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Biomedical subjects

A Gandolfi

Publications and source records attributed to A Gandolfi.

At least 19 recordsLinked to original sources

Well-differentiated endocrine tumours of the middle ear and of the hindgut have immunocytochemical and ultrastructural features in common.

The immunocytochemical analysis of two cases of well-differentiated endocrine tumours (carcinoids) of the middle ear revealed predominant cell populations producing pancreatic polypeptide (PP)-related peptides, glucagon-related peptides, and serotonin (the latter only in one case). In consecutive sections PP- and glucagon-related immunoreactivities mainly colocalized in the same tumour cells. Ultrastructurally tumour cells were characterized by medium-sized to large granules of moderate to high density, on which PP and glicentin were localized by the immunogold technique. No amphicrine cells were found. These features are consistent with those of similar tumours in the rectal mucosa that are mainly composed of L cells coexpressing both PP-related and glucagon-related peptides. Additional tumour antigens of hindgut type detected immunohistochemically were prostatic acid phosphatase and CAR-5 mucin. Expression of the CAR-5 antigen was also found in samples of normal middle ear mucosa, in which endocrine cells have not been identified. In case 1 peritumoral mucosal invaginations showed a proliferation of endocrine cells identical immunophenotypically to tumour cells, possibly representing a precursor lesion. It is concluded that well-differentiated endocrine tumours of the middle ear are a distinct pathological entity characterized by multiple hormone production, typically involving three classes of hormones (pancreatic polypeptide-related peptides, glucagon-related peptides, and serotonin) of the hindgut endocrine system.

Adult

Cell cycle analysis by the relative movement approach: effect of variability across S-phase of DNA synthesis rate.

Cell populations pulse-labelled with BrdUrd, and sampled at increasing times after the pulse, yield DNA-BrdUrd distributions from which the relative movement (RM) and the depletion function (DF) of labelled, undivided cells can be calculated. In this paper we present an extension of the equation for the time course of RM, given by White and Meistrich (Cytometry 1986, 7, 486-490), to the case in which the rate of DNA synthesis changes across S-phase. Some modalities of cell loss were also considered. Computer simulations showed that different patterns of DNA synthesis rate across S-phase can result in appreciably different RM curves. An analytical expression of the RM curve, in which the variability across S-phase of the rate of DNA synthesis is accounted for by only one parameter, was proposed. This expression was used for the simultaneous fitting of time sequences of RM and DF data of U937 cells, in order to estimate the phase transit times TS and TG2+M, and the potential doubling time Tpot. The use of the extended model gave better results than those obtained under the assumption of constant rate of DNA synthesis across S-phase.

Bromodeoxyuridine

[Transoral approaches to the skull base. An attempt of systematization].

This is a technical note concerning the classifications of the various operations possible via the buccal route towards the base of the skull and the first vertebrae. A part from the Hardy vestibulo-septal approach, mention must be made of the buccal and transpalatine approach, the direct buccal approach, the buccal approach widened downwards by transmandibular osteotomy, and finally the transmandibular and transcervical approach. These different technique enable the ablation of extradural and even intradural lesions at the level of the clivus, but are limited on the side by the pterygoid process and the large vessels.

Humans

Pharmacokinetic analysis of azelaic acid disodium salt. A proposed substrate for total parenteral nutrition.

Azelaic acid was the first dicarboxylic acid proposed as an alternative energy substrate in total parenteral nutrition. In this study, the pharmacokinetics of azelaic acid were investigated in 12 healthy volunteers, 7 receiving a constant infusion (10g over 90 min) and 5 a bolus dose (1g). The 24h urinary excretion and plasma concentration in blood samples taken at regular intervals were assayed by gas-liquid chromatography. Experimental data were analysed by a 2-compartment nonlinear model that describes both tubular secretion and cellular uptake in Michaelis-Menten terms. A high value of urinary excretion (mean 76.9% of infused dose) and a mean clearance of 8.42 L/h were found, suggesting the presence of tubular secretion. Estimating the population mean of the pharmacokinetic model parameters gave a maximal cellular uptake of 0.657 g/h. The model predicts that 90% of the maximal uptake should be reached in the plateau phase of a constant infusion of 2.2 g/h. The presence of extensive and rapid losses through urinary excretion, and the low estimated value of the maximal cellular uptake, indicate that azelaic acid is not suitable as an energy substrate for total parenteral nutrition.

Adult

MR cisternography of the cerebello-pontine angle and internal auditory canal in diagnosis of intracanalicular acoustic neuroma.

One hundred and fifteen patients, suffering from sensorineural hearing loss were tested with a 1.5 T superconducting magnet. The authors describe utility of both T1-weighted multiple slice and T2-weighted multiple echo images for the evaluation of cerebello-pontine angle, internal auditory canal and their neurovascular content. In seventy-three cases MR cisternography was normal. The remaining forty-two cases were subdivided into twenty extracanalicular masses, eleven small intra-extracanalicular and nine purely intracanalicular lesions. All the lesions were histologically proven acoustic neuromas, except one intracanalicular mass which was a meningioma. Examination was inconclusive only in two cases and decision was then made to follow the clinical course. Advantages of MR cisternography over CT and air CT cisternography, such as absence of ionizing radiation and contrast material, easy multiplanar evaluation of the region of interest and the possibility to delineate both the cisternal and canalar extremities of the tumor mass are pointed out.

Adult

Study of propidium iodide binding to DNA in intact cells by flow cytometry.

We studied the in situ binding of propidium iodide to DNA in fixed human lymphocytes, using flow cytometry. Experimental data of fluorescence emission vs dye concentration and vs cell concentration were obtained. Data were interpreted by means of two different mathematical models specific for the staining reaction, and the binding parameters were obtained by "best-fitting" of the data. A model based on two classes of binding sites with different affinity constants gave the most satisfactory fitting. The accessibility of the in situ chromatin turned out to be reduced with respect to the non in situ accessibility for ethidium bromide as reported in the literature. The present study shows the usefulness of the flow-cytometric technique for probing DNA structure in intact cells.

Binding Sites

Use of bispecific hybrid antibodies for the development of a homogeneous enzyme immunoassay.

Hybrid bispecific monoclonal antibodies reacting with carcinoembryonal antigen (CEA) and with the E. coli enzyme beta-galactosidase (GZ) were produced by fusion of hybridomas or chemical linkage of half-antibodies. Since the original anti-GZ antibody used in these experiments was capable of protecting GZ from thermal denaturation, it was possible, by hybridizing it with two different non-competitive anti-CEA antibodies, to design a homogeneous enzyme immunoassay for quantitation of CEA. In fact, a mathematical analysis of the reaction indicates that, under appropriate concentrations of the reactants, circular complexes can be formed which contain the two hybrid antibodies, the GZ enzyme and the CEA antigen. The stability of these complexes can be expected to be substantially greater than that of the more labile CEA-free GZ-antibody complexes, prompting a significant increase in the amount of enzyme molecules which are bound to antibody and are consequently protected from thermal denaturation. These expectations were supported by experimental results: under appropriate conditions, heat-resistant enzyme activity was indeed proportional to concentration of CEA in the range up to 75 ng/ml. As predicted by theory, however, in the presence of excess CEA - in fact at CEA concentrations which are higher than those of possible clinical relevance - circular complexes tended to open up, leading to a marked prozone effect.

Antibodies, Monoclonal

Retrolabyrinthine versus middle fossa vestibular neurectomy.

The authors' experience in treating incapacitating peripheral vertigo using the middle cranial fossa (MCF) and the retrolabyrinthine (RL) approaches is presented. Among 94 operated cases, 56 have been treated using the MCF approach and 38 the RL approach. In 18 of the RL cases, a simple vestibular neurectomy has been associated with different adjunctive techniques (i.e., drainage of the endolymphatic sac, section of the Wrisberg intermediary nerve, and neurovascular decompression of the eight nerve) in an attempt to influence the disease from a pathogenetic viewpoint. The RL approach has demonstrated to be a valid alternative to the MCF approach, since it allows the same results to be obtained in the control of vertigo, with fewer risks to the facial nerve and hearing functions. Moreover, it allows the association, although still in an experimental way, of the simple vestibular neurectomy and the other "pathogenetic" methods mentioned above.

Adult

Facial-nerve and vocal-cord monitoring during otoneurosurgical operations.

We describe a newly developed instrument to monitor facial muscles and vocal-cord function during neurosurgical and otoneurosurgical operations. The device (Myo-Alarm) transforms into acoustic signals the pressure variations that are induced by facial muscles and vocal-cord contractions on air-inflated rubber sensors that are positioned, respectively, beneath the superior lip and between the vocal cords. It represents an effective and dependable method to monitor facial and vocal-cord functional preservation during surgery.

Ear

Kinetic and survival response of the M14 cell line to lonidamine associated with adriamycin or hyperthermia.

Lonidamine (LND), an indazole-carboxylic acid derivative, was delivered alone and together with adriamycin (ADM) or hyperthermia to the human melanoma cell line M14, and cell survival was assessed. Cell cycle-specific effects were investigated by analyzing sequences of DNA content histograms by means of a suitable mathematical procedure. LND delivered for 1 h at a dose of 50 micrograms/ml did not affect proliferation and survival of the cells. Exposure of the cells for 1 h to ADM (1.0 microgram/ml) followed by LND for 1 h (50 micrograms/ml) produced the highest effect on the survival. Kinetic parameters were affected by the combined treatment slightly more than by ADM exposure alone. Simultaneous delivery of LND (50 micrograms/ml) with hyperthermia (42 degrees C, 1 h) reduced the survival and enhanced the block of cells in the G2M phase, as compared with the heat treatment alone. The effect of the treatments on cell survival appeared to be related to the perturbation of the G2M phase of the cycle.

Antineoplastic Agents

Hearing preservation in acoustic neuroma surgery. Middle fossa versus suboccipital approach.

Over the past few years there have been reports discussing the preservation of hearing after the removal of acoustic neuromas through the middle cranial fossa or the suboccipital approaches. This is a complex issue with many facets and controversies. In an attempt to answer at least some of these controversies, this article reviews the experience of our group. Preservation of hearing was attempted in thirty-four cases out of 220 acoustic neuromas. In twenty cases the middle fossa approach was used: All tumors were less than 2 cm from the fundus, and in four patients the tumor was bilateral. In sixteen of the twenty (80%) the cochlear nerve was spared; in ten of twenty (50%) measurable hearing was retained, but in only four (20%) was the postoperative hearing serviceable according to the 50/50 rule. In fourteen cases the suboccipital approach was used: All but two of the tumors were smaller than 2 cm. In three patients the tumor was bilateral. The cochlear nerve was preserved in ten of the fourteen cases (71.4%). Measurable hearing was present in four of fourteen cases postoperatively (28.6%); none had serviceable hearing according to the 50/50 rule. Hearing was not preserved in any bilateral tumor case. The middle fossa and the suboccipital approaches are discussed as well as the relative merits of each procedure in preservation of hearing.

Adult

Transmastoid extralabyrinthine approach in traumatic facial palsy.

Our experiences with thirty-six cases of intratemporal facial nerve palsies using the transmastoid extralabyrinthine (TMEL) approach are reported. Palsies were mostly traumatic in origin. The technique, first developed by us and reported in May 1980, spares the labyrinth and has the same indications for use as the middle cranial fossa approach to the seventh nerve. It avoids craniotomy and overcomes the limitations of the classic transmastoid approach, allowing exploration of the nerve from the descending portion to the geniculate ganglion and surrounding regions. When the ossicular chain is already damaged by trauma, surgery is made easier by removal of the head of the malleus and of the incus, which are then transposed at the end of surgery to reconstruct the chain. In particular cases the technique can also leave the chain intact. The TMEL approach has been used in 89% of patients with traumatic palsies due to longitudinal temporal bone fractures, with either an intact or, more often, a disconnected chain. Results of facial nerve and hearing function tests at twelve months are reported in detail. Our approach and similar techniques used by other authors represent an alternative to House's middle cranial fossa and Pulec's combined operations. Morbidity rate is lower and the operation can be performed by the majority of otologic surgeons.

Ear Ossicles