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Biomedical subjects

J Vaquero

Publications and source records attributed to J Vaquero.

At least 19 recordsLinked to original sources

Loss of heterozygosity for distal markers on 22q in human gliomas.

Loss of constitutional heterozygosity as determined through the analysis of restriction-fragment-length polymorphism (RFLP) on tumoral and constitutional DNA has proven to be helpful to delimit the location of tumor-suppressor genes in the human genome. In malignant gliomas this approach indicates that chromosomes 9p, 10, 17p, and 22 may contain genes of this category involved in its origin and/or progression. Regarding chromosome 22, the data so far provided by molecular studies confirmed those previously reported by cytogenetic studies, suggesting the existence of a sub-group of malignant gliomas characterized by monosomy of this chromosome. However, the precise location of the putative glioma suppressor gene on chromosome 22 remains ambiguous. We have performed a combined cytogenetic and RFLP study on a series of 31 gliomas, looking for structural abnormalities of this chromosome. In 3 instances, terminal deletions of the long arm of chromosome 22 were observed by both methodologies, suggesting that the band q13 region distal to the D22S80 marker might be the critical domain non-randomly involved in tumor suppression of gliomas.

Astrocytoma

The patella thinning osteotomy. An experimental study of a new technique for reducing patellofemoral pressure.

The authors describe an original procedure, the patella thinning osteotomy, as an alternative to advancement of the tibial tuberosity or patellectomy in cases of severe anterior knee pain. They present an experimental study on cadaveric knees prior to a clinical trial. This study on 13 knee specimens, using Fujifilm Prescale barosensitive film, shows that thinning of the patella by 7 mm diminishes to a significant degree the patellofemoral contact areas from 16.07% at 60 degrees of flexion to 27.90% at 30 degrees of flexion. Patellofemoral joint reacting forces, measured in 12 knees, also diminish in both medial and lateral surfaces at 30 degrees, 60 degrees and 90 degrees of flexion, the level of statistical significance being over 0.05, except for the lateral surface at 60 degrees of flexion. This technique decompresses the patellofemoral joint, and produces the biological effects found after other osteotomies.

Aged

Delayed transplantation of foetal cerebral tissue into injured spinal cord of adult rats.

Delayed transplantation of foetal cerebral tissue into injured spinal cord of adult rats was performed for the purpose of evaluating the usefulness of the procedure for reconstructing the spinal cord and providing motor recovery. Transplanted tissue showed a survival rate greater than 80% and integration with the host tissue. Nerve fibers of the host surrounded the transplanted tissue, penetrating it. Foetal cerebral neurons matured into recipient spinal cord, but they were not organized in layers. The experience obtained suggests that delayed transplantation of foetal cerebral tissue into contused spinal cord is useful in morphological spinal cord reconstruction. Nevertheless, at least during the first two months after transplantation, clinical assessment of motor recovery showed no differences between transplanted and nontransplanted rats.

Animals

Neurosurgical experience with tumours of the pineal region at Clinica Puerta de Hierro.

The clinicopathological experience with 50 cases of pineal region tumours at Clinica Puerta de Hierro is presented. In this series, 88% of the patients were evaluated by CT-scan. Pineal region tumours make up approximately 0.7% of the intracranial expansive processes in the Spanish population. The largest group of lesions appearing in this localization is that of the germinomas (38%), followed by nontumoural lesions (20%) and tumours generally considered to be of the vicinity, such as meningiomas, gliomas and metastases (18%), tumours of the pineal parenchyma (14%), and non-germinoma germinal tumours (10%). In our series, in addition to an intracranial hypertension syndrome, an ophthalmological and, to a minor degree, an endocrinological syndrome predominate in germ-cell tumours, with a cerebellar syndrome appearing in gliomas of the pineal region. All the patients in the series diagnosed as having a germinoma and treated by irradiation are alive, and free of disease, after follow-up ranging from 2 to 20 years (mean: 8 years). The experience obtained with the present series supports the opinion that, in radiosensitive tumours, surgical resection adds no therapeutic benefit to treatment with radiotherapy alone. We suggest that when dealing with a tumour of the pineal region, CT-scan and clinical assessment now permit an initial selection of patients susceptible to surgery as a first therapeutic option, indicating those patients who, because they are considered to have either a "probable germinoma" or a "tumour of uncertain diagnosis", should undergo stereotaxic biopsy or trial radiotherapy and, only when this has proved a failure, should be subjected to open surgery.

Adolescent

Interleukin 2 and interferon alpha modulation of the lymphocyte non-major histocompatibility-restricted lytic activity in glioblastoma patients.

We studied the non-major histocompatibility-restricted cytotoxic activity induced by interleukin 2 (IL-2) and interferon alpha (IFN-alpha) in mononuclear cells of peripheral blood (PBMNC) from glioblastoma patients. We observed a depressed cytotoxic activity against natural killer (NK)-sensitive target cells in PBMNC from all the patients studied. Culture of these PBMNC with IFN-alpha for 5 days augmented the cytotoxic activity against NK-sensitive target cells in a small group of patients. Incubation with IL-2 for 5 days normalizes the decreased cytotoxic activity against NK-sensitive target cells of PBMNC from all the glioblastoma patients studied. When PBMNC from these patients were incubated with IL-2 for 5 days and IFN-alpha was added to the culture medium in the last 2 h of culture, an enhancement of non-major histocompatibility-restricted cytotoxic activity was observed compared with that obtained with either IL-2 or IFN-alpha alone. This improvement of the cytotoxic activity was more relevant when it was tested against NK-resistant target cells. The potential utility of the sequential use of the two cytokines in generating non-major histocompatibility cytotoxic activity in glioblastoma patients is discussed.

Aged

Expression of neuronal markers in the so-called ENU-induced schwannomas.

The present data show that the so-called ENU-induced malignant schwannomas express neuronal markers. This finding supports the hypothesis that a population of tumor cells in these neoplasms are neuroblastic in nature, and suggests the classification of ENU-induced schwannomas as primitive neuroectodermal tumors.

Animals

Intratumoral immunotherapy with interferon-alpha and interleukin-2 in glioblastoma.

The combination of the cytokines interferon-alpha 2b and rIL-2, at doses of 10 x 10(6) IU and 9 x 10(6) IU, respectively, in a 1.5 cc solution, can be safely injected into cystic glioblastoma without any evidence of side effects or increase in surrounding tumoral oedema. Nevertheless, an immunotherapeutic protocol in ten glioblastoma patients with tumour growth, that consisted of one intralesional injection per week, over 4 weeks of this combination of cytokines, had no effect on tumour progression.

Brain Neoplasms

Synaptophysin expression in "ependymal tumors" induced by ethyl-nitrosourea in rats.

Synaptophysin expression was studied in seven "ependymomas" induced by transplacental administration of ethyl-nitrosourea in rats. In all the cases, strong positivity for synaptophysin was found on tumor cells. This finding supports previous studies suggesting that ENU-induced brain tumors considered to be ependymal neoplasms, are, in fact, primitive neuroectodermal tumors.

Animals

Influence of recombinant interleukin-2 and tumor necrosis factor-alpha on the development of ethyl nitrosourea-induced brain tumors.

Using the experimental model of brain tumors induced by ethyl-nitrosourea (ENU), human recombinant interleukin-2 (rIL-2) and tumor necrosis factor-alpha (TNF-alpha) were administered to Wistar rats in early stages of carcinogenesis. The results obtained suggest that IL-2 does not influence the development of nervous system tumors. In contrast, TNF-alpha was capable of modulating the development of ENU-induced tumors, producing a reduction in the number of schwannomas and a delay in the appearance of intraparenchymatous brain tumors.

Animals

Expression of neuronal and glial markers in so-called oligodendroglial tumors induced by transplacental administration of ethyl-nitrosourea in the rat.

A series of 18 tumors with histological features of oligodendrogliomas, induced in the rat by means of transplacental ethyl-nitrosourea administration were studied for immunohistochemical demonstration of neuronal (synaptophysin and neurofilament protein) and glial (gliofibrillar acidic protein and vimentin) markers. Most of the tumors showed cells with strong positivity to synaptophysin and to a lesser degree, to neurofilament protein, suggesting the neuronal character of these neoplasms. In 10 tumors, cells with strong positivity to vimentin were found, and in three cases, tumoral cells expressed gliofibrillar acidic protein. The observation that ENU-induced oligodendroglial tumors express neuronal and, to a minor degree, glial markers, suggests their interpretation as primitive neuroectodermal tumors with clear neuronal differentiation.

Animals

Toxicology and kinetics of long-term intraventricular infusion of phenytoin and valproic acid in pigs: experimental study.

The effect of continuous intraventricular infusion of phenytoin and valproic acid into the brain of pigs was studied through quantitative measurement of animal behavior, pathological study of animal's brain and measurement of the levels of these drugs in the blood and C.S.F. Two groups of five animals each were treated with increasingly doses of the drugs until the apparition of toxic effects and the dead of animals. Normal behavior was observed with doses up to 3 mg/day of phenytoin and 1.5 mg/day of valproic acid. Toxic effects consisted on severe unsteadiness and muscular rigidity. Pathological study of the brains revealed that there were no damage attributable to the intraventricular infusion of the drugs. The present study suggests that intrathecal or intraventricular infusion of phenytoin and valproic acid could be well tolerated by humans and it leads us to consider subsequent clinical studies in epileptic patients.

Animals

Clinico-morphological correlation in syringomyelia: a statistical study assisted by computer measurement of magnetic resonance images.

A computer-assisted measurement of synrinxes was performed on MR images in a series of 26 patients with syringomyelia-Chiari complex. Syrinx data such as length, surface area, contour, and greater diameter were statistically correlated to each other and with the main clinical symptomatology of the patients. In general, a direct relationship between the various measurements of the syrinxes exists. Nevertheless, although a slight relationship could be established between the presence of muscular atrophy and a greater length and contour of the syrinxes, the present study suggests that the evaluation of syrinx dimensions cannot be brought into relation with the nature or distribution of clinical symptomatology. Because a reduction in the syrinx is generally the aim of surgery, this conclusion should be born in mind when a surgical treatment is offered to syringomyelic patients.

Adult

Modulation by interferon alpha of the decreased natural killer activity in patients with glioblastoma.

It is known that natural killer (NK) cells are involved in immunosurveillance against tumours. This study examines the NK activity of mononuclear cells (MNC) from the peripheral blood of patients with glioblastoma. The cytotoxic inducer effect of interferon-alpha (IFN-alpha) upon these MNC has also been studied. A marked decrease in NK activity mediated by MNC from these patients was found. This functional defected in MNC is not due to a decrease in phenotypically defined NK cells. After long-term (5-day) incubation with IFN-alpha, MNC from 5 out of 14 patients showed strong lytic activity against NK-sensitive target cells. In this system, IFN-alpha failed to induce cytotoxic activity against NK-resistant target cells in MNC from all the patients studied. This in vitro induction of cytotoxic activity in MNC from some patients with glioblastoma by IFN-alpha suggests a potential immunotherapeutic use of the lymphokine in these subjects.

Brain Neoplasms

Image-directed functional neurosurgery with the Cosman-Roberts-Wells stereotactic instrument.

An isocentered system for functional stereotactic procedures with the Cosman-Roberts-Wells frame and a CT localizer that allows extrapolation of target data directly from the CT slice is presented. Based on anatomical landmarks and on the scaled corresponding transverse plates of the Schaltenbrand and Wahren atlas, we delineate the thalamic and cerebellar nuclei. Twenty three image-directed functional procedures were performed in one year on 18 patients (7 with Parkinson's disease, 4 with dystonia, 3 persons with essential tremor, 2 patients with choreo-athetosis and 2 with de-afferentiation pain). The 23 procedures included 19 thalamotomies, two dentatotomies and two stereotactic implantations of deep seated brain electrodes. Successful targeting was verified by intra-operative electrical stimulation and postoperative CT scan. Complete reduction of symptoms was observed in 4 persons with Parkinson's disease and in 2 patients with essential tremor with significant improvement observed in the rest of the patients with the exception of the individual with choreo-athetosis. There were no operation-related complications. The reported technique is safer and less distressing for patients than previous radiological procedures and it makes image-directed stereotactic functional neurosurgery available to many units with the CRW frame.

Athetosis

Immunotherapy of glioblastoma with intratumoural administration of autologous lymphocytes and human lymphoblastoid interferon. A further clinical study.

A clinical trial of an immunotherapy which consisted of intratumoural injections of autologous lymphocytes with human lymphoblastoid interferon was evaluated in 31 patients with intracranial glioblastoma. Immunotherapy was performed after stereotactic biopsy or surgical resection. The treatment was tolerated well by all patients. Three patients showed positive response to immunotherapy as documented by transient regression or stabilization of the tumour size on computed tomography. Nevertheless, there is no significant difference in the survival time of the patients treated with immunotherapy and those not treated. We conclude that this immunotherapeutic regimen is not beneficial in patients with glioblastoma when used as single treatment after tumoural biopsy or resection.

Brain Neoplasms

Chromaffin allografts into arachnoid of spinal cord reduce basal pain responses in rats.

In this present study, behavioral responses to a subcutaneous formalin test for pain are evaluated in rats that previously received an allograft of adrenal chromaffin tissue into arachnoid of the dorsal spinal cord and in control animals. In the group of rats with grafts, a significant basal analgesia, reversed by the opioid antagonist naloxone, is found. These findings suggest that the grafts secrete some substance that reduces the response to painful stimulation and whose action is blocked by naloxone.

Adrenal Medulla

Symptomatic diverticulum of the 4th ventricle.

A case of symptomatic diverticulum of the 4th ventricle in a 57-year-old man is presented. This clinicopathological observation supports a relationship between ventricular diverticula and ependyma-lined paraventricular cysts.

Brain Diseases