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Biomedical subjects

R Pena

Publications and source records attributed to R Pena.

10 recordsLinked to original sources

Conformational analysis and crystal structure of {[1-(3-chloro-4-fluorobenzoyl)-4-fluoropiperidin-4yl]methyl}[(5-methylpyridin-2-yl)methyl]amine, fumaric acid salt.

{[1-(3-Chloro-4-fluorobenzoyl)-4-fluoropiperidin-4yl]methyl}[(5-methylpyridin-2-yl)methyl]amine, fumaric acid salt (C(20)H(22)ClF(2)N(3)O, C(4)H(4)O(4)) (1) was synthesized and characterized by the complete (1)H, (13)C and (19)F NMR analyses. The conformation of the piperidin ring, in the solution state, was particularly studied from the coupling constants determined by recording a double-quantum filtered COSY experiment in phase-sensitive mode. (1)H NMR line-shape analysis was used, at temperatures varying between -5 and +60 degrees C, to determine the enthalpy of activation of the rotational barrier around the CN bond. Compound 1 crystallizes in the triclinic space group P1 with a=8.517(3) Angstrom, b=12.384(2) Angstrom, c=12.472(3) Angstrom, alpha=70.88(2) degrees, beta=82.04(2) degrees, gamma=83.58(2) degrees. The results strongly indicate that the solid and solution conformations are similar. Thermal stability and phases transitions were investigated by thermal gravimetric analysis (TGA) and differential scanning calorimetry (DSC). Furthermore polymorphism screening was studied from recrystallization of 1 performed in seven solvents and by slurry conversion in water. The X-ray powder diffraction (XRPD) and differential scanning calorimetry results suggested that 1 crystallizes into one crystalline form which melts at 157 degrees C (DeltaH=132 J g(-1)).

Calorimetry, Differential Scanning↗

Prolidase deficiency with hyperimmunoglobulin E: a case report.

Prolidase deficiency is a rare, inherited disorder characterized by ulceration of the skin, mental retardation, and massive urinary excretion of imidodipeptides. Most patients also have recurrent infections, an unusual facial appearance, and splenomegaly. We describe a girl presenting with chronic dermatitis, recurrent respiratory tract infections since her first months of life, and facial features characteristic of prolidase deficiency. The diagnosis of prolidase deficiency was made at 4.5 months of age. The immunologic study in this patient showed an extreme and progressive increase of total immunoglobulin E (IgE) in serum (reaching the value of 77,600 IU/l) and defective chemotactic function of the neutrophils. Treatment with a hyper-proteic diet supplemented with ascorbic acid, manganese chlorite, and topical proline resulted in reduction of the frequency and severity of the infections and significant improvement of the skin lesions. The authors discuss the immunologic alterations and the favorable evolution with treatment in this patient.

Amino Acid Metabolism, Inborn Errors↗

[Crystalline polymorphism of eflucimibe].

The importance, in therapeutics, of the concept of bioavailability and on-going quality research in the formulation of a drug has prompted us to examine the crystalline polymorphism of eflucimibe as from the research phase. This study has been carried out by re-crystallization of the product in organic solvents having a different polarity in a variety of experimental temperature and pressure conditions, then, subsequently, by re-cooling the previously dissolved substance. The analytical methods applied to identify and then describe the polymorphic forms are thermogravimetry analysis (TGA), differential scanning calorimetry (DSC), X-ray powder diffraction from synchrotron radiation (XRPD), infrared spectrometry (IR), solid-state nuclear magnetic resonance spectrometry (SSNMR) and lastly maximum solubility measurements. By means of XRPD, two polymorphic forms called A and B have been clearly identified at ambient temperature. These two crystalline forms were obtained in a reproducible way, then described by DSC, XRPD, IR and SSNMR. Differential scanning calorimetry analysis has shown for polymorphic form A two endothermic phenomena with low energy at about 35 masculine and 118 degrees C attributed by XRDP to conformational polymorphism. The complex endothermic event that extends between 75 masculine and 105 degrees C appears to correspond to successive alterations of a lamellar structure. The solid-solid transition observed at 110 degrees C is due to a change of crystalline phase, then the melting point occurring at about 130 degrees C. For form B, two changes of crystalline phase are clearly observed at about 80 masculine and 120 degrees C. The reversibility of these changes was observed by thermomicroscopy in polarized light. Form A, which is less soluble in absolute ethanol than form B, is the more stable thermodynamically in the temperature range from 25 masculine to 50 degrees C where the data have been obtained. The Van't Hoff diagram layout for each polymorphic form appears to reveal an A<-->B transition temperature in a temperature range lower than 25 degrees C. This study, undertaken as from the research phase, has enabled us to highlight the polymorphism of this new chemical entity by means of XRDP by explaining the nature of the endothermic phenomena observed by DSC, and lastly identify the thermodynamically more stable polymorphic form, thus contributing to a better knowledge of this future drug.

Anilides↗

An ice test for the diagnosis of myasthenia gravis.

OBJECTIVE: To determine whether ice application to a ptotic eyelid can differentiate myasthenic from nonmyasthenic ptosis. DESIGN: Prospective, multicenter, nonrandomized, comparative trial. PARTICIPANTS: Twenty patients with myasthenia gravis (MG) and ptosis were evaluated in the neuro-ophthalmology service. CONTROL SUBJECTS: Twenty patients with nonmyasthenic ptosis evaluated in the same locale. METHODS: Palpebral fissures were measured before and immediately after a 2-minute application of ice to the ptotic eyelid. MAIN OUTCOME MEASURES: The difference in palpebral fissures in millimeters before and after ice application. Two or more millimeters of improvement after ice application was considered a positive ice test result. RESULTS: A positive ice test result was noted in 16 of the 20 (80%) patients with MG and in none of the 20 patients without MG (P < 0.001). Of the 4 patients with MG and complete ptosis, 3 had a negative ice test result. CONCLUSIONS: The ice test is a simple, short, specific, and relatively sensitive test for the diagnosis of myasthenic ptosis. The sensitivity of the ice test in patients with complete ptosis decreases considerably.

Adult↗

Development of a community intervention programme on miners' health and working environment in Nicaragua.

Since 1983, a broad research and development programme has been carried out with the support of Sweden through the Swedish Agency for Research Cooperation in Developing Countries (SAREC). One of the medical research and development projects deals with the environment and state of health of the population of an entire village, and is referred to as the Abdon Vega project. It is pursued by the Department of Social and Preventive Medicine of the University of León, Nicaragua, with the support of the Department of Social Medicine at the Karolinska Institute in Stockholm. The project comprises two stages. The first one centres on the state of health of the workers and the mining environment. This article reports on the objectives of the project and the study area. It presents experience from the development work up to now and the difficulties encountered.

Community Health Services↗

Renal and extrarenal rhabdoid tumors in children: a clinicopathologic study of 14 patients.

The clinical and pathologic features of 14 children with rhabdoid tumors are presented. Eight patients had primary renal neoplasms and six had extrarenal tumors. The eight renal rhabdoid tumors were identified among 514 primary renal neoplasms collected at four pediatric institutions. Six patients were under 1 year of age; five children died of tumor-related causes, four of them within 4 months of diagnosis and one 17 months postnephrectomy. Another patient died of sepsis 12 days postnephrectomy. One is alive 13 months postnephrectomy, and one was lost to follow-up evaluation. The most common sites of metastasis were the lymph nodes (seven children) and the lungs (three patients). Three infants with renal rhabdoid tumors had, in addition, intracranial masses, two of which manifested clinically before the detection of the renal tumors, in one confirmed to be a primitive neuroectodermal tumor. Five of the 6 extrarenal tumors were identified among 155,926 surgical pathology specimens examined in the same children's hospitals over the same period of time; the remaining extrarenal rhabdoid tumor was received in consultation from a community hospital. The extrarenal rhabdoid tumors occurred in the dorsum of the right foot, liver, soft tissue of the right chest wall, left temporal lobe, left leg, and left thoracic paraspinal region. The ages ranged from 6 weeks to 15 years and two months. Three patients died of tumor-related causes within 4 months of diagnosis; one was a term stillborn. Two are alive, 1 month and 70 months postdiagnosis. Common sites for metastases included the lungs (three patients), and liver and lymph nodes (two children each). Patients with renal and extrarenal rhabdoid tumors are of similar age, have a similar clinical course, with early metastases and poor response to therapy. Primitive neuroectodermal intracranial tumors have been identified in several reported patients with renal rhabdoid tumors; similar brain tumors have not been documented in patients with extrarenal rhabdoid tumors. The histogenesis of this tumor remains unknown.

Brain Neoplasms↗

Clear cell sarcoma of the kidney: a clinicopathologic study of 21 patients with long-term follow-up evaluation.

The clinical and pathologic features of 21 children with clear cell sarcoma of the kidney are presented. These cases were identified among 517 primary renal tumors collected from four pediatric institutions. Abdominal mass and hematuria were the usual presenting signs. The male to female ratio was 1.3 to 1. Although the mean age at diagnosis was 3 years, the sarcomas were diagnosed earlier in boys (2 years, 7 months) than in girls (3 years, 7 months). Tumor size and weight may have accounted for this difference, since the average tumor weights were 899 g for boys and 635 g for girls. Right kidney locations predominated (14 cases). The most common site for metastasis was the skeleton (12 patients), and the skull was almost invariably involved (10 children). Bone metastases preceded the development of metastases elsewhere in nine patients, in five of whom the involvement was polyostotic. Of the 12 patients with osseous metastases, nine died within five years of diagnosis, and one died eight years and nine months after diagnosis; the remaining two patients were successfully treated with a combination of surgery, radiotherapy, and actinomycin D, vincristine, cyclophosphamide, and Adriamycin. Eight of the nine patients with lung metastases died within five years of diagnosis. Until substantial proof is found that clear cell sarcoma of the kidney is related to nephroblastoma, its identification as a non-Wilms' sarcoma would seem to be appropriate. This tumor is not the only sarcoma of the kidney, but it appears to be the most common renal sarcoma of childhood.

Adolescent↗

Comparison of anesthetic solutions used in lumbar and caudal peridural anesthesia.

Clinical observations on peridural anesthesia were made in 466 patients. The spread of various concentrations of anesthetics injected into the lumbar and caudal peridural space were followed by plotting analgesia-time profiles. Onset of anesthesia and the volume required to provide one dermatome of anesthesia varied little among different anesthetics given in different concentrations. The sequence of appearance of analgesia was also similar, with longer times being required to block larger roots. Quality of anesthesia was judged by the penetration of anesthestic solutions into the largest spinal nerve root (S1); rate of penetration depended on the type of drug and concentration. No drug concentration combination included all the ideal characteristics for block: minimal mass of anesthetic, maximum spread, long duration (minutes of anesthesia per milligram of drugs per segment), low incidence of failure, and fast stabilization time. However, depending on the surgical needs and the characteristics of the patients, some drugs and concentrations may be preferred. Stabilization and onset were slower and drug requirements larger for caudal than for lumbar peridural anesthesia.

Adult↗

PTCA, thrombolysis or atherectomy: rational treatment of recently occluded saphenous vein grafts.

Recently occluded saphenous vein grafts (SVG) contain abundant thrombus. Distal embolization and myocardial infarction often occur when recanalization of such SVG is attempted. In 80 patients with occluded SVG, we employed transcatheter devices to lyse, compress or extract thrombus. Primary treatment for these SVG was performed in the following manner; PTCA 29, intragraft urokinase 12, TEC atherectomy 39. Following urokinase or atherectomy, adjunctive PTCA was performed to diminish the residual stenosis. All patients had class III or IV angina. Clinically, SVG occlusions were 3 days to 3 months old. TIMI flow was grade 0, and occlusion length was greater than 6 cm for all SVG. Each strategy resulted in a similar procedure success rate. However, when used as a primary treatment, TEC may be associated with lower rates of distal embolization and myocardial infarction.

Angioplasty, Balloon, Coronary↗