Biomedical subjects
Publications and source records attributed to M Manrique.
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In the past years there has been an increasing interest in the surgical therapies for Parkinson's disease. This renewed interest is related to differents factors. First, pharmacological treatments are still unable to alter substantially the progression of the disease and after a few years they generally cause motor complications and dyskinesias. Secondly, the great advances in the surgical techniques, especially with the improvement of stereotactic surgery, have decreased morbidity in recent years. Finally, the introduction of deep brain stimulation, now allows surgical treatment without damaging brain structures. In this review, different surgical treatments are summarized. Ablative surgery, deep brain stimulation and reinervation therapies are described.
PTEN gene (10q23) is a relevant tumor suppressor gene whose protein is a phosphatase involved in the control of angiogenesis of some tumors including astrocytomas. There are no studies correlating molecular changes of PTEN and the immunohistochemical expression of its protein (pPTEN) with the expression of vascular endothelial growth factor (VEGF) in astrocytomas. Fifty-six surgically resected brain gliomas, 10 grade 2, 16 grade 3, and 30 grade 4, were studied by a combined approach, consisting of (1) PCR analysis using four microsatellite markers against the PTEN gene region (10q23), (2) the FISH technique to test chromosome 10 using a pericentromeric probe, and (3) immunohistochemical evaluation of pPTEN and VEGF. Loss of heterozygosity (LOH) of PTEN was observed in 10% of fibrillary grade 2 astrocytomas and all gemistocytic ones. In high-grade tumors, LOH was more frequent in grade 4 than in grade 3 (> or =2 loci deleted, 83% and 56%, respectively). Monosomy for chromosome 10 was observed especially in high-grade tumors (6% of grade 3 and 50% of grade 4) and in 20% of grade 2 tumors, corresponding to gemistocytic astrocytomas. Results with both antibodies against PTEN were concordant: loss of cytoplasmic immunoreactivity was frequently observed according to homogeneous or heterogeneous patterns in 70% and 50% of grades 4 and 3, respectively, but not in grade 2. Immunonegativity of pPTEN was associated with PTEN gene deletion (> or =2 loci deleted) (P = 0.04) but not with monosomy. Cytoplasmic immunoreactivity against VEGF was observed in high-grade and in gemistocytic astrocytomas, but not in conventional grade 2 tumors. Tumor expression of pPTEN was not associated with immunoreactivity against VEGF when the same areas were considered. In conclusion, loss of PTEN expression is frequent in high-grade astrocytomas, but not in grade 2 tumors, and correlates with PTEN deletion and loss of chromosome 10. PTEN immunoreactivity does not correlate with VEGF expression in astrocytomas when similar areas are considered.
Several groups have studied brainstem auditory evoked potentials (BAEPs) in non-human primates. However, the nomenclature of the waves elicited and their correspondence with human waves I-V differ among authors. BAEPs were recorded from six anaesthetised young cynomolgus macaques (Macaca fascicularis), using different sound stimuli parameters. A constant pattern of four main waveforms was present in all the animals with stimulus intensities over 60 dB SPL, although up to four smaller waveforms were observed in some of the individuals. Latency values increased with decreasing stimulus intensities and with increasing repetition rates. These results were similar to the BAEPs observed in other species of macaques. Although an approximate equivalence between human and monkey BAEPs is possible, some discrepancies suggest that there may be generators which contribute to different waves in both species. This is the reason for our proposal of a new nomenclature for BAEP waveforms in monkeys, following a descriptive order with Arabic numerals preceded by the letter M.
BACKGROUND: Stereotactic biopsy is currently being used in oncological neurosurgery despite its limitations. The purpose of this study is to compare its diagnostic reliability with that of the diagnosis based on clinical data and neuroimaging techniques. METHODS: We studied 200 patients (134 men and 66 women) who underwent 212 stereotactic biopsy procedures to assess brain tumors. All were subjected to CT scan and 71 patients also underwent MRI. A presumptive diagnosis of brain tumor was established in each case and the findings compared with the results of stereotactic biopsy and the clinical course. RESULTS: A clear presumptive diagnosis was established before stereotactic biopsy in 90% of the patients, and in 95% of this group, the diagnosis was confirmed by the biopsy and/or the clinical course. The stereotactic biopsy modified the presumptive diagnosis in eight patients (4%), without changing the clinical diagnosis of malignant lesion. In our present series, 10% of the procedures were of no help in determining a diagnosis and in 7% of patients, the stereotactic biopsy led to diagnostic errors that influenced the therapeutic management and resulted in an erroneous prognosis. CONCLUSIONS: These data confirm the need for clinical correlation with the findings obtained at stereotactic biopsy and suggest that stereotactic biopsy may not always be useful or necessary in the management of brain tumor patients. According to our present critical analysis, when a clear presumptive diagnosis of brain tumor can be made, it may be sufficient to base the management of the patient only on clinical and neuroimaging findings.
We present the case of a 25-year-old woman suffering from chronic severe headaches and syncope associated with an expanding cyst of the septum pellucidum. After a simple endoscopic fenestration of the cyst the symptoms resolved, resulting in an excellent clinical outcome. This case shows that simple endoscopic fenestration may produce a rapid and maintained symptomatic improvement in patients with an expanding cyst of the septum pellucidum.
We report changes in the cochlear nuclei (CNs) after 3 months of bilateral auditory deafferentation and simultaneous unilateral implantation of a dummy auditory brain stem implant (ABI) in 6 nonhuman primates (Macaca fascicularis). These specimens were compared to CNs of 9 controls and 7 bilaterally deafferented animals without implantation. The ABI array consists of 3 platinum electrodes mounted on a silicone pad with the back side covered with Dacron. No migration of the ABI was observed. All deafferented animals showed astrocytic reorganization in the CNs. Histologic changes consisted of superficial reactions around the implant, with formation of fibrillar bundles of fusiform cells, and the presence of giant cells close to the Dacron. Other findings were related to surgical trauma. The dummy ABI did not itself provoke serious adverse reactions in the CNs. Our observations support the possibility of ABI reimplantation surgery.
We report on the surgical technique for surface electro-auditory prosthesis (EAP) implantation, pathological changes occurring at the cochlear nucleus complex (CNC), and its relation with electrical stimulation. Fourteen Macaca fascicularis were operated upon for a translabyrinthine bilateral auditory neurectomy, and simultaneous unilateral EAP implantation. Six animals were not stimulated, and the remaining eight were connected to an external active device. Stimulation was planned for 1000 hours. Biotolerance to the materials was adequate without significant reactions in the CNC surface, but an ependymal reaction. Lesions attributed to surgical trauma were also found. Two animals being stimulated could not complete the planned course due to cable break or EAP extrusion. One stimulated animal developed an asymptomatic brainstem abscess. A good knowledge of CNC topography is required to avoid surgical trauma. Externally connected devices may facilitate extrusion of the EAP or ascending infections.
INTRODUCTION: Approximately 20% of all epileptic patients are not satisfactorily controlled by the available antiepileptic drugs. Some of these patients have epileptic syndromes which could potentially be treated by surgery. DEVELOPMENT: The technological advances applied to diagnostic and therapeutic methods have improved the identification of epileptic patients who may benefit from surgery. Up to 80% of the patients with focal epilepsies symptomatic of well defined lesions may become free of seizures after excision of the lesion or epileptogenic focus. Other forms of epilepsy, such as the so-called catastrophic infantile forms, may improve temporarily when techniques such as hemispherectomy or callosotomy are used. The morbidity and mortality of these surgical procedures are minimal. The results depend on correct selection of the patients. A strict protocol for rigorous evaluation of the patients should be used, with the collaboration of neurologists, epileptologist neuropaediatricians, neuropsychologists, neurophysiologists, neuroimaging specialists, psychiatrists and neurosurgeons. There should first be clear answers to three key questions: 1. Who is a good candidate? 2. How should the selection be made? and 3. When is the best time for evaluation? CONCLUSIONS: At present it seems clear that the surgery of epilepsy is used less than it could be. It is therefore necessary to encourage the development of specialist units to select patients and treat them, and to develop the means whereby patients can obtain this highly specialized attention.
BACKGROUND: Obesity is a threat to health due to its association with cardiovascular risk factors. AIM: To assess the change in metabolic risk factors after weight reduction in obese patients. PATIENTS AND METHODS: A retrospective analysis of 277 obese patients (198 female) aged 39.5 +/- 12 years old, that completed a six month treatment period, consisting in a calorie restricted diet (800-1200 Kcal/day), physical activity, education and group psychological counseling. At the beginning and at the end of the program, weight, waist circumference, resting energy expenditure (REE), serum lipid profile, plasma glucose and plasma insulin levels were measured. RESULTS: During the treatment period, body mass index decreased from 38 +/- 7 to 33.2 +/- 6.4 kg/m2 with a weight loss of 11.7 kg, waist circumference decreased from 106.6 +/- 14.6 to 93.9 +/- 13.5 cm, REE decreased from 1774 +/- 383 to 1585 +/- 267 Kcal/day, blood glucose fell by 5.8%, plasma insulin fell by 40.4%, total cholesterol fell by 7.5%, LDL cholesterol fell by 8.7%, triglycerides fell by 26.6%, and total cholesterol/HDL ratio fell by 12.2%. CONCLUSIONS: Weight loss was associated with improvement in metabolic cardiovascular risk factors in obese patients.
Neurectomy of the auditory nerve produces a massive deafferentation of the cochlear nuclei (CN) in the brainstem. Degenerating primary afferents are removed in the acute phase, and this is followed by a synaptic reorganization in the CN. As part of an ongoing study on the effect and applicability of auditory brain implants in the CN of Macaca fascicularis monkeys, we studied the chronic response of astrocytes in the CN to bilateral deafferentation of the VIIIth cranial nerve. Four control and five deafferentated animals were employed. The treated animals had a bilateral extradural section of the VIIIth cranial nerve and a survival of 3 months. Animals were euthanized and perfused, and the brainstem was serially sectioned. The astrocyte population of the CN was studied by glial fibrillary acidic protein (GFAP) immunohistochemistry and quantified by unbiased stereological methods. The total length of astrocyte processes, L(proc), was estimated as the product of nuclear volume V(nuc), which was estimated by the Cavalieri method, times the ratio L(V)(proc, nuc) of process length to nuclear volume. Mean nuclear volume was significantly lower in deafferented animals, whereas the mean ratio L(V)(proc, nuc) was higher (albeit no statistical significance was reached). However, the mean total astrocytic process length was virtually the same in both groups. The absence of a length increase in the glial processes indicates a decrease of the astrocytic reaction after the acute phase. No glial scar is present in the CN of the monkey after long-term deafferentation, so the usefulness of auditory brain implants to stimulate CN neurons directly as a means to overcome deafness resulting from direct damage to the VIIIth cranial nerve (i.e., acoustic neuromas) is plausible.
Previous animal research and clinical experiences in humans suggest the existence of an auditory critical period in language acquisition. We review the literature and present the changes within the cochlear nuclei in bilaterally deafferentated adult non-human primates. We also present and analyse the results of 98 prelingually deaf children and teenagers who underwent a cochlear implantation at the University of Navarra. Patients received a Nucleus 22 or 24 multichannel cochlear implant (CI). They were grouped in five categories according to their age at surgery. Performance is compared with a control group of 58 postlinguals. Only early-implanted prelingual children (before 6 years of age) achieved a complete open-set speech recognition, even with better performance than postlinguals. These results clearly demonstrate the existence of a period of high neural auditory plasticity within the first 6 years of life. The introduction of auditory stimulation with a CI can not restore the loss of neural plasticity out of this period. Prelingual children under 6 years of age should receive a CI as soon as there is a reliable diagnosis of bilateral sensorineural hearing loss.
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Autosomal dominant polycystic kidney disease (ADPKD) is an inherited disorder characterized by genetic heterogeneity. Up to three loci are involved in this disease, PKD1 on chromosome 16p13.3, PKD2 on 4q21, and a third locus of unknown location. Since the identification of the PKD1 gene, the interest was centered in the characterization of the mutations responsible for the disease. Most mutations found were diverse and situated throughout the gene with no phenotypic correlation. Here we describe a new mutation in exon 44 from PKD1 gene in a family previously characterized as PKD1 by linkage analysis. The mutation is a single base substitution from a C to a T at position 12220 originating a stop codon at the mutation site. This would lead to premature termination and the formation of a truncated protein lacking part of the carboxi-terminus.
BACKGROUND: An immunological damage of beta cells in the islets of Langerhans, plays a role in the pathogenesis of type 1 diabetes. Recently, the identification of individuals in pre clinical phase and with high risk of developing type 1 diabetes, has become possible by means of the detection of immune markers such as islet cell antibodies (ICA) and the measurement of first phase response of insulin (FPRI). SUBJECTS AND METHODS: We studied 1,021 first degree relatives of type 1 diabetics, aged 4 to 35 years. ICA were measured using poly-IgG peroxidase in sections of human pancreas. In those subjects with positive ICA and normal oral glucose tolerance test, the FPRI was measured. FPRI was defined as the sum of insulinemias at minutes 1 and 3 after a three minutes 0.5 g/kg glucose load. RESULTS: Thirty subjects were ICA (+), defined as having more than 20 juvenile diabetes foundation units (prevalence of 2.9%). No differences in age, sex and closeness of familial relationship was found between ICA (+) and ICA (-) individuals. FPRI was measured in 24 subjects with normal oral glucose tolerance test and was normal in five. Seventeen subjects had a decreased response (between percentiles 1 and 5) and two had a response below percentile 1. No relationship between ICA levels and FPRI was found. CONCLUSIONS: The early detection of populations at risk of developing type 1 diabetes should be regarded as an important tool to better understand the natural history of the disease and to develop preventive programs in the future.
INTRODUCTION: Cochlear implants (CI) have proved their clinical efficacy and have overcome a routine treatment for profound sensorineural impairment. In the present paper we review our CI program concerning surgical complications and equipment failures. MATERIAL AND METHODS: One-hundred and thirty-five patients (69 younger and 66 older than 14 years of age) are subjects of the study. They suffered from pre-lingual (86 cases) or post-lingual (49 cases) profound bilateral sensorineural hearing impairment, and all of them received a Mini Nucleus 22 CI in our CI program. We analyze minor and major surgical complications and also CI and external equipment failures. RESULTS: In 6.1% of the patients (8 cases) a surgical complication occurred, 3 of them flap-related complications. In 2 of these cases (1.54%) complications were major. Three patients (2.17%) developed a complete CI failure, while in 8 cases malfunction of one or more electrodes was detected. Cumulative survival of CI was 87 months, without significant differences related to age or gender. Cumulative survival of the processors was 78.6 months, without significant differences related to the type of processor (MSP or Spectra) or gender but related to the age. The microphone failed in 42.2% of the cases. CONCLUSIONS: The CI is a low-morbidity treatment with adequate characteristics of durability and reliability. Nevertheless, some of the external components remain quite vulnerable.
We report a case of granular-cell tumor (GCT) in the esophagus. This is a rare location for this tumor and only 80 cases have been described. The tumor was diagnosed in a 24-yr-old woman with epigastralgia. Endoscopic examination revealed a submucosal ulcerated lesion. The smears derived from esophageal brushings contained clusters of granular cells. Histologic examination of the endoscopic biopsy provided diagnostic confirmation of GCT. To our knowledge, this is the first reported case of esophageal GCT in which the characteristic tumor cells were seen in the endoscopic brushing material. This case demonstrates that a cytologic diagnosis of GCT is possible if the lesion is ulcerated and/or brushing is subsequent to taking the biopsy. Although rare in the esophagus, GCT should be considered in the differential diagnosis of esophageal neoplasms.