Transverse closure of mesenterico-portal vein after vein resection in pancreatoduodenectomy.

BACKGROUND: Resection of the involved mesenteric-portal vein (MPV) is increasingly performed in pancreatoduodenectomy. The primary aim of this study is to assess the rate of R0 resection in transverse closure (TC) versus segmental resection with end-to-end (EE) closure and the secondary aims are to assess the short-term morbidity and long-term survival of TC versus EE. METHODS: Patients undergoing pancreatoduodenectomy with MPV resection were identified from a prospectively database. The reconstruction technique were examined and categorized. Clinical, pathological, short-term and long-term survival outcomes were compared between groups. RESULTS: 110 patients underwent PD with MPV resection of which reconstruction was performed with an end-to-end technique in 92 patients (84%) and transverse closure technique in 18 patients (16%). Patients undergoing transverse closure tended to have had a shorter segment of vein resected (≤2 cm) compared to the end-to-end (83% vs. 43%; P = 0.004) with no difference in R0 rate. Short-term morbidity was similar. The median and 5-year survival was 30.0 months and 18% respectively for patients undergoing transverse closure and 28.6 months and 7% respectively for patients undergoing end-to-end reconstruction (P = 0.766). CONCLUSION: Without compromising the R0 rate, transverse closure to reconstruct the mesenteric-portal vein is shown to be feasible and safe in the setting when a short segment of vein resection is required during pancreatoduodenectomy. Synopsis - We describe a vein closure technique, transverse closure, which avoids the need for a graft, or re-implantation of the splenic vein when resection of the mesenteric-portal vein confluence is required during pancreatoduodenectomy.

Antimicrobial effects of a macrophage-derived cytotoxin from the serum of BCG-primed rabbits (tumour necrosis serum).

Previous studies have shown that a macrophage-derived cytotoxin, found in high titre in the serum of BCG-primed rabbits, killed malarial parasites and certain tumour cells. In this study, the macrophage cytotoxin was tested for activity against microorganisms other than protozoa. No activity was seen against a range of gram-negative or gram-positive bacteria or against Candida albicans. It is concluded that the macrophage cytotoxin has limited anti-microbial activity, perhaps restricted to certain intra-cellular parasites.

The influence of graft type on patency of infrainguinal arterial bypass grafts.

Between 1985 and 1992, 328 patients underwent 392 infrainguinal reconstructions. Indications for operation were disabling claudication in 126 patients, critical limb ischemia in 246 and uncomplicated popliteal aneurysm in 20. Grafts were to the above knee popliteal artery in 134 patients, below knee popliteal artery in 176 and infrapopliteal ("distal") in 82 patients. Graft types included 160 reversed saphenous vein (RSV), 95 polytetrafluoroethylene (PTFE), 84 nonreversed saphenous vein (NRSV), 41 composite grafts (PTFE plus vein) and 12 others. Results show the five year patency rate for all grafts of 58 percent and limb salvage (for limb ischemia) of 74 percent. Above knee and below knee popliteal grafts (three year patency rates of 72 and 66 percent) performed significantly better than distal grafts (51 percent three year patency rate, p < 0.025). NRSV grafts comprised 63 ex situ ("translocated") and 21 in situ grafts. No significant difference was shown between these (two year patency rates of 62 and 65 percent). There was no significant difference between RSV and NRSV grafts in this series, although RSV tended to show higher patency rates. Composite grafts (below knee, three year patency rate of 45 percent) had significantly lower three year patency rates than below knee RSV (79 percent, p < 0.005). RSV remains the conduit of choice in this unit, with long term patency comparable with other published series. Use of NRSV (translocated and in situ) allows increased use of autogenous vein with the associated higher patency rates compared with prosthetic materials and is the graft of choice if the long saphenous vein is not suitable for use in the standard reversed method. The translocated technique allows more flexibility in the use of nonreversed vein with results comparable with the in situ technique. Composite grafts provide a useful alternative to PTFE alone for infrageniculate grafting when insufficient autogenenous vein is available.

Preliminary results from attenuation-slope mapping of plaque using intravascular ultrasound.

Excised femoral and iliac artery segments have been examined with 20 MHz intravascular ultrasound followed by histological assessment. During the ultrasound examinations, radio-frequency (RF) data were recorded digitally, and used for calculating local values of attenuation slope throughout the tissue, using a frequency-domain technique. The RF data were also reconstructed as conventional ultrasound images, and the attenuation-slope information presented as a threshold colour overlay. Areas identified as degenerative plaque in the histological assessments were usually found to correspond to areas of high attenuation slope, and were clearly identified from the pattern of colours on the combined image. Some examples are presented, illustrating the appearance of various pathologies imaged by this technique.

Spectral tissue strain: a new technique for imaging tissue strain using intravascular ultrasound.

Spectral tissue strain (STS) is a new technique for measuring and imaging tissue strain from a set of images using intravascular ultrasound. The technique is based on the Fourier scaling property and uses the chirp z-transform (CZT) to estimate strain within the vessel walls. Some preliminary results, both in vitro and in vivo, are described. A novel display technique has also been developed for encoding radial strain and displaying the resulting colour map as an overlay on the original image.

Development of tumour cell resistance to tumour necrosis factor does not confer resistance to cytotoxic drugs.

Tumour necrosis factor (TNF) is a protein product of macrophages with potential anti-cancer activity. As with other anti-cancer agents, tumour cells can develop resistance to the cytotoxic effects of TNF. The aim of his study was to see whether development of resistance to TNF resulted in a concomitant resistance to other anti-cancer agents, in particular those associated with multidrug resistance. Three TNF-susceptible tumour cell lines (L929, U937 and RK13) and their TNF-resistant sublines were compared for susceptibility in vitro to several cytotoxic drugs. The TNF-resistant sublines were not significantly more resistant to these drugs. In addition, an L929 subline selected for resistance to actinomycin D retained its susceptibility to TNF. These observations show that tumour cell resistance to TNF develops independently of resistance to cytotoxic drugs.

Relationship between tumour cell morphology, gap junctions and susceptibility to cytolysis by tumour necrosis factor.

Tumour necrosis factor (TNF) is directly cytolytic to certain tumour cell lines in vitro, although TNF-resistant variants can be selected from these susceptible lines by exposure to TNF. While studying TNF-susceptible L929 cells and their resistant variant, L929/R, we noted that within L929 colonies the cells were widely spaced whereas they were closely packed in L929/R colonies. L929/R cells also adhered more strongly to plastic and differed from L929 in cell shape. Similar observations were made with TNF susceptible and resistant variants of two other cell lines (RK13 and a plastic adherent U937 subline). The tendency of resistant cells to grow closely together suggests the possibility of inter-cell communication for the TNF resistant state. However, like L929 and U937, L929/R and U937/R did not communicate by gap junctions and we could find no evidence of extracellular mediators of TNF resistance. Rather the differences in colonial morphology, cell shape and plastic adherence may be secondary to an underlying mechanism which defines TNF susceptibility/resistance.

Agents which modify colonial morphology of tumor cells also affect acid vesicle function and fibronectin deposition in the extracellular matrix.

The tumor cell line U937A is motile, weakly plastic-adherent and forms large, loosely packed colonies in vitro and is invasive and metastatic in vivo. U937A/R, a mutant selected for resistance to killing by tumor necrosis factor (TNF), is less motile, more adherent and forms small, tightly packed colonies and is not invasive or metastatic. U937A and U937A/R also have differing cytoplasmic distributions of acid vesicles, and unlike U937A, U937A/R fails to deposit fibronectin into its extracellular matrix. In this study we have sought reagents that could convert "loose" U937A cells into the nonmetastatic, "tight" colonial phenotype. Six effective reagents were found: wheat germ agglutinin, phytohemagglutinin-L, dexamethasone, chloroquine, promethazine, and monensin. All 6 reagents caused swelling and/or redistribution of acid vesicles but phytohemagglutinin-L, dexamethasone, and monensin also reduced fibronectin deposition in the extracellular matrix. Therefore, these agents probably reduce motility by interference with recycling of cell surface receptors through acid vesicles and also in some cases by altering the extracellular matrix.

Outcome of surgery for vascular access in patients commencing haemodialysis.

OBJECTIVE: assessment of surgical vascular access procedures for haemodialysis. DESIGN: retrospective cohort audit. MATERIALS AND METHODS: secondary patency was calculated from surgery until access failure, death, transplant, conversion to peritoneal dialysis, or loss to follow-up. All surgical procedures including immediate failures and failures to mature fistulae were included but not radiological interventions. RESULTS: four hundred and forty-five operations were undertaken in 197 patients over 87 months comprising 273 access creations and 172 revisions. Median follow-up was 26 months with a mortality of 9.4 deaths per 100 patient-years including eight perioperative deaths. Autogenous access was created in 147 (75%) patients with 142 based on the radial artery whilst 50 prosthetic grafts including 46 PTFE grafts and 40 forearm loops were placed. Patients receiving grafts were more likely to be older, female and die in follow-up. Grafts had higher patencies of 89, 75 and 68% at 1, 2 and 4 years, respectively compared to 69, 63 and 55% for autogenous access. This difference was significant (p=0.049) when the effects of the presence of diabetes and peripheral arterial disease were accounted for but more frequent revisions were required. The final access placed was autogenous in 110 (56%) and prosthetic in 87 (44%) patients. CONCLUSIONS: in our surgical unit, there was high secondary patency including for prosthetic grafts, high autogenous utilisation and relatively infrequent reintervention.

Colonial morphology of tumour cells and susceptibility to cytolysis by tumour necrosis factor. The role of cellular fibronectin deposition in the extracellular matrix.

The tumour cell lines U937A and L929 form large, loosely packed colonies in vitro and can be killed by the cytokine tumour necrosis factor (TNF). In contrast, their TNF-resistant mutants U937A/R and L929/R form tightly packed colonies. Since cells which form loose colonies have increased metastatic potential it is important to understand the factors governing colonial morphology. To this end, we have compared the extracellular matrices (ECMs) of the 'loose' lines, U937A and L929 with their 'tight' mutants. By immunofluorescence, a polyvalent anti-U937A serum revealed a fibrillar network in the ECMs of the 'loose' lines which was absent in the 'tight'. On Western blotting of ECMs the antiserum detected an additional 300 kDa protein in the 'loose' lines which was subsequently shown to be cellular fibronectin. The four lines secreted comparable amounts of fibronectin and this was qualitatively indistinguishable between 'loose' and 'tight' cells by peptide mapping or lectin binding. It is concluded that the differences in colonial morphology are due to the 'tight' mutants' inability to incorporate fibronectin into the ECM.

The influence of oestrone on the production of tumour necrosis factor by human peripheral blood adherent cells.

Human peripheral blood adherent cells (PBAC) incubated with oestrone in high concentration (10(-5) M) release, on exposure to bacterial endotoxin, an amount of tumour necrosis factor (TNF) greater than do cells incubated without the steroid. The finding may imply a non-endocrine hormonal process leading to heightened local TNF responses. This may be the basis of endotoxin hypersensitivity in pregnancy.

In vitro assessment of back pressure on ventriculoperitoneal shunt valves. Is laparoscopy safe?

BACKGROUND: Whereas there are case reports of laparoscopy in patients with ventriculoperitoneal shunts, there are no studies assessing the potential failure of shunt valves with the increased intra-abdominal pressure of laparoscopy. This study aims to assess this factor. METHODS: An in vitro model was used to assess the potential for retrograde failure of ventriculoperitoneal shunt valves in a commonly used shunt. Nine shunts were subjected to graded increases in back pressure and observed for retrograde valve leak. RESULTS: None of the shunts tested showed any signs of leak associated with the increased back pressure. However, disruption of shunt seals was noted in seven of the nine shunts, occurring at the minimal pressure of 80 mmHg. CONCLUSIONS: There appears to be minimal risk of retrograde failure of the valve system in the ventriculoperitoneal shunt tested. However, tests on different types of ventriculoperitoneal shunts would be needed to confirm these results if laparoscopy is to be considered safe in patients with ventriculoperitoneal shunts in situ.

Involvement of phospholipase A2 activation in tumour cell killing by tumour necrosis factor.

Earlier studies have indicated a possible role for arachidonate metabolism in the direct cytolysis of tumour cells by tumour necrosis factor (TNF) in vitro. In this study, the involvement of arachidonate metabolism has been investigated further with the following results: (i) Cytolysis of human U937 tumour cells by recombinant TNF was reduced by dexamethasone and quinacrine, agents which inhibit phospholipase A2. (ii) U937 and L929 cells, which are susceptible to TNF cytolysis, released arachidonic acid and its metabolites within 5 hr of TNF challenge, before cell death was apparent. In contrast, U937/R and L929/R, which are resistant to the cytolytic effects of TNF, did not release arachidonate products on TNF challenge. (iii) rTNF cytolysis of U937 cells was not reduced by inhibitors of the cyclo-oxygenase and lipo-oxygenase pathways of arachidonic acid metabolism. Cytolysis was reduced, however, by inhibitors of the arachidonate metabolic pathway involving cytochrome P450-dependent reductase, but only at reagent concentrations that also inhibited phospholipase A2 activity. Overall, these observations indicate a role for phospholipase A2 but not for arachidonic acid or its metabolites in the direct cytolysis of tumour cell lines by TNF.

Tumour cells which develop resistance to cytolysis by tumour necrosis factor have a different glycoform of a 105-kDa glycoprotein and lose the capacity to invade and metastasize.

A plastic-adherent variant of human myelomonocytic leukaemia cells (U937) is highly susceptible to direct TNF cytolysis in vitro. Previously, we found that a subline selected for resistance to TNF cytolysis (U937/R) was much less motile and more plastic-adherent than the parental line. In the present study we show that U937 and U937/R cells have different glycoforms of a 105-kDa cell-surface glycoprotein. This protein is predominantly N-glycosylated and has the physicochemical properties of the LAMP-I glycoprotein. In nude mice, U937 cells are highly malignant whereas U937/R cells form a benign, encapsulated tumour. Therefore, possession of a different glycoform of the 105-kDa glycoprotein by U937/R cells correlates not only with loss of TNF susceptibility but also with reduced invasiveness and metastasis.

Tumour-necrosis factor from the rabbit. IV. Purification and chemical characterization.

Serum from rabbits with BCG/endotoxin-induced shock is growth inhibitory or cytotoxic to a range ot tumour cell lines. The active component, tumour-necrosis factor (TNF), has been purified 1000-fold by sequential salt precipitation, ion-exchange chromatography and gel-filtration. TNF had a mol. wt of 67,000 on gradient PAGE and 39,000 on Ultrogel AcA44 gel-filtration. The isoelectric point was pH 5.1-5.2. TNF was susceptible to the proteolytic enzyme pronase, but resistant to trypsin or papain. On isopycnic ultracentrifugation it had a buoyant density of 1.27, confirming that it is protein in nature, with little or no carbohydrate. This is also suggested by its failure to bind to a range of lectins.

Antimicrobial properties of preterm breast milk cells.

The antimicrobial properties of preterm and term breast milk cells were compared. They were similar in cell numbers and in the capacity to phagocytose and kill staphylococci. Interferon production on endotoxin challenge appeared to be higher in preterm cells. The antibacterial activity of breast milk cells was retained after storage at 4 degrees C for 24-48 hours. Cell numbers were unaffected by passage through a standard oral paediatric feeding set.

Development of tumor cell resistance to tumor necrosis factor cytolysis results in reduced fibronectin binding and altered ganglioside expression.

U937A cells are highly susceptible to tumor necrosis factor (TNF) cytolysis. They are also motile and incorporate fibronectin into the extracellular matrix (ECM). This takes the form of a dense fibrillar network in confluent cultures, but in sparse cultures appears as a "snail trail" of insolubilized fibronectin behind the moving cell. In contrast, U937A/R cells selected for resistance to TNF cytolysis are poorly motile and, although they synthesize fibronectin, fail to incorporate it into the ECM. Compared to U937A/R, U937A cells spread more rapidly and extensively on fibronectin-coated plastic and also bound 125I-fibronectin more effectively. Inhibition of U937A spreading on fibronectin required higher doses of GRGDSPK peptide, indicating greater expression on U937A of integrin-type, fibronectin receptors. Gangliosides are non-integrin structures which can bind fibronectin, and there were also qualitative and quantitative differences in ganglioside expression with U937A having two to five times more than U937A/R. Therefore the development of TNF resistance by U937A/R cells is accompanied by a reduced ability to interact with fibronectin, and this probably accounts for the reduced motility and inability to deposit fibronectin in the ECM.

Fibromuscular hyperplasia in an aberrant subclavian artery and neurogenic thoracic outlet syndrome: an unusual combination.

An aberrant right subclavian artery arising distal to the origin of the left subclavian artery is the most common anomaly of the aortic arch. Degenerative diseases of aberrant subclavian arteries including aneurysms and occlusive disease have been reported previously. We believe that this case is the first reported case of fibromuscular hyperplasia affecting an aberrant subclavian artery. A 25-year-old woman admitted with a history consistent with neurogenic thoracic outlet syndrome was found to have a reduced pulse and blood pressure on the ipsilateral side caused by fibromuscular hyperplasia of an aberrant subclavian artery. A carotid-subclavian bypass via a supraclavicular incision was performed at the same time as thoracic outlet decompression. Histologic examination confirmed the presence of fibromuscular hyperplasia in the aberrant subclavian artery. This case is discussed with reference to the available literature.

Tumour necrosis factor activity in joint fluids from rheumatoid arthritis patients.

Although tumour necrosis factor (TNF) was first studied as an anti-cancer agent it is now recognized as a potent mediator of inflammation and could potentially play a role in rheumatoid arthritis. In this study TNF activity has been sought in fluids from arthritic joints. TNF was assayed by a well established bioassay which depends upon cytolysis of particular tumour cell lines and which has a limit of detection of c. 25 pg/ml. Of the 92 joint fluids tested (70 rheumatoid and 22 others) only three had demonstrable TNF activity. Despite this, joint fluid cells from all 14 patients tested (12 rheumatoid and two others) had the ability to synthesize TNF on stimulation in vitro. Subsequently it was shown that joint fluids contain a macromolecule which inhibits TNF activity in cytolytic assays and which may mask low levels of TNF activity in joint fluids.

Protective effect of an oestrogen against endotoxin-induced liver enzyme release.

Groups of mice were given oestrone acetate or vitamin E subcutaneously to determine how these treatments might modify responses to endotoxic lipopolysaccharide given intraperitoneally. Release of hepatic transaminase and tumour necrosis factor (TNF) into serum and induction of manganous superoxide dismutase in the liver were measured. Significantly less transaminase and TNF were released into the circulation in mice given the steroid or vitamin E before the endotoxin. In endotoxin-treated animals oestrogen administration did not influence induction of the superoxide dismutase. It is postulated that protection of the liver in these experiments arises from a direct pharmacological antioxidant effect of the oestrogen.