Gastric inhibitory polypeptide and glucagon-like peptide-1 in the pathogenesis of type 2 diabetes

The incretin effect denominates the phenomenon that oral glucose elicits a higher insulin response than does intravenous glucose. The two hormones responsible for the incretin effect, glucose-dependent insulinotropic hormone (GIP) and glucagon-like peptide-1 (GLP-1), are secreted after oral glucose loads and augment insulin secretion in response to hyperglycemia. In patients with type 2 diabetes, the incretin effect is reduced, and there is a moderate degree of GLP-1 hyposecretion. However, the insulinotropic response to GLP-1 is well maintained in type 2 diabetes. GIP is secreted normally or hypersecreted in type 2 diabetes; however, the responsiveness of the endocrine pancreas to GIP is greatly reduced. In approximately 50% of first-degree relatives of patients with type 2 diabetes, similarly reduced insulinotropic responses toward exogenous GIP can be observed, without significantly changed secretion of GIP or GLP-1 after oral glucose. This opens the possibility that a reduced responsiveness to GIP is an early step in the pathogenesis of type 2 diabetes. On the other hand, this provides a basis to use incretin hormones, especially GLP-1 and its derivatives, to replace a deficiency in incretin-mediated insulin secretion in the treatment of type 2 diabetes.     

Pulsatile Pump Decreases Risk of Delayed Graft Function in Kidneys Donated After Cardiac Death

Organ storage techniques have been under scrutiny to determine the best preservation method, particularly in donation after cardiac death (DCD) kidneys. Conflicting literature on the benefit of pulsatile perfusion (PP) over cold storage (CS) warrants further investigation. We analyzed the risk of developing delayed graft function (DGF) in recipients of DCD and donation after brain death (DBD) kidneys undergoing PP or CS. We stratified on basis of cold ischemic time (CIT) to determine the interaction of preservation techniques, CIT and DCD kidneys on developing DGF. Of 54 136 recipients, 4923 received DCD kidneys of which 3330 (67%) underwent PP. Of 49 213 DBD recipients, 7531 (15%) underwent PP. DCD had a higher risk of DGF versus DBD (adjusted odds ratio, AOR 3.2; 3.0–3.5). PP kidneys had less DGF (AOR 0.59; 0.56–0.63) compared to CS. Interaction models of method by donor type referenced to PP/DBD revealed CS/DBD kidneys had higher DGF (AOR 1.8; 1.7–1.9), whereas CS/DCD kidneys had the highest risk of DGF (AOR 5.01; 4.43–5.67). Even though suggestive for a benefit of PP on DGF, this retrospective analysis cannot address whether this is an intrinsic effect of PP or is associated with the logistics of PP such as discard of DCD kidneys based on pump parameters.     

Distribution of substance-P nerves inside the infrapatellar fat pad and the adjacent synovial tissue: a neurohistological approach to anterior knee pain syndrome

Introduction The purpose of the study was to determine the distribution and number of nerves inside the infrapatellar fat pad and the adjacent synovium, in particular with regards to nociceptive substance-P nerves.Materials and methods The infrapatellar fat pad of the knee was resected from 21 patients (4 male, 17 female, mean age 69 years) during the course of standard total knee arthroplasty operations performed in our clinic. The fat pad was dissected into five standardized segments, fixed in formalin and embedded in paraffin. Immunohistochemical techniques using antibodies against S-100 protein and substance-P (SP) were employed to determine and specify the nerves.Results Studying all the detectable nerves present in 50 observation fields (200-fold magnification), we found an average of 106 S-100 versus 25 SP nerves (24%) in the synovium and 27 S-100- versus 7 SP nerves (26%) in the interior of the fat pad. The total nerve count was significantly ( P <0.001) higher in the synovium than in the fat pad for both marker types. The number of S-100 nerves was significantly ( P <0.05) higher in the central and lateral segments of the fat pad, while SP nerves were equally distributed throughout all segments of the fat-pad. SP nerves were significantly more frequently associated with blood vessels inside the fat pad (43%, P <0.05) than in the synovial tissue (28%).Conclusion The occurrence and distribution of SP nerves inside the infrapatellar fat pad suggest a nociceptive function and a neurohistological role in anterior knee pain syndrome. The data support the hypothesis that a neurogenous infection of the infrapatellar fat pad could contribute to anterior knee pain syndrome.     

The multiply injured child

The treatment of multiple traumas in children requires knowledge of common injury patterns, incidence, mortality, and the consequences and differences between these injuries in children and adult patients. However, epidemiological studies concerning pediatric multiple trauma are rare. To address this, data were collected and analyzed from 682 multiple trauma patients treated at a Level I trauma center. The patients were divided into four age-related groups (< 6 years, 6-12 years, 13-18 years, and 18-40 years) and were evaluated for trauma mechanism, injury distribution, and cause of death. Children aged 6 to 17 years mostly were injured as pedestrians and cyclists whereas infants, preschoolers, and adults more commonly were injured as car passengers. Pediatric patients suffered a significantly higher mortality than adults, with a threefold increased risk of death when injured as passengers in car accidents. Injuries to the head and the legs were most common. A lower incidence of thoracic (28% versus. 62%), abdominal (20% versus 36%), pelvic (22% versus 35%), and upper limb (32% versus 43%) trauma was observed in children (< 18 years) than in adults (18-40 years). Nevertheless, trauma to the thorax, abdomen, and head were associated with a high risk of death in all groups. Spinal cord injuries, especially in the cervical region, also carried a high risk of mortality (36.8 in the group of patients younger than 18 years and 18.9 in the group of patients 18-40 years). Children younger than 6 years had the most severe head injuries. The data show that there are important differences in incidence, mortality, and injury patterns between pediatric and adult patients with multiple traumas.     

Composite aortic root replacement in acute type A dissection: time to rethink the indications?

OBJECTIVE: The indications for aortic root replacement in acute type A dissection are unclear. We reviewed the immediate and long-term outcome of consecutive patients in a series in which a low-threshold policy of composite aortic root replacement had evolved. METHODS: From a prospectively compiled aortic surgery database, we identified 162 patients who had either supracoronary interposition grafting, Group A (n=89), or composite root replacement, Group B (n=73) for acute type A dissection. Patients receiving total arch replacements were excluded. Operative and clinical details were analyzed and patient survival was compared to an age and gender matched census cohort. Need for reoperation on the proximal or distal aorta was also noted. Follow-up totaled 795.5 patient-years. RESULTS: Hospital mortality rates were identical in both groups (12.3%: 11 deaths in group A; 9 in group B). Chronic pulmonary disease, diabetes, malperfusion, hemodynamic compromise and aortic root dilatation were independent risk factors for hospital death. Actuarial survival estimates at 1, 5 and 10 years were 79% (71-88%), 64% (53-75%), and 55% (41-68%) for group A, and 79% (70-86%), 73% (62-83%), and 65% (52-78%) for group B (P=0.48). Age and operative patency of the ascending false lumen were independent risk factors for death after hospital discharge. Proximal aortic reoperation was required for four patients in group A and none in group B (P=0.085). CONCLUSION: A strategy of replacement rather than repair of the dissected aortic root for specific indications in type A dissection yielded high survival and low proximal reoperation rates. These results support an aggressive policy of composite root replacement in acute type A dissection.     

Erythromycin antagonizes the deceleration of gastric emptying by glucagon-like peptide 1 and unmasks its insulinotropic effect in healthy subjects

Glucagon-like peptide 1 (GLP-1) has been proposed to act as an incretin hormone due to its ability to enhance glucose-stimulated insulin secretion. Because GLP-1 also decelerates gastric emptying, it physiologically reduces rather than augments postprandial insulin secretory responses. Therefore, we aimed to antagonize the deceleration of gastric emptying by GLP-1 to study its effects on insulin secretion after a meal. Nine healthy male volunteers (age 25 +/- 4 years, BMI 25.0 +/- 4.9 kg/m2) were studied with an infusion of GLP-1 (0.8 pmol.kg(-1).min(-1) from -30 to 240 min) or placebo. On separate occasions, the prokinetic drugs metoclopramide (10 mg), domperidone (10 mg), cisapride (10 mg, all at -30 min per oral), or erythromycin (200 mg intravenously from -30 to -15 min) were administered in addition to GLP-1. A liquid test meal (50 g sucrose and 8% mixed amino acids in 400 ml) was administered at 0 min. Capillary and venous blood samples were drawn for the determination of glucose (glucose oxidase), insulin, C-peptide, GLP-1, glucagon, gastric inhibitory polypeptide (GIP), and pancreatic polypeptide (specific immunoassays). Gastric emptying was assessed by the phenol red dilution technique. Statistical analyses were performed using repeated-measures ANOVA and Duncan's post hoc test. GLP-1 significantly decelerated the velocity of gastric emptying (P < 0.001). This was completely counterbalanced by erythromycin, whereas the other prokinetic drugs used had no effect. Postprandial glucose concentrations were lowered by GLP-1 (P < 0.001 vs. placebo), but this effect was partially reversed by erythromycin (P < 0.05). Insulin secretory responses to the meal were lower during GLP-1 administration (P < 0.05 vs. placebo). However, when erythromycin was added to GLP-1, insulin concentrations were similar to those in placebo experiments. The suppression of meal-related increments in glucagon secretion by GLP-1 was reversed by erythromycin (P < 0.001). The time course of GIP secretion was delayed during GLP-1 administration (P < 0.05), but when erythromycin was added, the pattern was similar to placebo experiments. GLP-1 administration led to a reduction in pancreatic polypeptide plasma concentrations (P < 0.05). In contrast, pancreatic polypeptide levels were markedly increased by erythromycin (P < 0.001). Intravenous erythromycin counteracts the deceleration of gastric emptying caused by GLP-1, probably by interacting with the parasympathetic nervous system (pancreatic polypeptide responses). Despite augmented rises in insulin secretion, the glucose-lowering effect of GLP-1 is markedly reduced when the deceleration of gastric emptying is antagonized, illustrating the importance of this facet of the multiple antidiabetic actions of GLP-1.     

Predictors of Completion Axillary Lymph Node Dissection in Patients with Positive Sentinel Lymph Nodes

Background  Completion axillary lymph node dissection (CALND) is routinely performed in breast cancer patients with positive sentinel lymph nodes (SLN). We sought to determine the sociodemographic, pathologic, and therapeutic variables that were associated with CALND. Methods  From 7/1997 to 7/2003, 1,470 patients with invasive breast cancer were SLN positive by intraoperative frozen section or final pathologic exam by hematoxylin–eosin and/or immunohistochemistry (IHC). A comorbidity score was assigned using Adult Comorbidity Evaluation-27 system. Fisher’s exact, Wilcoxon tests, and multivariate logistic regression analysis were used. Results  CALND was performed less often in patients with age ≥ 70 years compared with age < 70 years, moderate or severe comorbidities compared with no or mild, IHC-only positive SLN and breast conservation therapy (BCT compared with mastectomy. Patients who did not undergo CALND were less likely than CALND patients to have grade III disease, lymphovascular invasion multifocal disease, tumor size > 2 cm or to receive adjuvant chemotherapy. However, they were more likely to undergo axillary radiotherapy (RT). On multivariate analysis, age ≥ 70 years [odds ratio (OR) 0.4, 95% confidence interval (CI) 0.26–0.63], IHC-only positive SLN (OR 0.13, 95%CI 0.09–0.19), presence of moderate to severe comorbidities (OR 0.64, 95%CI 0.41–0.99), tumor size ≤ 2 cm (OR 0.44, 95%CI 0.29–0.66), axillary RT (OR 0.39, 95%CI 0.20–0.78), and BCT (OR 0.54, 95%CI 0.37–0.79) were all independently associated with lower odds of CALND. Conclusions  The decision to perform CALND following positive SLN biopsy was multifactorial. Patient factors were a primary determinant for the use of CALND in our study. The decreased use of CALND in the BCT patients probably reflects reliance on the radiotherapy tangents to maintain local control in the axilla.     

Intradiaphragmatic extralobar sequestration—a rare pulmonary anomaly

Extralobar pulmonary sequestrations are most commonly found within the thoracic cavity, but have been described within the abdomen. We present the case of a 16-month-old boy with an intradiaphragmatic pulmonary sequestration and demonstrate a computed tomographic scan finding that might help identify this extremely rare abnormality preoperatively.     

PET/CT-guided Interventions: Personnel Radiation Dose

Purpose

To quantify radiation exposure to the primary operator and staff during PET/CT-guided interventional procedures.

Methods

In this prospective study, 12 patients underwent PET/CT-guided interventions over a 6 month period. Radiation exposure was measured for the primary operator, the radiology technologist, and the nurse anesthetist by means of optically stimulated luminescence dosimeters. Radiation exposure was correlated with the procedure time and the use of in-room image guidance (CT fluoroscopy or ultrasound).

Results

The median effective dose was 0.02 (range 0–0.13) mSv for the primary operator, 0.01 (range 0–0.05) mSv for the nurse anesthetist, and 0.02 (range 0–0.05) mSv for the radiology technologist. The median extremity dose equivalent for the operator was 0.05 (range 0–0.62) mSv. Radiation exposure correlated with procedure duration and with the use of in-room image guidance. The median operator effective dose for the procedure was 0.015 mSv when conventional biopsy mode CT was used, compared to 0.06 mSv for in-room image guidance, although this did not achieve statistical significance as a result of the small sample size (p = 0.06).

Conclusion

The operator dose from PET/CT-guided procedures is not significantly different than typical doses from fluoroscopically guided procedures. The major determinant of radiation exposure to the operator from PET/CT-guided interventional procedures is time spent in close proximity to the patient.