrocaval ureter (RCU) is a rare congenital abnormality, secondary to anomalous development of inferior vena cava (IVC) presenting as ipsilateral obstruction needing surgical intervention. The aim of this article is to present surgical techniques and outcome of transperitoneal laparoscopic ureteropyeloplasty in patients with RCU treated by a single surgeon at a tertiary care center and with review of literature. MATERIAL AND METHODS: We conducted a retrospective, institutional review board approved chart review of patients who underwent transperitoneal laparoscopic ureteropyeloplasty for RCU at our unit between January 2010 and December 2020. A total of 10 patients were identified. Preoperative evaluation involved a computed tomography-intravenous urography in addition to the conventional evaluation. All the patients underwent dismembered transperitoneal laparoscopic ureteropyeloplasty over a Double J stent. Data analyzed included the demographic profile, operative time difficulty if any, postoperative, intraoperative complications and functional outcome. RESULTS: All cases were completed laparoscopically and no open conversion was required. Average operating time was 96.6 minutes ± 8.16. Average blood loss was 71 ± 14.49 mL with an analgesia requirement of 115 ± 33.74 mg. One patient developed postoperative urinary leak and responded to percutaneous nephrostomy drainage. Patients were followed up for 3 to 12 months with a serial ultrasound and a follow-up diethylene-triamine-penta-acetic acid renal scan at 3 months to rule out any anastomotic site obstruction. CONCLUSION: Transperitoneal laparoscopic ureteropyeloplasty for RCU was associated with minimal morbidity and good outcomes.


Subject(s)
Laparoscopy , Retrocaval Ureter , Surgeons , Ureter , Humans , Retrocaval Ureter/surgery , Retrospective Studies , Ureter/surgery
6.
Clin Cancer Res ; 26(11): 2477-2486, 2020 06 01.
Article in English | MEDLINE | ID: mdl-31992589

ABSTRACT

PURPOSE: The relevance of the MET/hepatocyte growth factor pathway in endometrial cancer tumor biology supports the clinical evaluation of cabozantinib in this disease. PATIENTS AND METHODS: PHL86/NCI#9322 (NCT01935934) is a single arm study that evaluated cabozantinib (60 mg once daily) in women with endometrial cancer with progression after chemotherapy. Coprimary endpoints were response rate and 12-week progression-free-survival (PFS). Patients with uncommon histology endometrial cancer (eg, carcinosarcoma and clear cell) were enrolled in a parallel exploratory cohort. RESULTS: A total of 102 patients were accrued. Among 36 endometrioid histology patients, response rate was 14%, 12-week PFS rate was 67%, and median PFS was 4.8 months. In serous cohort of 34 patients, response rate was 12%, 12-week PFS was 56%, and median PFS was 4.0 months. In a separate cohort of 32 patients with uncommon histology endometrial cancer (including carcinosarcoma), response rate was 6% and 12-week PFS was 47%. Six patients were on treatment for >12 months, including two for >30 months. Common cabozantinib-related toxicities (>30% patients) included hypertension, fatigue, diarrhea, nausea, and hand-foot syndrome. Gastrointestinal fistula/perforation occurred in four of 70 (6%) patients with serous/endometrioid cancer and five of 32 (16%) patients in exploratory cohort. We observed increased frequency of responses with somatic CTNNB1 mutation [four partial responses (PRs) in 10 patients, median PFS 7.6 months] and concurrent KRAS and PTEN/PIK3CA mutations (three PRs in 12 patients, median PFS 5.9 months). CONCLUSIONS: Cabozantinib has activity in serous and endometrioid histology endometrial cancer. These results support further evaluation in genomically characterized patient cohorts.


Subject(s)
Anilides/therapeutic use , Carcinosarcoma/drug therapy , Endometrial Neoplasms/drug therapy , Neoplasm Recurrence, Local/drug therapy , Pyridines/therapeutic use , Adult , Aged , Aged, 80 and over , California , Carcinosarcoma/secondary , Cohort Studies , Endometrial Neoplasms/pathology , Female , Follow-Up Studies , Humans , Middle Aged , Neoplasm Recurrence, Local/pathology , Prognosis , Survival Rate
7.
Anesth Essays Res ; 14(3): 515-520, 2020.
Article in English | MEDLINE | ID: mdl-34092868

ABSTRACT

BACKGROUND: Caudal anesthesia has emerged as a reliable and effective anesthetic technique in the pediatric age group. However, the limited duration of action of the local anesthetic drugs proves to one of the major hindrances in the complete utilization of caudal block as an effective analgesic technique. To overcome this shortcoming, adjuvant drugs were introduced into clinical practice. AIM: Our aim was to determine which of the two drugs - dexamethasone and tramadol - serves as a better adjuvant for caudal analgesia in pediatric patients. SETTINGS AND DESIGN: This was a prospective, randomized, double-blind study that comprised 90 American Society of Anesthesiologist (ASA) physical status I and II pediatric patients posted for lower abdominal surgeries. MATERIALS AND METHODS: Ninety ASA physical status I and II children aged 5-12 years posted for lower abdominal surgeries were chosen. They were randomly divided into three groups - Group R received 0.5 ml.kg-1 of 0.2% ropivacaine plus 0.9% normal saline; Group T received 0.5 ml.kg-1 of 0.2% ropivacaine plus 2 mg.kg-1 tramadol; and Group D received 0.5 ml.kg-1 of 0.2% ropivacaine plus 0.1 mg.kg-1 dexamethasone. Postoperative pain was assessed using a modified objective pain score and time to first rescue analgesia (duration of sensory block) was recorded. Postoperative sedation and any other postoperative adverse effects were noted. STATISTICAL ANALYSIS: Student's independent t-test was employed for comparing continuous variables and Chi-square test for categorical variables. Kruskal-Wallis test was used for postoperative pain and sedation score data. RESULTS: The duration of sensory block was significantly longer with dexamethasone than tramadol. No significant postoperative sedation or any other adverse effect was noted in any patient. CONCLUSION: Dexamethasone is superior to tramadol as an adjuvant to ropivacaine for pediatric lower abdominal surgeries.

8.
Cell Mol Immunol ; 17(7): 728-740, 2020 07.
Article in English | MEDLINE | ID: mdl-31197255

ABSTRACT

Synovial macrophages are crucial in the development of joint inflammation and bone damage; however, the pathways that control macrophage remodeling in inflammatory M1 cells or bone-eroding osteoclasts are not fully understood. We determined that elevated IL-7R/CD127 expression is the hallmark of rheumatoid arthritis (RA) M1 macrophages and that these cells are highly responsive to interleukin-7 (IL-7)-driven osteoclastogenesis. We established that lipopolysaccharide (LPS), interferon-γ (IFNγ), and tumor necrosis factor-α (TNFα), the classic M1 macrophage mediators, enhance IL-7R expression in RA and murine macrophages. The local expression of IL-7 provokes arthritis, predominantly through escalating the number of F480+iNOS+ cells rather than CD3+ T cells. Ectopic LPS injection stabilizes IL-7-induced arthritis by increasing myeloid IL-7R expression, in part via IFNγ induction. Hence, in RAG-/- mice, IL-7-mediated arthritis is suppressed because of the reduction in myeloid IL-7R expression due to the lack of IFNγ. Moreover, the amelioration of IL-7-induced arthritis by anti-TNF therapy is due to a decrease in the number of cells in the unique F480+iNOS+IL-7R+CCL5+ subset, with no impact on the F480+Arginase+ cell or CD3+ T cell frequency. Consistent with the preclinical findings, the findings of a phase 4 study performed with RA patients following 6 months of anti-TNF therapy revealed that IL-7R expression was reduced without affecting the levels of IL-7. This study shifts the paradigm by discovering that IL-7-induced arthritis is dependent on F480+iNOS+IL-7R+CCL5+ cell function, which activates TH-1 cells to amplify myeloid IL-7R expression and disease severity.


Subject(s)
Arthritis, Rheumatoid/pathology , Interleukin-7/metabolism , Macrophages/pathology , Animals , Bone Marrow Cells/metabolism , Cell Differentiation , Humans , Interferon-gamma/metabolism , Lipopolysaccharides , Macrophages/metabolism , Mice , Mice, Inbred C57BL , Middle Aged , Myeloid Cells/metabolism , Osteoclasts/metabolism , Receptors, Interleukin-7/metabolism , Tumor Necrosis Factor-alpha/metabolism
9.
J Anaesthesiol Clin Pharmacol ; 35(3): 340-347, 2019.
Article in English | MEDLINE | ID: mdl-31543582

ABSTRACT

BACKGROUND AND AIMS: ProSeal laryngeal mask airway (PLMA) is an established device for airway management, while Air-Q Blocker (AQB) is a relatively new supraglottic device. The aim of this study is to compare AQB against PLMA in adults undergoing laparoscopic cholecystectomy under general anesthesia. MATERIAL AND METHODS: Eighty-eight adult patients scheduled for laparoscopic cholecystectomy under general anesthesia were randomly allocated into two groups. A drain tube (gastric tube for PLMA and blocker tube for AQB) was inserted through the drain channel of the respective device. PLMA was inserted in Group P (n = 44) and AQB was inserted in Group A (n = 44) to secure the airway. The primary endpoint was airway seal pressure. Secondarily, we sought to compare overall insertion success, ease of insertion, hemodynamic effects after initial placement, ease of drain tube placement, and perioperative oropharyngolaryngeal morbidity between the devices. RESULTS: Oropharyngeal seal pressures for AQB and PLMA were 31.5 ± 2.41 and 29.41 ± 2.14 cm H2O, respectively (P = 0.01). Insertion time was longer with AQB than PLMA, 25.59 ± 5.71 and 18.66 ± 3.15 seconds, respectively (P = 0.001). Ease and success rate of insertion was better with PLMA compared to AQB. Failure of device insertion was seen in 2 cases of Group A. Gastric distension was seen in 4 patients in Group A, requiring replacement with endotracheal tube in two patients. Ventilation was successful in all 44 patients with PLMA. Both the devices were comparable in providing a patent airway and adequate oxygenation during controlled ventilation. There was an increased trend of airway trauma and complications in the AQB group. CONCLUSION: Both PLMA and AQB show similar efficacy in maintaining ventilation and oxygenation, during laparoscopic surgery. However, proper positioning and functioning of the blocker tube of AQB is a limiting factor, and needs further evaluation.

10.
J Anaesthesiol Clin Pharmacol ; 35(2): 176-181, 2019.
Article in English | MEDLINE | ID: mdl-31303705

ABSTRACT

BACKGROUND AND AIMS: The present study evaluated the effects of two 5-HT3 serotonin receptor antagonists; granisetron and palonosetron on hemodynamics, sensory, and motor blockade induced by intrathecal bupivacaine in patients undergoing abdominal hysterectomy. MATERIAL AND METHODS: In total, 126 female patients (ASA I and II physical status) undergoing abdominal hysterectomy under spinal anesthesia with intrathecal bupivacaine were randomly divided into three groups out of which 40 patients in each group were evaluated for final outcome. Group G received intravenous 1 mg granisetron, group P received intravenous palonosetron 0.075 mg, and group C received intravenous normal saline. Study drug was given 5 min before the spinal anesthesia. Systolic, diastolic and mean arterial blood pressure, heart rate, sensory and motor blockade were assessed. RESULTS: The systolic blood pressure, diastolic blood pressure, mean arterial pressure, and heart rate showed no significant differences among the three groups. Time to reach peak sensory block and modified Bromage 3 motor block, time to two segmental regression of sensory block, and motor regression to modified Bromage score of 0 were not statistically different among the three groups. Although statistically significant early regression of sensory block to segment S1 was seen in group G as compared to group P and group C, it was of no clinical significance. The incidence of nausea and vomiting was significantly lower in group G and P. CONCLUSION: Intravenous administration of granisetron and palonosetron before intrathecal bupivacaine does not attenuate the hemodynamic changes in patients undergoing abdominal hysterectomy. Further, both 5-HT3 receptors antagonists do not have clinically significant effects on the spinal blockade produced by hyperbaric bupivacaine.

11.
J Pharm Sci ; 108(7): 2406-2414, 2019 07.
Article in English | MEDLINE | ID: mdl-30849460

ABSTRACT

Particulate matter present in drug products intended for parenteral administration to patients is typically monitored and controlled in the finished drug product to minimize potential risks to patients. In contrast to particulates found in drug products, the current study evaluated particulates representative of materials and operations typically used in the dose preparation and administration of drug products. A comprehensive assessment of intrinsic and extrinsic sources of subvisible and submicron particulates arising from materials associated with subcutaneous and intravenous dose preparation and administration was conducted. In particular, particles arising from disposable syringes, commercial sterile diluents, and intravenous supplies were quantitated using established methods for subvisible (light obscuration, flow imaging) and submicron particles (resistive pulse sensing). Each of these sources contributed varying amounts of particulates; therefore, owing to sources from materials required for administration, it is inadequate to assume that the total particulate load delivered to patients arises solely from the drug product. Careful consideration of the administration method and supplies used can improve the predictability of particulate levels present in dose preparations or administration volumes.


Subject(s)
Particulate Matter/chemistry , Pharmaceutical Preparations/chemistry , Administration, Intravenous/methods , Drug Compounding/methods
13.
J Immunol ; 193(8): 3902-13, 2014 Oct 15.
Article in English | MEDLINE | ID: mdl-25200955

ABSTRACT

Our aim was to examine the impact of TLR5 ligation in rheumatoid arthritis (RA) and experimental arthritis pathology. Studies were conducted to investigate the role of TLR5 ligation on RA and mouse myeloid cell chemotaxis or osteoclast formation, and in addition, to uncover the significance of TNF-α function in TLR5-mediated pathogenesis. Next, the in vivo mechanism of action was determined in collagen-induced arthritis (CIA) and local joint TLR5 ligation models. Last, to evaluate the importance of TLR5 function in RA, we used anti-TLR5 Ab therapy in CIA mice. We show that TLR5 agonist, flagellin, can promote monocyte infiltration and osteoclast maturation directly through myeloid TLR5 ligation and indirectly via TNF-α production from RA and mouse cells. These two identified TLR5 functions are potentiated by TNF-α, because inhibition of both pathways can more strongly impair RA synovial fluid-driven monocyte migration and osteoclast differentiation compared with each factor alone. In preclinical studies, flagellin postonset treatment in CIA and local TLR5 ligation in vivo provoke homing and osteoclastic development of myeloid cells, which are associated with the TNF-α cascade. Conversely, CIA joint inflammation and bone erosion are alleviated when TLR5 function is blocked. We found that TLR5 and TNF-α pathways are interconnected, because TNF-α is produced by TLR5 ligation in RA myeloid cells, and anti-TNF-α therapy can markedly suppress TLR5 expression in RA monocytes. Our novel findings demonstrate that a direct and an indirect mechanism are involved in TLR5-driven RA inflammation and bone destruction.


Subject(s)
Arthritis, Experimental/pathology , Arthritis, Rheumatoid/pathology , Myeloid Progenitor Cells/cytology , Toll-Like Receptor 5/immunology , Tumor Necrosis Factor-alpha/immunology , Animals , Antibodies/immunology , Cell Differentiation/immunology , Cell Movement/drug effects , Cells, Cultured , Collagen , Female , Flagellin/pharmacology , Humans , Inflammation/drug therapy , JNK Mitogen-Activated Protein Kinases/immunology , Male , Mice , Mice, Inbred C57BL , Mice, Inbred DBA , Middle Aged , Monocytes/immunology , Myeloid Progenitor Cells/immunology , NF-kappa B/immunology , Osteoclasts/cytology , Phosphatidylinositol 3-Kinases/immunology , Phosphorylation , Proto-Oncogene Proteins c-akt/immunology , RANK Ligand/biosynthesis , Receptor Activator of Nuclear Factor-kappa B/biosynthesis , Synovial Fluid/cytology , Toll-Like Receptor 5/biosynthesis , Tumor Necrosis Factor-alpha/biosynthesis
14.
J Immunol ; 190(10): 5256-66, 2013 May 15.
Article in English | MEDLINE | ID: mdl-23606539

ABSTRACT

Although the role of IL-7 and IL-7R has been implicated in the pathogenesis of rheumatoid arthritis (RA), the majority of the studies have focused on the effect of IL-7/IL-7R in T cell development and function. Our novel data, however, document that patients with RA and greater disease activity have higher levels of IL-7, IL-7R, and TNF-α in RA monocytes, suggesting a feedback regulation between IL-7/IL-7R and TNF-α cascades in myeloid cells that is linked to chronic disease progression. Investigations into the involved mechanism showed that IL-7 is a novel and potent chemoattractant that attracts IL-7R(+) monocytes through activation of the PI3K/AKT1 and ERK pathways at similar concentrations of IL-7 detected in RA synovial fluid. To determine whether ligation of IL-7 to IL-7R is a potential target for RA treatment and to identify their mechanism of action, collagen-induced arthritis (CIA) was therapeutically treated with anti-IL-7 Ab or IgG control. Anti-IL-7 Ab treatment significantly reduces CIA monocyte recruitment and osteoclast differentiation as well as potent joint monocyte chemoattractants and bone erosion markers, suggesting that both direct and indirect pathways might contribute to the observed effect. We also demonstrate that reduction in joint MIP-2 levels is responsible for suppressed vascularization detected in mice treated with anti-IL-7 Ab compared with the control group. To our knowledge, we show for the first time that expression of IL-7/IL-7R in myeloid cells is strongly correlated with RA disease activity and that ligation of IL-7 to IL-7R contributes to monocyte homing, differentiation of osteoclasts, and vascularization in the CIA effector phase.


Subject(s)
Arthritis, Experimental/immunology , Arthritis, Experimental/metabolism , Interleukin-7/metabolism , Receptors, Interleukin-7/metabolism , Adult , Animals , Antibodies/therapeutic use , Arthritis, Experimental/drug therapy , Arthritis, Rheumatoid/metabolism , Cell Differentiation/drug effects , Chemokine CXCL2 , Disease Progression , Extracellular Signal-Regulated MAP Kinases/metabolism , Female , Humans , Interleukin-7/immunology , Male , Mice , Mice, Inbred DBA , Middle Aged , Monocytes/metabolism , Myeloid Cells , Osteoclasts/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Synovial Fluid/enzymology , Synovial Fluid/immunology , Synovial Fluid/metabolism , Tumor Necrosis Factor-alpha/metabolism
16.
Pharm Res ; 28(4): 873-85, 2011 Apr.
Article in English | MEDLINE | ID: mdl-21213025

ABSTRACT

PURPOSE: To investigate the cause of unexpected and erratic increase in aggregation during long-term storage of an IgG2 monoclonal antibody in a trehalose formulation at -20°C. METHODS: Frozen matrix was sampled, stored frozen at various temperatures and analyzed by SEC over time. RESULTS: Aggregation increased with time at -20°C but not at -40°C or -10°C. The cause of the instability was the crystallization of freeze-concentrated trehalose from the frozen solute when the storage temperature exceeds the glass transition temperature of the matrix (-29°C). Crystallization at -20°C deprives the protein of the cryoprotectant, leading to a slow increase in aggregation. Storage at -10°C also leads to crystallization of trehalose but no increase in aggregation. It is hypothesized that significantly higher mobility in the matrix at -10°C allows protein molecules that are unfolded at the ice interface on freezing to refold back before significant aggregation can occur. In contrast, lack of mobility at -40°C prevents crystallization, refolding, and aggregation. CONCLUSIONS: Aggregation in the frozen state when stored above the glass transition temperature is a consequence of balance between rate of crystallization leading to loss of cryoprotectant, rate of aggregation of the unfolded protein molecules, and rate of refolding that prevents aggregation.


Subject(s)
Antibodies, Monoclonal/chemistry , Freezing , Immunoglobulin G/chemistry , Trehalose/chemistry , Crystallization , Drug Stability , Drug Storage , Protein Folding , Protein Stability , Protein Unfolding , Thermodynamics , Time Factors , Viscosity
17.
Rev. colomb. anestesiol ; 38(2): 234-239, mayo-jul. 2010. ilus, tab
Article in English, Spanish | LILACS | ID: lil-594534

ABSTRACT

Metachromatic leukodystrophy is a progressive, inherited and neurodegenerative disease. A patient suffering from this disease poses a lot of anaesthetic problems. We have successfully anaesthetized a female child with general anaesthesia who was suffering from metabolic leukodystrophy.


La leucodistrofia metacromática es una enfermedad progresiva hereditaria y neurodegenerativa. Un paciente que sufre de esta enfermedad representa múltiples problemas anestésicos. Hemos anestesiado exitosamente una niña que sufre de leucodistrofia metacromática con anestesia general.


Subject(s)
Humans , Male , Female , Child , Adolescent , Young Adult , Middle Aged , Anesthesia, General , Leukodystrophy, Metachromatic , Anesthesia
18.
Orbit ; 28(5): 285-9, 2009.
Article in English | MEDLINE | ID: mdl-19874121

ABSTRACT

A 35-year-old lady presented with recurrent episodes of painful right upper lid swelling and ptosis of 6 months' duration. The symptoms would subside with oral antibiotics and painkillers. She had also been undergoing treatment for 1 year for multiple painful osteolytic lesions in the long bones and axial skeleton for which no definite diagnosis had been made, despite several radiological and serological investigations having been performed. Computed tomographic scan showed a soft tissue lesion in the superolateral part of the right orbit with erosion of the adjacent bone. Lacrimal gland biopsy showed non-specific inflammatory changes. She was referred for full work-up to exclude lymphoma and metastasis. Magnetic resonance imaging revealed an enhancing soft tissue mass in the right anterior cranial fossa eroding the lateral orbital wall and extending into the orbit. Another mass encased the superior sagittal sinus. Bone marrow biopsy showed near total replacement of marrow cells by a round cell tumour. Immunohistochemical studies revealed that the tumour cells expressed neuron specific enolase and chromogranin. The pathological findings suggested a diagnosis of neuroendocrine tumour though neuroblastoma could not be unequivocally ruled out. A(131) I-metaiodobenzylguanidine scan showed no uptake. Radiologic studies suggested multiple bony metastases. No other site of primary tumour was found so there was a strong possibility of it being a primary orbito-cranial neurogenic tumour. Neuroblastomas and neuroendocrine tumours are very rare in adults. The orbit is an unusual site for a primary of this nature. In addition, it is quite difficult to make a specific diagnosis in a less differentiated tumour.


Subject(s)
Brain Neoplasms/diagnosis , Neuroblastoma/diagnosis , Orbital Neoplasms/diagnosis , Adult , Brain Neoplasms/therapy , Fatal Outcome , Female , Humans , Neuroblastoma/therapy , Orbital Neoplasms/therapy
19.
Orbit ; 28(2-3): 203-7, 2009.
Article in English | MEDLINE | ID: mdl-19839915

ABSTRACT

A 35-year-old lady presented with recurrent episodes of painful right upper lid swelling and ptosis of 6 months' duration. The symptoms would subside with oral antibiotics and painkillers. She had also been undergoing treatment for one year for multiple painful osteolytic lesions in the long bones and axial skeleton for which no definite diagnosis had been made, despite several radiological and serological investigations having been performed. Computed tomographic scan showed a soft tissue lesion in the superolateral part of the right orbit with erosion of the adjacent bone. Lacrimal gland biopsy showed non-specific inflammatory changes. She was referred for full work-up to exclude lymphoma and metastasis. Magnetic resonance imaging revealed an enhancing soft tissue mass in the right anterior cranial fossa eroding the lateral orbital wall and extending into the orbit. Another mass encased the superior sagittal sinus. Bone marrow biopsy showed near total replacement of marrow cells by a round cell tumour. Immunohistochemical studies revealed that the tumour cells expressed neuron specific enolase and chromogranin. The pathological findings suggested a diagnosis of neuroendocrine tumour though neuroblastoma could not be unequivocally ruled out. (131) I-metaiodobenzylguanidine scan showed no uptake. Radiologic studies suggested multiple bony metastases. No other site of primary tumour was found so there was a strong possibility of it being a primary orbito-cranial neurogenic tumour. Neuroblastomas and neuroendocrine tumours are very rare in adults. The orbit is an unusual site for a primary of this nature. In addition, it is quite difficult to make a specific diagnosis in a less differentiated tumour.


Subject(s)
Brain Neoplasms/diagnosis , Neuroblastoma/diagnosis , Orbital Neoplasms/diagnosis , Adult , Brain Neoplasms/therapy , Fatal Outcome , Female , Humans , Neuroblastoma/therapy , Orbital Neoplasms/therapy
20.
Indian J Ophthalmol ; 56(5): 413-6, 2008.
Article in English | MEDLINE | ID: mdl-18711272

ABSTRACT

Variations in the bony components of the nose are often encountered. One such variation was found in a 49-year-old male who had undergone conventional external dacryocystorhinostomy for adult onset nasolacrimal duct blockage. Intraoperatively, a thick bar of bone was seen beneath and parallel to the lacrimal sac fossa after a complete osteotomy had been made. Another osteotomy had to be fashioned in this bone to reach the nasal cavity. Postoperative 3D computed tomographic scan revealed the bone to be an anatomical variation of the uncinate process of the ethmoidal bone which was rather anteriorly placed, much thicker than usual, and attached to the nasal roof. The uncinate process is thin, curved and its anterior edge may frequently overlap some part of the lacrimal fossa. However, to our knowledge, the presence of such a large and thick uncinate process necessitating an additional large osteotomy has not been reported.


Subject(s)
Dacryocystorhinostomy/methods , Nasal Bone/anatomy & histology , Endoscopy , Humans , Lacrimal Duct Obstruction/diagnosis , Male , Middle Aged , Tomography, X-Ray Computed
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