[The acute compartment syndrome of the arm]. / Het acute compartimentsyndroom van de arm.

Two 37-year-old men, both drug addicts, and a 32-year-old homeless woman presented themselves with a painful arm. Except for the first patient, there was a delay in diagnosing the compartment syndrome of the arm. In the first patient emergency fasciotomy led to a good functional recovery, however kidney function was lost despite proper treatment, possibly due to combined heroine use and muscle breakdown. In the second patient prolonged immobility and altered consciousness by drug use should have increased clinical suspicion. Poor arm function remained even after fasciotomy. In the third patient inadequate clinical examination delayed surgery. Major early symptoms of compartment syndrome are progressive disproportional pain and sensory loss, not relieved by analgesia. If left untreated, the ischaemic tissue damage is potentially limb and even life threatening. The acute compartment syndrome is a clinical diagnosis and a low threshold for surgical exploration and fasciotomy is advocated.

Effect of IGF-rich colostrum on bowel adaptation in neonatal piglets with short bowel syndrome.

BACKGROUND: Insulin-like growth factor 1 (IGF-1), a polypeptide growth factor with mitogenic effects on intestinal epithelial crypt cells occurs naturally in high concentrations in colostrum. The hypothesis for this study was that colostrum rich in IGF-1 could promote small bowel adaptation in neonatal piglets with short bowel syndrome. METHODS: Twenty-four piglets, aged 7 days, underwent 75% small bowel resection and were fed 525 kJ x kg(-1) x d(-1) (125 kcal) of colostrum-based formula (Rs(+)) or placebo formula (Rs(-)). Immunoglobulin G (IgG) accounted for 35% of the protein and was compensated with casein and whey protein in the control feed. The piglets were weighed daily and killed 28 days after surgery. Bowel samples were taken at surgery and at death. RESULTS: Relative body-weight increase did not differ between the Rs(+) and Rs(-) group (84% +/- 9% vs. 90% +/- 12%, P = 0.83). There was a significant relative increase in crypt depth in the Rs - compared with the Rs + group (201% +/- 15% vs. 147% +/- 17%, P = 0.02) and total protein (mg/cm bowel) (482 +/- 51 vs. 278 +/- 46, P = 0.008). Increase in villus length, DNA/RNA content, and mitotic index did not differ between groups. CONCLUSION: Colostrum supplement rich in IGF-1 has no benefits over protein-enriched feed with respect to growth and bowel adaptation in neonatal piglets with short bowel syndrome.

Functional protection by acute phase proteins alpha(1)-acid glycoprotein and alpha(1)-antitrypsin against ischemia/reperfusion injury by preventing apoptosis and inflammation.

BACKGROUND: Ischemia followed by reperfusion (I/R) causes apoptosis, inflammation, and tissue damage leading to organ malfunction. Ischemic preconditioning can protect against such injury. This study investigates the contribution of the acute phase proteins alpha(1)-acid glycoprotein (AGP) and alpha(1)-antitrypsin (AAT) to the protective effect of ischemic preconditioning in the kidney. METHODS AND RESULTS: Exogenous AGP and AAT inhibited apoptosis and inflammation after 45 minutes of renal I/R in a murine model. AGP and AAT administered at reperfusion prevented apoptosis at 2 hours and 24 hours, as evaluated by the presence of internucleosomal DNA cleavage, terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling, and the determination of renal caspase-1- and caspase-3-like activity. AGP and AAT exerted anti-inflammatory effects, as reflected by reduced renal tumor necrosis factor-alpha expression and neutrophil influx after 24 hours. In general, these agents improved renal function. Similar effects were observed when AGP and AAT were administered 2 hours after reperfusion but to a lesser extent and without functional improvement. Moreover, I/R elicited an acute phase response, as reflected by elevated serum AGP and serum amyloid P (SAP) levels after 24 hours, and increased hepatic acute phase protein mRNA levels after 18 hours of renal reperfusion. CONCLUSIONS: We propose that the antiapoptotic and anti-inflammatory effects of AGP and AAT contribute to the delayed type of protection associated with ischemic preconditioning and other insults. This mechanism is potentially involved in the course of many clinical conditions associated with I/R injury. Moreover, exogenous administration of these proteins may provide new therapeutic means of treatment.

A successful short-bowel syndrome model in neonatal piglets.

BACKGROUND: With the higher survival rate of premature neonates as a result of improved neonatal intensive care, the incidence of necrotizing enterocolitis, and thus the incidence of short-bowel syndrome, is increasing. An appropriate animal model resembling the (premature) neonate with short-bowel syndrome suitable for clinically relevant neonatal bowel adaptation and intervention studies, is not available at present. The purpose of this study was the development of a short-bowel syndrome model that mimics the clinical state of the affected neonatal patient. METHODS: Sixteen 7-day-old piglets received either a small bowel transection (group A) or a 75% resection (group B). The piglets were fed 125 kcal/kg body weight per day, including additional electrolytes. The animals were weighed daily and were killed 28 days after surgery. Bowel samples were obtained at both time points. RESULTS: Mortality rates in groups A and B were 0% and 8%, respectively. Body weight gain was significantly higher in group A than in group B (156% vs. 93%; P = 0.01). Jejunal villus length was higher in group B than in group A (74% vs. -2%; P = 0.006), and crypt depth was higher in group B in both jejunum (201% vs. 67%; P = 0.001) and ileum, (197% vs. 20%; P = 0.001), than in group A. CONCLUSIONS: In 7-day-old piglets 75% small bowel resection leads to a clinical short-bowel syndrome, demonstrated by reduced weight gain and typical changes in bowel adaptation parameters. The excellent survival of the animals provides a possibility for the study of bowel adaptation in a neonatal model as well as in intervention studies.

Inhibition of apoptosis induced by ischemia-reperfusion prevents inflammation.

Ischemia followed by reperfusion leads to severe organ injury and dysfunction. Inflammation is considered to be the most important cause of tissue injury in organs subjected to ischemia. The mechanism that triggers inflammation and organ injury after ischemia remains to be elucidated, although different causes have been postulated. We investigated the role of apoptosis in the induction of inflammation and organ damage after renal ischemia. Using a murine model, we demonstrate a relationship between apoptosis and subsequent inflammation. At the time of reperfusion, administration of the antiapoptotic agents IGF-1 and ZVAD-fmk (a caspase inactivator) prevented the early onset of not only renal apoptosis, but also inflammation and tissue injury. Conversely, when the antiapoptotic agents were administered after onset of apoptosis, these protective effects were completely abrogated. The presence of apoptosis was directly correlated with posttranslational processing of the endothelial monocyte-activating polypeptide II (EMAP-II), which may explain apoptosis-induced influx and sequestration of leukocytes in the reperfused kidney. These results strongly suggest that apoptosis is a crucial event that can initiate reperfusion-induced inflammation and subsequent tissue injury. The newly described pathophysiological insights provide important opportunities to effectively prevent clinical manifestations of reperfusion injury in the kidney, and potentially in other organs.

Insulin-like growth factor-1 (IGF-1) and growth hormone (GH) in immunity and inflammation.

In recent years many efforts have been undertaken to elucidate the complex interactions between mediators of the endocrine system and the immune system. The main effector of growth hormone (GH) is insulin-like growth factor-1 (IGF-1), an endocrine mediator of growth and development under physiological conditions. Besides this important function, IGF-1 also plays a prominent role in the regulation of immunity and inflammation. This article will address the involvement of IGF-1 in innate as well as acquired immunity and host-defense. We also discuss the role of IGF-1 in the course of inflammatory disorders, including sepsis and sepsis-induced catabolism as well as degenerative arthritis. Based on recent insights, we finally examine the pathophysiological background, potential pitfalls and perspectives of IGF-1 suppletion therapy in these conditions.