Coupling of lactose molecules to the carrier protein hinders the spleen and bone marrow uptake of doxorubicin conjugated with human albumin.

Several attempts have been made to enhance doxorubicin (DOXO) concentrations in tumour cells by drug conjugation with human albumin (HSA). HSA-DOXO has the drawback of causing DOXO accumulation in spleen and bone marrow, with a consequent leucopoenia not produced when lactose molecules are coupled to the carrier protein. In the present experiments we demonstrated that the effect of HSA lactosamination is not a consequence of a more rapid disappearance from the bloodstream of the lactosaminated conjugate (L-HSA-DOXO), which is rapidly internalized by the liver through the asialoglycoprotein receptor, but is due to a hindered uptake by spleen and bone marrow cells caused by the coupled lactose molecules. Experiments in vitro showed that HSA-DOXO produced an inhibition of murine macrophage proliferation not caused by L-HSA-DOXO. This result can be explained by higher amounts of the former conjugate entering in these cells and suggests macrophages as the cell type responsible for the spleen and bone marrow internalization of HSA-DOXO hindered by lactose coupling. Importantly, lactosamination of HSA did not reduce the marked uptake of HSA-DOXO by chemically induced rat hepatocellular carcinoma. L-HSA-DOXO, by avoiding DOXO accumulation in bone marrow is an attractive candidate for clinical trials against tumors which were found to actively internalize this conjugate in laboratory animals, such as hepatocellular carcinoma.     

Angioplasty of the deep femoral artery using a semirigid PTFE prosthesis. Experimental studies

Underlining the importance of Profundus Femoral Artery and its capacity to make up for lower limb's haemodynamics during obliterative arteriopathy, the Authors conceive a funnel-shaped intravascular prosthesis, Goretex constructed (PTFE), to introduce, in case of obstruction, in the artery lumen with a suitable instrument. The research is performed through ten oldster dogs whose average weight is twenty-four kilograms. Isolated the deep Femoral Artery and carried out an arteriotomy of about two centimetres on the Common Femoral Artery, we bring the prothesis in Profundis Femoral Artery and we fix it to the wall of the Common Femoral Artery with 8/O microsurgical dots. After thirty days, the arteriographic test shows the patency of the endoprosthesis with normal peripheral flow in nine animals out of ten. By virtue of this preliminary experiment, the Authors point out the semplicity of this intervention, also feasible in local anaesthesia, the good tolerability of the prosthesis and its perfect integration with the surrounding arterious wall, without shifts or dissecting laminar flows between the external prosthesis wall and the vessel lumen of the animal.     

Transurethral resection of the prostate and metastatic prostate cancer

Demonstration of malignant cells in blood specimens collected during transurethral resection of the prostate (TURP) has implicated TURP in the dissemination of prostatic cancer. Of 153 patients who underwent radiation therapy for prostate cancer between January 1977 and June 1990 and were retrospectively analyzed, 93 were evaluable. Fifty-nine patients required TURP before radiation therapy for prostatic obstruction (BPH and/or cancer); the remaining 34 patients underwent radiation therapy after fine-needle aspiration biopsy. No statistically significant difference in failure rate could be detected between these groups, with a failure rate of 47% (28 of 59 patients) at a median follow-up time of 49 months (range, 8 to 146 months) in the TURP group versus a failure rate of 47% (16 of 34 patients) at a median follow-up time of 50 months (range, 3 to 122 months) in the group who underwent biopsy only (Fisher's exact test, P = 0.23). Within the confines of this retrospective study, it appeared that TURP did not enhance the development of metastatic disease.     

A phospholipid spin label used as a liposome-associated MRI contrast agent

Given current clinical use of phospholipid bilayer structures (liposomes/vesicles) as nontoxic drug delivery vehicles, we have addressed the possibility of employing the phospholipids themselves as MRI contrast agents. To this end we have synthesized phosphatidylcholine with a nitroxide spin label replacing one methyl residue of the choline headgroup. This material was mixed with natural phosphatidylcholine in mole ratios from 1:50 to 1:1 and used to prepare sonicated unilamellar vesicles in saline. Expected structural features of these vesicles were verified by freeze-fracture electron microscopy. Proton T1 values of saline were readily decreased to less than 0.3 s by such preparations, yielding a net relaxivity of 0.6 M-1 s-1. The approach seems to be a realistic way of firmly associating a contrast agent of minimal toxicity with ordinary liposomes/vesicles in a manner that is not subject to leakage.     

Discriminant analysis in diagnosing carcinoma of the pancreas and of the papilla of Vater

The clinical and biochemical presentation of carcinoma of the pancreas (PC) and of the papilla of Vater (CPV) are very similar, and, consequently, detailed investigations are required to correctly distinguish between them. The aim of the present study was to select the clinical and biochemical variables that would most efficiently discriminate the precise site of tumor origin. The study group consisted of 72 patients with PC and 22 patients with CPV consecutively hospitalized in our department. The following clinical parameters were considered: age, asthenia, anorexia, vomiting, weight loss, pain, fever, pruritis, and constipation; the biochemical parameters considered were total, direct, and indirect bilirubin, glucose, alkaline phosphatase, gamma glutamy transferase, transaminase, total protein, amylase, and occult blood in stools. The results indicated that in the initial phase of PC the most frequent clinical parameters were weight loss (P<0.0001), anorexia (P<0.02), constipation (P<0.001), and pruritus (P<0.01). In contrast, in CPV, fever (P<0.003) was most frequent in the same phase. There was a statistically significant difference in occult blood in stools (P<0.0001), total (P<0.03) and direct bilirubin (P<0.02), alkaline phosphatase (P<0.05), and transaminase (P<0.002) values in the two groups. On discriminant analysis, weight loss, constipation, pruritus, nausea, anorexia, and fever were the variables which best discriminated between the two types of tumors. In fact, the presence of weight loss, anorexia, asthenia, constipation, and pruritus correctly classified 87.5% of the patients with PC, while the presence of fever and nausea correctly classified 72.7% of the patients with CPV.     

Comparing different methods for homocysteine determination.

Slightly elevated values of homocysteine are commonly associated with thromboembolic diseases, while high values can be found in patients with congenital metabolic defects or nutritional problems. The clinical use of homocysteine as an independent marker of cardiovascular disease was limited in the past by technical problems with its measurement, the instrumentation (HPLC, radioenzymatic assays, gas chromatography-mass spectrometry, etc.) and the necessary skills required. Commercially available immunoassays now permit a simpler and more rapid measurement of homocysteine, that is more suitable for routine clinical laboratories; in this paper we analyze the results obtained by using three fully automated methods for homocysteine determination (Abbott IMx immunoassay, Abbott AxSYM immunoassay and Immulite 2000 homocysteine immunoassay) and their correlation with the widely used HPLC method. The results clearly indicate that all three automated immunochemical methods correlate well with the HPLC method (slope 0.97-1.03; intercept 0.95-1.91 with a recovery above 95% for all three methods).