Use of amino acids in peritoneal dialysis solutions.
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Biomedical subjects
Publications and source records attributed to M Bruno.
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Angiogenesis is defined as the formation of new blood capillaries from preexisting vessels. It takes place in physiological and pathological conditions, such as cancer. Tumor angiogenesis depends on the release of angiogenic growth factors by tumor cells and infiltrating inflammatory cells, and from the extracellular matrix following degradation by tumor proteases. Human melanoma progresses through different steps: nevocellular nevi, dysplastic nevi, in situ melanoma, radial growth phase melanoma (Breslow index < or = 0.75 mm), vertical growth phase melanoma (Breslow index > 0.75 mm), and metastatic melanoma. In agreement with progression, it acquires a rich vascular network, whereas an increasing proportion of tumor cells express the laminin receptor, which enables their adhesion to the vascular wall. Hence, both phenomena favour tumour cell extravasation and metastases. Melanocytic cells produce and release Fibroblast Growth Factor-2 (FGF-2), mainly in the steps of dysplastic nevus and melanoma in vertical growth phase. Melanoma cells also secrete the Vascular Endothelial Growth Factor (VEGF), in parallel with the switch from the radial to the vertical growth phase and the metastatic phase. It is becoming clear that anti-angiogenic agents will interfere with or block melanoma progression.
BACKGROUND: Changes in angiogenesis and expression of extracellular matrix-degrading enzymes have been substantiated during tumour changeover and progression. METHODS: Tissues from 64 biopsies of endometrial carcinoma (EC) and 15 biopsies of normal (control) endometrium were investigated immunohistochemically to determine their microvessel number, and by in situ hybridisation to determine the expression of mRNA of the matrix metalloproteinase-2 (MMP-2, gelatinase A) and metalloproteinase-9 (MMP-9 gelatinase B). EC were grouped according to both histological grade (G) G1 to G3 and depth of myometrial (M) invasion M1 to M3. RESULTS: EC as a whole gave significantly higher counts over control endometria. Counts of the G1 group overlapped those of the control group, increased significantly in the G2 and even more in the G3 group. G3 biopsies in particular also displayed most microvessels widely scattered in the tumour tissue, in close association with tumour cells, and as winding and arborized tubes, often dilated in microaneurysmatic segments. Counts also increased in M2 and M3. Expression of the MMP-2 and MMP-9 mRNA, evaluated as percentages of positive biopsies and intensity of expression, were upregulated with the transition from control and G1 groups to G2 and G3, and in relation to advancing depth of invasion. In EC, MMP-2 and MMP-9 mRNA were also expressed by host stromal cells, including microvascular endothelial cells, fibroblasts and macrophages. In the control biopsies, poor expression of MMP-2 mRNA in few endothelial cells and no expression of MMP-9 mRNA were detected. CONCLUSION: These in situ data suggest that angiogenesis and degradation of extracellular matrix occur simultaneously with EC upgrading and advancing depth of invasion, and that EC cells and some host stromal cell populations cooperate in tumour progression.
BACKGROUND: The tenet that peritoneal dialysis is capable of either normalizing or improving blood pressure control in uraemic patients is based on outdated or monocentric experiences. Therefore, we assessed the prevalence of hypertension and the efficacy of antihypertensive therapy in a large, multicentric cohort of patients on peritoneal dialysis. METHODS: Twenty seven out of the 50 centres belonging to the Italian Co-operative Peritoneal Dialysis Study Group took part in the study. The main patient selection criteria were: peritoneal dialysis therapy for at least 3 months and no peritonitis or changes in dialysis technique for at least 1 month. Clinical blood pressure was measured according to WHO/ISH guidelines. Ambulatory blood pressure monitoring was carried out using a SpaceLabs 90207 recorder. Hypertension was defined according to WHO/ISH criteria and staged according to the criteria of the Joint National Committee on Detection, Evaluation and Treatment of High Blood Pressure (JNC), 5th Report. Ambulatory blood pressure monitoring recordings were used to evaluate white-coat hypertension, blood pressure load and the dipping phenomenon. RESULTS: Five hundred and four subjects were evaluated. Hypertension was prevalent in 88.1% of the population, and 362 out of 444 hypertensive patients were on antihypertensive therapy. JNC staging revealed that 188 patients had moderate to severe hypertension. Blood pressure load was pathological in 77.3% of the patients receiving antihypertensive treatment. White-coat hypertension was identified in 9.1% of the hypertensive patients not on antihypertensive therapy, and 53.1% of the patients were non-dippers. CONCLUSIONS: The study demonstrates that hypertension is a dramatic, unsolved problem in uraemic patients treated with peritoneal dialysis, and casts doubts on the effectiveness of our current peritoneal dialysis strategies and pharmacological management of hypertension.
Calcium nephrolithiasis (CaNL) accounts for more than 70% of all renal stones, and its prevalence has increased in the last decades. Under this definition are included patients passing stones, composed of calcium oxalates and/or calcium phosphates. Current views of the pathogenesis of CaNL are based on the role of metabolic abnormalities which concur to render urines more conducive to crystallization. Therefore, the diagnostic approach is aimed at detecting these abnormalities, and the medical treatment assumes that a decrease in the risk of lithogenesis will result in remission or improvement of recurrences. The workup of the patients with CaNL begins with the analysis of passed stones and X-ray, sonography or other imaging techniques. Eligible patients, that is, both recurrent active stone formers and single-stone formers with individual risk factors, are considered for a metabolic evaluation, by which a number of blood and urine parameters are measured and others calculated. These include estimates of urine state of saturation with calcium and uric acid salts, net gastrointestinal alkali absorption, renal threshold of phosphate and other renal clearances and net acid and total nitrogen excretions. Basically, this screening is informative on renal function, metabolic abnormalities and their pathophysiology, risk of stone formation and dietary habits. During treatment it gives information about patient compliance and adverse effects of therapy. The cost of a comprehensive screening in Piedmont is 192,000 ITL (100 Euro) and rises to 300,000 ITL (154 Euro) if hormones and hydroxyproline are measured. In individual patients second- and third-level studies are performed, in order to detect systemic diseases which account for about 20% of CaNL in our series. Cost-to-benefit analysis has shown that the medical procedures for CaNL yield considerable saving in terms of difference between expenditure for drugs and testing and reduction of stone events. However, the current workup cannot be considered exhaustive, because misleading events may hamper the relation between laboratory findings and clinical outcome, and factors other than urine composition have appeared on the scenario of nephrolithiasis. These represent our challenge for the third millennium.
To determine the role of surfactant protein-A(SP-A) in antiviral host defense, mice lacking SP-A (SP-A-/-) were produced by targeted gene inactivation. SP-A-/- and control mice (SP-A+/+) were infected with respiratory syncytial virus (RSV) by intratracheal instillation. Pulmonary infiltration after infection was more severe in SP-A-/- than in SP-A+/+ mice and was associated with increased RSV plaque-forming units in lung homogenates. Pulmonary infiltration with polymorphonuclear leukocytes was greater in the SP-A-/- mice. Levels of proinflammatory cytokines tumor necrosis factor-alpha and interleukin-6 were enhanced in lungs of SP-A-/- mice. After RSV infection, superoxide and hydrogen peroxide generation was deficient in macrophages from SP-A-/- mice, demonstrating a critical role of SP-A in oxidant production associated with RSV infection. Coadministration of RSV with exogenous SP-A reduced viral titers and inflammatory cells in the lung of SP-A-/- mice. These findings demonstrate that SP-A plays an important host defense role against RSV in vivo.
BACKGROUND: In this paper, the clinical and metabolic patterns of nephrolithiasis in different ages of adulthood are studied. METHODS: Eight-hundred patients observed at the Mauriziano Hospital between 1990 and 1995, were classified into 3 groups, on the basis of age at the onset of disease: A: 20 through 39 years; B: 40 through 59; C: 60 years and over. RESULTS: Calcium-oxalate stones had a lower recurrence in C (19.1%) and B (31.5%) than in A (41.7%). Pure uric acid stones recurred in 18.9% of C, 16.7% of B and 4.3% of A. The prevalence of hypercalciuria was higher in A (50.3%) than in B (35.9%) and C (36%); so did hypocitraturia. Hyperuricuria was lower in A (5%, p < 0.05) than in B (9.4%) and C (10%). Low urine pH (< 5.5) was 13% in A, 21.3% in B, 38% in C. Prevalence of hyperoxaluria was about 14% in all groups. The whole prevalence of secondary forms of stone disease was 13% in A, 12% in B and 30% in C. Differences among groups were mainly due to prevalence of urological abnormalities and urinary tract infection. In patients without metabolic disturbances. urological abnormalities or urinary tract infections altogether, were 4.6% in A; 5.2% in B; 33% in C. Urological approach removed 8% of stones in A, 5.6% in B and 10.2% in C. CONCLUSIONS: Higher morbidity in younger patients could be due to a lower prevalence of easier-passing uric acid stones. The higher occurrence of urological disturbances and struvite stones in the elderly could explain the higher morbidity in this group.
Uracil and tegafur (in a molar ratio of 4:1 [UFT]) has proven activity against breast cancer and is delivered in an easy-to-administer oral formulation. Orzel, which combines UFT with the oral biomodulator, calcium folinate, may provide even greater antitumor efficacy against breast cancer. Here, we describe the preliminary results of this phase II trial investigating the feasibility of 250 mg/m2/day of UFT plus 45 mg/day of oral calcium folinate administered to highly pretreated patients with advanced breast cancer. The results indicate a highly tolerable regimen and an overall response rate of 27.8% in a group of poor-prognosis patients. These findings warrant continued investigation.
The preservation of fossil human soft tooth tissue from extinct populations which inhabited the northeast of Argentina (fourteenth and fifteenth centuries) is described. Studies were performed using both Scanning Electron Microscopy (SEM) and Transmission Electron Microscopy (TEM). The preservation of the surface structure in Tomes fibrils and in odontoblastic processes was determined by SEM; whereas by TEM we could observe the dentin ducts occupied by acellular material, being the inner structure of the odontoblastic processes poorly preserved. It is suggested that such preservation is due to an "instantaneous phosphatization" occurring immediately after death as a result of the presence of calcium phosphate deposits.
BACKGROUND: Although anti-endomysium antibodies (EmA) are the most reliable serological markers of celiac disease (CD), there is a need for low-cost methods for screening programs, as clinically silent disease is increasingly recognized. AIM: To evaluate the suitability of monkey, rat and rabbit jejunum as a substrate for the determination of anti-jejunum antibodies (JAB) in CD. METHODS: JAB of IgA class were detected by indirect immunofluorescence on frozen sections of jejunum from monkeys, white rats and domestic rabbits. Sera from 61 untreated adults with biopsy-proven CD and EmA positivity in 57 out of 61 entered the study as true positives, while sera from 60 controls were considered as true negatives. RESULTS: The sections of monkey jejunum showed the characteristic pattern of elongated villous fluorescence, a ring-like positivity of the cryptal basement membrane, an endomysium-like fluorescence along the smooth muscle layers in the tunica muscularis, while pericryptal fluorescence was not so evident on rat and rabbit jejunum. As compared to EmA positivity, the prevalence of JAB on monkey, rat and rabbit tissues was respectively 57/57, 54/57, 52/57. Two sera among 4 Ema negatives proved positive for JAB. No false positivity resulted from EmA and JAB on monkey jejunum, while a lower specificity was found for JAB on rat and rabbit substrates. CONCLUSIONS: Although monkey, rat and rabbit small intestine appeared to be a suitable alternative substrate for determination of IgA-JAB, because of its lower cost and higher availability, it cannot replace monkey oesophagus, and be recommended for wide use.
BACKGROUND: Coeliac disease may be associated with a wide variety of diseases of known or suspected immunological aetiology. OBJECTIVE: To screen for both (a) the prevalence of coeliac disease in adults with autoimmune thyroid diseases, and (b) thyroid impairment among adults with coeliac disease, as compared to sex- and age-matched controls. DESIGN: Prospective cohort study. SETTING: University teaching hospital. PATIENTS: A total of 152 consecutive adults with autoimmune thyroid diseases, 185 consecutive coeliac disease patients (53 newly diagnosed and 132 already on a gluten-free diet) and 170 sex- and age-matched controls. METHODS: Screening for coeliac disease was done by means of IgA anti-endomysium antibodies, detected by indirect immunofluorescence on monkey oesophagus. Patients with positive sera underwent duodenal biopsy for diagnostic confirmation. Thyroid function was assessed by measuring the levels of serum thyroid-stimulating hormone, free T3, free T4, thyroperoxidase and thyroid microsome antibodies. Autoimmune thyroid diseases were classified according to the American Thyroid Association guidelines. RESULTS: Anti-endomysium antibodies were positive in five of 152 autoimmune thyroid disease patients (3.3%) and coeliac disease was histologically confirmed in all: this prevalence is 10-fold higher than expected. Only one patient presented with gastrointestinal complaints, but iron deficiency was found in three and alterations at bone mineralometry in all. The overall prevalence of autoimmune thyroid diseases was significantly higher (38/185, 20.5%) in coeliac patients than in controls (19/170, 11.2%). The prevalence of both hypo- and hyperthyroidism was not different from that of controls, while the prevalence of autoimmune thyroid disease with euthyroidism was 13% in patients and 4.7% in controls. CONCLUSIONS: The association of coeliac disease with autoimmune thyroid disease is not surprising as they share common immunopathogenetic mechanisms. It is advisable to screen autoimmune thyroid disease patients for coeliac disease as there is an increased risk for gluten intolerance. In contrast, thyroid function assessment in coeliac disease patients is probably less justified, although the need for a strict clinical follow-up of those patients with euthyroidism and autoimmune thyroid disease, who could develop overt thyroid impairment, remains an open question.
OBJECTIVES: To evaluate the prevalence of hypertension, the average blood pressure level, the 24 h blood pressure profile, and the efficacy of antihypertensive therapy for a large population of peritoneal dialysis patients.DESIGN: A cross-sectional, observational multicenter study. METHODS: From 504 peritoneal dialysis patients (18% of the Italian peritoneal dialysis population) involved in a multicenter observational study, we selected 414 who had undergone successful ambulatory blood pressure monitoring (i.e. no hours with data absent, >/= 75% successful readings and monitoring duration >/= 24 h). Office blood pressure measurements and ambulatory blood pressure monitoring were performed for each patient on the same day with a standard mercury sphygmomanometer and a SpaceLabs 90207 device, respectively.RESULTS: According to World Health Organization/International Society of Hypertension criteria, 44 peritoneal dialysis patients (10.6%) were normotensive and 370 patients (89.4%) were hypertensive, 304 (82.1%) of whom were being administered antihypertensive therapy. Daytime systolic and diastolic blood pressures were both significantly lower than office systolic and diastolic blood pressures (140.7 +/- 19.7/72.1 +/-11.1 versus 148.3 +/- 23.6/85.6 +/- 12 mmHg; P < 0.001). The difference between office blood pressure and daytime blood pressure was significantly correlated to office blood pressure (P < 0.001 for systolic and P < 0.001 for diastolic). The diurnal blood pressure rhythm evaluated by visual inspection of hourly mean plots was not influenced by sex, age, antihypertensive treatment, and peritoneal dialysis modality. Systolic and diastolic blood pressures exhibited a day-night mean decreases of 8.6 +/- 11.7 and 7.7 +/- 6.9 mmHg, respectively, and daytime blood pressure values were significantly higher than night-time ones (P < 0.001). Two hundred and twenty patients (53.1%) were nondippers according to O'Brien's criteria, 247 patients (59.7%) were nondippers according to Verdecchia's criteria, and 269 patients (65.0%) were nondippers according to Staessen's criteria. Only 39 patients (9.4%) had a reversed circadian rhythm. The day-night differences of systolic and diastolic blood pressures were in a unimodal distribution. Among hypertensive patients not being administered antihypertensive therapy, only six patients ( five women and one man) had white-coat hypertension. Among hypertensive patients being administered antihypertensive therapy, 235 patients (77.3%) had 24 h blood pressure loads > 30%.CONCLUSION: There is a high prevalence of hypertension among peritoneal dialysis patients. White-coat hypertension is very rare in this population. Despite the extensive use of antihypertensive therapy, control of blood pressure is maintained in a large number of our peritoneal dialysis patients. Any classification of patients into dipers and nondippers must be interpreted cautiously.
A questionnaire was sent to the 23 Dialysis Centers of the Piedmont and Aosta Valley Regions to probe present trend on the choice of peritoneal catheter, its setting, the tunnel conformation, the first use and its maintenance. The nephrologists attach great importance to a well fixed subcutaneous tract of the catheter: this goal is obtained with wide use of pre-molded catheters, often with long and curvilinear tunnel. Avoiding an early use of the catheter and the choice of small volumes in the first weeks will permit an efficient stability of the cuff and the reduction of the risk of leakage. The choice in maintenance and monitoring of the exit-site are various and it often has a protection covering; clinical controls are made on a monthly basis.
Polypoid tumors of the esophagus present diagnostic and therapeutic problems. Liposarcomas are infrequent among them. We report a recent case. A 73-year-old male patient was seen in May 1995 in the Ear, Nose and Throat (ENT) Department, Clínica Modelo de Morón, with intermittent dysphagia and dyspnoea due to recurrent vomiting. A laryngeal lineal tomography showed a subglottic obstruction due to extrinsic compression. The patient was referred to the Gastroenterology Department, where an upper gastrointestinal (upper GI) series demonstrated mega-esophagus with abundant retained food. Endoscopy showed a large intraluminal mass covered by normal mucosa which arose on the posterior wall. Videofluoroscopy and chest CT diagnosed a probable polypoid lipoma due to its densitometric characteristics. The tumour was resected by left cervicotomy and left esophagotomy. The patient's progress to date is favourable. Pathology studies showed a well-differentiated liposarcoma. According to the literature, the first case was reported in 1983, and ours is only the seventh case in the world to be documented.
A case of severe accidental hypothermia (core temperature 20 degrees C) in an elderly woman successfully treated by warmed lavage of peritoneal cavity is reported. The various available rewarming techniques and some observations about the differential diagnosis between the severe hypothermic patient with cardiac arrest and the hypothermic dead person are briefly reviewed on the basis of current literature.
BACKGROUND: Although anti-endomysium antibodies (EmA) are the most reliable serological markers of celiac disease (CD), there is a need for low-cost methods for screening programs, as clinically silent disease is increasingly recognized. AIM: To evaluate the suitability of monkey, rat and rabbit jejunum as a substrate for the determination of anti-jejunun antibodies (JAB) in CD. METHODS: JAB of IgA class were detected by indirect immunofluorescence on frozen sections of jejunum from monkeys, white rats and domestic rabbits. Sera from 61 untreated adults with biopsy-proven CD and EmA positivity in 57 out of 61 entered the study as true positives, while sera from 60 controls were considered as true negatives. RESULTS: The sections of monkey jejunum showed the characteristic pattern of elongated villous fluorescence, a ring-like positivity of the cryptal basement membrane, an endomysium-like fluorescence along the smooth muscle layers in the tunica muscolaris, while pericryptal fluorescence was not so evident on rat and rabbit jejunum. As compared to EmA positivity, the prevalence of JAB on monkey, rat and rabbit tissues was respectively 57/57, 54/57, 52/57. Two sera among 4 Ema negatives proved positive for JAB. No false positivity resulted from EmA and JAB on monkey jejunum, while a lower specificity was found for JAB on rat and rabbit substrates. CONCLUSIONS: Although monkey, rat and rabbit small intestine appeared to be a suitable alternative substrate for determination of IgA-JAB, because of its lower cost and higher availability, it cannot replace monkey oesophagus, and be recommended for wide use.
A randomized trial to compare adjuvant treatment with an alternating regimen with conventional chemotherapy was performed. A total of 589 node-positive patients were included and stratified according to number of positive nodes (N1-3 and N > 4) and menopausal status. Premenopausal N1-3 patients were randomized to cyclophosphamide, methotrexate and fluorouracil (CMF) or CMF/4'-epirubicin, cyclophosphamide (EC), post-menopausal N1-3 patients to fluorouracil, 4 epirubicin, cyclophosphamide (FEC) or CMF/EC and pre- and post-menopausal patients with N > or = 4 to fluorouracil, 4' epirubicin, cyclophosphamide, methotrexate, prednisone (FECMP) or CMF/EC. In premenopausal patients, CMF was superior to CMF/EC in terms of disease-free survival (DFS) (65% vs 45%, P = 0.0149) and survival (72.3% vs 50.2%, P = 0.0220) whereas, for N > or = 4 patients, differences between FECMP and CMF/EC did not achieve statistical significance (DFS 35% vs 26.2%; survival 50% vs 38.1%, P = NS). For post-menopausal patients, FEC was superior to CMF/EC in DFS (58.6% vs 36.8%, P = 0.0215) and survival (66.2% vs 46%, P = 0.0155). In post-menopausal patients with N > 4, differences favouring CMF/EC were significant in DFS (40.4% vs 22%, P = 0.0371) but not in survival (47.4% vs 32.2%, P = 0.1185). Alternating regimens did not offer better results in premenopausal and post-menopausal N1-3 patients. Results regarding post-menopausal N > 4 women require further confirmation.
BACKGROUND: Immunoglobulin A (IgA) anti-endomysium antibodies, the most reliable immunological marker for both the screening and follow-up of coeliac disease, need monkey oesophagus as antigenic substrate; this limits their use because of high costs and the exploitation of endangered species. OBJECTIVES: (1) To compare the diagnostic accuracy of anti-endomysium antibodies detected by indirect immunofluorescence on monkey oesophagus and on human umbilical cord; (2) to evaluate their reliability during follow-up in detecting non-compliant patients. PATIENTS: One hundred and four untreated adults with biopsy-proven coeliac disease and 94 controls were investigated. RESULTS: Endomysium antibodies were found in 99 patients (95%) on both substrates, with a specificity, respectively, of 100% and 99% on monkey oesophagus and umbilical cord. One year after gluten withdrawal, out of 47 patients who were investigated, only six presented with complete mucosal recovery: none of these subjects was positive on either substrates, while, among patients with persistent histological alterations, endomysium positivity persisted in only 10 on monkey oesophagus, but in 32 on umbilical cord. Histology (recovery or persistent involvement) was in agreement with endomysium (negative or positive) in 34% on monkey oesophagus, but in 81% on umbilical cord (P < 0.0001). CONCLUSION: Human umbilical cord, with its comparable diagnostic efficiency, could replace monkey tissues, with the advantages of saving both money and monkeys. Moreover, it seems the most suitable substrate in the follow-up, as it enables detection of non-compliant patients with persisting mucosal alterations.