Determinants and Reference Ranges of Serum Immunoglobulins in Middle-Aged and Elderly Individuals: a Population-Based Study

Purpose

In clinical practice, currently one reference range for serum immunoglobulin (Ig) A, G, and M is applied to all adults, although various factors may influence Ig serum levels. Population-based data on determinants of IgA, IgG, and IgM and recommendations for subgroup specific reference ranges are lacking. We aimed to provide an overview of determinants of IgA, IgG, and IgM in community-dwelling middle-aged and elderly individuals and explore determinants that influence Ig reference ranges.

Methods

Within the Rotterdam Study, we performed linear regression analyses for the association of demographic, lifestyle, and cardiovascular factors with serum IgA, IgG, and IgM. We furthermore calculated Ig reference ranges (based on percentiles), both overall and within relevant subgroups.

Results

We included 8768 participants (median age 62 years). IgA and IgG increased non-linearly with higher age (P?<?.0001 for both). Women had lower IgA (beta:???0.24; 95% confidence interval [95% CI]:???0.29;???0.20) and IgG (beta:???0.33; 95% CI:???0.44;???0.23), but higher IgM levels (beta: 0.08; 95% CI: 0.04;0.13) than men. Former and particularly current smoking were associated with lower IgA and IgG (betas between???0.07 and???1.03). Higher alcohol consumption was associated with lower IgG (beta for heavy drinking:???0.70; 95% CI:???0.91;???0.48). Corticosteroid use was associated with lower IgG (beta:???1.12; 95% CI:???1.58;???0.66). Associations with cardiovascular factors were heterogeneous and differed between sexes.

Conclusion

Age, sex, smoking, alcohol consumption, corticosteroid use, and cardiovascular factors are determinants that should be considered when interpreting serum Ig levels in middle-aged and elderly individuals and may require adjusted reference ranges.

     

Abdominal Dermis-Fat Graft Versus Conventional Temporalis Myofascial Flap Interposition in Temporomandibular Joint Ankylosis: A Prospective Clinical Comparative Study

IntroductionTemporomandibular joint (TMJ) ankylosis is an extremely disabling condition with almost complete inability to open the jaws causing difficulty in chewing, speech, poor oral hygiene and cosmetic disfigurement. Temporalis myofascial flap still remains the most common interpositional material used; however, patients usually complain of pain during movement, unesthetic bulging in the temporal region and trismus due to scar contracture. The main aim of the study was to evaluate the efficacy of abdominal dermis-fat graft and compare it with temporalis myofascial flap as to see which of the two grafts offers more advantages and provides better postoperative results following TMJ ankylosis surgery. Materials and MethodsA total of 30 diagnosed cases of TMJ ankylosis were randomly divided into two groups of 15 patients each. All the patients underwent TMJ ankylosis release under general anesthesia followed by abdominal dermis-fat interposition in Group A and temporalis muscle in Group B. The patients were assessed for pre-operative and postoperative mouth opening (immediate and 6 month postoperative), pain during physiotherapy, donor and surgical site complications and recurrence of ankylosis.ResultsThe mean maximum inter-incisal opening in dermis-fat group was significantly higher than temporalis group both at immediate and 6 month postoperative periods (p = 0.041, 0.001). Physiotherapy was less painful in dermis-fat group than in temporalis group, and the differences in VAS scores among the 2 groups showed high statistical significance (p < 0.001). Hypertrophic scar developed at the donor site in 2 patients in dermis-fat group; however, it was located below the beltline and hardly noticeable. A total of 9 patients (4 in Group A and 5 in Group B) developed temporary facial nerve weakness, and no case of re-ankylosis was noted in either group.ConclusionDermis-fat graft in temporomandibular joint ankylosis showed better results than conventional temporalis myofascial flap in terms of postoperative mouth opening, physiotherapy and jaw function with esthetically acceptable results.     

Conformational dynamics of superoxide dismutase (SOD1) in osmolytes: a molecular dynamics simulation study

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease caused by the misfolding of Cu, Zn superoxide dismutase (SOD1). Several earlier studies have shown that monomeric apo SOD1 undergoes significant local unfolding dynamics and is the predecessor for aggregation. Here, we have employed atomistic molecular dynamics (MD) simulations to study the structure and dynamics of monomeric apo and holo SOD1 in water, aqueous urea and aqueous urea–TMAO (trimethylamine oxide) solutions. Loop IV (zinc-binding loop) and loop VII (electrostatic loop) of holo SOD1 are considered as functionally important loops as they are responsible for the structural stability of holo SOD1. We found larger local unfolding of loop IV and VII of apo SOD1 as compared to holo SOD1 in water. Urea induced more unfolding in holo SOD1 than apo SOD1, whereas the stabilization of both the form of SOD1 was observed in ternary solution (i.e. water/urea/TMAO solution) but the extent of stabilization was higher in holo SOD1 than apo SOD1. The partially unfolded structures of apo SOD1 in water, urea and holo SOD1 in urea were identified by the exposure of the hydrophobic cores, which are highly dynamic and these may be the initial events of aggregation in SOD1. Our simulation studies support the formation of aggregates by means of the local unfolding of monomeric apo SOD1 as compared to holo SOD1 in water.

Change in conformations of apo and holo SOD1 in water and in osmolytes in terms of configurational entropy (S).     

Study of Surgical Emergencies of Tubercular Abdomen in Developing Countries

To study the various modes of presentation, diagnosis, and management of surgical emergencies of tubercular abdomen. This prospective study of surgical emergencies of tubercular abdomen was conducted in 50 patients who attended our surgical emergency from 2006 to 2008. Patients were evaluated thoroughly with history, physical examination, routine investigations, and special investigations such as ELISA, PCR, barium studies of gastrointestinal tract, and diagnostic laparoscopy as required and managed with medical and surgical treatment as necessary. The most of patients were from rural areas, in the third to sixth decades with slight male preponderance. Abdominal pain, vomiting, and constipation were commonest presenting symptoms. About 20 % patients had history of pulmonary tuberculosis and 16 % patients presented with ascites. PCR for blood and ascitic fluid was positive in 72 and 87.5 % patients, respectively. About 24 % patients were managed nonoperatively and responded to ATT. About 76 % patients needed surgery among which one-fifth of patients were operated in emergency. Procedures like adhesiolysis of gut (47.3 %), strictureplasty (10.5 %), resection anastomosis (5.2 %), right hemicolectomy (5.2 %), and ileotransverse anastomosis (7.8 %) were performed in 30 patients and peritoneal biopsy and lymph node biopsy in the remaining 8 patients. Both medically and surgically managed patients were put on antitubercular therapy. Abdominal tuberculosis is a disease of middle-aged rural people, presenting commonly with abdominal pain and vomiting with right lower abdominal tenderness. PCR (blood and ascites) for tuberculosis is much more sensitive than IgM ELISA (blood and ascites). The most of patients required surgical procedures and all patients responded dramatically to antitubercular therapy symptomatically with increase in the hemoglobin level and decrease in ESR.     

Comparison of effects on low-density lipoprotein cholesterol and high-density lipoprotein cholesterol with rosuvastatin versus atorvastatin in patients with type IIa or IIb hypercholesterolemia.

This randomized, double-blind, placebo-controlled trial was conducted in 52 centers in North America to compare the effects of the new, highly effective statin, rosuvastatin, with atorvastatin and placebo in hypercholesterolemic patients. After a 6-week dietary run-in, 516 patients with low-density lipoprotein (LDL) cholesterol > or =4.14 mmol/L (160 mg/dl) and < 6.47 mmol/L (250 mg/dl) and triglycerides < or =4.52 mmol/L (400 mg/dl) were randomized to 12 weeks of once-daily placebo (n = 132), rosuvastatin 5 mg (n = 128), rosuvastatin 10 mg (n = 129), or atorvastatin 10 mg (n = 127). The primary efficacy end point was percent change in LDL cholesterol. Secondary efficacy variables were achievement of National Cholesterol Education Program (NCEP) Adult Treatment Panel II (ATP II), ATP III, and European Atherosclerosis Society LDL cholesterol goals and percent change from baseline in high-density lipoprotein (HDL) cholesterol, total cholesterol, triglycerides, non-HDL cholesterol, apolipoprotein B, and apolipoprotein A-I. Rosuvastatin 5 and 10 mg compared with atorvastatin 10 mg were associated with greater LDL cholesterol reductions (-40% and -43% vs 35%; p <0.01 and p <0.001, respectively) and HDL cholesterol increases (13% and 12% vs 8%, p <0.01 and p <0.05, respectively). Total cholesterol and apolipoprotein B reductions and apolipoprotein A-I increases were also greater with rosuvastatin; triglyceride reductions were similar. Rosuvastatin 5 and 10 mg were associated with improved achievement in ATP II (84% in both rosuvastatin groups vs 73%) and ATP III (84% and 82% vs 72%) LDL cholesterol goals, and rosuvastatin 10 mg was more effective than atorvastatin in achieving European Atherosclerosis Society LDL cholesterol goals. Both treatments were well tolerated.     

Association of FcγRIIa Polymorphism with Clinical Outcome of Dengue Infection: First Insight from Pakistan

Dengue illness has been a major health concern in Pakistan during the last decade. Dengue infection can result in a spectrum of clinically distinct outcomes, ranging from asymptomatic infection to potentially life-threatening forms of dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). A single-nucleotide polymorphism in FcγRIIa (rs1801274) results in altered affinity of the receptor for different subclasses of immunoglobulin G, and is a key player in determining the susceptibility to or protection from severe clinical infection of dengue. In this study, we analyzed the allelic and genotypic distribution of rs1801274 in subjects of Pakistani origin with subclinical dengue infection (n = 40), dengue fever (DF) (n = 40), and DHF/DSS (n = 30). We found that HH homozygotes and heterozygotes were significantly more likely to develop clinical dengue (odds ratio [OR] = 3.21, 95% confidence interval [CI] = 1.29–7.97, P = 0.009), either DF (OR = 2.82, 95% CI = 1.00–7.97, P = 0.045) or DHF/DSS (OR = 3.90, 95% CI = 1.13–13.07, P = 0.024) than the asymptomatic dengue infection. Results of allelic distribution comparisons and logistic regression analysis also supported the same relationship. The results suggest complex nature of interacting factors in determining the course for severe dengue illness.