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Blood transfusion is given according to haemoglobin thresholds aimed at restoration of arterial oxygen-carrying capacity. Patient survival after severe haemorrhagic shock depends on restoration of microvascular perfusion, tissue oxygen delivery, endothelial function and organ integrity. We investigated a novel crystalloid fluid designed for tissue oxygen delivery, Oxsealife® , with components that generate microvascular nitric oxide and scavenge reactive oxygen species generated during ischaemia-reperfusion injury. The amount of dissolved oxygen in blood progressively increased during step-wise in vitro haemodilution with this fluid, suggesting that the oxygen solubility coefficient of blood is dynamic, not static. We performed a pilot safety and efficacy study to compare resuscitation with this novel crystalloid vs. whole blood transfusion in a swine haemorrhagic shock model with animals bled to an arterial lactate oxygen debt target. Despite contributing no haemoglobin, viscosity nor oncotic potential, resuscitation with Oxsealife after severe haemorrhagic shock restored central haemodynamic parameters comparable to stored allogeneic blood transfusion. Tissue perfusion, oxygenation and metabolic outcomes were equivalent between treatment groups. Increased consumption of bicarbonate in animals given Oxsealife suggested greater capillary recruitment and enhanced clearance of acidic tissue metabolites. Serum markers of organ function, animal activity during recovery and histological analysis of tissue morphology and endothelial glycocalyx integrity confirmed functional recovery from haemorrhagic shock. We conclude that recovery of tissue oxygen delivery and organ function after haemorrhagic shock may not be dependent on treatments that increase haemoglobin levels. Oxsealife shows promise for treatment of severe haemorrhagic shock and may reduce the requirement for allogeneic blood products.

Sentinel lymph node biopsy (SLNB) as a staging procedure in multiple breast cancer is a controversial issue. We have aimed to evaluate the efficacy of sentinel node (SN) detection in patients with multifocal or multicentric breast cancer as well as the safety of its clinical application after a long follow-up.A prospective descriptive study was performed. Eighty-nine patients diagnosed of multiple breast cancer (73 multifocal; 16 multicentric) underwent SLNB. These patients were compared to those with unifocal neoplasia. Periareolar radiocolloid administration was performed in most of the patients. Evaluation was made at an average of 67.2 months of follow-up (32-126 months).Scintigraphic and surgical SN localization in patients with multiple breast cancer were 95.5% and 92.1%, respectively. A higher percentage of extra-axillary nodes was observed than in the unifocal group (11.7% vs 5.4%) as well as a significantly higher number of SN per patient (1.70 vs 1.38). The rate of SN localization in multicentric cancer was slightly lower than in multifocal cancer (87.5% vs 93.1%), and the finding of extra-axillary drainages was higher (20% vs 10%). Number of SN per patient was significantly higher in multicentric breast cancer (2.33 vs 1.57). No axillary relapses have been demonstrated in the follow-up in multiple breast cancer patients group.SLNB performed by periareolar injection is a reliable and accurate staging procedure of patients with multiple breast cancer, including those with multicentric processes.

The aim of this study was to establish the efficacy and safety of sentinel lymph node biopsy for lymph node staging in patients with breast cancer and prior breast surgery, considering its extension, localization and time since the previous surgical procedure.A sentinel lymph node biopsy was performed in 38 patients with early breast cancer and previous breast surgery: recent excisional biopsy in 22 patients (Group I), previous lumpectomy or mammoplasty in 16, including one case of cancer treated with breast-conserving surgery (tumor recurrence). Lymphoscintigraphy was performed after periareolar injection, also sometimes adding an injection near to the surgical scar. After removing the sentinel node, axillary lymph node dissection was performed when the lymph node was positive (and not localized).The efficacy of the scintigraphic localization of the sentinel node was 92.1% of the patients, with 15.8% of extra-axillary drainages. Axillary intraoperative detection was 81.6%. The identification rate after recent excisional biopsy or previous surgery was similar (81.8 vs 81.2%). However, extra-axillary sentinel nodes were more frequent in Group II (9.1 vs 25%). Having a localization of previous surgical procedures in upper outer quadrant caused drainages outside of the axilla more frequently (27.2 vs 11.1%). Axillary detection rate was similar to other quadrants (81.8 vs 81.5%). The rate of breast cancer-related events was 5.2% (2/38), without axillary recurrences (mean follow-up: 3 years).Sentinel lymph node biopsy in patients with previous but not extensive breast surgery is safe. Extra-axillary drainages are more common when the previous surgical area was wide, especially in the upper-outer quadrant.

Among the therapeutic alternatives to orthotopic liver transplantation, hepatocyte transplantation (HT) offers the best potential in a number of liver diseases, mainly inborn errors of metabolism. Nevertheless, HT presents several inconveniences such as the scarce knowledge of the functionality of the transplanted hepatocytes, which has given rise to controversy about the specificity or unspecificity of the transplant, and the lack of a suitable system for preserving the cells. This study was designed to test a system for cryopreserving hepatocytes and to assess their functionality over prolonged periods after their ectopic transplantation. A medium and a freezing schedule which are reproducible and yield elevated viability have been used, and a number of hepatospecific parameters have been assessed: the activity of ornithine carbamoyltransferase—an enzyme of primary importance in the urea cycle—lipogenesis, gluconeogenesis, glucose-6-phosphatase and cytochrome oxidase activities, the presence of albumin—as an index of plasma protein synthesis—and IDA uptake and metabolism, showing the UDP-glucuronyl transferase activity. As dedifferentiation markers, γ-glutamyl transpeptidase and α-fetoprotein have been studied. From the results, it can be deduced that hepatocytes can be cryopreserved and transplanted and that under these conditions they maintain hepatic features for a long time. Following transplantation, several specific liver functions appear or are enhanced in the spleen. Freshly isolated and cryopreserved transplanted hepatocytes have similar behaviors, although a difference in the expression of the function can be observed. It can be concluded, then, that cryopreserved transplanted hepatocytes develop into what could be referred to as an “ectopic liver,” with the implications that this phenomenon could have in the clinical potential of this kind of transplant.

Pancreatoduodenectomy is the only potentially curative treatment for peripapillary tumors. However, postoperative mortality remains as high as 5% and as many as 50% of patients have postoperative morbidity. Preoperative endoscopic retrograde cholangiopancreatography and placement of a biliary drainage stent aim to achieve a precise diagnosis, reduce jaundice and improve the results of surgery for biliary malignancies, but the effectiveness of preoperative biliary drainage in the prevention of postoperative infections is controversial. A retrospective analysis was performed in a series of 58 patients with periampullary tumors who underwent pancreatoduodenectomy and the relationship between preoperative biliary drainage and postoperative complications was examined. Biliary drainage (25.8%) before pancreatoduodenectomy was significantly associated with more frequent biliary and pancreatic anastomotic leakage (60% with drainage versus 20.9% without drainage), higher postoperative morbidity, and greater mean postoperative length of hospital stay (33.3 days with drainage versus 21.6 without drainage). No significant difference was found between the two groups in postoperative mortality at 30 days (13.7%). The effectiveness of biliary drainage before surgery in patients with pancreatic and peripancreatic lesions has not been well established, but we believe that this procedure should be avoided whenever possible in patients with potentially resectable pancreatic and peripancreatic lesions. Prospective randomized studies are required to clarify the indications for preoperative biliary drainage in these patients.

To estimate cytologic volume-weighted mean nuclear volume and correlate it with other prognostic factors, such as tumor diameter and cytologic grading in relation to nodal infiltration.The relationships between nodal status and nuclear VV, tumor diameter and cytologic grading, according to the modified Black nuclear grading system, were analyzed on fine needle aspirates of 49 cases of breast cancer by univariate and multivariate logistic regression.Volume-weighted mean nuclear volume (nuclear VV) estimated on fine needle aspiration smears showed a significant correlation with grade of tumor differentiation.Stereologic evaluation of nuclear size by nuclear VV is an objective method for the cytologic grading of ductal carcinoma of the breast and has independent prognostic value in relation to nodal status higher than those of tumor diameter and cytologic grade.

We analyzed the prognostic factors and evaluated the usefulness of mitotic index to predict the behavior of gastrointestinal stromal tumors (GIST).Fifty three patients operated on for stromal tumors of the digestive tract were studied retrospectively. Mean follow-up was 6 years. The number of mitosis/10 high power fields was the definitive criterion for classification, regardless of their inmunohistologic differentiation. Twelve tumors had 0 mitoses, 34 from 1 to 9 mitoses, and 7 hador = 10 mitoses. The survival rate was analyzed and the morphological characteristics and evolution were correlated according to mitotic index.The incidence of advanced illness was related to the number of mitoses: 29% in the group with 1 to 9 mitoses, and 86% when there wereor = 10 mitoses. The recurrence intervals were 44 and 8 months respectively. No tumor with 0 mitoses evolved aggressively. The survival rate was significantly related (p0.001), to the mitotic index. The group with 0 mitoses had a survival rate of 100% after 10 years, those with 1 to 9 mitoses 69% and those withor = 10 mitoses 14%. The other factors which influenced the prognosis (location, size, local invasion and resection) depended, as well, on the mitotic index.The classification of digestive tract stromal tumors by mitotic index is an efficient method because it distinguishes 3 entities with different biological behavior in the long term.

Colorectal cancer has been studied from the point of view of the relationships between several variables, including proliferative activity and p53 protein expression. However, stereologic evaluation of nuclear size has not been thoroughly described. In the present study, measurements of the volume-weighted mean nuclear volume (nuclear Vv), have been performed in well, moderately and poorly differentiated colorectal adenocarcinomas and correlated with the Dukes' stage and other factors such as proliferative activity and p53 protein immunoreactivity. Although the mean values of nuclear Vv were higher in poorly differentiated cancers or Dukes' CD stage than in well and moderately differentiated tumors or Dukes' AB stage, these differences were not significant. However, the variability of nuclear size in colorectal cancers was more relevant than the mean values of nuclear Vv with respect to their invasive classification. The carcinomas which extended beyond the serosa (Dukes' stage CD) had higher biologic variation than those grouped as Dukes' stage AB. The results of the present study also indicate that nuclear size in colorectal cancers has a positive correlation with both proliferative activity and p53 protein expression. The relationship between nuclear Vv and proliferative activity emphasizes the possible prognostic relevance of this stereologic estimate of nuclear size in colorectal adenocarcinoma.

The reactivity of the dog cavernous carotid artery to stretch, field electrical stimulation, and norepinephrine was studied using arterial segments under isometric conditions. Light microscopy revealed that this artery is of muscular type and its external surface is covered by venous endothelium, and fluorescence microscopy showed a dense adrenergic innervation. On stretch, arteries exhibited an immediate, transient contraction (phasic response) and a late, maintained contraction (tonic response) that were unaffected by tetrodotoxin (10(-6) M) or endothelium removal but were reduced by the inhibitors of cyclooxygenase indomethacin (10(-6) M), acetylsalicylic acid (3 x 10(-5) M), or meclofenamate (10(-5) M). Electrical stimulation (0.5-4 Hz) contracted the arteries in a frequency-dependent manner, and the response was reduced by tetrodotoxin, phentolamine, (10(-6) M), or the inhibitors of cyclooxygenase used but was unaffected by endothelium removal. Norepinephrine (10(-9)-3 x 10(-4) M) caused dose-dependent contraction that was blocked by phentolamine and by the inhibitors of cyclooxygenase but was not modified by endothelium removal. The results indicate that the dog cavernous carotid artery develops myogenic tone on stretch and contracts on adrenergic stimulation. They also suggest that in these responses prostaglandins but not the endothelium are involved. Therefore, the cavernous carotid artery, because of its location and reactivity, could be of relevance in regulating blood flow or pressure within the cerebral circulation when arterial pressure or adrenergic activity increases.

To determine the mechanics of arteries forming the carotid rete mirabile of goat and cattle, the wall tension-circumference length relationship was recorded isometrically in isolated retial arteries of 350-600 microns in external diameter under relaxed and potassium-activated conditions. The results are compared to those of pial arteries of similar size. In relaxed retial and cerebral vessels, tension-length relationship had nonlinear characteristics and the incremental elastic modulus rose as the circumference length increased, the modulus being lower in retial than in pial arteries. However, the stiffness of the artery considered as a whole (stiffness parameter beta) was similar in the two types of vessels. In activated arteries, force development was a function of length and the magnitude of the response increased until an optimal length was reached after which the response decreased with further stretch. In all stretches studied the developed force was much lower in retial arteries. The calculated active stress at the various lengths was also smaller in retial than in cerebral arteries and the maximum active stress for retial arteries was about 30-50% of that for cerebral arteries. Therefore, the passive mechanical properties of retial arteries closely resemble those of cerebral arteries but retial arteries have a small contractility. This suggests that the carotid rete mirabile of Artiodactyla has a minor role in actively controlling blood supply to the brain. Comments on the hemodynamic significance of the carotid rete are included.

One case of recurrent pneumothorax, coinciding with menstruation, is documented. The ethiopathogenesis of this syndrome remains unknown, after studying the 44 cases. Their association with pleural endometriosis has only been found in nine cases. This new publication with pleural endometriosis and menstrual hemoptysis supports an endometriosis etiology. The surgical treatment of pneumothorax is effective, and a main disclosure of this syndrome would facilitate the research and enlightenment of the ethiopathogenesis.

The development of a reproducible, effective system of cryopreservation of hepatocytes would create new possibilities for metabolic studies, as well as the clinical application of hepatocellular transplants in diverse hepatic disorders. For the purpose of dealing with both questions, we have studied different media and procedures of freezing, and have chosen that combination which afforded the best results for long-term studies of function. A series of intrasplenic transplants were performed with freshly isolated hepatocytes as well as cryopreserved ones, and several hepatospecific parameters (Alanine aminotransferase, ornithine carbamoyl transferase, lipogenesis, uptake of 99mTc-N-(p-butylphenylcarbamylmethyl)iminodiacetic acid, G6Pase, albumin, and gamma-glutamyl transpeptidase (gamma-GT) were quantified for 9 months. The histological study of the cells reveals that they acquired an architecture characteristic of the liver. All of the parameters indicative of hepatic function were detected throughout the 9-month period in the transplanted spleens. All the spleens, controls and transplanted, were found negative for the presence of the dedifferentiation marker gamma-GT. These results clearly indicate the possibility of recovering hepatocytes which maintain their specific functions after being subjected to a freezing-thawing process, with the corresponding implications for future clinical application as well as for hepatic biochemistry.

A small epidemic of tinea corporis due to M. gypseum is reported. There were 13 children affected, ages 1-15 years. These children belonged to 6 neighbouring families and all used a common "playground", an empty lot located nearby. Cultures were positive for M. gypseum in the 13 children and the agent was also isolated from 2 soils collected in the playing-ground. Soil isolates were classified as N. gypsea. Clinically, the lesions were circinated and had active borders, they were preferentially located in the trunk. Most children (8/13) had multiple lesions. These and other pertinent aspects are discussed in the text.