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Biomedical subjects

M Borghi

Publications and source records attributed to M Borghi.

At least 19 recordsLinked to original sources

Thoracolumbar disc extrusion associated with extensive epidural haemorrhage: a retrospective study of 23 dogs.

OBJECTIVES: To describe the clinical features and outcome in dogs suffering from thoracolumbar disc extrusion associated with extensive epidural haemorrhage (DEEH) and treated with extensive hemilaminectomy (from three to seven vertebrae). METHODS: The records of 23 dogs with surgically confirmed DEEH were reviewed retrospectively. RESULTS: All cases were characterised by rapid progression to severe neurological dysfunction (grade III, V and VI). Myelography was performed in 21 cases and showed an absence (16 cases) or attenuation (five cases) of contrast medium column along three to seven vertebrae. In two dogs, magnetic resonance imaging was accurate in confirming extradural compression due to disc material and haemorrhage, determining the extent of compression and side of the lesion. All cases were treated surgically with extensive hemilaminectomy involving all the compressed spinal segments. Twenty-one dogs (91 per cent) recovered and regained ambulatory function. Two dogs, without deep pain perception before surgery, did not improve. A two-year follow-up history was available for 15 dogs. Disc extrusion recurred in two dogs (9 per cent), two and 20 months after surgery. CLINICAL SIGNIFICANCE: Extensive hemilaminectomy can adequately decompress the spinal cord after DEEH and may produce a recovery and recurrence rate similar to thoracolumbar disc extrusion not complicated by extensive epidural haemorrhage.

Animals↗

Detection and quantification of CD8(+) T cells specific for HLA-A*0201-binding melanoma and viral peptides by the IFN-gamma-ELISPOT assay.

Blood lymphocytes from HLA-A*0201-subtyped melanoma patients and healthy controls were screened for the presence of T cells specific for HLA-A*0201-binding melanoma and viral peptide antigens by the enzyme-linked immunoSPOT (ELISPOT) assay. CD8(+) cells were tested for peptide-specific IFN-gamma release immediately after selection as well as after 2 weeks of in vitro stimulation. After in vitro stimulation, CD8(+) T cells specific for influenza were measured in all patients and controls, whereas these T cells could be detected among nonstimulated CD8(+) cells in only 52% of individuals. Similarly, T cells specific for EBV were more frequently measured among in vitro-stimulated than nonstimulated CD8(+) cells. In nonstimulated CD8(+) cells, T cells specific for MART-1/Melan-A, gp100, tyrosinase and CAMEL were present in 4 (33%), 1 (8%), 1 (8%) and 3 (25%) of 12 patients, respectively. Only MART-1/Melan-A-specific CD8(+) T cells were found in 1 (11%) of 9 healthy controls. CD8(+) T cells specific for MAGE-2 were not observed. After in vitro stimulation, CD8(+) T cells specific for MART-1/Melan-A could be demonstrated in 6 (46%) of 13 patients and 2 (20%) of 10 controls. CD8(+) T cells specific for gp100 were detected in 1 patient after in vitro stimulation. No CD8(+) T cells specific for tyrosinase, MAGE-2 or CAMEL could be measured after in vitro stimulation. These data show that the ELISPOT assay allows direct ex vivo detection of CD8(+) T cells specific for viral and melanoma antigens. Furthermore, the data show that the sensitivity of the ELISPOT assay to measure influenza- and EBV-specific CD8(+) T cells can be enhanced by a short in vitro stimulation step, whereas opposing effects on numbers of CD8(+) T cells specific for melanoma antigens have been observed.

Antigens, Neoplasm↗

Endometrial dating and determination of the window of implantation in healthy fertile women.

OBJECTIVE: To reassess endometrial morphological criteria of normality identifying the best morphological and molecular "implantation window" indicators in normal women. DESIGN: Prospective clinical study. SETTING: Assisted reproductive unit. PATIENT(S): Fourteen healthy volunteers. INTERVENTION(S): Blood sampling for LH, E(2), and progesterone (P4) determinations. Daily vaginal ultrasounds. Two endometrial biopsies per volunteer, 7 days apart, during luteal phase. MAIN OUTCOME MEASURE(S): Endometrial dating, pinopodes formation, immunohistochemical determination of integrins (alphavbeta3, alpha4beta1), leukemia inhibitory factor (LIF), interleukin-1 receptor type I (IL-1R tI), mouse ascites Golgi (MAG), the transmembrane mucin (MUC-1), and P4 receptor expression. RESULT(S): In 26 of 28 biopsies observers agreed; in two biopsies there was a discrepancy (difference of 72 hours). With use of LH peak, 24 of 26 samples were in phase, and 2 were 3 days behind. Pinopodes appeared on days 20-21 and persisted through day 28 in small groups or larger areas. beta3 Integrin was highly expressed in luminal and glandular epithelium from day 22 through 28; 48 hours thereafter pinopodes appeared. alpha4 Subunit exhibited luminal epithelium reaction positivity on days 22-23 and glands on days 18-23. LIF and IL-1R tI showed weak, erratic expression. MAG antibodies showed luminal epithelium expression up to day 22 and glands up to day 25. MUC-1 showed positivity during the whole luteal phase. P4 receptors were positive through day 20 and at the end of the luteal phase. CONCLUSION(S): The three most cited markers that frame the window of implantation do not correlate in our material. Pinopodes are present from day 20 on; beta3 and alpha4 integrin subunits indicate a window opening on days 22-23.

Adult↗

Effect of high-flux dialysis on the anaemia of haemodialysis patients.

BACKGROUND: Anaemia is one of the major clinical characteristics of patients with chronic renal failure, and has a considerable effect on morbidity and mortality. Adequate dialysis is of paramount importance in correcting anaemia by removing small and medium-sized molecules, which may inhibit erythropoiesis. However, high-molecular-weight inhibitors cleared only by means of highly porous membranes have also been found in uraemic serum and it has been claimed from uncontrolled studies that high-flux dialysis could improve anaemia in haemodialysis patients. METHODS: We therefore planned this multicentre randomized controlled trial with the aim of testing whether the use of a large-pore biocompatible membrane for a fixed 12-week follow-up improves anaemia in haemodialysis patients in comparison with the use of a conventional cellulose membrane. Eighty-four (5.3%) of a total of 1576 adult haemodialysed patients attending 13 Dialysis Units fulfilled the entry criteria and were randomly assigned to the experimental treatment (42 patients) or conventional treatment (42 patients). RESULTS: Haemoglobin levels increased non-significantly from 9.5+/-0.8 to 9.8+/-1.3 g/dl (dP=0. 069) in the population as a whole, with no significant difference between the two groups (P:=0.485). Erythropoietin therapy was given to 32/39 patients (82%) in the conventional group, and 26/35 (74%) in the experimental group (P:=0.783) with subcutaneous administration to 26/32 patients in conventional and to 23/26 patients in experimental group, P:=0.495. Dialysis dose (Kt/V) remained constant in both groups (from 1.30+/-0.17 to 1.33+/-0.20 in the conventional group and from 1.28+/-0.26 to 1.26+/-0.21 in the experimental group, P:=0.242). Median pre- and post-dialysis beta(2)-microglobulin levels remained constant in the conventional group (31.9 and 34.1 mg/dl at baseline) and decreased in the experimental group (pre-dialysis values from 31.1 to 24.7 mg/dl, P:=0.004 and post-dialysis values from 24.8 to 20.8 mg/dl, P:=0.002). Median erythropoietin doses were not different at baseline (70 IU/kg/week in conventional treatment and 90 IU/kg/week in experimental treatment, P:=0.628) and remained constant during follow-up (from 70 to 69 IU/kg/week in the conventional group and from 90 to 91 IU/kg/week in the experimental group, P:=0.410). Median erythropoietin plasma levels were in the normal range and remained constant (from 12.1 to 12.9 mU/ml in the conventional group and from 13.2 to 14.0 mU/ml in the experimental group, P:=0.550). CONCLUSIONS: This study showed no difference in haemoglobin level increase between patients treated for 3 months with a high-flux biocompatible membrane in comparison with those treated with a standard membrane. When patients are highly selected, adequately dialysed, and have no iron or vitamin depletion, the effect of a high-flux membrane is much less than might be expected from the results of uncontrolled studies.

Aged↗

[Correlation between computed axial tomography and ileum obturating lymphadenectomy in localized adenocarcinoma of the prostate].

OBJECTIVE: To correlate the findings of CT and ileoobturator lymphadenectomy in patients with localized adenocarcinoma of the prostate. METHODS: 94 patients with adenocarcinoma of the prostate were evaluated. Ileoobturator lymphadenectomy and brachytherapy were performed in 61.1%, radical prostatectomy in 22.5% and lymphadenectomy with prostatic labeling for subsequent external radiation therapy in 5%. Lymph node CT and pathology findings were correlated. RESULTS: Of 92 patients with a normal CT scan, 18 had positive nodes and 19.1% were understaged. Two patients with a CT scan suggestive of metastatic adenopathy had negative pathology findings. Seventy-two of the 92 patients with normal CT scans had negative nodes, accounting for a specificity of 76.6%. CONCLUSION: Pelvic lymph node involvement changes the prognosis of prostate cancer. However, the ability of CT to detect lymph node metastasis is limited. It is therefore not a reliable method and raises the costs of staging unnecessarily.

Adenocarcinoma↗

Peptide-pulsed dendritic cells induce tumoricidal cytotoxic T lymphocytes from healthy donors against stably HLA-A*0201-binding peptides from the Melan-A/MART-1 self antigen.

The melanoma antigen Melan-A/MART-1 was screened for the presence of potential HLA-A*0201-binding cytotoxic T lymphocytes (CTL) epitopes. The immunodominant nonamer epitope AAGIGILTV demonstrated weak binding to T2 but a significant half-life of binding to HLA-A*0201 in contrast to the decamer EAAGIGILTV. In addition to the immunodominant CTL epitope, we describe two peptides, GILTVILGV and ALMDKSLHV, that display stable binding to HLA-A*0201. Using cultured autologous dendritic cells pulsed with these peptides, CTL lines were induced from peripheral blood lymphocytes that displayed reactivity with HLA-A2+, Melan-A/MART-1+ melanoma cells. CTL reactivity against the immunodominant epitope could be induced with the nonamer epitope alone, but not with the decamer variant. CTL clones generated from an (EAAGIGILTV + AAGIGILTV)-induced CTL line recognize the appropriate melanoma cells and normal melanocytes. Upon further characterization of one of these CTL clones, it was found to be of surprisingly high affinity considering that it is directed against a self antigen. This study demonstrates that immunogenic peptides can be selected based on stability (half-life) of peptide/HLA binding. In addition, cultured DC were found to efficiently induce CTL responses in vitro against such selected peptides, and some of these CTL were capable of recognizing endogenously processed antigen.

Amino Acid Sequence↗

Activation of epitope-specific memory cytotoxic T lymphocyte responses by synthetic peptides.

Cytotoxic T lymphocytes (CTL) recognize antigens as short peptides selected for presentation by their ability to bind to MHC class I molecules. Polyclonal Epstein-Barr virus (EBV)-specific memory CTL responses, reactivated from blood lymphocytes of HLA-A11-positive individuals by stimulation with the autologous EBV-transformed lymphoblastoid cell line (LCL), are often dominated by reactivites directed to the peptide epitope IVTDFSVIK (IVT), corresponding to amino acids 416-424 of EBV nuclear antigen-4 (EBNA4). We now report the selective activation of IVT-specific CTL by stimulation of lymphocytes with the corresponding synthetic peptide. A more than 10-fold increase in frequency of CTL clones with this specificity (from 8% to 96%) was obtained when the peptide was presented by HLA-A11-transfected T2 cells (T2/A11). Titration of synthetic peptide in cytotoxic assay demonstrated that clones activated under these conditions are as efficient as clones activated by conventional LCL stimulations. Induction of memory CTL responses required low surface density of MHC: peptide complexes, since reactivation was achieved by stimulation with T2/A11 cells pulsed with concentrations of peptide that are suboptimal for induction of target cell lysis. This protocol of activation revealed the presence of IVT-specific CTL precursors in a donor that failed to mount an IVT-specific response upon stimulation with the autologous B95.8 virus-transformed LCL. The results suggest that stimulation with synthetic peptide epitopes can be efficiently used for induction of memory CTL responses, and may be particularly helpful for the selective expansion of subdominant CTL specificities.

Amino Acid Sequence↗

Ethylene-oxide and steam-sterilised polysulfone membrane in dialysis patients with eosinophilia.

Eosinophilia and some acute dialysis side-effects, such as itching, flushing and bronchospasm, are often associated with the presence of ethylene oxide (ETO) as dialyzer sterilizing agent. This study evaluated the effects of two different polysulfone (PS) hollow-fiber dialysers sterilized with ETO and steam in 31 chronic dialysis patients with eosinophilia. Clinical symptoms, metabolic and biochemical parameters, complement (C3a and C5a) activation and production were evaluated in each patient dialysed for two months at a time with Cuprophan dialyser, ETO-PS dialyser and steam-PS dialyser. The steam-sterilizer agent does not alter the purifying capacity of the PS membrane which maintains its superiority over Cuprophan in terms of biocompatibility. Using steam-PS, intradialytic eosinophil kinetics seems to improve. In some patients with high serum levels of ETO-specific IgE these levels tend to diminish. Generic intradialytic symptoms do not differ between the two sterilization methods, although some hypersensitivity symptoms during the first dialysis hour are considerably lower in some patients when steam-sterilized PS is used.

Adult↗

Free D-serine concentration in normal and Alzheimer human brain.

We have analyzed both free L- and D-serine in frontal cortex of normal and Alzheimer human brain by high-performance liquid chromatography (HPLC). There was no significant difference between the two brains. In normal brain, L- and D-serine concentrations were 666 +/- 222 and 66 +/- 41 nmol/g of wet tissue, respectively, and the ratio of D-isomer to L-isomer (D/L) was 0.099 +/- 0.031. In Alzheimer brain, the concentrations were 750 +/- 150 and 66 +/- 40 nmol/g, respectively, and the D/L ratio was 0.086 +/- 0.040. Thus, it was shown that the free D-serine concentration in the Alzheimer brain was comparable to that in the normal brain.

Aged↗

Analysis of the factors influencing bicarbonate balance during acetate-free biofiltration.

In acetate-free biofiltration (AFB), the physical separation between the base losses and the gains could facilitate the modeling of intradialytic bicarbonate (HCO3) balance. In order to verify this hypothesis, we analyzed in a multicenter study, 126 AFB sessions in which differing parameters were evaluated (dialysis time, blood flow, ultrafiltration, infused HCO3, pre- and post-dialytic HCO3, hematocrit and body wt). Statistical analysis performed with multiple linear regression showed that the post-dialysis HCO3 was significantly dependent (F = 21.68, d.f. 5.95, P < 0.001) directly on the amount of infused HCO3, the level of pre-dialysis HCO3 and the final body weight, and inversely on the dialysis time and the blood flow. HCO3 values predicted by the statistical model correlated well with the observed ones (r = 0.788, P < 0.0001) with a mean absolute difference of 2.138 mEq/liter. This modeling approach allowed us to predict, with a computer-aided procedure, the quantities of HCO3 to be infused to obtain a desired and personalized acidosis correction.

Acetates↗

Long-term comparison between captopril and nifedipine in the progression of renal insufficiency.

To verify the hypothesis that angiotensin-converting enzyme (ACE) inhibitors possess a unique renoprotective effect in progressive chronic renal disease, we decided to compare the effects of an ACE inhibitor and a calcium antagonist on both hypertension and the progression of non-diabetic renal insufficiency in a long-term study. A four-year, multicenter, prospective, randomized trial was conducted on 142 hypertensive patients (pts) with established chronic renal failure from six Italian nephrology departments. They were on standard antihypertensive therapy with a low-protein diet and underwent twice-monthly surveillance for a one year pre-randomization period. After that year, 121 pts were randomly allocated to captopril or slow-release nifedipine therapies for a three-year study period. The progression of renal insufficiency was monitored every two months. Blood pressure control was significantly better after randomization than during the year of standard antihypertensive therapy. The progression rate before randomization (BR) was definitely higher before than after randomization (AR): Creatinine clearance (CCr) change BR = -0.46 +/- 0.45 ml/min/month, creatinine clearance change AR = -0.23 +/- 0.43 ml/min/month (P less than 0.01). After randomization, the mean blood pressure values were virtually the same throughout the three year period of the study in the two groups treated by captopril (group I), or nifedipine (group II).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

[The use of high-dose amiodarone for cardioversion in patients with chronic atrial fibrillation].

Through this work, we reveal the possibility of converting into sinus rhythm the atrial chronic fibrillation based on vascular disease. The drug used for the cardioversion is "amiodarone". The results are excellent. Before the sinus rhythm became stable phenomena occurred that can be interpreted on the basis of an arteriosclerosis and ischemia type. This work has made use of the echographic instrument to prove the progress of the anatomical and functional conditions.

Aged↗

Relationship between the frequency of piezoelectric shock waves and the quality of renal stone fragmentation. In vitro study and clinical implications.

Nine renal stones were separated into 5 fragments of similar weight and size. One fragment was analyzed chemically and the other 4 fragments were submitted to treatment by piezoelectric shock waves according to the following modalities: 3,000 shock waves at firing frequencies of 1.25, 2.5, 5 and 10 shock waves/s. In the case of hard stones, better quality fragmentation was obtained with low frequencies than with high frequencies. With friable stones, using only 800 shock waves, the result was the same regardless of the frequency used. Treatment of hard stones by shock waves for 20 min at various frequencies revealed that a slightly better result was obtained with a frequency of 5 shock waves/s, although the result was not significantly better. In conclusion, slow frequencies of 1.25 or 2.5 shock waves/s allow better fragmentation of hard stones at the cost of a longer mean treatment than at high frequencies. High frequencies do not give significantly better results than low frequencies when the same firing time is used. In the clinical situation, it is therefore preferable to use low frequencies which allow treatment without anesthesia or analgesia and without admission to hospital.

Humans↗