Regression of rat Dunning R-3327-H prostate carcinoma by treatment with targeted cytotoxic analog of luteinizing hormone-releasing hormone AN-207 containing 2-pyrrolinodoxorubicin

The effects of AN-207, a new targeted cytotoxic analog of LH-RH, were evalued in rats bearing hormone-dependent Dunning R-3327-H prostate carcinomas. AN-207 consists of the agonist [D-Lys(6)]LH-RH linked to 2-pyrrolino-doxorubicin, an intensely potent derivative of doxorubicin. In the first experiment, 2-pyrrolinodoxorubicin was administered at a concentration of 50 nmol/kg, as a single drug (AN-201) and as an unconjugated mixture with [D-Lys(6)]LH-RH or conjugated to the carrier [D-Lys(6)]LH-RH (AN-207). Following the second administration of radical AN-201 alone or mixed with the carrier, all rats died with signs of general toxicity, but all animals treated with the conjugate AN-207, survived. After 5 weeks of treatment with a total dose of 150 nmol/kg AN-207, the tumors regressed from an initial volume of 8.35 +/- 1.7 cm(3) to 4.47 +/- 0.8 cm(3), while tumors in the control group measured 17.84 +/- 2.2 cm(3). The therapy with AN-207 also significantly reduced tumor weight and tumor burden. In the second experiment, we compared the efficacy and toxicity of 3 injections of 25 nmol/kg AN-201 or 25 nmol/kg and 50 nmol/kg AN-207. The initial tumor volume in all groups was between 3.9 and 4.5 cm(3). After 5 weeks of therapy, the tumors of rats treated with 50 nmol/kg AN-207 regressed to 2.3 +/- 0.51 cm(3), whereas 25 nmol/kg AN-201 was still toxic in contrast to 25 nmol/kg AN-207, while the reduction in final tumor volume was similar (6.76 +/- 1.4 cm(3) and 6.74 +/- 1 cm(3), respectively), as compared to 15.6 +/- 2.2 cm(3) for untreated animals. High capacity LH-RH receptors were found in the membranes of untreated Dunning tumor specimens, but after treatment with AN-207, they could no longer be detected. This is the first demonstration that the new targeted cytotoxic LH-RH analog AN-207 is an effective antitumor agent. Our work indicates that the cytotoxic analog AN-207 is much less toxic than the antineoplastic radical (AN-201) incorporated, and significantly more active in inhibiting tumor growth. Further development of approaches based on targeted cytotoxic analog AN-207 may lead to major improvements in current palliative therapy of prostate cancer.     

Poly (triethylenglycol monomethacrylate) and poly(glycerol monomethacrylate) cross-linked gel as potential viscoelastics for intraoperative use

Background: The highly swelling poly(glycerol monomethacrylate) gel (polyGLYMA) and hydrophilic polymer poly(triethylenglycol monomethacrylate (polyTEGMA) were tested as potential viscoelastics for intraopertive use in anterior segment surgery. Methods: PolyGLYMA was implanted into the anterior chamber in 5 rabbits, and 40% polyTEGMA in 16 rabbits. The eyes were enucleated 1 week to 3 months after the operation. The corneal endothelium was examined with specular microscopy, and then the whole eye histopathologically. Results: In all eyes of the polyGLYMA group, the clinical findings were characterized by a marked ciliary injection and severe secondary glaucoma, and the histologic ones by a marked inflammatory infiltration and thickening of Descemet's membrane in the anterior chamber angle. Specular microscopy revealed a decrease in the endothelial cell density and polymorphism of the endothelial cells. In the polyTEGMA group, the anterior segment and the fundus were physiologic all the time, and specular microscopy and histologic findings showed no degenerative and/or inflammatory changes. Conclusions: PolyGLYMA proved unsuitable for intracameral application in rabbits. The new polymer polyTEGMA is characterized by high biologic tolerance after its implantation into the anterior chamber of rabbits. PolyTEGMA 40% might be considered as a potential viscoelastic material in humans.     

Surgical management of villous and tubulovillous adenomas of the rectum]

One hundred four cases of middle and low rectal villous and tubulovillous adenomas have been operated on with transanal polypectomy (8), transanal endoscopic microsurgery--TEM (80), anterior rectum resection with double stapled straight sigmoideorectosomy (7), and deep rectum resection, bi-directional mucosectomy and hand sutured straight sigmoideoanostomy (9). The option of the authors to remove the tumours in 5 cm to the dentate line are the transanal polypectomy or transanal mucosectomy corresponding to their size. The transanal endoscopic microsurgical technic is recommended to manage the polyps smaller than 4 to 5 cm in the middle rectum. The best radicallity in removal of the circular, extended villous adenomas could be achieved with deep rectum resection, bi-directional mucosectomy and transanal straight, hand sewn sigmoideoanostomy.     

Abdominal actinomycosis presenting as a malignant tumor--report of a case and review of the literature

Actinomyces israelii is a normal inhabitant in the gastrointestinal tract of humans, it rarely causes disease. Abdominal involvement occurs in only 20 percent of all cases and can mimic malignant diseases, tuberculosis and inflammatory bowel disease. A case of a 36 years old female patient with abdominal actinomycosis and review of the literature is reported. Symptoms was presented as an acute abdomen associated with painful epigastric and left subcostal mass. The pathologic process infiltrated the retroperitoneal space simulated sarcoma or lymphoma. Diagnosis was established only at the second laparotomy, when histologic examination of the removed lymph node disclosed actinomycosis. The patient is completely free of symptoms 6 month after the second operation.     

Relationship between clinical and radiological diagnostic criteria for Alzheimer's disease and the extent of neuropathology as reflected by 'stages': a prospective study

The distribution of pathology related to Alzheimer's disease (AD) is not uniform throughout the brain. Sites which have a predilection for the development of Alzheimer-type pathology are the limbic regions and neocortical association areas. The changes in these areas of the brain develop gradually, following a well-determined sequence that allows a pathological staging of the disease process. According to the staging hypothesis, the first pathological alterations develop in the transentorhinal and entorhinal regions. The neurofibrillary pathology then spreads into the hippocampus, but not until the final stages does it affect the neocortex. In this study we analyse the relationship between the pathological stages of AD, according ot the staging hypothesis, and the clinical diagnosis in a prospectively assessed patient group. Prediction of any given pathological stage from the clinical diagnosis was found to be poor. This may be partly due to the fact that additional pathologies can alter the clinical picture and severity of dementia in patients who are only in the initial stages of AD. Nevertheless, the NINCDS-ADRDA clinical criteria had a high sensitivity for detection of AD-related pathology: the 'probable AD' category included 22/38 (57.9%) of those in the late isocortical stage, while the 'possible AD' category included 19/23 (82.6%) of those in the limbic stage. Using proposed neuro-imaging protocols for improved identification of patients with AD-related pathology, we largely identified subjects in whom the extent of pathology had spread to the neocortex.     

The concordance and discordance of cardiovascular risk factors in a group of twin children

The cross-sectional study of epidemiological screening type has permitted to evaluate some cardiovascular risk factors in two groups of monozygotic (MZ) and dizygotic (DZ) twins born between 1975-1990, in the town of Ia?i. In the 89 MZ pairs and 112 DZ pairs, certain constitutional and behavioural cardiovascular risk factors have presented values of prevalence with statistical signification (p < 0.05) in terms of their age, sex, the urbanisation time and the educational level of their parents. In risk factors existence or absence to both of the twins have put into evidence, to the MZ, most enhanced values of concordance as regards: overweight (66.6%), excessive consumption of salt (56.9%), food with atherogenic risk (50.9%). The concordance values have been less in DZ compared to MZ concerning all the risk factors excepting compartmental type A (77.7%). By analysing the concordance variants, an preponderant influence of the environment has been noted in the studied MZ and heredity and environment influence in DZ. By measuring the arterial blood pressure values at the twins and the twins parents, a prevalence of the essential arterial hypertension is noticed to both of the twins, 6.2% in MZ pairs and 6.9% in DZ ones.     

PEG-Hemoglobin as a resuscitation solution in the treatment of hypovolemic shock in the anesthetized rat

This study was designed to determine the advantages of using the hemoglobin-based oxygen carrier, polyethylene glycol conjugated bovine hemoglobin (PEG-Hb), as an additive to Ringer's lactate solution (RLS) for the treatment of acute hemorrhage in anesthetized female rats. Different compositions of PEG-Hb and RLS were administered intravenously in a paradigm that provided 30 ml/kg of resuscitation fluid following an episode of 15 min of hypotension. Hypotension was achieved by the removal of blood (1 ml/min) from the femoral vein until the mean arterial pressure was lowered to or below 50 mmHg and subsequently maintained until resuscitation. Short-term cardiovascular assessment showed that resuscitation fluids containing PEG-Hb resulted in higher mean arterial pressure, aortic blood flow, renal blood flow, and less dramatic shifts in arterial base excess and respiratory blood gases than plain RLS. The long-term survival experiment showed lower lactate dehydrogenase, alkaline phosphatase, and serum glutamic pyruvic transaminase levels in most groups resuscitated with solutions containing PEG-Hb, but no differences in survival (100%) were observed. The data suggest that the addition of PEG-Hb to RLS improves its resuscitative effects. Specifically, a solution of 50% RLS:50% PEG-Hb appeared to have the most favorable cardiovascular and metabolic effects in this anesthetized rat hypovolemic shock resuscitation model. Presumably, the improved effects seen with the addition of PEG-Hb were due to its innate plasma expansion and oxygen-delivery capabilities.     

A note on the early history of renal transplantation: Emerich (Imre) Ullmann

In January 1902 at the Vienna Medical Society Meeting, the surgeon Emerich Ullmann reported the first case of renal autotransplantation performed in the neck of a dog. In the same year, he presented the first xenotransplantation of the kidney (a goat with a dog's kidney). These publications immediately had a great impact on the medical word. After his failed attempt to transplant a pig's kidney into a young uraemic woman he stopped his research in this field in order to devote himself to other lines of surgical research. However, his idea survived him, because, nowadays, nearly 100 years later, pigs appear to be the most suitable donors for human renal xenotransplantation. Ullmann was born in Pécs, Hungary, on February 23, 1861. After a distinguished undergraduate career in 1878 his father (being also a medical doctor) sent him to study medicine at the world-famous Vienna Medical School. He graduated in 1884 and was immediately invited to the Surgical Department where Billroth worked. Next year, because of his interest in bacteriology he visited Pasteur in Paris and successfully volunteered to serve as a healthy subject to prove the effectiveness of Pasteur's antisera against rabies. Although Ullmann did not succeed in doing a human transplantation he gave birth to the era of the organ transplantation, stimulated vascular surgery and the development of transplantation immunology.     

The role of diagnostic laparoscopy in staging of pancreatic cancers

Authors report elective diagnostic laparoscopy, and the role of this method in evaluating operability of pancreatic cancer. At their department 11 diagnostic laparoscopic procedures of pancreatic cancer were performed during the last 5 years. In 3 cases tumor proved to be resectable despite preoperative imaging results of unresectable condition. On the basis of international literature authors give brief summary of indications, cost and benefit of diagnostic laparoscopy, and its place in the diagnostic algorythm of pancreatic cancer.     

Photoreceptor cells with unusual functional properties on the ventral nerve of Limulus

Normal photoreceptor cells on the ventral nerve of Limulus respond to a moderately intense flash with a large receptor potential or current. Occasionally, cells are found in which the same flash evokes only a small receptor potential or current. Our investigations reveal physiological reasons for the poor light sensitivity in these "unusual cells." In unusual cells prolonged illumination with intense light evokes a step-like inward current with an amplitude of some nanoamperes, but without a large transient peak. The current appears to be summed up of single photon responses with amplitudes smaller than about 50 pA. Their time course is similar to that of small single photon responses forming the so-called macroscopic C1 component in normal cells. The macroscopic current evoked by an intense flash has slow activation and deactivation kinetics and reaches a saturated amplitude of about 4-5 nanoamperes. The light-intensity dependence of the current evoked by flashes or by prolonged illumination has a slope of about 1 in log-log plots. The decay kinetics of the current is similar to that of the C1 component measured in normal cells after the block of the C2 component. Occasionally, the step-like current is superposed by large standard bumps. These bumps are blocked by the Ca2+-ATPase inhibitor cyclopiazonic acid, while the sustained inward current persists. We conclude that in unusual cells the light-activated current is identical to the C1 component of normal cells. The phospholipase C pathway that in normal cells presumably gives rise to the C2 component functions only with a low efficiency in unusual cells.