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Biomedical subjects

A Merlo

Publications and source records attributed to A Merlo.

At least 73 records · Page 4Linked to original sources

Effects of different culture protocols on the expression of discrete T-cell receptor variable regions in human tumour infiltrating lymphocytes.

Therapeutic effects of tumour infiltrating lymphocytes (TIL) rely on T-cell receptor (TCR) engagement. In this work, the expression of five TCR alpha/beta variable (V) domains was quantitatively analysed by means of a panel of monoclonal antibodies (Mab) recognising gene products from TCR V alpha 2, V beta 5, V beta 6, V beta 8 and V beta 12 families in freshly isolated TIL and in autologous peripheral blood mononuclear cells (PBMC) from patients with neoplasms. In 3 out of 6 cases, differences in the expression of V beta 5, V beta 6, V beta 8 or V beta 12 could be detected. TIL populations were expanded by using recombinant human interleukin-2 (rhIL-2) alone or in addition to solid phase bound anti-CD3 Mab. Cultured TIL showed similar CD4/CD8 ratios and cytotoxic activity against autologous neoplastic target cells, regardless of the activation protocol. In 4 patients, the expression of TCR alpha/beta V gene products, as compared with TIL from freshly excised tumours, was found to be modified in cultured TIL, especially in cell populations activated with rhIL-2 only. These results indicate that TCR V gene usage in TIL may quantitatively differ from that in PBMC. TIL culture protocols using rhIL-2 alone or in combination with solid phase bound anti-CD3 may result in differential expression of discrete TCR V families.

Aged↗

Mixed renal tumor with carcinomatous and fibroleiomyomatous components, associated with angiomyolipoma in the same kidney.

A 54-year-old woman, without the stigmas of tuberous sclerosis, underwent radical nephrectomy for simultaneous occurrence of an Angiomyolipoma (AML) and a carcinomatous and fibroleiomyomatous mixed tumor in the same kidney, diagnosed by computerized tomography, selective renal arteriography and anatomopathological examination. The peculiar findings of the mixed neoplasia, characterized by a mixture of carcinomatous and fibroleiomuscular components are stressed. The latter component is considered to be a proliferative element interacting with the carcinomatous one. After review of the pertinent literature, this is the first example of an association of AML and renal cell carcinoma (RCC) in which the RCC is constituted by a mixture of carcinomatous and fibroleiomyomatous cells.

Adenocarcinoma, Clear Cell↗

T-cell receptor V-gene usage in neoplasms of the central nervous system. A comparative analysis in cultured tumor infiltrating and peripheral blood T cells.

The use of tumor-infiltrating lymphocytes in the treatment of central nervous system (CNS) neoplasms has met with serious obstacles due to difficulty of culture and poor characterization. Since in other tumors the therapeutic effects of tumor-infiltrating lymphocytes have been shown to rely on T-cell receptor engagement, the authors addressed the question as to whether expression of T-cell receptor variable (V) domains in cultured tumor-infiltrating lymphocytes from CNS is different from that of autologous cultured peripheral blood mononuclear cells. Infiltrating lymphocytes from CNS neoplasms, including primary malignancies, metastatic cancers, and meningiomas, were cultured in the presence of interleukin-2 and anti-CD3 monoclonal antibodies (MoAb's) in order to obtain optimum growth of T cells. Autologous peripheral blood mononuclear cells from the same patients were similarly cultured. After 4 to 5 weeks of culture, 97.3% +/- 2.6% (mean +/- standard deviation) of the resulting cell populations were CD3-positive lymphocytes. The expression of T-cell receptor V domains was then studied by using a panel of 12 MoAb recognizing gene products from T-cell receptor V-alpha 2, V-beta 5, 6, 8, and 12, V-gamma 4 and 9 families, and from two subfamilies of V-delta 2. Remarkably, in over 70% of all paired measurements, percentages of T cells expressing discrete T-cell receptor V-gene products were found to be virtually identical in tumor- and peripheral blood-derived cultured cell populations, with differences never exceeding 1%. In contrast, a different expression of individual V-gene products, concerning both alpha/beta and gamma/delta T-cell receptors, could be detected between cultured tumor-infiltrating lymphocytes and autologous peripheral blood-derived T lymphocytes in seven of 12 patients. In two cases, significant differences between the two populations were also observed in the proliferative responses obtained upon stimulation with staphylococcal enterotoxins that trigger defined V-beta T-cell receptors. Altogether, these data suggest that the T-cell receptor repertoire of cultured tumor-infiltrating lymphocytes from CNS tumors, suitable for use in adoptive immunotherapies, differs from that of autologous cultured peripheral blood mononuclear cells.

Adult↗

[Evaluation of the specific delayed cutaneous hypersensitivity response(DTCH) after specific active immunotherapy (SAI) using autologous tumor cells in patients operated upon for renal carcinoma].

From Dec 1986 to Dec 1990, 113 consecutive patients radically resected for renal cell carcinoma, have been randomized after surgery to observation or to Active Specific Immunotherapy (A.S.I.). 43 patients stage I-II and 13 p. stage III, according to TNM entered the treatment arm consisting of 10 autologous irradiated tumor cells injected intradermally, either mixed with BCG 10(7) (on days 28th and 35th after surgery) or alone (on day 42th). At randomization and 1, 6 and 12 months after treatment, patients were evaluated for the development of a DTCH to autologous tumor and to autologous normal cells, obtained by mechanical and enzymatic dissociation of the surgical specimens. Baseline DTCH were negative in all patients. One month after completing A.S.I. 36 out of 50 evaluable patients displayed a significant DTCH response to autologous tumor, which remained positive in 23/40 patients at 6 months. Our data clearly indicate that Active Specific Immunotherapy with autologous tumor cells mixed with BCG can elicit a specific immune response to autochthonous tumor as measured by DTCH.

Adult↗

Ciprofloxacin-resistant methicillin-resistant Staphylococcus aureus in an acute-care hospital.

Use of ciprofloxacin as an alternative to vancomycin for treatment of methicillin-resistant Staphylococcus aureus infection has been paralleled by the emergence of resistant strains. This phenomenon has also been noticed in our hospital. To confirm our observation, methicillin and ciprofloxacin susceptibilities were tested by disk diffusion and broth microdilution techniques. We studied 83 methicillin-resistant Staphylococcus aureus isolates obtained from various sources over a 4-month period. Ciprofloxacin resistance (MIC, greater than 2 micrograms/ml) was detected in 69 isolates (83%). Prior use of ciprofloxacin was reported for 24 of 69 patients with ciprofloxacin-resistant strains and 0 of 14 patients with ciprofloxacin-susceptible strains. The day of detection during the hospital stay and the location of the source patient were not significantly different between resistant and susceptible strains. Bacteriophage typing showed a higher occurrence of nontypeable strains among ciprofloxacin-resistant strains (54%). Review of our microbiology register showed a progressive increase in the rate of resistance to ciprofloxacin during the first year of use, with initial rates being about 10% and recent rates being higher than 80%. On the other hand, methicillin-susceptible S. aureus remained uniformly susceptible to ciprofloxacin (98.4%). We conclude that prior use of ciprofloxacin is an important factor for the selection of ciprofloxacin-resistant strains and that ciprofloxacin has limited usefulness against methicillin-resistant S. aureus.

Acquired Immunodeficiency Syndrome↗

[Does post-puncture syndrome following lumbar puncture depend on needle diameter?].

The impact of needle size on the frequency of post-lumbar puncture syndrome (PPS) was investigated in 77 patients undergoing diagnostic lumbar puncture. 22-gauge needles were used in 44 patients (group A) and 19-gauge needles in 33 (group B). Because of severe postdural headache, an epidural blood patch was applied in 6 patients and resulted in immediate relief of symptoms. In the remaining 71 patients, PPS occurred in 57% of group A and in 48% of group B. A statistically significant relationship could not be found between needle size and duration of PPS (p = 0.2), but an inverse ratio was found between age and duration of post-lumbar puncture headache (p = 0.006). A review of previous studies in this field shows that needles with a diameter smaller than 24 gauge reduce the incidence of PPS. However, technical skill is also of prime importance in lowering the frequency of postdural headache.

Adult↗

Anterior speech region. Asymmetry and weight-surface correlation.

Results of this work show, in the inferior frontal gyrus and in the different portions into which it was divided, asymmetry of weight and cortical surface and left predominance in the posterior portion, which is concerned with language. In spite of the difference among the absolute individual values, the correlation between weight and surface values is excellent in all cases, and the weight and surface ratio is the same for the portions related to language and different for the remainder of the inferior frontal gyrus.

Adult↗

Mitomycin C treatment of advanced, hormone-resistant prostatic carcinoma: a phase II study.

From February 1984 to February 1987, 29 patients with advanced, hormone-resistant prostatic carcinoma were treated with mitomycin-C at a dose of 20 mg/m2 every 6 weeks (15 mg/m2 in patients greater than 75 years old and in those who had undergone previous radiotherapy). In the 27 evaluable patients, there were no complete remissions (CR), 2 partial remissions (PR), 14 stabilizations (STAB), and 11 cases of progressive disease (PRO). Ten stabilized patients showed significant pain reduction. Toxicity was minimal. The actuarial median survival was 10.8 months. In this study, mitomycin C was not active in terms of CR + PR; however, a beneficial symptomatic effect was frequently observed.

Aged↗

Locked-in state in Borrelia burgdorferi meningitis.

The case is reported of a 28-year-old woman with persistent tetraplegia following acute meningitis due to Borrelia burgdorferi infection. The patient developed erythema chronicum migrans before radicular pain occurred in the upper extremities. The poor clinical outcome was suggestive of pontine infarction due to vasculitis of branches of the basilar artery.

Adult↗

Vasoactive intestinal peptide. An inhibitor of feline gastric smooth muscle in vitro.

Dose-response characteristics of feline corpus circular muscle were studied in vitro for three neuropeptides individually and with vasoactive intestinal peptide. Bombesin, substance P, and cholecystokinin-octapeptide each elicited concentration-dependent isometric contractions that were reduced by 10(-8) M or 10(-7) M vasoactive intestinal peptide (P less than 0.01). The concentration of each neuropeptide producing a half-maximal response was increased more than one logfold to greater than or equal to 10(-6) M by vasoactive intestinal peptide. Tetrodotoxin blocked responses to bombesin (P less than 0.001) and reduced responses to substance P (P less than 0.05), but had no effect on responses to cholecystokinin-octapeptide (P greater than 0.1). These results demonstrate inhibition of neuropeptide responses of gastric smooth muscle and support vasoactive intestinal peptide as an inhibitory regulator of gastric motor function.

Animals↗

Buserelin treatment of advanced prostatic cancer: a phase II study.

From August 1986 to September 1988, 76 eligible patients with advanced prostatic carcinoma, measurable or evaluable disease, no previous hormonal treatment, were treated with Buserelin at a dosage of 500 micrograms every 8 h for 7 days, followed by 400 micrograms intranasally three times a day. No concomitant antiandrogens were administered. In the 63 evaluable patients (11 patients not yet evaluable because of short treatment time, two lost to follow-up), three complete remissions, 28 partial remissions, 30 stable disease and two progressions were obtained (National Prostatic Cancer Project criteria). Median duration of response was 55+ weeks. Side effects were modest, mostly related to the endocrinological effects of Buserelin. Transient increase in serum testosterone levels was found in 37% of the evaluable patients, but transitory 'flare-up' was present in seven patients only. With a median follow-up time of 11.5 months, median survival has not been reached. In conclusion, this study confirmed the activity of Buserelin and the feasibility of its middle-term administration.

Aged↗

Presurgery chemotherapy (CT) in locally advanced bladder carcinoma: a feasible and possibly effective approach.

In October 1984, a prospective pilot study aiming to evaluate the feasibility and to preliminarily test the efficacy of the chemotherapy--surgery sequence in locally advanced bladder carcinoma was started at our institutions. Chemotherapy consisted of adriamycin 50 mg mq-2 and cisplatin 50 mg mq-2 on day 1 and fluorouracil 500 mg mq-2 and teniposide 100 mg mq-2 on days 1 and 8; chemotherapy was repeated every 3 weeks for three cycles and followed by surgery (radical cystectomy; TUR if radical surgery medically contraindicated). The characteristics of the 28 patients so far treated include: T3b in 26 patients, local relapse after surgery in two, nodal metastases in seven. Twenty-five patients were male and three female, median age was 61 yr (range 42-75). Clinical response following chemotherapy was: complete remission (CR) in five patients, partial remission (PR) in 15, stable disease (SD) in three, progression (PRO) in two. Three patients are not evaluable. Treatment was moderately well tolerated. Thirteen patients underwent radical surgery, three exploratory surgery, three TUR; refusal in three patients, early death in two, too early in one. No evidence of disease was found in the surgical specimen of five patients (three CR, two PR), microscopic residual disease in four PR patients, gross residual disease in 11 patients (one CR, six PR, two SD, two PRO). Actuarial median survival (all 28 patients) is 45% at 36 months. These preliminary results suggest that the combination of chemotherapy and surgery is feasible and may be effective in these poor prognosis patients.

Adult↗

Mechanics and neuropeptide responses of feline pylorus and gastric muscle in vitro.

Mechanical properties and neuropeptide responses were compared for feline pyloric and gastric muscle under isometric conditions in vitro. Total tension in antral circular muscle (0.699 +/- 0.003 kg/cm2) was less than in corpus circular (1.597 +/- 0.007 kg/cm2) or longitudinal muscle from the lesser and greater curvatures (1.256 +/- 0.009 and 1.253 +/- 0.007 kg/cm2, n greater than or equal to 55, P less than 0.05). The components of tension at optimal length were similar for all gastric muscles (P greater than 0.1). The pylorus maintained less total tension (0.335 +/- 0.003 kg/cm2) and a greater component of resting tension (75.6%) than gastric muscle (P less than 0.01). Substance P, cholecystokinin-8 (CCK-8), and neurotensin varied in potency and efficacy in circular muscle of the antrum, corpus, and inferior portion of the pyloric ring. Longitudinal muscle and the superior portion of pylorus responded poorly if at all to neuropeptides. Substance P- but not CCK-8- or neurotensin-induced contractions of gastric muscle were reduced by tetrodotoxin (TTX) and atropine (P less than 0.05). Substance P-induced pyloric contractions were TTX sensitive (P less than 0.05) but were unaffected by atropine. We concluded that 1) length-tension properties of gastric muscle are similar and distinct from the pylorus and that 2) neuropeptide efficacy varies regionally within the feline stomach and within the pylorus.

Acetylcholine↗

Swallowing disorders.

Swallowing is a coordinated activity that enables solids and liquids to pass uninterruptedly from the mouth to the stomach. Dysphagia occurs when this process is disrupted by organic or functional alterations at the level of swallow initiation or esophageal emptying. The differential diagnosis includes obstructive lesions and motility disorders. Symptoms and clinical features help distinguish these diseases.

Deglutition Disorders↗

Neuropeptide responses and mechanics of the proximal and distal feline colon in vitro.

Mechanical properties and responses to neuropeptides were compared for proximal and distal feline colonic muscle. Proximal longitudinal (PL), proximal circular (PC), distal longitudinal (DL), and distal circular (DC) muscles were studied in vitro under isometric conditions. Total tension in DL [1.636 +/- 0.009 (SE) kg/cm2] was greater than in DC (0.699 +/- 0.004 kg/cm2) or PC (0.710 +/- 0.005 kg/cm2, P less than 0.05). Longitudinal muscle developed proportionately more active tension than circular muscle at each region (80.9% in DL vs. 54.1% in DC and 77.1% in PL vs. 52.3% in PC, P less than 0.01). Neuropeptides varied in potency and efficacy. Cholecystokinin octapeptide (CCK-8) was the most potent and efficacious in PL and substance P was the most efficacious in PC muscle (P less than 0.05). Substance P was more efficacious whereas CCK-8 and neurotensin were less efficacious in PC than PL muscle (P less than 0.01). DL muscle did not respond to CCK-8. DC muscle did not respond to CCK-8 or neurotensin. Isometric contractions to each neuropeptide were insensitive to tetrodotoxin. We conclude that 1) mechanical properties of circular and longitudinal colonic muscle differ and 2) responses to neuropeptides depend on anatomic region and intrinsic properties.

Acetylcholine↗

Tubular handling of sodium and phosphate in non-ascitic liver cirrhosis.

The renal response to a maximal water load was evaluated in eight cirrhotic patients free of ascites and without previous evidence of ascites and in seven controls. Fractional sodium reabsorption in the proximal and diluting segment was estimated by clearance methods during hypotonic diuresis. Since phosphate excretion has been proposed as a proximal marker in liver cirrhosis, sodium reabsorption in the proximal tubule was compared with phosphate fractional excretion. In spite of a normal sodium balance during the pre-study period, non-ascitic cirrhotics showed a blunted proximal natriuretic response to maximal water load. In fact sodium excretion during hypotonic diuresis was reduced (p less than 0.05) and proximal sodium reabsorption increased (p less than 0.005) in cirrhotics. Fractional phosphate excretion was not impaired in our patients, and no correlation was found between phosphate excretion and proximal sodium reabsorption, as evaluated by clearance methods. This study demonstrates that an increased reabsorption of sodium in the proximal tubule is responsible for the impaired response to maximal water load in non-ascitic cirrhotics. Abnormalities in tubular handling of phosphate may account for the dissociation between proximal sodium reabsorption and phosphate excretion during hypotonic diuresis in these patients.

Adult↗