bluuebunny/crossref_metadata_2025 huggingface dataset:
Reperfusion injury is greater with delayed restoration of venous outflow in concurrent arterial and venous limb injury
Authors: Harkin D W , Barros D'Sa A A B , Yassin M M I , Young I S , McEneny J , McMaster D , McCaigue M D , Halliday M I , Parks T G
Published: March 2003

Background

Complex limb trauma often involves combined arterial and venous injury, and the resultant ischaemia–reperfusion injury (IRI) causes both local and remote organ injury. This study assessed the influence of the timing of restoration of venous drainage on IRI.

Methods

Male New Zealand white rabbits (n = 36) were randomized into six groups: sham operation (group 1) and unilateral hind limb arterial and venous occlusion for 1 h followed by no reflow for 2 h (group 2), arterial and venous reflow for 2 h (group 3), arterial reflow alone for 2 h (group 4), arterial reflow alone for 1 h followed by arterial and venous (delayed) reflow for a further 1 h (group 5), and pretreatment with an enteral combination antioxidant before occlusion of both artery and vein and delayed venous reflow (group 6). Plasma hydroperoxide (HPO) and glutathione peroxidase concentration, hind limb skeletal muscle and lung tissue wet: dry weight ratios and myeloperoxidase (MPO) concentration were measured.

Results

The plasma HPO level in the femoral vein effluent was significantly greater after delayed venous reflow (mean(s.e.m.) 2·02(0·54) μmol/l) than in control animals (0·98(0·10) μmol/l) (P < 0·05). There was also a significantly greater tissue wet: dry weight ratio after delayed venous reflow than in controls, in skeletal muscle (mean(s.e.m.) 6·89(0·14) versus 5·34(0·54); P < 0·05) and lung (9·20(1·14) versus 7·23(0·38); P < 0·05) tissue. Lung tissue MPO activity was significantly greater after delayed venous reflow compared with controls (3·20(0·28) versus 1·86(0·14) units/g; P < 0·005), and also in comparison to simultaneous arterial and venous reflow (2·40(0·24) units/g; P < 0·05). In the antioxidant pretreatment group there was no significant increase in plasma HPO concentration, tissue MPO level or tissue wet: dry weight ratio compared with the control group.

Conclusion

In combined major arterial and venous injury of the limb, delayed restoration of venous drainage leads to significantly greater local skeletal muscle injury and remote neutrophil-mediated lung injury. These results support the clinical rationale for early restoration not only of arterial inflow but also venous drainage by means of intraluminal shunts.
Molecular technology and pancreatic cancer
Authors: Manu M , Buckels J , Bramhall S
Published: March 2003

Background

Pancreatic cancer is the fifth leading cause of cancer death in the Western world. Despite improvement in operative mortality rates, little impact has been made on overall 5-year survival. This review discusses the molecular changes peculiar to pancreatic cancer and how the use of molecular technology might affect detection, screening, diagnosis and treatment of the disease.

Methods

A literature review was performed using the National Library of Medicine's Pubmed database; this was combined with ongoing work within the Queen Elizabeth Hospital, Birmingham.

Results

Over the past 20 years great strides have been made in our understanding of the molecular basis of disease. Advances in molecular biology are now reshaping how diseases are screened for, diagnosed, investigated and treated. In recent years collaboration between clinicians and basic scientists has revealed a unique pattern of genetic and molecular events in pancreatic cancer. This review discusses how these advances may impact on patients with this disease.

Conclusion

The past decade has seen some improvement in outlook for patients with pancreatic cancer, but the ‘molecular age’ promises to deliver even better results.
Anal vector volume analysis complements endoanal ultrasonographic assessment of postpartum anal sphincter injury
Authors: Fynes M M , Behan M , O'Herlihy C , O'Connell P R
Published: March 2003

Background

The aim of this study was to determine the role of anal vector manometry in the assessment of postpartum anal sphincter injury and to establish the most suitable method of anal vector volume analysis for identifying significant external anal sphincter (EAS) injury in an at-risk parous population.

Methods

A total of 101 consecutive women with a history of instrumental or traumatic vaginal delivery was recruited. Anal ultrasonography and anal vector manometry were performed. Receiver–operator characteristic curves were used to determine the usefulness of anal manometry and anal vector volume analysis in the identification of significant EAS disruption (full thickness, more than one quadrant involved) detected by ultrasonography.

Results

Seventeen women had significant EAS disruption identified by anal ultrasonography. Anal vector manometry provided complementary functional information. Anal vector symmetry index (VSI), determined by analysis of mean maximum squeeze pressure, yielded 100 per cent sensitivity for significant EAS disruption, with a positive predictive value of 61 per cent.

Conclusion

Anal vector manometry complements endoanal ultrasonography. VSI, determined by means of the squeeze pressure profile, correlates best with significant EAS disruption identified at anal ultrasonography.
Hyperthermic intraperitoneal chemoperfusion in the treatment of locally advanced intra-abdominal cancer
Authors: Ceelen W P , Hesse U , de Hemptinne B , Pattyn P
Published: March 2003

Background

Surgical treatment of intra-abdominal cancer is often followed by local recurrence. In a subgroup of patients, local recurrence is the sole site of disease, reflecting biologically low-grade malignancy. These patients might, therefore, benefit from local treatment. Recently, debulking surgery followed by hyperthermic chemoperfusion has been proposed in the treatment of locally advanced or recurrent intra-abdominal cancer. This paper reviews the rationale and assesses the currently accepted indications for and results of this novel treatment.

Methods

A systematic web-based literature review was performed. Information was also retrieved from handbooks, congress abstracts and ongoing clinical trials.

Results

A growing body of experimental evidence supports the use of hyperthermia combined with chemotherapy as an adjunct to cytoreductive surgery. Randomized clinical trials are available to support its use in the treatment and prevention of peritoneal carcinomatosis following resection of pathological tumour stage pT3 or pT4 gastric cancer; several other phase III trials are ongoing. Numerous phase I and II trials have reported good results for various other indications, with acceptable morbidity and mortality rates. Case mix, limited patient numbers and absence of a standardized technique are, however, a drawback in many of these series.

Conclusion

For a subgroup of patients with peritoneal cancer without distant disease, debulking surgery followed by hyperthermic chemoperfusion may offer a chance of cure or palliation in this otherwise untreatable condition. This novel therapy should, however, be considered experimental until further results from ongoing phase III trials become available.
Administration of nitric oxide restores the abolished hepatic artery buffer responses in early porcine endotoxaemia
Authors: Götzinger P , Jørgensen P F , Scholz T , Gundersen Y , Függer R , Sautner T , Aasen A O
Published: March 2003

Background

Among other organs, the liver may be severely compromised by the altered haemodynamic conditions of septic shock. The hepatic artery buffer response (HABR), which is mediated mainly by adenosine 5′-triphosphate and nitric oxide as the second messenger, and is ablated during endotoxaemia, plays a central role in the autoregulation of liver perfusion. It was hypothesized that a temporarily decreased synthesis of nitric oxide during early endotoxaemia might be responsible for the dysfunction of the HABR and that administration of nitric oxide could re-establish the autoregulation of hepatic blood flow.

Methods

The experiment was performed in 15 juvenile Landrace pigs, which were randomly assigned to receive endotoxin (ET) 1·7 μg kg−1 min−1 (Escherichia coli) and the non-enzymatic nitric oxide donor sodium nitroprusside (SNP) 3 μg kg−1 min−1 (ET-SNP group; n = 7) or ET 1·7 μg kg−1 min−1 (E. coli) and vehicle (ET group; n = 8). ET and nitric oxide were administered into the portal vein. Study measurements (haemodynamic measurements, liver perfusion) were performed for 5 h.

Results

ET caused a significant decrease in liver perfusion after 5 h. Hepatic arterial flow (Qha) was reduced by 50 per cent and portal vein flow (Qpv) by 38 per cent. The additional administration of nitric oxide ameliorated liver perfusion; Qha and Qpv were not altered significantly in the ET-SNP group. The mechanical reduction of Qpv to approximately 50 per cent of baseline increased Qha in all animals before administration of ET. Flow increase in the hepatic artery due to partial Qpv occlusion (HABR) was lost in the ET group, while nitric oxide preserved a mean increase of 28 per cent in Qha (P < 0·01). At time zero the Qpv reduction decreased mean hepatic artery resistance (HAR) in both groups. Thereafter ET infusion led to a continuous loss of the response of HAR to reduction of Qpv, while nitric oxide administration kept the response of HAR at pre-ET levels throughout the experiment. At 4 and 5 h the reactivity of HAR to manipulations of Qpv had returned to baseline levels in the ET group.

Conclusion

Early administration of the non-enzymatic nitric oxide donor SNP during endotoxaemia is able to re-establish an autoregulatory response of the hepatic artery following reduction of hepatic blood flow.
Immune dysfunction following haemorrhage can be restored by interleukin 10 in males but not in females
Authors: Kahlke V , Dohm C , Brötzmann K , Schreiber S , Schröder J
Published: March 2003

Background

Recent studies have shown depressed immune responses following haemorrhagic shock in males, whereas they are enhanced in females. Furthermore, this results in a lower mortality rate in females following subsequent sepsis. Interleukin (IL) 10 has been shown to play a potential role in treatment of the early proinflammatory state following haemorrhagic shock. Although beneficial effects of treatment with IL-10 have been shown, it remains unclear whether the effects are sex related.

Methods

Male and female CBA/J mice were subjected to haemorrhage (35 ± 5 mmHg for 90 min and fluid resuscitation) or sham operation. At resuscitation each received either intraperitoneal recombinant murine IL-10 or placebo. In vitro splenic T cell responses were determined 48 h after resuscitation.

Results

IL-10 release of splenocytes was not enhanced after IL-10 treatment. Proinflammatory immune function was depressed (i.e. proliferation, IL-2, IFN-γ) in males receiving placebo compared with no change in females. IL-10 treatment restored the depressed proinflammatory immune response in males following haemorrhagic shock (Fig. 1). In contrast, the immune response in females receiving IL-10 was not significantly changed. However, IL-10 treatment of sham-operated male mice led to immune depression compared with placebo-treated animals.

Conclusion

Early IL-10 anti-inflammatory treatment following haemorrhage has potential beneficial effects in males only.
Effect of bacteria and antibiotic treatment on whole blood-mediated endothelial permeability in vitro
Authors: Nooteboom A , Hendriks T , van der Linden C J
Published: March 2003

Background

During Gram-negative sepsis bacterial endotoxin or lipopolysaccharide (LPS) may activate and damage endothelial cells resulting in systemic vascular leakage. Antibiotic treatment of Gram-negative bacteria results in significant release of LPS, inducing production of cytokines by leucocytes in vitro. The biological relevance of this finding is not well understood. A whole blood assay and cultured endothelial monolayers have been used to evaluate the effect of antibiotic treatment of bacteria on endothelial permeability.

Methods

Heat-inactivated (HI) Escherichia coli (ATCC 25922) was treated with either cefuroxime (CXM), imipenem–cilastin (IPM) or polymyxin B (poly B). The cultures were incubated with heparinized whole blood from healthy donors in a final concentration of 105 colony-forming units ml−1 and incubated at 37°C for 24 h. Plasma was then collected and added to human umbilical vein endothelial cell monolayers cultured on semipermeable Transwell COL membranes. The permeability of the monolayers was determined using fluorescein isothiocyanate-labelled (FITC) albumin and rhodamine-β-isothiocyanate-labelled (RITC) dextran. The production of interleukin (IL) 1β, IL-6, IL-1ra and tumour necrosis factor (TNF) α in whole blood was measured using radioimmunoassay.

Results

In whole blood, HI bacteria alone induced the production of IL-1β, IL-6, IL-1ra and TNF-α. CXM treatment of HI E. coli before incubation in blood induced significantly more IL-1β, TNF-α and IL-6 than the HI control, while poly B treatment induced less cytokine production. IPM did not significantly alter the production of cytokines. In the permeability assay, whole blood treated with HI bacteria alone induced a permeability increase of 2·3 times control monolayer permeability (P < 0·05). While CXM or IPM treatment resulted in a significant further enhancement of the permeability, there was no significant difference between these antibiotic treatments (permeability increase 2·9 and 2·8 times the control respectively). In contrast, treatment with poly B almost completely abrogated the permeability effect of HI bacteria (1·1 times control; P > 0·05).

Conclusion

Since neutralization of LPS by poly B reduces the E. coli-induced production of cytokines in whole blood and prevents increased permeability, free LPS may be the driving force of cytokine-mediated endothelial permeability. Treatment of bacteria with CXM or IPM induces a significantly different cytokine production in whole blood. However, in both cases the resulting plasma leads to a similar increase in permeability. Thus, the fact that individual antibiotics can release different amounts of LPS may be irrelevant to endothelial permeability.
Risk factors in surgical patients with intra-abdominal Candida infection in intensive care
Authors: Bouchantouf T , Meis J F G M , Neeleman C , Kuiper D R , van Goor H
Published: March 2003

Background

Candida species have been isolated with increasing frequency during intra-abdominal infection, yet their role as pathogens or co-pathogens and as determinants for outcome, especially in patients who are frequently reoperated on, is not well understood. Furthermore, the value of antimycotic therapy is the subject of discussion.

Methods

Candida cultures from the abdomen of surgical patients over the past 10 years (1989–1999) were documented. Medical records of the patients were reviewed for risk factors for morbidity and death.

Results

Some 72 patients (45 men, 27 women), of mean age 60 (range 18–88) years, had Candida cultured from the abdomen during operation. Indications for surgery included duodenal ulcer perforation in 15 patients (21 per cent), gastrointestinal malignancy in 15 (21 per cent), pancreatitis in nine (12 per cent) and various disorders in the remaining 33. A total of 361 relaparotomies was performed in 72 patients (mean 5, range 0–48). Cultures were positive at the first laparotomy in 19 patients, at the first relaparotomy in 20 patients and in 33 patients at the second or more relaparotomy. All but one patient were treated in the intensive care unit. Some 45 (62 per cent) of 72 patients died a mean of 44 (range 3–234) days after the first laparotomy. Risk factors for death, which appeared not to be significant, are shown in the Table.

Conclusion

The number of relaparotomies among patients with Candida-positive cultures was high. No significant risk factors for death could be identified in surgical patients with intra-abdominal Candida infection in intensive care.
Translocation of Enterococcus in jaundiced and anergic rats
Authors: Cainzos M , Prieto D , Mena E , Lage P , Seoane R , Viñuela J , Mora M
Published: March 2003

Background

Translocation of bacteria from the gut to other organs is one cause of systemic complications in obstructive jaundice. Furthermore, hyperbilirubinaemia appears to cause anergy. This study investigated whether these responses (translocation of gut bacteria and anergy) increase the postoperative mortality rate in rats in which obstructive jaundice is induced surgically by ligature of the bile duct.

Methods

Some 88 male Wistar rats were divided into six groups. All rats except those in group 1 received gentamicin by the oral route (0·7 mg in 1 ml water, daily for 6 days) to ensure intestinal decontamination. On day 7, all rats except those in groups 1 and 2, which had vehicle only, received Enterococcus. Statistical analysis was by Student's test and Fishers's exact test.

All animals underwent standard blood testing, delayed hypersensitivity tests, haematimetry and serum endotoxin determinations. Flow cytometry was used to count CD3-, CD4- and CD8-positive lymphocytes. On the day 5 after surgery, these assays were repeated and, in addition, the rats were killed for microbiological analysis of gut and viscera contents (liver, spleen, mesentery and lung).

Results

Five days after surgery, mean bilirubin levels in groups 5 and 6 were greater than 14 mg dl−1. In addition, all rats in groups 5 and 6 showed absence of the delayed hypersensitivity response, indicating anergy. Lymphocyte counts in each group are shown in the Table.

The mean proportion of CD8-positive lymphocytes in rats that had received Enterococcus (groups 3–6) was 16 per cent compared with 25 per cent in groups 1 and 2 (P < 0·05). The mean percentage of CD3-positive lymphocytes in groups 5 and 6 was 51 per cent, but 71 per cent in all other groups (P < 0·05). Likewise, the mean percentage of CD4-positive lymphocytes in groups 5 and 6 was 32 per cent, but 47 per cent in all other groups (P < 0·05). The postoperative mortality rate in group 4 (17 per cent) was significantly lower than that in the obstructive jaundice groups 5 and 6 (62 per cent) (P < 0·01). Post-mortem microbiological analyses revealed translocation of Enterococcus only in groups 5 (80 per cent) and 6 (70 per cent). Enterococci were most frequently present in the mesentery (80 and 70 per cent respectively), followed by the liver (40 and 40 per cent), spleen (20 and 20 per cent) and lungs (10 and 10 per cent).

Conclusion

(1) Obstructive jaundice in rats leads to immunological alterations including anergy. (2) Obstructive jaundice in rats favours translocation of enterococci from the gut to other organs. (3) The postoperative mortality rate in jaundiced rats was much higher than that in sham-operated rats.
Bacterial lipoprotein induces tolerance in human THP-1 monocytes with reduced tumour necrosis factor α production via a CD14-independent pathway
Authors: Doyle M , Wang J H , Wu Q D , Blankson S , Redmond H P
Published: March 2003

Background

Endotoxin (lipopolysaccharide; LPS) tolerance is characterized by diminished production of tumour necrosis factor (TNF) α during prolonged exposure to LPS, and therefore represents an essential control mechanism during sepsis. However, it is unknown whether bacterial lipoprotein (BLP), another major component of bacterial walls, can cause tolerance. This study sought to determine whether BLP pretreatment can induce tolerance in human THP-1 monocytes.

Methods

Human THP-1 monocytic cells were pretreated with culture medium alone and medium containing LPS 10 ng ml−1 or BLP 10 ng ml−1 for 24 h. Cells were further stimulated with high doses (0·1–1 mg ml−1) of LPS or BLP for 6 h. TNF-α levels were determined by enzyme-linked immunosorbent assay. CD14 receptor expression on THP-1 monocytes was assessed by flow cytometry.

Results

When THP-1 cells were incubated with culture medium, BLP stimulation resulted in much higher TNF-α levels than LPS stimulation (P < 0·05). Following LPS pretreatment, LPS stimulation-induced TNF-α production was significantly attenuated, whereas BLP stimulation still produced a small amount of TNF-α. However, BLP pretreatment prevented both LPS and BLP stimulation-induced TNF-α production from THP-1 cells. FACScan analysis revealed that THP-1 monocytes do not express CD14 receptor.

Conclusion

These results demonstrate that BLP has a more potent effect than LPS on THP-1 monocyte TNF-α production. Furthermore, BLP pretreatment is capable of inducing both BLP as well as LPS tolerance via a CD14-independent pathway, indicating a unique ability to cause cross-tolerance.
Decreased incidence of ventilator-associated pneumonia caused by Pseudomonas aeruginosa over 3 years
Authors: Fiore M , van Nieuwenhoven C A , Ramsay G
Published: March 2003

Background

Ventilator-associated pneumonia (VAP) is a frequently occurring infection among critically ill patients. Pseudomonas aeruginosa, Staphylococcus aureus, Klebsiella pneumoniae and Escherichia coli are the most common micro-organisms causing VAP. The aim of this study was to ascertain the incidence of VAP diagnosed with bronchoalveolar lavage (BAL) by these possible pathogenic micro-organisms (PPMOs). Because VAP is often preceded by colonization of the oropharynx with the causative pathogen, sputum cultures were compared with the BAL cultures.

Methods

Over a 3-year period, all ventilated patients in two intensive care units (n = 1136) were reviewed for pneumonia. A VAP was present when the bacterial count of the BAL was more than 104 colony-forming units ml−1. The microbial results of all patients with a VAP (polymicrobial or monomicrobial) were recorded.

Results

The mean incidence of VAP was 8 per cent (n = 92), decreasing only slightly during the period (P > 0·05). The most frequent aetiological agents were P. aeruginosa (n = 34), S. aureus (n = 22), E. coli (n = 16) and K. pneumoniae (n = 10). The percentage of VAPs due to P. aeruginosa has declined progressively from 53 to 31 per cent. Concurrently, the incidence of Pseudomonas colonizing the sputum culture has declined (from 54 to 44 per cent). On the other hand, the incidence of VAP due to E. coli has increased from 13 (n = 2) to 36 per cent (n = 6). Colonization of the sputum with E. coli has similarly increased (from 13 to 27 per cent).

Conclusion

The incidence of VAP in the intensive care unit is in accordance with the literature, when diagnosed with strict criteria. No significant change in the incidence of VAP was noted during the 3-year period. Neither the decrease in incidence of VAP caused by P. aeruginosa nor the increase in E. coli pneumonia can be explained by a change in antibiotic regimens in the period studied. Hypothetically, cross-colonization of PPMOs by healthcare personnel can be influenced by hand-washing and wearing gloves. This can especially influence colonization by P. aeruginosa, thus explaining the decrease.
Evidence of a prognostic value for platelet surface antigen expression in severe abdominal sepsis
Authors: Salat A , Kroess S , Felfenig-Boehm D , Schmidt D , Sautner T , Mueller M R , Fuegger R
Published: March 2003

Background

There is evidence for the involvement of platelets under septic conditions. Alterations of platelet surface antigen expression at the onset of septic shock have been reported previously. The aim of this study was to investigate platelet activation as well as changes in platelet receptors during the course of severe sepsis.

Methods

The study population included six patients with severe sepsis because of peritonitis or necrotizing pancreatitis. Platelet investigations were performed daily. For analysis three characteristic time points during the course were defined restrospectively (A, onset of septic shock; B, significant clinical improvement; C, last sample before death). A double-colour flow cytometric assay was performed in whole blood to determine platelet surface expression of CD63, CD62P, CD42B, CD36 and CD31.

Results

At the onset of septic shock (A) all patients showed similar antigen expression (CD63, 1·24; CD62P, 0·59; CD42B, 30·9; CD36, 28·0; CD31, 18·2). In surviving patients (B, n = 2) antigen expression was lower (CD63, 0·70; CD62P, 0·38; CD42B, 27·8; CD31, 12·4) or higher (CD36, 27·6) than in patients (C, n = 4) who died (CD63, 1·55; CD62P, 0·72; CD42B, 36·5; CD36, 24·1; CD31, 21·1).

Conclusion

Although the study population was very small and heterogeneous, these results point to a correlation of platelet surface antigen expression with clinical outcome (survival). It is hypothesized that platelet surface antigen expression, reflecting platelet activation, might be a predictive factor in the course of severe sepsis.
Hepatitis B virus transmission from a surgeon to patients during high-risk as well as low-risk procedures: unnoticed transmissions over a 4-year period
Authors: Spijkerman I J B , van Doorn L J , Janssen M H W , Wijkmans C J , Bilkert-Mooiman M A J , Coutinho R A , Weers-Pothoff G
Published: March 2003

Background

Three cases of reported acute hepatitis B virus (HBV) led to the identification of a chronically HBV-infected surgeon, with a high viral load, who was a non-responder after vaccination.

Methods

A retrospective cohort study was conducted on 1564 patients operated on by this surgeon over a 4-year period.

Results

Forty-nine patients (3·1 per cent) were positive for HBV markers. Based on HBV DNA sequencing and epidemiological data, transmission from the surgeon was confirmed in eight, probable in two, possible in 18 and excluded in 21 patients. One case of secondary transmission was identified from a patient to his wife, who died, presumably from fulminant hepatitis. A case–control study identified the duration of operation, the potential risk of the surgical procedure and the occurrence of complications during or after surgery as significant risk factors for HBV infection. At least eight of the 28 patients were infected during low-risk procedures.

Conclusion

Transmission from surgeons to patients at a low rate can remain unnoticed for a long period of time. Prevention requires a more stringent strategy for vaccination and testing of surgeons. It also requires revision of policies allowing HBV-infected surgeons to perform presumed ‘low-risk’ procedures.
Transforming growth factor β-mediated inhibition of src kinases is regulated by SHP-1
Authors: Sir Ö , Choudhry M A , Sayeed M M
Published: March 2003

Background

Transforming growth factor (TGF) β has been shown to suppress T cell effector functions. Although the mechanisms of such T cell suppression are not known, a disuption of the balance between protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs) has been implicated. The present study investigated the roles of the src-related PTKs, P59fyn and P56lck, and the PTPs SHP-1 and SHP-2 in TGF-β-mediated T cell suppression.

Methods

Splenic T cells from rats were pretreated with TGF-β 25 ng ml−1 and subsequently stimulated with either anti-CD3 or anti-CD3 plus pervanadate (a PTP inhibitor). After incubation with specific antibodies and immunoprecipitation, the kinase activity of the PTKs was assessed by in vitro kinase assay. Phosphorylation of the PTPs was assessed using antiphosphotyrosine antibodies and immunoblotting.

Results

Incubation of T cells with TGF-β resulted in decreased activity of P59fyn and P56lck. Although TGF-β treatment resulted in a concomitant increase in SHP-1 activity, no change in SHP-2 activity was observed. When T cells were stimulated with anti-CD3 in the presence of pervanadate, the TGF-β-mediated decrease in P59fyn and P56lck activity was completely prevented.

Conclusion

These findings show that TGF-β treatment of T cells results in suppression of src kinases, and suggests that such inhibition of kinase activity is mediated by upregulation of SHP-1.
Hypertonic saline–dextran is ineffective for resuscitation after thoracic blast and haemorrhage
Authors: Sawdon M , Kirkman E , Ohnishi M , Stapley S A , Watkins P
Published: March 2003

Background

Small-volume resuscitation using hypertonic solutions is increasing in popularity for the treatment of hypovolaemia. However, its effect in the blast casualty is unknown. The present study compared the effects of resuscitation with hypertonic saline–dextran with those of whole blood and colloid (Haemaccel) in an experimental model of blast injury and haemorrhage.

Methods

Male Wistar rats (235–264 g body-weight) were used in three groups of six animals anaesthetized with intravenous alphadolone–alphaxalone 19–21 mg kg−1 h−1. Heart period (HP) was measured from the electrocardiogram and mean arterial blood pressure (MBP) via the tail artery. Body temperature was maintained at 38·0°C. At the end of the study the animals were killed with an overdose of anaesthetic. Each group received a blast wave focused on the ventral thorax. Some 10 min after the blast all groups received a haemorrhage of 40 per cent total estimated blood volume (BV, 6·06 mg kg−1) at 2 per cent BV min−1.

Results

Blast (group 1) induced a significant bradycardia (HP increasing to mean(s.e.m.) 543(64) ms from 155(4) ms; P < 0·05, analysis of variance) and hypotension (fall in MBP to 35(3) mmHg from 106(4) mmHg). Thereafter there was partial recovery before subsequent haemorrhage significantly reduced MBP to 26(3) mmHg and increased HP to 189(15) ms. The response in groups 2 and 3 was not significantly different from that in group 1. Some 20 min later resuscitation with 40 per cent prehaemorrhage blood volume using autologous blood (group 1) or colloid (group 2) restored MBP to 113(7) and 98(2) mmHg respectively. The effects of blood and colloid were maintained for the remaining 30 min of the study. Although resuscitation with 7·5 per cent saline−6 per cent dextran 70 (4 ml kg−1) in group 3 increased MBP to 92(5) mmHg initially, it fell significantly within 5 min, reaching 43(5) mmHg 30 min after resuscitation. This was associated with a significant tachycardia (HP 127(4) ms), which was not seen in the other groups.

Conclusion

These data provide no support for the use of hypertonic saline–dextran in resuscitation following blast and haemorrhage.
Operative treatment of pseudocysts in patients with chronic pancreatitis
Authors: Usatoff V , Brancatisano R , Williamson R C N
Published: March 2003

Background

Pseudocysts associated with chronic pancreatitis are generally intrapancreatic and associated with parenchymal disease. They tend to persist and cause complications. Minimally invasive methods of treatment challenge the traditional techniques of operative management. Surgical operation allows definitive treatment of the pseudocyst with the option of dealing appropriately with the diseased pancreas and excluding a neoplastic process. The aim of this study was to review the safety and efficacy of a surgical approach to the management of pseudocysts associated with chronic pancreatitis.

Methods

A personal series of 112 consecutive patients operated for pseudocysts in the setting of chronic pancreatitis was reviewed. Chronic pancreatitis was confirmed by imaging studies in association with exocrine and/or endocrine failure. Cysts were multiple in 31 patients and presented with complications other than pain in 47. Data were collected prospectively regarding the clinical presentation, the nature of the operation and its outcome.

Results

Forty-eight patients (43 per cent) underwent drainage procedures, 56 (50 per cent) had a resection and eight (7 per cent) had a combination. Larger cysts and those located in the head and neck tended to be drained, while smaller and distal cysts were more often resected. The morbidity rate was 28 per cent and the operative mortality rate was 1 per cent. The cyst recurrence rate was 3 per cent and pain was relieved in 74 per cent of patients.

Conclusion

Operative management of pseudocysts associated with chronic pancreatitis is effective with low morbidity and mortality rates. The introduction of newer minimally invasive techniques will have to withstand comparison to this traditional approach.
Endoscopic stent placement for pancreaticocutaneous fistula after surgical drainage of the pancreas
Authors: Boerma D , Rauws E A J , van Gulik T M , Huibregtse K , Obertop H , Gouma D J
Published: March 2003

Background

Spontaneous closure of an external pancreatic fistula is unlikely when a concomitant downstream obstruction of the pancreatic duct inhibits downstream flow. Early endoscopic retrograde pancreatography (ERP) and stent insertion may enhance fistula closure in these patients.

Methods

The results of endoscopic stenting of the pancreatic duct were evaluatedin 15 patients with an external pancreatic fistula that developed after operative necrosectomy and debridement of the pancreas (seven men and eight women, median age 45 (range 25–68) years).

Results

Median drainage before ERP was 50–800 ml/day, with an amylase content of 21 000–493 000 units/l. ERP was performed after a median time of 35 days and revealed leakage of the duct and a downstream obstruction in all patients. An endoprosthesis was inserted beyond the site of obstruction. Within a median time of 10 (range 2–64) days drainage stopped in all patients. In one patient ERP failed and pancreaticojejunostomy was performed. During follow-up (median 24 (range 2–55) months) three patients required resection of the pancreatic tail because of pseudocyst formation, all of whom originally had leakage from the tail area.

Conclusion

Based on these data, an active approach for external pancreatic fistula seems warranted. Early ERP and stent insertion enhances fistula resolution, facilitates wound care and surgery is postponed or even avoided.
Helix-loop transcription factor, Id1, is overexpressed in medullary thyroid cancer
Authors: Kebebew E , Treseler P A , Duh Q-Y , Clark O H
Published: March 2003

Background

The helix-loop transcription factor (Id1) protein inhibits differentiation, enhances cell proliferation and is required for cell-cycle progression. Id1 is highly expressed in a variety of tumour-derived cell lines, increases following mitogenic stimuli and is overexpressed in some human neoplasms. It was therefore reasoned that the Id1 gene may play a role in medullary thyroid carcinogenesis.

Methods

Id1 protein expression in human medullary thyroid cancer (MTC) and corresponding normal thyroid tissue was determined by Id1 immunohistochemistry. Calcitonin immunohistochemistry was used to determine the cellular localization of Id1 immunostaining. In a well characterized human MTC cell line (TT), the effects of growth stimulation (with serum) and redifferentiation (with phorbol esters) on Id1 expression were determined by Northern blot analysis.

Results

Id1 immunostaining intensity in MTC (n = 9; six sporadic MTCs, two familial MTCs and one multiple endocrine neoplasia type 2A MTC) was moderate to strong whereas in the corresponding normal thyroid tissues (n = 9) it was absent or faint in the C cells and follicular cells. Id1 immunostaining was significantly higher in MTC than the corresponding normal thyroid tissue based on the percentage of positive cells and immunostaining intensity (P = 0·002, rank sum test). The 1·2-kilobase Id1 transcript was expressed in the TT cell line under basal culture conditions. Interestingly, Id1 messenger RNA (mRNA) expression was markedly upregulated (4·0 fold) following growth stimulation with 10 per cent fetal bovine serum. In addition, phorbol ester (which is known to induce redifferentiation of the TT cell line) downregulated Id1 mRNA expression in the TT cell line.

Conclusion

Id1 is overexpressed in MTC. Furthermore, increased Id1 expression is associated with an enhanced proliferative potential in MTC. The inappropriate proliferation and dedifferentiation of the C cells that lead to MTC, at least in part, may be regulated by the Id1 gene.
Multiple endocrine neoplasia type 2A c804 RET mutation as an indication for prophylactic thyroidectomy
Authors: Frohnauer M K , Bigos S T , Peacock M L , Decker R A
Published: March 2003

Background

Missense mutations in five exons of the RET proto-oncogene have been found to cosegregate with the inherited cancer syndrome, multiple endocrine neoplasia type 2A (MEN2A). Sequence abnormalities involving c804 in exon 14 occur rarely and to date have been found in five kindreds. Initial reports linked the c804 mutation to a mild C-cell disease phenotype with low penetrance and an indolent course, and questioned the appropriateness of aggressive strategies such as prophylactic thyroidectomy in early childhood. The purpose of this study is to report the clinical correlates of five additional MEN2A kindreds that harbour the c804 RET mutation, with the intention of clarifying therapeutic recommendations in asymptomatic carriers.

Methods

Thirty-eight members from five distinct kindreds at risk for the c804 mutation underwent genetic analysis using genomic DNA and direct DNA sequencing. Operative and pathology reports were reviewed. Detection of C-cell hyperplasia (CCH) or medullary thyroid carcinoma (MTC) was accomplished biochemically by baseline or pentagastrin-stimulated calcitonin determinations.

Results

Twenty-three gene carriers were identified. The predisposing c804 missense mutation in each case resulted in a TTG, ATG or CTG substitution. Of the 23 patients testing genetically positive, 14 proceeded to thyroidectomy. At operation, MTC was found in seven patients (age 6–56 years), CCH in six patients (age 13–40 years) and normal thyroid histology was present in a single patient (age 27 years). One of the seven patients with MTC died from widespread metastases at age 12 years. Nine of the 23 gene carriers delayed operative intervention. Four of the nine patients have undergone biochemical testing. Three of the four patients have a raised calcitonin level and a single patient remains clinically and biochemically negative at age 40 years.

Conclusion

Penetrance of the c804 mutation is highly variable. In contrast to initial reports, however, MTC associated with sequence abnormalities at this site has aggressive potential. Therefore, prophylactic thyroidectomy remains a reasonable approach in children testing genetically positive.
Intraoperative decay profile of intact (1–84) parathyroid hormone in surgery for secondary hyperparathyroidism in a consecutive series of 50 patients on haemodialysis
Authors: Lokey J , Pattou F , Mondragon-Sanchez A , Minuto M , Mullineris B , Wambergue F , Proye C A G
Published: March 2003

Background

The usefulness of rapid intraoperative monitoring of intact (1–84) parathyroid hormone (PTH) is not clearly defined in the surgical management of secondary HPT in the patients on haemodialysis. The aim of this study was to define the normal pattern of decay during surgery for secondary HPT using the rapid intact (1–84) PTH assay during operation.

Methods

Fifty patients on haemodialysis underwent neck exploration for secondary HPT. The therapeutic goal in all patients was the subtotal resection of four or more glands and bilateral transcervical thymectomy. PTH levels were monitored using a rapid immunochemiluminometric assay. Peripheral blood samples were assayed at induction of anaesthesia, after dissection but before resection, and 20 and 40 min after resection in all patients. All patients were followed up for at least 6 months. PTH levels were expressed as absolute values, as multiples of the upper limit of normal and as the percentage decline from pre-excision values.

Results

Forty-eight patients (96 per cent) were considered cured after surgery. Twenty patients (40 per cent) had a PTH level less than twice normal and 20 patients (40 per cent) had a PTH level between two and four times normal at 20 min. At late follow-up, all these patients were cured. Ten patients (20 per cent) had a PTH level greater than four times normal at 20 min. Eight of these patients were cured. Seven of these eight had a PTH level at 20 min, while not less than four times normal, less than 40 per cent of the original value. In contrast, the two failures had neither a decline to less than four times normal nor a decay to less than 40 per cent of the original value. One has been reoperated with resection of a fifth gland and one awaits reoperation.

Conclusion

The intraoperative decay of PTH during surgery for secondary HPT in patients on haemodialysis is slower than that in patients with normal renal function. However, 20 min after resection, a decline to less than four times the upper limit of normal is predictive of cure. Variability of decay slopes in individual patients may reflect molecular heterogeneity or biphasic metabolism of the hormone.
Evaluation of Wilm's tumour suppressor gene and insulin-like growth factor receptors in parathyroid glands
Authors: Wong C , Newcomb P , Sheffield E , Holly J M P , Brown K , Farndon J
Published: March 2003

Background

The precise cause of hyperparathyroidism (HPT) is uncertain. Alteration of growth factors (epidermal growth factor, fibroblast growth factor) and genetic mutations (parathyroid hormone (PTH) gene (11p15), PRAD1 oncogene (11q13) and multiple endocrine neoplasia type 1 (MEN1) gene (11q13)) are implicated in the pathogenesis. The escape of secretory function from physiological control and excess growth is still incompletely understood. The insulin-like growth factor (IGF) axis is a ubiquitous growth and regulatory system (IGF-1 and -II, IGF receptors (IGFRs) and binding proteins (IGFBPs)). Hormonal/endocrine signals (e.g. androgens, thyroid-stimulating hormone) and tumour supressor genes (e.g. Wilms' tumour suppressor gene (WT-1) (11p13) and p53) modulate the IGF axis. Expression of the WT-1 gene is tissue specific (kidney, mesothelium, prostate). Wild-type WT-1 governs normal kidney development and mutation results in Wilm's tumour. Loss of transcriptional repression of WT-1 and IGF control can lead to mitogenesis. A mutation (chromosome 11) appears to be the key event in the evolution of primary HPT. This mutation may increase IGFR expression, IGF production giving rise to unregulated autocrine growth. In polyclonal hyperplasia (secondary HPT and MEN1) a serum factor initiates polyclonal growth, thereby increasing the susceptibility to mutation and resulting in nodular hyperplasia.

Methods

Immunohistochemical examination of paraffin-embedded parathyroid glands was done using polyclonal anti-WT-1 (C19, Santa Cruz) and anti-IGFR-I (C20, Santa Cruz) antibodies and a horseradish peroxidase-labelled secondary antibody for detection. The strength of immunoreactivity was graded using a standardized colour chart and assessed independently by three observers.

Results

Two hundred and fifty-four parathyroid glands from 112 patients were examined. There were 81 women and 31 men (2·6: 1). Of these, 94 had primary HPT (70 women) and 18 secondary HPT (11 women). Immunoreactivity to WT-1 was found in normal parathyroid glands. In contrast, reduced WT-1 immunostaining was observed in abnormal parathyroid glands. Positive immunostaining for IGFR-I was found in all parathyroid glands. Increased immunoreactivity was found in pathological compared with normal glands.

Conclusion

WT-1 and IGFR are expressed in parathyroid cells. Abnormal expression of WT-1 and the IGF axis may play a role in the pathogenesis of HPT.
Laparoscopic adrenalectomy for malignancy
Authors: Li R , Whang K , Ituarte P , Siperstein A , Clark O , Du Q-Y
Published: March 2003

Background

Controversy exists as to whether laparoscopic adrenalectomy should be performed for malignant or potentially malignant tumours affecting the adrenals.

Methods

This was a retrospective analysis of all patients undergoing laparoscopic adrenalectomy at this institution from 1993 to 1999. Patients were classified by their preoperative diagnosis and analysed with respect to their final pathological diagnosis, operation and postoperative course.

Results

Some 121 patients underwent 133 laparoscopic adrenalectomies. Preoperative classification was type I (benign disease; 67 patients), type II (possibly malignant disease; 46 patients) and type III (malignant disease; eight patients). After operation, 11 patients had malignancy on pathological diagnosis including all eight patients with known preoperative malignancy (one adrenocortical carcinoma (3 × 3 cm) presenting as a virilizing tumour, two neuroblastomas, one lymphoma, one bilateral staged adrenalectomy for metastatic colon cancer, two metastatic lung cancers and one metastatic renal cell carcinoma). One patient with adrenocortical cancer (8 × 6 cm) had incorrect preoperative classification by cytology (type I; oncocytoma). Two of 14 patients with Cushing's adrenal tumour (type II) had adrenocortical cancer (12 × 9 cm and 3 × 3 cm). Mean length of stay was 1·8 days in patients with malignancy. No procedure was converted to open adrenalectomy and no significant complications were encountered. Only the four patients with adrenocortical carcinoma had a recurrence (two required open re-resection 3 months and 2 years after initial operation, one had laparoscopic re-resection 2 years after operation for local recurrence and one presented with recurrence 1 year after operation).

Conclusion

Forty-five per cent of patients undergoing laparoscopic adrenalectomy may be classified as having potentially malignant disease (type II or III). Most malignant tumours of the adrenals can be treated laparoscopically, but adrenocortical carcinomas are at high risk of recurrence after laparoscopic adrenalectomy.
Non-insulinoma pancreatogenous hypoglycaemia syndrome
Authors: Service F J , Thompson G B , Natt N , Grant C S , van Heerden J A , Andrews J C , Lloyd R V
Published: March 2003

Background

The authors have reported a newly recognized hypoglyacemic disorder, non-insulinoma pancreatogenous hypoglycaemia syndrome (NIPHS), which is characterized by postprandial hyperinsulinaemic hypoglycaemia, negative 72-h fast, negative transabdominal and intraoperative ultrasonography, spiral computed tomography and coeliac axis angiography, positive selective arterial calcium stimulation test (SACST), absence of insulinoma but presence of islet hypertrophy and nesidioblastosis, and relief of symptoms from gradient-guided partial pancreatectomy. Experience with the next five patients with this disorder (6–10; 1998–1999) compared with the original five (1–5; 1996–1998) is reported.

Results

Wide age range, male predominance, postprandial occurrence of symptoms, negative radiological localization, nesidioblastosis/islet hypertrophy, but no insulinoma characterized all ten cases. Response to SACST indicated widespread islet hyperfunction in patients 1 and 5; limitation to distribution of the SPA and GDA in patients 3, 4, 6 and 8, to distribution of the SPA in patients 2, 7 and 9, and to distribution of the SMA in patient 10. Except for patient 5, pancreatic resection to the left of the SMV was performed when only the SPA was positive on the SACST. Patients 5 and 8 have had recurrence of symptoms; they resolved within 3 months for patient 5.

Conclusion

NIPHS can usually be treated successfully with gradient-guided partial pancreatectomy.