bluuebunny/crossref_metadata_2025 huggingface dataset:
Dopamine attenuates neutrophil–endothelial interaction and is a putative anti-inflammatory cytokine
Authors: Sookhai S , Wang J H , McCourt M , Winter D C , Kirwan W O , Redmond H P
Published: March 2003

Background

Activated neutrophil (PMN) adherence to vascular endothelium comprises a key step for both transendothelial migration and initiation of potentially deleterious release of PMN products. Previous work has shown that the biogenic amine dopamine (DA) functions as an anti-inflammatory cytokine by inducing PMN apoptosis. The effect of DA on PMN transendothelial migration and adhesion receptor expression as well as on the endothelial molecules, E-selectin and intercellular adhesion molecule (ICAM) 1, was evaluated.

Methods

PMNs were isolated from healthy controls, stimulated with lipopolysaccharide (LPS) and tumour necrosis factor (TNF) α and treated with DA. CD11b and CD18 PMN adhesion receptor expression was assessed flow cytometrically. In a separate transwell experiment, the effect of the chemo-attractant peptide interleukin (IL) 8 on PMN migration was assessed. Human umbilical vein endothelial cells were stimulated with LPS/TNF-α, incubated with DA, and ICAM-1 and E-selectin endothelial molecule expression was assessed.

Results

There was a significant increase in transendothelial migration in stimulated PMNs as well as in CD11b/CD18, endothelial E-selectin and ICAM-1 expression compared with normal PMNs. DA attenuated these changes. The chemoattractant effect of IL-8 was also abolished.

Conclusion

These results show that DA attenuates the initial interaction between PMNs and endothelium, providing further evidence that it also functions as an anti-inflammatory cytokine.
Impact of relaparotomy in patients with abdominal sepsis
Authors: Verwaal V J
Published: March 2003

Background

This study determined whether relaparotomy has a positive or negative effect on prognostic scoring systems.

Methods

Between April 1995 and January 1997, 46 patients with abdominal sepsis were treated. The diagnosis of abdominal sepsis was defined as meeting the Bone criteria for sepsis before operation, in combination with infection of the abdomen proven by laparotomy. After the first laparotomy there were 41 relaparotomies in these 46 patients. From 2 days before to 3 days after the relaparotomy, data were collected to compile the Acute Physiology and Chronic Health Evaluation (APACHE) III and Multiple Organ Failure (MOF) scores. The scores were compared before and after relaparotomy, and were also compared between patients who had a recurrent infection in the abdomen and those who did not.

Results

During 41 relaparotomies, 16 patients were found to have a pus collection. Of these clinical infections only 11 had a positive culture. Overall the APACHE III and MOF scores were not significantly different before and after operation. In patients with clinical infection there was also no difference pre and post operative. The same applied for patients with and without positive intraabdominal cultures.

Conclusion

Relaparotomy in patients with abdominal sepsis did not have a negative effect on prognosis within a few days after reoperation. The authors did not find any reason to use APACHE III or MOF scoring as an indication for relaparotomy.
Risk factors for nosocomial infection after elective pulmonary thoracic surgery
Authors: Scriba D , Förster E , Gandawidjaja L , Hau T
Published: March 2003

Background

The aim was to identify risk factors for the development of infection after pulmonary surgery.

Methods

A retrospective analysis of 440 consecutive patients operated on between August 1987 and July 1997 was conducted.

Results

Nosocomial infections (NIs) were observed in 122 patients (27·7 per cent): pneumonia in 75 (17·0 per cent), urinary tract infection (UTI) in 40 (9·1 per cent), surgical site infection (SSI) in 37 (8·4 per cent), nine of which were pleural empyemas (2·0 per cent), and other infections in six (1·4 per cent). The infection-related mortality rate was 3·2 per cent (14 patients). Multivariate analysis of 21 variables revealed that the following were independent predictors for the development of NI:

No operation-related factor, such as infection, indication for surgery, extension of pulmonary resection, duration of operation or transfusion requirements, had a significant influence on the development of NI.

Conclusion

The results indicate that impairment of the patient's ability to respond to surgical trauma is more important for the development of postoperative infection than factors related to the operation.
Surgical treatment of infected pancreatic necrosis
Authors: Gruca Z , Dobosz M , Makarewicz W
Published: March 2003

Background

Twenty-six cases of infected pancreatic necrosis (IPN) treated by means of operation in the years 1997–1999 are presented.

Methods

The diagnosis of IPN was established before surgery by means of contrast-enhanced computed tomography and fine-needle aspiration of the infected pancreatic and peripancreatic tissue. Microbiological findings of infected tissue most commonly showed Escherichia coli (12) and Klebsiella pneumoniae (eight). Candidiasis was observed in three cases. All patients were stratified according to Acute Physiology and Chronic Health Evaluation (APACHE) II score within 24 h of admission to the ward and before planned surgery. Wide surgical exploration of the omental sac and retroperitoneal space, gentle necrosectomy of necrotic tissue, and continuous omental sac lavage in connection with an ‘open abdomen’ technique was carried out within 4–22 (mean 10) days from the onset of the disease. Planned relaparotomies were performed every 4–5 days until all the necrotic tissue was removed and granulation of the operating area was observed. Closure of the abdomen was performed within 14–34 (mean 23) days after primary laparotomy.

Results

Six patients died (mortality rate 23 per cent) during the postoperative period from multisystem organ failure accompanying septic shock. The poor outcome was related to a high APACHE II score (11–15). During the postoperative period the following complications were observed: respiratory insufficiency requiring mechanical ventilation (24 cases), colonic fistula (five), pancreatic fistula (three), renal insufficiency requiring haemofiltration (three), upper gastrointestinal bleeding (two) and gastric fistula (one). Incisional hernia developed in five patients who left hospital. The hospital stay for survivors ranged between 26 and 52 (mean 36) days.

Conclusion

Diagnosis of IPN based on dynamic computed tomography and bacteriological examination of necrotic aspirate and the consecutive surgical treatment, including wide repeated necrosectomy and continuous lavage combined with an ‘open abdomen’ technique, is the management of choice, and may improve the results of treatment.
Benchmarks and control charts for surgical site infections
Authors: Gustafson T L
Published: March 2003

Background

Although benchmarks and control charts are basic quality improvement tools, few surgeons use them to monitor surgical site infection (SSI). Obstacles to widespread acceptance include: (1) small denominators, (2) complexities of adjusting for patient risk and (3) scepticism about their true purpose (cost cutting, surgical privilege determination or improving outcomes).

Methods

The application of benchmark charts (using US national SSI rates as limits) and control charts (using facility rates as limits) was studied in 51 hospitals submitting data to the AICE National Database Initiative. SSI rates were risk adjusted by calculating a new statistic, the standardized infection ratio (SIR), based on the risk index suggested by the Centers for Disease Control National Nosocomial Infection Surveillance Study. Fourteen different types of control chart were examined and 115 suspiciously high or low monthly rates were flagged. Participating hospital epidemiologists investigated and classified each flag as ‘a real problem’ (potentially preventable) or ‘not a problem’ (beyond the control of personnel at this facility).

Results

None of the standard, widely recommended, control charts studied showed practical value for identifying either preventable rate increases or outbreaks (clusters due to a single organism). On the other hand, several types of risk-adjusted control chart based on the SIR correctly identified most true opportunities for improvement. Sensitivity, specificity and receiver–operator characteristic (ROC) analysis revealed that the XmR chart of monthly SIRs would be useful in hospitals with smaller surgical volumes (ROC area = 0·732, P = 0·001). For larger hospitals, the most sensitive and robust SIR chart for real-time monitoring of surgical infections was the mXmR chart (ROC area = 0·753, P = 0·0005).
Role of tumour necrosis factor in lung injury caused by intestinal ischaemia–perfusion
Authors: Kuzu M A , Köksoy C , Kuzu I , Ergün H , Gürhan I
Published: March 2003

Background

Despite the well known inflammatory effects of tumour necrosis factor (TNF), the mechanism of TNF-mediated lung injury following ischaemia–reperfusion (IR) is still unclear. In this study, the role of TNF in the development of acute lung injury following intestinal IR was investigated.

Methods

Male Wistar rats underwent either sham operation (n = 10) or 1 h of superior mesenteric artery occlusion and 2 h of reperfusion (IR; n = 10) or pretreatment with anti-TNF polyclonal antibody 2 mg kg−1 and IR (n = 6). Lung injury was evaluated by Evans blue dye concentration, immunohistochemical staining and morphometric analysis. Intestinal injury was assessed by Evans blue dye concentration and histological examination.

Results

Intestinal IR resulted in lung injury characterized by an increase in Evans blue dye concentration, polymorphonuclear neutrophil (PMN) sequestration, and obvious staining for expression of pulmonary CD11b and CD18. Pretreatment of animals with anti-TNF antibodies led to a reduction in the sequestration of PMNs (P < 0·05), a decrease in expression of pulmonary intercellular adhesion molecule 1 and CD18 (P < 0·01), and a diminished histological grade compared with the IR-only group. Anti-TNF antibody pretreatment also reduced the intestinal microvascular injury after intestinal IR.

Conclusion

Treatment with an anti-TNF antibody resulted in significant attenuation of lung injury following intestinal IR, which is at least partially TNF mediated. The data indicate that TNF is an important trigger for upregulation of pulmonary endothelial and neutrophil adhesion molecules after intestinal IR.
Luminal endotoxin modifies reaction to gut ischaemia–reperfusion injury in the pig
Authors: van der Hoven B , Groeneveld A B J , Thijs L G
Published: March 2003

Background

Translocation of bacteria and their products through the intestinal mucosa during ischaemia–reperfusion (I/R) may contribute to gut I/R injury.

Methods

In order to study the role of luminal endotoxin in gut I/R injury, two groups of seven germ-free pigs each were studied by clamping of the superior mesenteric artery, with and without luminal administration of endotoxin. Two control groups of seven germ-free pigs, with and without endotoxin, were not clamped. Translocation of an inert indicator (polyethyleneglycol (PEG) 3350), mucosal ischaemia (measured by tonometry) and haemodynamics were assessed.

Results

Both clamped groups showed ischaemic injury as measured by raised PEG 3350 urinary levels, lowered intestinal pH, and increased intramucosal arterial and intramucosal portal partial pressure of carbon dioxide gradients. Luminal endotoxin application did not aggravate this I/R injury, nor did it influence haemodynamics. The PEG 3350 level in the clamped endotoxin group was significantly lower than that in the clamped control group (mean(s.d.) 0·55(0·37) versus 1·82(0·70); P = 0·001), suggesting a blunting influence of endotoxin on the I/R injury. This might be explained by a desensitizing effect on leucocytes in the gut wall by luminal endotoxin before clamping and diminishing the I/R-induced production of cytokines in the gut wall.

Conclusion

Endotoxin does not significantly mediate gut I/R injury in the pig and might desensitize the gut wall leucocytes, resulting in decreased translocation of large molecules, including bacterial products and endotoxin.
Two-hit model of haemorrhagic shock and Pseudomonas sepsis
Authors: Eissner B , von Engelhardt K , Röschmann A , Ungelenk B , Mertens A , Wudke J , Smorodschenko A , Valerio M , Hahn H , von Specht B U , Haberstroh J
Published: March 2003

Background

Shock or trauma is a frequent prerequisite of bacterial sepsis. This has not, however, been reported in connection with related animal models. Therefore a porcine two-hit model was established with haemorrhage and resuscitation followed by the induction of sepsis with Pseudomonas aeruginosa.

Methods

Thirteen pigs were anaesthetized and permanently catheterized. Seven were subjected to haemorrhagic shock (bleeding until a mean of 50 per cent of the estimated blood volume remained) for 45 min, and then resuscitated with crystalloid, colloid and shed blood. A further six animals without shock served as controls. All pigs were fully conscious. The following day a continuous intravenous infusion of P. aeruginosa (1·6 × 107 colony-forming units kg−1 h−1) was given for 24 h, followed by a reduced dose (1·6 × 106 colony-forming units kg−1 h−1) for a further 24 h. The animals were then observed for another 48 h.

Results

All animals fulfilled the criteria for sepsis. However, the initial fever, arterial pressure and systemic vascular resistance were significantly lower in the shock group. In contrast, the pulmonary pressure, pulmonary vascular resistance and cardiac index were raised (P < 0·05, shock versus control group).

Conclusion

These data indicate that sepsis is aggravated by a preceding haemorrhagic shock. This two-hit model considers one important precondition of human sepsis and may contribute to the development of a better treatment for this condition.
Blockade of Kupffer cells by gadolinium chloride or dichloromethylene diphosphonate influences hepatic microcirculation after sepsis and haemorrhagic shock
Authors: Herzog C , Kuntz W , di Liberto A , Bauer C , Rooijen N , Marzi I
Published: March 2003

Background

The liver plays a key role in the host defence response after haemorrhagic shock–resuscitation (H/R) and sepsis. Kupffer cells (KCs) have been shown to be a trigger and motor of the subsequent inflammatory response syndrome. This may lead to hepatocellular dysfunction, microcirculatory alterations and liver injury involving, for example, tumour necrosis factor α, interleukin (IL) 1 and IL-6. In a double-blind study the effect of KC blockade with either gadolinium chloride or liposome-entrapped dichloromethylene diphosphonate (DMD) on hepatic microvascular flow after H/R and sepsis was investigated.

Methods

After pretreatment with intravenous gadolinium chloride 10 mg kg−1, DMD 1 mg kg−1 or saline 24 h before induction of shock, male Sprague-Dawley rats (n = 6–10 per group and time) were subjected to either haemorrhagic shock (mean arterial pressure 40 mmHg) for 60 min followed by resuscitation or lipopolysaccharide (LPS) 1 mg kg−1 intravenously. Microvascular flow was assessed by intravital microscopy of fluorescence-marked leucocytes in liver sinusoids at baseline, and 1, 6 and 12 h after shock induction.

Results

In saline groups, the mean(s.d.) leucocyte flow was significantly (P < 0·05) higher at 1 h (20 759(2901) μm3 s−1) and 6 h (16 278(2916) μm3 s−1) after H/R as well as at 6 h after LPS (17 661(3949) μm3 s−1) compared with the baseline value (13 509(1580) μm3 s−1). Animals pretreated with gadolinium chloride showed a significant flow increase compared with baseline (11 797(1124) μm3 s−1) at l h following H/R (26 269(5909) μm3 s−1). In DMD-pretreated animals leucocyte flow showed no significant change over time, following either H/R or LPS treatment. However, flow was significantly higher at baseline (18 054(998) μm3 s−1) versus gadolinium chloride and saline groups. In addition, DMD-treated animals showed higher flow values 1 h after LPS challenge (20 665(2337) μm3 s−1) compared with gadolinium chloride (13 110(1224) μm3 s−1) and saline (15 311(800) μm3 s−1) groups. Similarly, at 12 h after H/R the DMD group (21 782(1887) μm3 s−1) had higher flow values than the gadolinium chloride (14 026(1616) μm3 s−1) and saline (15 999(3175) μm3 s−1) groups.

Conclusion

These results imply a significant influence of KCs on regulation of microvascular perfusion in liver sinusoids under normal conditions as well as after H/R and sepsis. The data indicate differential pathways and effects of blocking KCs by gadolinium chloride and DMD.
Alteration of inflammatory response following small-volume resuscitation
Authors: Gebhard F , Liener U C , Helm M , Lampl L , Kinzl L , Brückner U B
Published: March 2003

Background

Small-volume resuscitation is rather effective in the primary volume treatment of major trauma. Blood pressure stabilizing effects occur immediately but last for a limited period only. Influences on inflammatory reactions in humans have not been reported so far. This prospective randomized study therefore analysed the inflammatory response in the very early (pre)clinical period after administration of crystalloids plus starch, hyperosmolar/hyperoncotic starch and lyophilized plasma solutions.

Methods

Upon approval of the ethics committee, 41 patients were enrolled with multiple injuries (injury severity score (ISS) mean 34 (range 9–75)). The patients received randomly either standard solutions, i.e. starch plus crystalloids (group C (control); n = 14), hyperosmolar/hyperoncotic starch (group S (small volume); n = 14) or lyophilized plasma (group L (lyoplasma); n = 13). Subsets were performed according to the different solutions as well as to the severity of trauma (ISS below 17, 18–31, 32 or more) and survivors/non-survivors. The first blood sample was obtained at the scene of the accident before cardiopulmonary resuscitation, when appropriate. Subsequently, blood samples were collected hourly. All samples were spun immediately at 4°C and stored at −70°C. Interleukin (IL) 6 as well as several different prostaglandins (PGI2, thromboxane A2, PGE2) were determined to characterize the overall inflammatory response.

Results

Eleven casualties (seven men and four women, mean age 31 years) died because of major trauma within 24 h after the incident. In all patients IL-6 levels promptly increased within the first 2 h, most pronounced in patients with the severest trauma (ISS greater than 32) and non-survivors. Patients in groups C and S had a comparable time course of IL-6 plasma levels with a slightly higher release in minor injuries (ISS less than 30). The same was true for prostaglandins. In contrast, patients in group L had clearly higher IL-6 concentrations during the first 2–12 h, again most pronounced in those with the severest trauma (ISS greater than 32).

Conclusion

These results demonstrate that the early systemic inflammatory response after small-volume resuscitation is rather similar to that of patients infused with standard-volume therapy after trauma. In contrast, lyoplasma seems to increase the inflammatory response regardless of the injury severity.
Cytokine induction by non-lipopolysaccharide components of Neisseria meningitidis
Authors: Sprong T , Stikkelbroeck N , van der Ley P , Steeghs L , van der Meer J W M , van Deuren M
Published: March 2003

Background

Lipopolysaccharide (LPS), or endotoxin, is considered responsible for the pattern of cytokine activation and the subsequent pathophysiological events during Gram-negative septic shock. To determine whether non-LPS components of Neisseria meningitidis are able to induce cytokine activation, the cytokine-inducing capacities of serogroup B wild-type N. meningitidis H44/76, of an LPS-deficient mutant (Plak 33) and of meningococcal LPS in human peripheral blood mononuclear cells were studied.

Methods

2-Keto-3-deoxyoctanate spectrophotometry was used to obtain a molar-based quantitative comparison between LPS and bacteria.

Results

Whole meningococci H44/76 were more potent inducers of cytokine production than isolated LPS; the LPS-deficient meningococci, Plak 33, were also able to induce cytokine production. LPS-deficient meningococci supplemented with an amount of LPS equivalent to that present in the wild-type strain produced the same amount of cytokines as the wild-type meningococcus.

Conclusion

LPS is not the sole toxic element in meningococcal sepsis, because non-LPS components of N. meningitidis are able to induce cytokine activation substantially. Antiendotoxin therapy alone may not be sufficient to inhibit the pattern of cytokine activation and the subsequent pathophysiological events during meningococcal septic shock.
Role of resection and primary anastomosis of the left colon in the presence of peritonitis
Authors: Biondo S , Jaurrieta E , Ragué J Martí , Ramos E , Deiros M , Moreno P , Farran L
Published: March 2003

Background

Classically a primary colonic anastomosis is not performed in the presence of left colonic peritonitis. Recently there has been a trend towards resection and anastomosis in selected patients, but no prospective study concerning the safety of this approach has been published. The objective of this study was to define the role of intraoperative colonic lavage with resection and primary anastomosis (RPA) in left colonic peritonitis, and to evaluate the differences in outcome in patients with diffuse or localized peritonitis.

Methods

Between January 1994 and December 1998, 127 patients underwent emergency operation for a distal large bowel perforation. RPA was the operation of choice and was performed in 61 patients, 38 with localized and 23 with diffuse peritonitis. Septic shock, faecal peritonitis, immunocompromised status and American society of Anesthesiologists grade IV were contraindications to the one-stage procedure. Alternative operations used in high-risk patients were Hartmann's procedure in 55 patients, subtotal colectomy in eight and colostomy in three.

Results

There were two deaths (3 per cent) among 61 patients treated by RPA and one (2 per cent) case of clinical anastomotic dehiscence. Overall morbidity was 39 per cent and the overall mean(s.d.) hospital stay was 18(15) days. No statistical differences were observed between patients with localized and diffuse peritonitis treated by RPA.

Conclusion

RPA may be the operation of choice in selected patients with left colonic diffuse peritonitis.
Tacrolimus has less fibrogenic potential than cyclosporin A in a model of renal ischaemia–reperfusion injury
Authors: Jain S , Bicknell G R , Nicholson M L
Published: March 2003

Background

Cyclosporin is associated with significant chronic nephrotoxicity, manifest in the long term mainly as renal fibrosis. There have been claims that tacrolimus is a less fibrotic drug than cyclosporin, and this study was designed to determine the effect of the two drugs on the expression of fibrosis-associated genes.

Methods

Male Wistar rats underwent clamping of the right renal pedicle for 45 min together with left nephrectomy; this model has previously been shown to be associated with upregulation of fibrosis-associated genes. Experimental groups (six animals per group) received cyclosporin A 10 mg/kg daily, tacrolimus 0·2 mg/kg daily or no treatment. Animals were killed at 16 weeks, and the renal cortical expression of fibrosis-associated genes was studied by means of quantitative reverse transcriptase–polymerase chain reaction.

Results

Tacrolimus-treated animals developed significantly less proteinuria and had lower serum creatinine levels than those receiving cyclosporin. Tacrolimus administration also significantly reduced the expression of transforming growth factor β and tissue inhibitor of metalloproteinases 1, both the products of genes associated with fibrosis. Although cyclosporin treatment reduced levels of the matrix-degrading enzymes, matrix metalloproteinase (MMP) 2 and MMP-9, this was not statistically significant.

Conclusion

Tacrolimus has less nephrotoxicity than cyclosporin in this model. It also appears to have less fibrogenic potential, and this may have implications for the choice of long-term immunosuppressant in renal transplantation.
Mitogenic effects of oestrogen mediated by a non-genomic receptor in human colon
Authors: Winter D C , Taylor C , O'Sullivan G C , Harvey B J
Published: March 2003

Background

Oestrogens are important mitogens in epithelial cancers, particularly where tumours express complementary receptors. While the traditional model of oestrogen action involves gene-directed (genomic) protein synthesis, it has been established that more rapid, non-genomic steroid hormone actions exist. This study investigated the hypothesis that oestrogen rapidly alters cell membrane activity, intracellular pH and nuclear kinetics in a mitogenic fashion.

Methods

Crypts isolated from human distal colon and colorectal cancer cell lines were used as robust models. DNA replication and intracellular pH were measured by radiolabelled thymidine incorporation (12 h) and spectrofluorescence imaging respectively. Genomic protein synthesis, sodium–hydrogen exchanger (NHE) and protein kinase C (PKC) activity were inhibited with cycloheximide, ethylisopropylamiloride and chelerythrine chloride respectively.

Results

Oestrogen induced a rapid (less than 5 min) cellular alkalinization of crypts and cancer cells that was sensitive to NHE blockade (P < 0·01) or PKC inhibition (P < 0·01). Oestrogen increased thymidine incorporation by 44 per cent in crypts and by up to 38 per cent in cancer cells (P < 0·01), and this was similarly reduced by inhibiting the NHE (P < 0·01) or PKC (P < 0·05).

Conclusion

Oestrogen rapidly activates cell membrane and nuclear kinetics by a non-genomic mechanism mediated by PKC but not gene-directed protein synthesis.
Primary hyperparathyroidism in India
Authors: Mishra S K , Agarwal G , Kar D K , Agarwal A , Gupta S K , Mithal A , Rastad J
Published: March 2003

Background

Primary hyperparathyroidism (PHPT) in Indians has some unique clinical features, such as early age of onset, extreme osteopenia, crippling bone involvement, large parathyroid tumours, higher proportion of malignancy and severe, prolonged postparathyroidectomy hungry bone syndrome. The current study aimed to study (1) whether these features of PHPT in Indians are due to a variant form of PHPT and (2) pathogenetic factors of such variant disease.

Methods

Clinical, investigative and pathological features of 29 consecutive patients with PHPT (24 females, five males) who underwent parathyroidectomy at 13–60 (mean 38) years of age were reviewed. Spearman's correlation coefficient was calculated between serum calcidiol levels and biochemical variables, bone mineral density (BMD) before surgery and parathyroid tumour weight.

Results

Median duration of symptoms was 2·5 (range 1–26) years. Mean total serum calcium, iPTH and ALP levels were 12·4 mg dl−1 (normal 8·5–10·8 mg dl−1), 955 pg ml−1 (normal 9–55 pg ml−1) and 850 units l−1 (normal 35–125 units l−1) respectively, while mean(s.d.) serum calcidiol and calcitriol concentrations were 14(6) ng ml−1 and 52(29) pg ml−1 (versus 9(9) and 30(14) pg ml−1 in matched controls). All patients had symptomatic osteitis fibrosa cystica and eight were bedridden. Single or multiple spontaneous fractures occurred in 14 patients, brown tumours in 20, and long bones were barely visible on plain films in four. BMD z-scores at distal radius and lumbar spine (mean) were −4·2 and −3·8. Palpable parathyroid tumours occurred in 14 patients and nine had renal damage, mainly nephrocalcinosis. Parathyroidectomy invariably resulted in long-standing severe hypocalcaemia, necessitating intravenous calcium infusion for 6 days on average, and long-term oral calcium and vitamin D supplementation. The mean parathyroid gland weight was 8·6 (range 2–36·6) g and signs of carcinoma were found in four. There was a negative correlation (P < 0·05) between serum calcidiol and serum iPTH, and serum ALP and parathyroid gland weight.

Conclusion

PHPT in Indians manifests as severe, symptomatic musculoskeletal and renal disease. In spite of the severe hyperparathyroidism, the serum calcium levels are only moderately raised. These patients have signs of rapid parathyroid tumour growth resulting in large adenomas and a high proportion of parathyroid carcinomas. The signs of rapid cell proliferation, excessive calcium insensitivity of PTH release and peripheral PTH resistance may clarify roles of widely prevalent vitamin D deficiency in pathogenesis of this variant of PHPT.
Surgery versus surveillance of pancreaticoduodenal endocrine tumours in multiple endocrine neoplasia type 1
Authors: Bartsch D K , Langer P , Schilling T , Wild A , Celik I , Nies C , Rothmund M
Published: March 2003

Background

Management of pancreaticoduodenal endocrine tumours remains controversial in multiple endocrine neoplasia type 1 (MEN1). The authors' experience with MEN1-related pancreaticoduodenal tumours has been reviewed in order to evaluate a rational therapeutic approach.

Methods

Twenty-one patients with MEN1 with pancreaticoduodenal endocrine tumours were analysed with special regard to outcome of surgery and surveillance. In addition, a phenotype/genotype analysis was performed based on MEN1 gene mutation analysis.

Results

Twelve of 21 patients had multiple tumours. Nine patients had gastrinomas, six non-functioning tumours, three insulinomas, two insulinomas and gastrinomas, and one had a vipoma. Six tumours were malignant with lymph node metastases (five gastrinomas, one vipoma). Seventeen patients were treated initially by either pancreatic left resection with tumour enucleation of the duodenum and/or pancreatic head (n = 9), tumour enucleation alone (n = 7) or pylorus-preserving partial pancreatectomy (PPPD; n = 1). Sixteen of 17 patients were cured biochemically after initial surgery and 11 remained free of disease after a median follow-up of 55 (range 2–197) months. Six patients underwent reoperation for recurrence and/or lymph node metastases, including two PPPDs in patients with gastrinoma. All six patients remained asymptomatic and three remained biochemically free of disease. Three of the 17 operated patients died from either unrelated causes (n = 2) or postoperative complications (n = 1). On the other hand, four asymptomatic patients with either gastrinomas (n = 2) or non-functioning tumours (n = 2) were closely surveyed and showed no progress or metastases on somatostatin (SMS) scans and computed tomography after 9–110 months. The genotype/phenotype analysis revealed that patients with truncating nonsense or frameshift MEN1 gene mutations in the N- or C-terminal regions (exons 2, 9 or 10) had a significantly higher rate of malignant tumours (55 versus 8 per cent; P = 0·04) and tended to have shorter disease-free intervals (28 versus 120 months; P = 0·11) than patients with other mutations.

Conclusion

An aggressive surgical approach is justified for pancreaticoduodenal tumours in patients with MEN1 since symptom-free long-term survival can be achieved. However, MEN1 gene mutations in exons 3–8 seem to be associated with mild behaviour of pancreaticoduodenal tumours which might allow close surveillance in asymptomatic patients with MEN1.
Normal preoperative levels of parathyroid hormone signify a mild form of primary hyperparathyroidism
Authors: Bergenfelz A , Lindblom P , Westerdahl J
Published: March 2003

Background

Primary hyperparathyroidism (pHPT) is characterized by an inappropriate serum level of parathyroid hormone (PTH) in relation to the serum level of calcium. Nowadays, patients often are diagnosed with an overtly asymptomatic pHPT with mild or even intermittent hypercalcaemia. Indeed, health screening surveys have shown that a significant proportion of patients with pHPT is normocalcaemic. Most studies also demonstrate patients with PTH levels in the upper normal range. The aim of the present study was to define subgroups of patients with mild pHPT, which potentially could give valuable insights into the pathogenesis of the disease.

Methods

Two hundred and seven consecutive patients, 157 women and 50 men, operated for pHPT were investigated with biochemical variables known to reflect PTH activity and calcium metabolism, and bone mineral content. The preoperative diagnosis of pHPT was based on the presence of hypercalcaemia combined with an inappropriate serum concentration of PTH. Thus, no patient was persistently normocalcaemic. Mean(s.d.) age of the patients was 64(14) years and mean(s.d.) serum level of calcium was 2·78(0·19) mmol l−1. On the basis of serum levels of PTH and calcium the day before surgery, patients were divided into subgroups.

Results  

One hundred and sixty-two patients (78 per cent) had raised levels of PTH and calcium the day before surgery (group 1), 25 patients (12 per cent) had a raised level of PTH and normal level of calcium (intermittent normocalcaemia) (group 2) and 20 patients (10 per cent) had a normal PTH level and raised calcium level (group 3). Between-group analyses demonstrated differences between groups in age, bone density, renal function and adenoma weight, and serum levels of alkaline phosphate, osteocalcin and urate. Except for lower adenoma weights, patients in group 2 did not essentially differ from those in group 1. However, patients in group 3 were younger, had better renal function, lower biochemical bone turnover and higher bone mineral content than patients in the other two groups.

Conclusion

These data support the existence of subgroups of mild pHPT. Patients with a serum level of PTH within the normal range were characterized by less biochemical derangement and better bone mineral content. This finding suggests that PTH rather than calcium reflects the severity of the disease.
Endoscopic endocrine neck surgery with carbon dioxide insufflation: the effect on intracranial pressure
Authors: Rubino F , Pamoukian V N , Zhu J F , Deutsch H , Inabnet W B , Gagner M
Published: March 2003

Background

The endoscopic approach to the thyroid and parathyroid glands requires insufflation with carbon dioxide at 10–15 mmHg. This may decrease the cerebral venous return and increase intracranial pressure (ICP). The aim of this study was to evaluate the effect of carbon dioxide neck insufflation on ICP and haemodynamic variables.

Methods

Twelve 25-kg pigs underwent endoscopic thyroid dissection using carbon dioxide insufflation at 0 mmHg (sham), 10 mmHg (G10), 15 mmHg (G15) and 20 mmHg (G20). Three pigs were used in each group. ICP, mean arterial pressure, central venous blood pressure (CVP), cardiac output and blood gas were measured at baseline, 30, 60 and 120 min.

Results

There were no differences in mean ICP between the sham group and G10. However, ICP significantly increased in G15 and G20. The partial pressure of carbon dioxide was similar in G10 and G15 (mean(s.d.) 49·8(2·4) and 49·8(5·2) mmHg respectively at 120 min), while it was dramatically increased in G20 (63·1(6·9) mmHg at 120 min). Haemodynamic parameters were stable in all groups except for G20 in which CVP significantly increased with respect to baseline (8·5(2·1) versus 1·3(1·5) mmHg; P < 0·01). Jugular vein collapse occurred during endoscopic dissection at all insufflation pressures, but pigs operated at 10 mmHg were able to maintain an intermittent blood flow.

Conclusion

A severe increase in ICP occurs with insufflation pressures higher than 15 mmHg, possibly owing to decreased cervical venous blood flow. Carbon dioxide insufflation up to 10 mmHg does not alter ICP, and is recommended for clinical application in endoscopic endocrine neck surgery.
Management of incidentally discovered adrenal masses and risk of malignancy
Authors: Favia G , Lumachi F , Basso S , D'Amico D
Published: March 2003

Background

Incidentally discovered adrenal masses larger than 1 cm are relatively frequent, but the correct management of such lesions is not well established.

Methods

Between 1980 and 1999, 158 patients (73 men (46 per cent) and 85 women (54 per cent), of median age 53 years) with adrenal incidentalomas larger than 2 cm were observed. Sixty-eight patients (43 per cent) underwent adrenalectomy. The reasons for surgery were: (1) suspicious appearance on computed tomography (CT) or magnetic resonance imaging (MRI) or no uptake at 75-selenium-norcholesterol scintigraphy (NCS) (n = 22), (2) increase in size of more than 1 cm (n = 15), (3) subclinical endocrine hyperfunction (n = 14), (4) size greater than 5 cm (n = 12) and (5) suspicious imaging-guided fine-needle aspiration cytology (FNAC) (n = 5).

Results

Pathological examination showed 39 adrenocortical adenomas (57 per cent), 20 adrenal malignancies (29 per cent) (15 carcinomas, three unsuspected metastases and two non-functioning malignant phaeochromocytomas) and nine various benign lesions (13 per cent). All masses increased in size were benign. Seven malignant tumours were 3–4 cm and 14 benign lesions were 5–6 cm in size. Sensitivity and specificity in detection of malignancy were 100 and 100 per cent for NCS (n = 34) and FNAC (n = 9), 75 and 94 per cent for CT (n = 68), and 88 and 100 per cent for MRI (n = 26) respectively.

Conclusion

To differentiate benign and malignant incidentalomas NCS and FNAC are more sensitive than CT and MRI, while the size criteria are of little value.
Ultrasonography and sestamibi as the only preoperative imaging tests in reoperation for parathyroid adenoma
Authors: Feingold D , Alexander H R , Chen C , Libutti S K , Shawker T , Simonds W , Spiegel A , Marx S , Skarulis M C , Doppman J L , Bartlett D L
Published: March 2003

Background

Various non-invasive and invasive tests are used for the localization of parathyroid adenomas in the reoperative setting. To help determine the most efficient algorithm for the evaluation of these patients, use of a combination of ultrasonography and sestamibi as the only preoperative imaging tests was explored.

Methods

This was an analysis of outcomes of 62 consecutive patients (21 men; mean age 55 years) treated between January 1995 and May 1999, and referred for persistent hyperparathyroidism after one (n = 47) or more (n = 15) previous explorations at which no abnormal parathyroid glands were found. While all patients underwent ultrasonography (all interpreted by one radiologist), computed tomography (CT), magnetic resonance imaging and sestamibi, the success of localization and reoperation was analysed using only the results of ultrasonography and sestamibi. Intraoperative ultrasonography (IOUS) was available in all cases.

Results

Sixty-one patients (98 per cent) had curative reoperations with solitary adenomas confirmed pathologically. One adenoma was not found at operation. Forty-six adenomas (74 per cent) were ectopic including 14 in the tracheo-oesophageal groove and 12 in the anterior mediastinum. The sensitivity, positive predictive value and accuracy for ultrasonography were 91, 87 and 84 per cent respectively; the corresponding values for sestamibi were 75, 94 and 71 per cent. In 58 (94 per cent) of 62 patients preoperative ultrasonography and/or sestamibi accurately identified the adenoma. In three patients cured by operation, in whom combined ultrasonography and sestamibi was inaccurate, one gland was found by IOUS in strap muscle, one by blind cervical thymectomy and one by sternotomy based on CT findings. Thirty-seven patients (60 per cent) underwent IOUS. In nine of these patients IOUS was essential in guiding resection of the adenomas.

Conclusion

This study supports an algorithm of obtaining ultrasonography and sestamibi as the initial and perhaps only preoperative localization tests for patients with persistent hyperparathyroidism after failed operation at which no abnormal glands were found. Using this algorithm, reoperation should be successful in almost 95 per cent of cases.
Normalization of intraoperative parathyroid hormone does not predict normal postoperative parathyroid function
Authors: Starr F , Betlej T , DeCresce R , Prinz R
Published: March 2003

Background

Intraoperative measurement of intact parathyroid hormone (iPTH) has been used increasingly as a means of confirming complete removal of hyperfunctioning parathyroid tissue. It remains uncertain, however, whether normalization of iPTH levels at operation accurately predicts postoperative values of iPTH.

Methods

Forty-five consecutive patients with primary hyperparathyroidism underwent parathyroidectomy between March and November 1999. Baseline intraoperative iPTH levels were measured before and at manipulation, then subsequently at 5 and 10 min after tissue was removed. Follow-up values were measured at 1- and 3-month intervals.

Results

Before operation the mean(s.d.) iPTH concentration was 211(182) pg ml−1 with a mean serum calcium level of 11·4(1·0) mg dl−1. In all but four patients, the final intraoperative iPTH normalized to absolute values below 60 pg ml−1 (mean 38(36) pg ml−1). One week after operation, serum calcium levels had returned to normal (mean 9·2(0·9) mg dl−1) and this correlated directly with final intraoperative iPTH values when assessed by linear regression analysis (r = 0·373, P < 0·03). By 1 month, all but two patients were normocalcaemic (mean 9·6(0·6) mg dl−1) with a mean iPTH of 81(99) pg ml−1. There was no correlation between the final intraoperative iPTH and postoperative iPTH values as determined by linear regression analysis (r = 0·035, P < 0·881). Both patients with persistent hypercalcaemia at 1 month had appropriate intraoperative decreases in iPTH level.

Conclusion

Although there is significant correlation between intraoperative iPTH levels and postoperative serum calcium levels, this does not hold true for postoperative iPTH levels. There was a 4 per cent failure rate in correcting postoperative calcium levels and a 20 per cent failure rate in normalizing postoperative iPTH levels despite appropriate intraoperative decreases in iPTH.
Clinical and genetic analysis of patients with pancreatic neuroendocrine tumours associated with von Hippel-Lindau disease
Authors: Libutti S K , Linehan W M , Choyke P L , Glenn G , Zbar B , Klausner R D , Alexander H R , Bartlett D L , Lubensky I , Walther McC
Published: March 2003

Background

Patients with von Hippel-Lindau disease (VHL) are at risk of developing pancreatic cysts, microcystic adenomas and neuroendocrine tumours. Pancreatic neuroendocrine tumours (PNETs) are found in 19 per cent of families with VHL. These tumours can behave in a malignant fashion, with up to 17 per cent of patients developing distant disease. The authors' initial experience with the diagnosis and management of these lesions, with resection based on size greater than 3 cm in imaging studies, has been reported previously. This is a report on their prospective experience using these criteria as well as on the role of genotype/phenotype analysis of germline VHL gene mutations in predicting clinical course.

Methods

Some 389 patients with VHL were screened between December 1998 and December 1999. The diagnosis of PNET was made by either pathological analysis of tissues or by characteristic radiographic appearance on computed tomography and magnetic resonance imaging. VHL gene germline mutations were determined by quantitative Southern blotting to detect deletions of the gene, Southern blotting to detect gene rearrangements, fluorescence in situ hybridization to confirm deletions and complete gene sequencing.

Results

Forty-four patients with PNET have been identified. Of these, 25 have undergone definitive surgical resection, five were found to have metastatic disease and 14 are being followed prospectively. No patient who has undergone resection based on the aforementioned tumour size criteria has developed metastatic disease. These patients represent 36 families (19 per cent) of a total of 188 VHL families who have had germline mutation analysis. Compared with all 188 VHL families, those with PNETs are more likely to have missense mutations (58 per cent) and more likely to have intragenic mutations. Four of five patients with metastatic disease have mutations in exon 3 compared with 18 of 39 patients without metastatic disease.

Conclusion

An aggressive approach to imaging for detection and surgical resection based on established size criteria has resulted in the successful management of patients with VHL and PNETs. Analysis of germline mutations may help predict those patients with VHL who are at risk of developing a PNET and which patients with a PNET may benefit from earlier surgical intervention to prevent spread of disease.
The ‘false’ non-recurrent inferior laryngeal nerve
Authors: Rafaelli M , Henry J F
Published: March 2003

Background

A communication between the middle cervical sympathetic ganglion (MCSG) and the inferior laryngeal nerve (ILN) has been described. The anastomotic branch (sympathetic–inferior laryngeal anastomotic branch; SILAB) is usually thin, but is sometimes larger and has the same diameter as the ILN. The purpose of this study was to evaluate prospectively the frequency of this condition and its implications during neck exploration.

Methods

From November 1998 to October 1999, 791 neck explorations were performed: 677 for thyroid, 99 for parathyroid and 15 for concomitant lesions. Some 1253 ILNs were dissected: 656 (52·3 per cent) on the right and 597 (47·7 per cent) on the left side.

Results

The ILN was identified in all cases. On the right side a non-recurrent ILN (NRILN) was found in three patients (0·5 per cent) and a large SILAB in ten (1·5 per cent). No anomalous branch was found on the left side. The SILAB originated from the superior cervical sympathetic ganglion (SCSG) in two patients and directly from the sympathetic chain (SC) above the MCSG in eight. No branch originating from the MCSG was found. The SILAB connected with the ILN less than 2 cm from the cricoid in all patients.

Conclusion

The SILAB may originate not only from the MCSG but also from the SCSG and directly from the SC. When the SILAB is as large as the ILN, it could be mistaken for a NRILN. Before concluding that the anomalous branch is a NRILN, one should check if it originates from the vagus or from the cervical sympathetic system. Awareness of this anatomical condition during neck exploration may help the surgeon to avoid injuries of an ILN running in the usual pathway.