A practical guide to using insulin

Normally, the level of total body water is maintained by natural elimination and intake. However, several variables can influence the rate of water loss, and if mechanisms that regulate thirst malfunction, intake can be affected as well. The resulting water imbalance can cause excessive or deficient sodium levels. Dr Brown describes the interrelationship between water and sodium concentrations, explains how to calculate a given patient's requirements, and presents a safe approach to the various types of imbalance.     

Lymphokine-induced phagocytosis in angiocentric immunoproliferative lesions (AIL) and malignant lymphoma arising in AIL

A factor that augmented the phagocytosis of IgG-coated ox red blood cells by the human monocyte/macrophage line U937 was identified in cell culture supernatants from two of two patients with angiocentric peripheral T cell lymphomas, three of three patients with angiocentric immunoproliferative lesions that were not frankly malignant, and one of two patients with T lymphoblastic malignancies. The factor was not present in supernatants derived from 14 nonangiocentric peripheral T cell lymphomas of other histologic types nor in ten cases of B cell lymphoma and two cases of Hodgkin's disease. A similar factor was present in the supernatants of concanavalin A (Con A)-stimulated normal peripheral blood mononuclear cells and in the supernatants of IL-2- dependent T cell lines derived from normal peripheral blood. The factor had an apparent mol wt of greater than 50,000 daltons, was heat labile (100 degrees C for two minutes), and stable at pH 2.0. Its stimulation of phagocytosis was independent of any increase in number of Fc receptors. Thus, this factor is probably not gamma-interferon. This factor may play a pathogenetic role in the hemophagocytic syndromes associated with certain T cell malignancies and immunodeficient states.     

SOD1, ANG, TARDBP and FUS mutations in amyotrophic lateral sclerosis: a United States clinical testing lab experience

SOD1, ANG, TARDBP and FUS mutations have been associated with amyotrophic lateral sclerosis (ALS). Our goal was to extend molecular genetic analysis to newly identified ALS genetic loci and to determine the frequency of mutations, distribution of disease genes, and variant spectrum of these genes in a large United States ALS-phenotype cohort. We screened 1220 probands with an ALS phenotype, referred originally for SOD1 molecular genetic analysis. 1128 SOD1-negative probands were screened for ANG, and 277 and 223 SOD1- and ANG-negative samples were screened for TARDBP and FUS, respectively. One hundred additional probands were specifically screened only for FUS exon 15. We identified a total of 36 different SOD1 mutations, including three novel mutations, in 92 probands. ANG screening identified three mutations, including two novel mutations, and TARDBP screening identified two previously reported TARDBP mutations. We also identified four mutations in FUS, including the reported FUS in-frame deletion, c.430_447del, p.Gly144_Tyr149del, in a patient with inclusion body myositis, and two known FUS missense mutations. From this study, we estimate frequencies for SOD1, ANG, TARDBP and FUS mutations, in this United States cohort, to be 7.5%, 0.71%, 0.72% and 1.9%, respectively. In conclusion, we identify novel variants in SOD1, ANG, TARDBP and FUS, and expand the FUS-associated clinicopathologic phenotype.     

A Multi-institutional Analysis of Duodenal Neuroendocrine Tumors: Tumor Biology Rather than Extent of Resection Dictates Prognosis

Introduction

Duodenal neuroendocrine tumors (NETs) are rare neoplasms with poorly defined management. We sought to evaluate the outcomes of patients undergoing resection of duodenal NETs.

Methods

Using a multi-institutional database, 146 patients who underwent resection for duodenal NETs between 1993 and 2015 were identified. Data on clinicopathologic characteristics and outcomes were collected and analyzed.

Results

Local surgical resection (LR) was performed in 57 (39.0 %) patients, while 50 (34.3 %) patients underwent pancreaticoduodenectomy (PD) and 39 (26.7 %) patients an endoscopic resection (ER). Factors associated with worse RFS included advanced tumor grade and metastasis at diagnosis (both P?<?0.05) but not procedure type (P?>?0.05). Among patients who had at least one lymph node examined (n?=?85), 50 (58.8 %) had a metastatic lymph node; lymph node metastasis (P?=?0.04) and advanced tumor grade (P?=?0.04) were more common among patients with tumors >1.5 cm. Median length-of-stay was longer for PD versus LR (P?<?0.001). PD patients were at increased risk for severe postoperative complications (P?=?0.01).

Conclusion

Recurrence of duodenal NETs was dependent on tumor biology rather than procedure type. PD was associated with a longer hospital stay and higher risk of perioperative complications. For patients with tumors ≤1.5 cm, LR or ER may be appropriate with PD reserved for larger lesions and those not amenable to a more local approach.

     

Inhibition of p38 mitogen-activated protein kinase protects human islets from cryoinjury and improves the yield, viability, and quality of frozen-thawed islets

The development of an optimal islet cryopreservation method will permit transplantation of islets from multiple donors in a single procedure and contribute to alleviation of the islet shortage. In this study, we have improved human islet cryopreservation methods under serum-free conditions using an intracellular-based islet cryopreservation solution (ICS), especially supplemented with a p38 pathway inhibitor (p38IH) to suppress p38 mitogen-activated protein kinase (MAPK) activation. Three different solutions were compared for freezing and thawing of human islets (1) conventional RPMI1640 medium, (2) ICS, and (3) ICS supplemented with a p38IH, SD-282 (ICS-p38IH). Islet cryopreservation with ICS-p38IH significantly improved islet recovery, viability, and quality after thawing of cryopreserved islets. This improvement may allow the use of cryopreserved islets in clinical islet transplantation.     

Carcinoid tumors of the duodenum

BACKGROUND: Carcinoid tumors of the duodenum are rare, and their natural history has not been defined. Consequently, there is no consensus on the optimal extent of surgical treatment. METHODS: The authors reviewed the records of all patients with primary carcinoid tumors of the duodenum treated at their institution from 1969 through 2004. Patients with primary periampullary tumors and gastrinomas were excluded. RESULTS: Twenty-four patients had a pathologic diagnosis of duodenal carcinoid tumor. The majority (89%) of tumors measured less than 2 cm in diameter, and most (85%) were limited to the mucosa or submucosa. Lymph node metastases were identified in the surgical specimen in 7 (54%) of 13 patients in whom lymph nodes were examined, including 2 patients with tumors smaller than 1 cm and limited to the submucosa. At a mean follow-up of 46 months, the disease-specific survival rate was 100%, and only 2 patients have had recurrences in regional lymph nodes. No patient has had distant metastases or the carcinoid syndrome. CONCLUSIONS: Carcinoid tumors of the duodenum are indolent. The presence of regional lymph node metastases cannot be predicted reliably on the basis of tumor size or depth of invasion, and their impact on survival is uncertain.     

Redistribution of joint moments is associated with changed plantar pressure in diabetic polyneuropathy

Background  

Patients with diabetic polyneuropathy (DPN) are often confronted with ulceration of foot soles. Increased plantar pressure under the forefoot has been identified as a major risk factor for ulceration. This study sets out to test the hypothesis that changes in gait characteristics induced by DPN related muscle weakness are the origin of the elevated plantar pressures.     

Soldier attitudes toward mental health screening and seeking care upon return from combat

OBJECTIVE: This study examined soldier attitudes about postdeployment mental health screening, treatment, barriers to care, strategies for overcoming barriers, and settings, personnel and timing for conducting postdeployment mental health screening. METHODS: Deploying soldiers participated in a voluntary anonymous survey. RESULTS: Of 3,294 soldiers, 2,678 (81.3%) responded to the survey. When the three most endorsed perceived barriers to mental health care (negative perception by unit members, negative perception by leaders, and being viewed as weak) were examined, approximately 15% fewer soldiers endorsed the perceptions, compared with a previous study conducted at the beginning of the war. Receipt of training focused on managing psychological problems associated with increased agreement to seek treatment. Participants endorsed surveys, interviews, and unit providers as preferred instruments and providers for postdeployment screening. Soldiers endorsed encouragement from family members and friends as the preferred approach to reducing barriers to mental health care. CONCLUSION: Extensive educational programs seemed to have reduced the stigma related to receiving mental health care. Programs that focus on friend and family member encouragement of soldiers to seek mental health assistance should continue. Postdeployment screening should be conducted under conditions in which soldiers are most likely to report problems honestly.     

Results of Surgical Salvage after Failed Chemoradiation Therapy for Epidermoid Carcinoma of the Anal Canal

Background The standard treatment for epidermoid carcinoma of the anal canal consists of combined radiation and chemotherapy. For patients who present with persistent or locally recurrent disease, salvage abdominoperineal resection is the treatment of choice. The purpose of this study is to review our experience with salvage surgery in this group of patients. Methods From 1990–2002, 31 patients underwent radical salvage surgery with curative intent after failure of initial sphincter-conserving therapy, and the medical records of these patients were retrospectively reviewed. Clinicopathologic variables were determined and comparisons performed with the Cox proportional hazards model. Survival was calculated by the Kaplan–Meier method. Results Eleven patients underwent radical salvage surgery for persistent disease and 20 patients for recurrent disease. The median follow-up time was 29 months. The actuarial 5-year overall survival was 64%. Twelve patients developed recurrent disease after radical salvage surgery. Patients who received an initial radiation dose of less than 55 Gy had a significantly worse survival than those who received at least 55 Gy as part of their initial treatment (5-year overall survival 37.5% vs. 75%; age-adjusted hazard ratio 8.2 [95% CI: 1.1–59.8], P = .037). The presence of positive lymph nodes at presentation also adversely affected survival (P < .05). Factors that were not found to have an impact on survival included the presence of persistent versus recurrent disease, tumor (T) stage, and margin status of resection. Conclusions Long-term survival following salvage surgery for persistent or locally recurrent epidermoid carcinoma of the anal canal can be achieved in the majority of patients. However, patients who initially present with node-positive disease and patients who receive a radiation dose of less than 55 Gy as part of their initial chemoradiation therapy regimen have a worse prognosis after radical salvage surgery.