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Abstract The HELLP syndrome (haemolysis, elevated liver blood tests and low platelets) is a serious complication in pregnancy characterized by haemolysis, elevated liver enzymes and low platelet count occurring in 0.5 to 0.9% of all pregnancies and in 10–20% of cases with severe preeclampsia. Hepatic capsular rupture is a rare yet dramatic complication of HELLP syndrome. The majority of cases occur in multiparous women over the age of 30. Classically it presents with acute onset right upper quadrant pain in the presence of constitutional symptoms such as vomiting and pyrexia. However, symptoms and signs are usually non specific. Spontaneous hepatic rupture can be preceded by signs of hypovolaemic shock; yet the diagnosis is infrequently made prior to emergent laparotomy. We present the case of a 35 year old nulliparous woman with a second trimester gestational hepatic rupture associated with HELLP syndrome. We briefly discuss the aetiology, diagnostic difficulties and treatment options associated with this rare presentation.

Abstract Diaphragmatic rupture due to trauma is both well recognised and uncommon. The difficulties in diagnosing traumatic diaphragmatic rupture at the first admission are the most common causes of latent morbidity and mortality. Herniation of the abdominal viscera is the most common sequel with strangulation and perforation the most serious complication. This case outlines the delayed presentation of diaphragmatic rupture and herniation presenting as an acute tension faecopneumothorax. We review the relevant literature, with particular emphasis on the difficulties in diagnosis at presentation.

Tumour stroma gene expression in biopsy specimens may obscure the expression of tumour parenchyma, hampering the predictive power of microarrays. We aimed to assess the utility of fluorescence-activated cell sorting (FACS) for generating cell populations for gene expression analysis and to compare the gene expression of FACS-purified tumour parenchyma to that of whole tumour biopsies. Single cell suspensions were generated from colorectal tumour biopsies and tumour parenchyma was separated using FACS. Fluorescence-activated cell sorting allowed reliable estimation and purification of cell populations, generating parenchymal purity above 90%. RNA from FACS-purified and corresponding whole tumour biopsies was hybridised to Affymetrix oligonucleotide microarrays. Whole tumour and parenchymal samples demonstrated differential gene expression, with 289 genes significantly overexpressed in the whole tumour, many of which were consistent with stromal gene expression (e.g., COL6A3, COL1A2, POSTN, TIMP2). Genes characteristic of colorectal carcinoma were overexpressed in the FACS-purified cells (e.g., HOX2D and RHOB). We found FACS to be a robust method for generating samples for gene expression analysis, allowing simultaneous assessment of parenchymal and stromal compartments. Gross stromal contamination may affect the interpretation of cancer gene expression microarray experiments, with implications for hypotheses generation and the stability of expression signatures used for predicting clinical outcomes.

Resident host microflora condition and prime the immune system. However, systemic and mucosal immune responses to bacteria may be divergent. Our aim was to compare, in vitro, cytokine production by human mononuclear and dendritic cells (DCs) from mesenteric lymph nodes (MLNs) and peripheral blood mononuclear cells (PBMCs) to defined microbial stimuli. Mononuclear cells and DCs isolated from the MLN (n = 10) and peripheral blood (n = 12) of patients with active colitis were incubated in vitro with the probiotic bacteria Lactobacillus salivarius UCC118 or Bifidobacterium infantis 35624 or the pathogenic organism Salmonella typhimurium UK1. Interleukin (IL)-12, tumor necrosis factor (TNF)-alpha, transforming growth factor (TGF)-beta, and IL-10 cytokine levels were quantified by ELISA. PBMCs and PBMC-derived DCs secreted TNF-alpha in response to the Lactobacillus, Bifidobacteria, and Salmonella strains, whereas MLN cells and MLN-derived DCs secreted TNF-alpha only in response to Salmonella challenge. Cells from the systemic compartment secreted IL-12 after coincubation with Salmonella or Lactobacilli, whereas MLN-derived cells produced IL-12 only in response to Salmonella. PBMCs secreted IL-10 in response to the Bifidobacterium strain but not in response to the Lactobacillus or Salmonella strain. However, MLN cells secreted IL-10 in response to Bifidobacteria and Lactobacilli but not in response to Salmonella. In conclusion, commensal bacteria induced regulatory cytokine production by MLN cells, whereas pathogenic bacteria induce T cell helper 1-polarizing cytokines. Commensal-pathogen divergence in cytokine responses is more marked in cells isolated from the mucosal immune system compared with PBMCs.

Background: The exact mechanism by which cyclooxygenase-2 (COX-2) promotes inflammation in pancreatitis in obscure. This study was undertaken to investigate the role of COX-2 inhibition in an animal model of pancreatitis, a disease process characterized by a systemic inflammatory response and ensuing neutrophil-mediated lung injury., Methods: Pancreatitis was induced in 24 Sprague-Dawley rats by intraperitoneal injection of 20% L-arginine (500 mg/100 g body weight). The animals were randomized into 3 groups (8 rats in each group): controls and rats with pancreatitis intravenously resuscitated with either normal saline (0.9% NaCl 3 ml/kg)at 24 and 48 hours or COX-2 inhibitor (parecoxib 1 mg/kg). Pancreatic and lung injuries were assessed histologically. Lung injury was assessed utilizing wet:dry ratio and myeloperoxidase activity to indicate pulmonary neutrophil infiltration. A Western blot was used to determine COX-2 protein expression in pancreatic tissue., Results: The animals treated with COX-2 inhibitors displayed significantly less pancreatic and lung injuries than their normal saline counterparts. Histological pancreatic and lung injury scores were significantly reduced (P<0.05) in the COX-2 treated group. Lung wet:dry ratios were significantly improved and pulmonary neutrophil infiltration was attenuated in the COX-2 group (P<0.05). Western blot analysis confirmed attenuated COX-2 protein expression., Conclusion: This study shows, for the first time in a rat model, that adjuvant COX-2 inhibition significantly attenuates the severity of both pancreatitis and its associated systemic inflammatory response and end-organ injury.

Objective: This study sought to determine whether hypertonic saline (HTS) infusion modulates the host response to bacterial challenge., Methods: Sepsis was induced in 30 Balb-C mice by intraperitoneal injection of Escherichia coli (5 x 107 organisms per animal). In 10 mice, resuscitation was performed at 0 and 24 hours with a 4 mL/kg bolus of HTS (7.5% NaCl), 10 animals received 4 mL/kg of normal saline (0.9% NaCl), and the remaining animals received 30 mL/kg of normal saline. Samples of blood, spleen, and lung were cultured at 8 and 36 hours. Polymorphonucleocytes were incubated in isotonic or hypertonic medium before culture with E. coli. Phagocytosis was assessed by flow cytometry, whereas intracellular bacterial killing was measured after inhibition of phagocytosis with cytochalasin B. Intracellular formation of free radicals was assessed by the molecular probe CM-H(2)DCFDA. Mitogen-activated protein (MAP) kinase p38 and ERK-1 phosphorylation, and nuclear factor kappa B (NFkappaB) activation were determined. Data are represented as means (SEM), and an analysis of variance test was performed to gauge statistical significance., Results: Significantly reduced bacterial culture was observed in the animals resuscitated with HTS when compared with their NS counterparts, in blood (51.8 +/- 4.3 vs. 82.0 +/- 3.3 and 78.4 +/- 4.8, P = 0.005), lung (40.0 +/- 4.1 vs. 93.2 +/- 2.1 and 80.9 +/- 4.7, P = 0.002), and spleen (56.4 +/- 3.8 vs. 85.4 +/- 4.2 and 90.1 +/- 5.9, P = 0.05). Intracellular killing of bacteria increased markedly (P = 0.026) and superoxide generation was enhanced upon exposure to HTS (775.78 +/- 23.6 vs. 696.57 +/- 42.2, P = 0.017) despite inhibition of MAP kinase and NFkappaB activation., Conclusions: HTS significantly enhances intracellular killing of bacteria while attenuating receptor-mediated activation of proinflammatory cascades.

In the normal resolution of an acute inflammatory response apoptosis of neutrophils is essential to maintain immune homeostasis and limit inappropriate host tissue damage by decreasing neutrophil tissue load, function, and release of phlogistic reactive oxygen species and proteases. The systemic inflammatory response syndrome (SIRS), a massive pro-inflammatory immune state, is associated with delayed neutrophil apoptosis, however, the systemic circulating factors and intracellular signal transduction pathways important in regulating neutrophil apoptosis in SIRS are poorly described. Neutrophils isolated from patients with SIRS on admission to the intensive care unit showed significantly (p<.01) delayed spontaneous neutrophil apoptosis compared with healthy neutrophils as quantified using annexin V-FITC and terminal deoxyuridine triphosphate (dUTD) nick end labeling (TUNEL) flow cytometry methods. Plasma from SIRS patients markedly (41.5+/-7.2%, p<.01) inhibited apoptosis of healthy neutrophils compared with controls (69.7+/-4.8%) indicating the presence of soluble circulating factors that can modify the expression of neutrophil apoptosis. Various pro-inflammatory (IL-6, granulocyte macrophage colony-simulating factor, interleukin (IL)-1beta, tumor necrosis factor-alpha) mediators, known to modulate neutrophil apoptosis in vitro, were elevated in the plasma of our cohort of SIRS patients compared with controls. However, the anti-apoptotic effect of SIRS plasma was specifically attenuated (75.5%, p<.01) by neutralizing SIRS plasma of granulocyte macrophage-colony-stimulating factor, but not IL-6, IL-1beta, tumor necrosis factor-alpha. Although the anti-inflammatory cytokine IL-10 was elevated in SIRS plasma (median level 7.2 pg/mL), further boosting SIRS plasma with recombinant human IL-10 (10 ng/mL, levels found in septic shock patients) significantly countered (63.8%, p<.01) the inhibitory effect of SIRS plasma on neutrophil apoptosis. Suppression of neutrophil apoptosis was concomitant with delayed spontaneous elevation of reactive oxygen species, quantified as peroxide production, and reversed by addition of neutralizing antibodies to GM-CSF, and recombinant human IL-10 to SIRS plasma. These results identify circulating GM-CSF as a significant inhibitor of neutrophil apoptosis in patients with SIRS, and that this effect can be countered by boosting SIRS plasma with IL-10. GM-CSF and IL-10 appear to modulate neutrophil apoptosis by altering reactive oxygen species generation in neutrophils.

Hysterectomy is associated with severe constipation in a subgroup of patients, and an adverse effect on colonic motility has been described in the literature. The onset of irritable bowel syndrome and urinary bladder dysfunction has also been reported after hysterectomy. In this prospective study, we investigated the effect of simple hysterectomy on ano-rectal physiology and bowel function. Thirty consecutive patients were assessed before and 16 weeks after operation. An abdominal hysterectomy was performed in 16 patients, and a vaginal procedure was performed in 14. The parameters measured included the mean resting, and maximal forced voluntary contraction anal pressures, the recto-anal inhibitory reflex, and rectal sensation to distension. In 8 patients, the terminal motor latency of the pudendal nerve was assessed bilaterally. Pre-operatively, 8 patients were constipated. This improved following hysterectomy in 4, worsened in 2, and was unchanged in 2. Symptomatology did not correlate with changes in manometry. Although, the mean resting pressure was reduced after hysterectomy (57 mmHg-53 mmHg, P = 0.0541), the maximal forced voluntary contraction pressure was significantly decreased (115 mmHg-105 mmHg, P = 0.029). This effect was more pronounced in those with five or more previous vaginal deliveries (P = 0.0244, n = 9). There was no significant change in the number of patients with an intact ano-rectal inhibitory reflex after hysterectomy. There was no change in rectal sensation to distension, and the right and left pudendal nerve terminal motor latencies were unaltered at follow-up. Our results demonstrate that hysterectomy causes a decrease in the maximal forced voluntary contraction and pressure, and this appears to be due to a large decrease in a small group of patients with previous multiple vaginal deliveries.

The disappearance and subsequent return of the recto-anal inhibitory reflex following low anterior resection was investigated using manometric and histological studies. Ten female greyhound dogs were randomised into 2 groups. All underwent low anterior resection. Five had stapled EEA anastomosis of the rectum and 5 were handsewn. The recto-anal inhibitory reflex was measured before and after surgery using a microtransducer tipped catheter. Six months postoperatively the recto-anal inhibitory response was again measured and the animals sacrificed. The colorectal anastomoses were examined histologically using light microscopy to determine the pattern of innervation at the anastomotic site. Manometric studies showed the recto-anal inhibitory reflex present in all cases pre-operatively, in only 1 case on the tenth postoperative day and was present in eight cases after 6 months. Histological examination of longitudinal sections across the anastomoses showed clear evidence of regenerating nerve trunks at the anastomotic site in both stapled and handsewn groups. We conclude that the return of the recto-anal inhibitory reflex is associated with regeneration of intramural autonomic nerves across the anastomotic scar.

Oesophageal achalasia is uncommon in children and in its familial form it is a rarity. The presentation and management of two male siblings who presented with oesophageal achalasia as infants are reported. A high degree of consanguinity in the parents of the children existed, suggesting autosomal recessive transmission.

Colonic motor activity was initiated by infusions of bile salts into the caecum or rectum of the anaesthetized rabbit. Primary bile acids were examined proximally and distally in the colon and elicited marked motor responses. Sinc dihydroxy bile acids are known to be potent inhibitors of electrolyte and water absorption in the colon, the secondary bile acid deoxycholic acid, the dihydroxyl compound most related to cholic acid which is the main bile acid in the rabbit, was examined distally and was also active, but to a lesser extent than cholic acid conjugates in this species. In man, a relationship was found between the faecal bile acid excretion and colonic motility: the introduction of bile acids directly into the human sigmoid colon and rectum also stimulated colonic motility. In man, the dihydroxy compound chenodeoxycholic acid was slightly more active than conjugates of cholic acid.

Two different types of commercially available bran were studied. One of these was composed of flake-like particles (coarse bran) whereas the other had smaller, finer particles with a floury component (fine bran). The effectiveness of the two preparations in lowering intraluminal pressure and decreasing transit time in patients with constipation and diverticular disease was assessed. Only coarse bran promoted changes at the dose used. The physical properties of the brans were examined in an effort to explain their differing effects. It is concluded that water-holding capacity, upon which the beneficial effect of bran may depend, is a function of particle size. The greater water-holding capacity of coarse bran makes it preferable for the treatment of colonic disorders.