Effect of blood transfusion on gene expression of transforming growth factor beta-1 and the alpha subunit of interleukin-2 receptor in a model of colonic wound healing.

Blood transfusions have been shown in the past to compromise wound healing in experimental models of colonic anastomosis. Transforming growth factor beta (TGFbeta) has been proposed to play a major role in the process of colonic wound healing, and its expression is believed to be modulated by interleukin-2 (IL2). According to an earlier report, the postoperative administration of the histamine receptor-2 antagonist ranitidine increases the blood levels of soluble IL2 receptor in humans undergoing abdominal surgery and could thus affect molecular determinants of colonic anastomosis. In this study we examined the effect of blood transfusions, with and without ranitidine administration, on the gene expression of TGFbeta(1) and the specificity-conveying alpha subunit of the receptor for IL2, in rat perianastomotic tissue. Analysis of gene expression by semiquantitative RT-PCR revealed a tendency for downregulation of both genes, albeit in a statistically nonsignificant manner. This effect was not prevented by the postoperative administration of ranitidine. On the other hand, there appears to be a significant correlation between expression of TGFbeta(1) and that of IL2 receptor alpha subunit, irrespective of treatment.

A new approach in the management of urothelial tumors using GM-CSF on marker lesions: an ultrastructural and immunohistochemical study on the macrophage population in bladder mucosa.

Our purpose was to investigate a new therapeutic model, GM-CSF-targeted immunomodulation on transitional cell carcinoma (TCC) marker lesions and to evaluate the immunologic response of the bladder mucosa. Eleven patients with pTa or pT1 bladder cancer were eligible for the study. All lesions were removed by transurethral resection (TUR) except for a marker lesion. All patients received 8 weekly instillations of 300 microg of GM-CSF, after which cystoscopy with bladder biopsies +/- TUR was repeated on adjacent urothelium or tumor or both. Paraffin-embedded sections were immunohistochemically stained with CD68, which labels monocytes and macrophages. The CD68+ cell population was evaluated as 1+ to 3+. Comparable specimens were routinely processed for ultrastructural analysis. Complete response was observed in 6 patients (55%), persistent tumor occurred in 4 patients (approximately 36.4%), and 1 patient (8.6%) showed recurrence. Immunohistochemically, an at least twofold increase in the number of the CD68+ cells was observed in all responders. Submicroscopically, migration of macrophages to the surface layer occurred. Macrophages showed an extensive lysosomal system and pseudopodia. This study indicates that the prophylactic treatment of TCC with GM-CSF may induce immunomodulatory effects on macrophage activities, which could be associated with the clinical evolution of the disease.

Cardiac effects of exercise rehabilitation in hemodialysis patients.

Exercise training has well documented beneficial effects in a variety of cardiac disorders. End stage renal disease patients present many cardiovascular complications and suffer from impaired exercise capacity. No study to date has adequately examined the cardiac responses to exercise training in renal patients on hemodialysis (HD). To determine the effects of an exercise rehabilitation program on the left ventricular function at rest and during submaximal effort, 38 end-stage renal disease patients on maintenance HD were randomised into three groups. Sixteen of them (group A--mean age 46.4+/-13.9 years), without clinical features of heart failure, participated in a 6-month supervised exercise renal rehabilitation program consisting of three weekly sessions of aerobic training, 10 (group B--mean age 51.4+/-12.5 years) followed a moderate exercise program at home, and the other 12 (group C--mean age 50.2+/-7.9 years) were not trained and remained as controls. The level of anemia and the HD prescription remained constant during the study. Fifteen sex- and age-matched sedentary individuals (group D--mean age 46.9+/-6.4 years) were the healthy controls. All subjects at the start and end of the program underwent physical examination, laboratory tests, treadmill exercise testing, M-mode and 2-D echocardiograms performed at rest and at peak of supine bicycle exercise. Left ventricular volumes (EDV, ESV) and mass (LVM) were measured and ejection fraction (EF), stroke volume index (SVI) and cardiac output index (COI) were calculated by standard formulae. The maximal oxygen consumption increased by 43% (P<0.001) and the exercise time by 33% (P<0.001) after training in group A, by 17% (P<0.001) and 14% (P<0.01), respectively, in B, and both remained unchanged in group C. Training in group A was also associated with an increase in LVIDd (from 52.1+/-6.4 to 54.0+/-6.1 mm, P<0.001) and LVM (226+/-67 to 240+/-84 g, P<0.05) at rest with no change noted in groups B and C. Following a 6-month exercise training in group A an increase was also found in the resting EF by 5% (P<0.01) and SVI by 14% (P<0.001). There was no change found in groups B and C. Supine bicycle exercise after training in group A was associated with an improvement in EF by 14% compared to the pre-training change (P<0.001), SVI by 14% (P<0.001) and COI by 73% (P<0.001). These changes from rest to submaximal exercise were less pronounced in group B following training at home. The untrained patients demonstrated no changes in LV systolic function over the 6-month period. These results demonstrate that intense exercise training improves LV systolic function at rest in HD patients; both intense and moderate physical training leads to enhanced cardiac performance during supine submaximal exercise.

Congenital double pyloric ostium in the adult.

Duplication of the pylorus, an extremely rare congenital anomaly of the stomach, consists of two openings connecting the antrum of the stomach to the duodenal bulb. Approximately 70 cases of double pylorus have been described in the literature, most of which are associated with the presence of chronic peptic ulcers, thus indicating an acquired origin of the condition. We report a case of congenital double pylorus in a 64-year-old man who complained about mild postprandial epigastric discomfort and nausea of approximately 3 months' duration. Endoscopic examination of the stomach showed a double pyloric ostium connecting the stomach to the duodenum. No signs of acute or chronic peptic ulcer were noted. A biopsy was taken from the region between the two openings, which showed normal mucosa and a muscularis mucosae layer. Apart from a mild gastritis, no other pathology (chronic peptic ulcer, ulcerated malignancy) suggesting an acquired origin of the double pylorus was observed. Therefore, the case was considered to be congenital in origin. The patient was successfully treated conservatively with antacids and gastrokinetics.

Hippocratic views with reference to the anatomical characteristics of "arteries" and "veins".

The anatomical knowledge, in the collection of books named after Hippocrates' the Hippocratic Corpus, is usually vague and limited. This is mainly due to the respect for the dead held by the ancients. Though the Hippocratic books, for the first time, supported the rationality of the aetiology of diseases, and prognosis and treatment were based on observation, the absence of dissection restricted the means of obtaining knowledge of the interior of the body until almost the time of the Renaissance. However in some cases, surprisingly enough, this ignorance is absent. In this essay we will attempt to elucidate some of the Hippocratic views--either erroneous or up to date--on the anatomy of the vascular system, mainly the "arteries" and "veins".

Natural killer (NK) cell assay within bladder mucosa of patients bearing transitional cell carcinoma (TCC) after interferon (IFN) therapy: an immunohistochemical and ultrastructural study.

The authors studied the number and the ultrastructural evidence of NK cell activation in the non-involved urothelium in patients with transitional cell carcinoma (TCC) of the urinary bladder, before and after transurethral resection (TUR) and interferon (IFN) therapy. Eight male patients, free of recurrence 1 year after TUR and IFN-a2b therapy, were studied. Each patient received 22 instillations of 50MU of IFN-a2b over a period of 1 year. Two specimens from the non-involved urothelium, one adjacent to and another away from the tumour, were obtained before and after therapy, for immunohistochemical and ultrastructural studies. The number of NK cells was evaluated immunohistochemically in paraffin sections with the CD57 monoclonal antibody, and their activation was detected by routine electron microscopy processing. Before treatment, few NK cells were randomly found in the lamina propria. At the end of therapy, however, their number increased and NK cells were found to infiltrate the urothelium, a finding that was not observed before treatment. The number of NK cells did not correlate with the degree of the inflammatory infiltrate of the mucosa. Moreover, the ultrastructural study revealed activation of NK cells with enhanced cytolytic activity. IFN therapy increases the number and promotes the activation of NK cells within the bladder mucosa. This finding could be of clinical significance in the prevention of tumour recurrence, given that NK cells enhance the immunological defense mechanisms of the bladder.

Orbital depth measurements of human skulls in relation to retrobulbar anesthesia.

To investigate the orbital depth in human skulls in relation to retrobulbar anesthesia, we measured the distance between the lateral margin of the optic foramen and the border of the medium and outer third of the inferior orbital rim (retrobulbar needle pathway) in 50 skulls (25 males and 25 females). This distance varied from 4.4 to 5.7 cm in males (mean 5.024, SD 0.272) and from 4.5 to 5.5 cm in females (mean 4.9, SD 0.204). There was no real difference between males and females (p>0.05). For the total of 50 skulls the mean distance was 4.962 cm (SD 0.246). Shallow and deep orbits exist in both males and females but individuals with shallow orbits are obviously more susceptible to optic nerve injury by the retrobulbar needle.

The risk of optic nerve injury in retrobulbar anesthesia: a comparative study of 35 and 40 mm retrobulbar needles in 12 cadavers.

PURPOSE: This study was designed to demonstrate the increased risk of optic nerve injury by the 40 mm needle when fully inserted into the orbit. METHODS: Retrobulbar anesthesia needles 35 and 40 mm long were inserted into the orbits of 12 well-embalmed cadavers, as for typical retrobulbar anesthesia. The needle was seen directly through a fenestration of the orbital roof and by dissection of the orbital structures overlying the optic nerve. RESULTS: In all orbits the 40 mm needle reached and in seven cases significantly pushed against the optic nerve and could obviously penetrate its sheaths. The 35 mm needle could just slightly touch the outer optic nerve sheath only in two cases. CONCLUSIONS: We conclude that the 40 mm retrobulbar needle should not be fully inserted into the orbit and the 35 mm retrobulbar needle must be used with caution.

Microanatomy of the vasa vasorum of the human thoracic aorta: a study utilizing a polyester resin casting technique.

We have studied the vasa vasorum of the human thoracic aorta using a polyester resin casting technique, coupled with the tissue clearing method of Spalteholz. We found that the vasa vasorum originated from intercostal arteries. They ramified and formed networks within the aortic adventitia and the outer layers of the media. Venous networks were identified in the adventitia as wall. In addition to being a usefull research tool, the methodology utilized in this study produces specimens that can be used in teaching vascular anatomy to medical students.

New aspects on the topography of the tendon of the long head of the biceps brachii muscle. One more stabilizer factor of the shoulder joint.

There are little variations in descriptions on the origin of the tendon of the long head of the biceps brachii muscle, in the classical text books of Anatomy. Most authors define as the main origin of the tendon of the long head of the biceps brachii muscle, the supraglenoid tubercle and adjoining part of the glenoid labrum of the scapula. In the present study we found that the origin of the tendon of the long head of the biceps brachii muscle extended towards almost the whole periphery of the glenoid cavity on the glenoid labrum except from a small area near to the supraglenoid tubercle.

An unusual unilateral deformity of the hand: a case report.

A rare case of a congenital unilateral deformity of the right upper extremity is described consisting of: absence of the carpal bones except the capitate and hamate, absence of the first three metacarpal bones and phalanges and a thumb-like extension to the palm of the dislocated radius. No hereditary family history was found.

Immunohistological phenotyping of the stomach infiltrating lymphocytes in chronic gastritis.

Subsets of lymphocytes infiltrating the gastric mucosa were phenotyped by their surface antigens in biopsies of 30 patients with chronic gastritis (12 with superficial, 9 with atrophic gastritis and 9 with gastric atrophy) and 10 controls. Using direct and indirect immunofluorescent staining, monoclonal antibodies OKT3, OKT4, OKT8, OKB7, antiLeu11b and anti-IL-2 receptor were employed to detect T cell subsets, B cells, NK cells and activated cells. Most of the infiltrating lymphocytes were T cells expressing the CD4 phenotype. B cell proportions were found to increase in relation to the severity of the gastric lesion. IL-2 receptor positive cells were significantly increased in superficial gastritis. These findings indicate an involvement of T cells in the pathogenesis of chronic gastritis. Furthermore, the predominance of CD4 positive cells together with the increase of B cells parallel to the severity of the gastric lesion possibly support the concept of a T-B cooperation leading to tissue damage.

Histochemical and ultrastructural characteristics of leg muscle fibres in patients with repairative abdominal aortic aneurysm (AAA).

Tibialis anterior (ta) muscle biopsies before and after elective abdominal aortic aneurysm (AAA) repair operation were obtained, in order to observe possible changes after the aortic declamping reperfusion. Open muscle biopsies were taken from each of eight patients (60-75 years old) which were processed for enzyme histochemistry, and for transmission electron microscopy (EM). Morphometric analysis was applied to estimate the number and the area of muscle fibres of each fibre type. Rectus abdominis muscle biopsies were served as controls. Before the operation the predominant elements found were the presence of atrophic muscle fibres, fibre size diversity, localised cellular reactions, increased extent of connective tissue, disappearance, in many cases, of the mosaic pattern, predominance of type I and oxidative fibres, and existence of fibres with core-like structures in the sarcoplasm. Type I fibres consisted of 66.95 +/- 9% of all muscle fibres, the mean cross sectional area of which was 3,372.8 +/- 1,016 microm(2) and of type II fibres was 3,786.5 +/- 6,046 microm(2). After the aortic clamping was performed mitochondrial swelling was found, as well as disorganisation of sarcomeres. After declamping of the aorta, there were also severe edema, local fibre necrosis, and adhesion of leucocytes, whereas muscle fibre areas became 3,935.18 micro 531 microm(2) for type I and 5,804 +/- 1,075 microm(2) for type II. The short ischemic period during aortic clamping and the subsequent reperfusion resulted mainly in ultrastructural changes.

Annular pancreas in adults: embryological development, morphology and clinical significance.

Three cases (two male, one female) of annular pancreas are presented, which were found and operated on within the last three decades. Diagnosis was made using imaging techniques, especially ultrasonography and computed tomography. In two cases there was incomplete obstruction, while in the other obstruction was complete. It is characteristic that in the case of complete obstruction the annular portion of the pancreas attached to a circular band of connective tissue, while in the two cases of incomplete obstruction there was a complete ring of pancreatic tissue. In all cases surgical intervention was needed in order to create a bypass. In the first case gastroenterostomy and truncal vagotomy was performed, in the second latero-lateral duodeno-jejunostomy and in the third latero-lateral antropyloroduodeno-jejunostomy. The embryology and morphology of the annular pancreas, the morphology of its duct system, diagnosis, differential diagnosis and the surgical treatment of this rare condition are reviewed.

An electron microscopic study of human olfactory mucosa.

Two intranasal biopsies of human olfactory mucosa were studied with the electron microscope, after confirming with the light microscope that they were in fact from the olfactory region. It was noted that the end of the dendrite of the human olfactory cell is flat or dome-shaped, and is not a bulb-like projection (olfactory vesicle). Moreover, the cilia are in the long axis of the olfactory cell, perpendicular to the epithelial surface, and do not lie parallel to it as described in some species. The supporting cells had multiple long microvilli, and definite points of contact with the olfactory cells; they appeared to spread their secretion over the microvilli in a novel manner, producing a layer of regularly spaced, spike-like granules.

The effects of exercise training on muscle atrophy in haemodialysis patients.

BACKGROUND: Patients with end-stage renal disease on haemodialysis (HD) have limited work capacity. Many structural and functional alterations in skeletal muscles contribute to this disability. METHODS: To evaluate the effects of exercise training on uraemic myopathy, seven HD patients (mean age 44.1+/-17.2 years) were studied. Open muscle biopsies were taken from their vastus lateralis muscle before and after a 6-month exercise rehabilitation programme and examined by routine light- and transmission electron-microscopy. Histochemical stainings of frozen sections were performed and morphometric analysis was also applied to estimate the proportion of each fibre type and the muscle fibre area. Spiroergometric and neurophysiological testing and peak extension forces of the lower limbs were measured before and after exercise training. RESULTS: All patients showed impaired exercise capacity, which was associated with marked muscular atrophy (mean area 2548+/-463 microm2) and reduction in muscle strength and nerve conduction velocity. All types of fibres were atrophied, but type II were more affected. The ultrastructural study showed severe degenerative changes in skeletal muscle fibres, mitochondria, and capillaries. Exercise training had an impressive effect on muscular atrophy; in particular the proportion of type II fibres increased by 51% and mean muscle fibre area by 29%. Favourable changes were also seen on the structure and number of capillaries and mitochondria. These results were confirmed by a 48% increase in VO2 peak and a 29% in exercise time, as well as an improvement in the peak muscle strength of the lower limbs and in nerve conduction velocity. CONCLUSIONS: Skeletal muscle atrophy in HD patients contribute to their poor exercise tolerance. The application of an exercise training rehabilitation programme improved muscle atrophy markedly, and therefore had beneficial effects in overall work performance.

Effect of ranitidine on healing of normal and transfusion-suppressed experimental anastomoses.

BACKGROUND: Histamine has been shown to participate in immune response. Wound healing is a process of immune system. This experimental study was done to find the effect of histamine2 receptor antagonist ranitidine on the healing process of intestinal anastomosis in rats. METHODS: Eighty Wistar rats in four groups of 20 each underwent colon resection and anastomosis. They were given 2 ml saline or blood, twice daily 0.4 ml saline or 0.4 ml saline containing 0.7 mg ranitidine. The animals were killed 3 or 7 days postoperatively and the anastomotic strength assessed by bursting pressure. RESULTS: The ranitidine group developed fewer anastomotic abscesses (p<0.001). Anastomotic strength was significantly reduced either on day 3 or 7 in animals given blood transfusions (p<0.04, p<0.001), whereas in animals given ranitidine this effect was partially reversed. CONCLUSIONS: These data indicate that ranitidine has no influence in anastomotic bursting pressure, but has a lower incidence of septic complications.