Dynamic Hyperinflation Correlates with Exertional Oxygen Desaturation in Patients with Chronic Obstructive Pulmonary Disease

Background

Dynamic hyperinflation (DH) causes exercise limitation and exertional dyspnea in patients with chronic obstructive pulmonary disease (COPD). Exertional desaturation (ED) also occurs commonly in COPD but neither routine physiologic parameters nor imaging predict ED accurately. In this study we evaluated the relationship between DH and ED during 6-min walk testing (6MWT).

Methods

We measured ED and DH in patients with stable COPD. SpO₂ was measured by continuous pulse oximetry during 6MWT. ED was defined as a decline in SpO₂ (ΔSpO₂) ≥4 %. DH was determined by measuring inspiratory capacity (IC) before and after the 6MWT using a handheld spirometer. DH was defined as ΔIC >0.0 L. We correlated DH and ED with clinical and pulmonary physiologic variables by regression analysis, χ ², and receiver operator curve (ROC) analysis.

Results

Thirty males [age = 65 ± 9.4 years, FEV₁ % predicted = 48 ± 14 %, and DLCO % predicted = 50 ± 21 % (mean ± SD)] were studied. ΔSpO₂ correlated with ΔIC (r = 0.49, p = 0.005) and age (r = 0.39, p = 0.03) by univariate analysis; however, only ΔIC correlated on multivariate regression analysis (p = 0.01). ΔSpO₂ did not correlate with FEV₁, FVC, FEF_25–75, RV, DLCO % predicted, BMI, smoking, BORG score, or distance covered in 6MWT. DH strongly correlated with ED (p = 0.001). On ROC analysis, DH had an area under the curve of 0.92 for the presence of ED (sensitivity = 90 %; specificity = 77 %, p < 0.001).

Conclusion

Routine pulmonary function test results and clinical variables did not correlate with ED in patients with stable COPD. Dynamic hyperinflation strongly correlates with exertional desaturation and could be a reason for this desaturation.     

Same-day or historical ESR for disease activity score measurement: does it matter?

Several guidelines recommended routine use of Disease Activity Score-28 (DAS28) to monitor disease and the response to treatment for rheumatoid arthritis (RA). In practice, it may be appropriate to use historical erythrocyte sedimentation rate (ESR) values in place of same-day ESR, thereby preventing unnecessary delay in adjusting intervention. We asked whether ESR blood samples taken up to 3 months prior to the clinic appointment were adequate to accurately assess RA disease activity using the DAS28. RA patients (N?=?66) who met the inclusion criteria were assessed at baseline and ESR obtained on the day of review to calculate the DAS28 and compared with the DAS28 derived from the latest previous ESR (mean interval, 38.6 days; range, 6–99 days). Limits of agreement (LoA) were used to assess the agreement between the DAS28 pairs. The mean age of the participants was 61.5 years (range, 20–83 years), with mean disease duration of 11.0 years (range, 0.1–40 years). Comparing the DAS28 using same-day ESR versus pre-recorded historical ESR showed a small statistical difference (mean, ?0.09; 95 %CI, ?0.1602 to ?0.017) in the DAS28 score. The calculated LoA (?0.66 and 0.48) demonstrated acceptable agreement between DAS28 pairs, with 7.6 % of patients residing outside the LoA, all of whom had a significant treatment change. Disease misclassification occurred in 9.1 % of patients who were close to disease activity boundaries. Our results indicate that differences in the DAS28 due to a previous or same-day ESR are unlikely to be clinically significant for RA patients with established disease. A decision to adjust treatment therefore may be confidently made for most patients using the most recent ESR for calculating the DAS28, provided there was no major change in treatment since the last ESR measurement.     

Metabolic Effects of Bariatric Surgery in Patients With Moderate Obesity and Type 2 Diabetes: Analysis of a randomized control trial comparing surgery with intensive medical treatment

OBJECTIVE

To evaluate the effects of two bariatric procedures versus intensive medical therapy (IMT) on β-cell function and body composition.

RESEARCH DESIGN AND METHODS

This was a prospective, randomized, controlled trial of 60 subjects with uncontrolled type 2 diabetes (HbA_1c 9.7 ± 1%) and moderate obesity (BMI 36 ± 2 kg/m²) randomized to IMT alone, IMT plus Roux-en-Y gastric bypass, or IMT plus sleeve gastrectomy. Assessment of β-cell function (mixed-meal tolerance testing) and body composition was performed at baseline and 12 and 24 months.

RESULTS

Glycemic control improved in all three groups at 24 months (N = 54), with a mean HbA_1c of 6.7 ± 1.2% for gastric bypass, 7.1 ± 0.8% for sleeve gastrectomy, and 8.4 ± 2.3% for IMT (P < 0.05 for each surgical group versus IMT). Reduction in body fat was similar for both surgery groups, with greater absolute reduction in truncal fat in gastric bypass versus sleeve gastrectomy (−16 vs. −10%; P = 0.04). Insulin sensitivity increased significantly from baseline in gastric bypass (2.7-fold; P = 0.004) and did not change in sleeve gastrectomy or IMT. β-Cell function (oral disposition index) increased 5.8-fold in gastric bypass from baseline, was markedly greater than IMT (P = 0.001), and was not different between sleeve gastrectomy versus IMT (P = 0.30). At 24 months, β-cell function inversely correlated with truncal fat and prandial free fatty acid levels.

CONCLUSIONS

Bariatric surgery provides durable glycemic control compared with intensive medical therapy at 2 years. Despite similar weight loss as sleeve gastrectomy, gastric bypass uniquely restores pancreatic β-cell function and reduces truncal fat, thus reversing the core defects in diabetes.Type 2 diabetes mellitus and obesity are closely interrelated chronic conditions growing in incidence worldwide, with diabetes-related deaths projected to double between 2005 and 2030 (1). The development of both insulin resistance and insulin secretory defects is the hallmark of type 2 diabetes, resulting in progressive hyperglycemia, subsequent microvascular complications, and macrovascular complications. Although lifestyle modifications and oral hypoglycemic agents improve glycemic control, the majority of patients do not achieve the optimal glycohemoglobin (HbA_1c) levels recommended by current guidelines (≤7.0%). The disease inexorably progresses in the majority of patients, ultimately requiring insulin replacement therapy. Most patients with type 2 diabetes are overweight or obese (BMI ≥30 kg/m²), and abdominal adiposity, particularly, is tightly linked to induction of insulin resistance, metabolic syndrome, and increased cardiovascular risk. Many hypoglycemic agents, especially insulin, exacerbate weight gain and thwart lifestyle efforts, potentially contributing to the underlying pathophysiologic disorder.Because of the limitations to medical therapy, surgical approaches for the treatment of obesity have increased 10-fold in the past decade. Roux-en-Y gastric bypass surgery is the most commonly performed in the United States, followed closely by the sleeve gastrectomy (2). Recently, two randomized controlled trials (3,4) demonstrated improved glycemic control in patients undergoing bariatric surgery compared with intensive medical therapy, resulting in the ability to withdraw or reduce glucose-lowering medications. The rapid rate of glucose lowering, disproportionate to degree of weight loss, suggests that bariatric surgery reverses the fundamental pathophysiological defects of type 2 diabetes. Animal studies suggest that bariatric surgery increases insulin secretion or improves enteroinsulinar responses, specifically, the main incretin hormones glucagon like peptide-1 (GLP-1) and gastric inhibitory peptide (GIP) (5–7). Previous small-scale studies from matched case-control and observational studies in severely obese diabetic individuals have reported that weight loss improves insulin sensitivity, reduces hyperinsulinemia, and improves pancreatic β-cell function by weight-independent mechanisms related to an incretin effect (8–10). However, there are no data from a randomized controlled trial examining the prolonged metabolic adaptations in conjunction with clinical efficacy outcomes after bariatric surgery relative to the effects of intensive medical therapy in moderately obese subjects with poorly controlled type 2 diabetes.The STAMPEDE trial evaluated the efficacy and safety of intensive medical therapy (IMT) alone or intensive medical therapy combined with Roux-en-Y gastric bypass or sleeve gastrectomy to achieve a primary end point of HbA_1c level of ≤6% (with or without medications) after 1 year of follow-up (11). The current report is a 2-year extension of a metabolic substudy of the STAMPEDE trial designed to thoroughly evaluate the effects of the three treatments on glucose regulation, pancreatic β-cell function (insulin secretion/sensitivity), and body composition in a subset of 60 subjects.     

Monitoring of Acute Allograft Rejection by Cytological, Immunocytochemical, and Immunohistochemical Studies Following Rat Small-Bowel Transplantation

u ) to Lewis recipients and syngeneic transplantation using Lewis (RTl^l) rats were carried out. Twenty centimeters of the proximal jejunum was transplanted as a Thiry-Vella loop. The luminal fluid on days 0, 3, and 6 was examined cytologically using Papanicolaou, periodic acid-Schiff, and Giemsa staining, and immunocytochemically with monoclonal antibodies for macrophages (ED1 and ED2). Full thickness biopsies of graft tissue were evaluated by both immunofluorescence (ED1 and ED2) and by standard histological methods. The cytological examination on day 6 revealed an increase in the number of enterocytes, lymphocytes, and neutrophils, the presence of bacteria, and the depletion of goblet cells in the allografts. Histologically, significant morphological changes of acute rejection were first seen on day 6. Immunofluorescence predicted the acute rejection of the allografts earlier than a histological examination by showing an increase in the number of ED1- and Ed2-positive cells on day 3. Graft luminal fluid cytology and immunofluorescence analysis of ED1 and ED2 cells could thus be used to recognize early acute allograft rejection following small-bowel transplantation. (Received for publication on Sept. 18, 1997; accepted on Nov. 6, 1997)     

Job stress among Muslim immigrants in North America: Moderating effects of religiosity

This study examined the relationship of job stress with psychosomatic health problems, happiness in life, job satisfaction, job motivation, organizational commitment and turnover motivation in a sample of Muslims living in Canada and the USA. Data were collected by means of a structured questionnaire (N = 325). Results generally supported the prediction that job stress will be positively related to psychosomatic health problems and turnover motivation, and negatively related to happiness in life, job satisfaction, job motivation and organizational commitment. Degree of religiosity was proposed as a moderator of job stress-outcome relationships. Results from moderated multiple regression indicated that for this sample of Muslims religiosity was an important moderator of the stress-outcome relationships. Implications of the findings for stress management and for future research in the racioethnic area are highlighted.     

Improved experimental cardiac xenograft survival with cyclophosphamide and intrathymic donor cells

Abstract: Tolerance to cardiac allografts can be induced by pretreatment of the recipient with antilymphocyte serum (ALS) and intrathymic donor cells. Our previous efforts to extend this observation to experimental cardiac xenografts in a usually concordant species combination led to antibody and complement mediated hyperacute rejection. Hyperacute rejection can be abrogated by the use of cobra venom factor but this agent even in combination with intrathymic pretreatment is not successful in prolonging xenograft survival in this model. In contrast to the immune response to allografts, which is predominately mediated by T cells, a B cell antibody mediated response plays an important role in xenotransplantation. Cyclophosphamide is active against dividing B cells. In the present experiments in a concordant hamster to rat cardiac xenograft model, we used the combination pretreatment of cyclophosphamide (20 mg/kg IV) injected on days -19, -16, -13, and-10 prior to heart transplantation, ALS (1 ml intraperitoneally), and hamster spleen cells (25 × 10⁶ intrathymically) given on day -18, 1 day after the first dose of cyclophosphamide. Grafted hearts were assessed by daily palpation of the graft pulse through the abdominal wall of the recipient. In untreated control recipients, graft survival was uniformly 3 days. Significant prolongation of graft survival was seen in pretreated animals whose grafts survived 4, 5, 5, 6, and 6 (mean 5.2) days (P<0.01). These studies show that an anti B cell regimen, when coupled with intrathymic pretreatment, results in prolongation of experimental cardiac xenograft survival. However, in contrast to allotransplantation, permanent tolerance cannot be achieved by this pretreatment protocol.