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Biomedical subjects

F Molina

Publications and source records attributed to F Molina.

At least 37 records · Page 2Linked to original sources

Surgical treatment of submucous cleft palate: a comparative trial of two modalities for palatal closure.

Submucous cleft palate is a congenital malformation with specific clinical and anatomical features. It can be present with or without velopharyngeal insufficiency. Surgical treatment of this malformation is indicated only when velopharyngeal insufficiency has been demonstrated. This article compares two modalities of surgical treatment for submucous cleft palate. The first includes a minimal incision palatopharyngoplasty, as described in a previous report. The second combines the first technique with additional individualized velopharyngeal surgery (individualized pharyngeal flap or sphincter pharyngoplasty) performed simultaneously. The individualized part of the procedure was selected and performed according to the findings of videonasopharyngoscopy and multiview videofluoroscopy, as reported previously. Two hundred and three patients with submucous cleft palate were studied from 1990 to 1999. Videonasopharyngoscopy and multiview videofluoroscopy demonstrated velopharyngeal insufficiency in 72 patients, who were randomly divided into two groups. Those in group 1 (n = 37) underwent a minimal incision palatopharyngoplasty. Patients in group 2 (n = 35) also underwent that procedure but simultaneously received individualized pharyngeal flap or sphincter pharyngoplasty, according to the findings of videonasopharyngoscopy and multiview videofluoroscopy. The median age of the patients from both groups was not significantly different (p > 0.5). The frequency of residual velopharyngeal insufficiency after palatal closure was not significantly different in both groups of patients (14 percent versus 11 percent; p > 0.5). The mean size of the gap at the velopharyngeal sphincter during speech was not significantly different in both groups of patients before surgery (23 percent versus 22 percent; p > 0.5). After the surgical procedures, there was a nonsignificant difference between both groups of patients in mean residual size of the gap in cases of velopharyngeal insufficiency (7 percent versus 8 percent; p > 0.5). It seems that minimal incision palatopharyngoplasty is a safe and reliable procedure for palatal closure in patients with submucous cleft palate. The use of additional individualized velopharyngeal surgery performed simultaneously did not seem to decrease the frequency of residual velopharyngeal insufficiency. Moreover, the residual size of the gap at the velopharyngeal sphincter was not significantly reduced when an additional surgical procedure was performed simultaneously with palatal closure.

Articulation Disorders↗

Retention of concurrent taste aversion learning after electrolytic lesioning of the interpositus-dentate region of the cerebellum.

Lesions in the interpositus-dentate region of the cerebellum impair short-term, or concurrent, TAL. In this type of learning, animals must discriminate between two flavor stimuli presented at the same time, one of which is associated with an aversive product. The task is learned by the control animals, and within this group the animals that acquire it adequately enough (15/22, 70% criterion) retain the learned taste discrimination when they are subjected to it again after being lesioned in the interpositus-dentate region. These results suggest that the deep nuclei are essential in the concurrent TAL acquisition process, but not in its retention.

Animals↗

Dissection of an antibody paratope into peptides discloses the idiotope recognized by the cognate anti-idiotypic antibody.

Using methods of parallel synthesis, the complete amino acid sequence of an Ab 1 antibody (Tg 10, an anti-human thyroglobulin monoclonal antibody) was made in the form of a set of 100 synthetic overlapping peptides. This set of immobilized peptides was allowed to react with the cognate Ab2 (AI 10, a highly purified rabbit anti-idiotypic polyclonal antibody to Tg 10). A dominant peptide idiotope, INTFSGVPTYA, was thus mapped, which corresponds mainly to the CDR2 region from the V(H) domain of the Tg 10 mAb. A synthetic peptide replica of this idiotope was found to bind to AI 10 with an affinity (K(D) in the 10(-8) M range, as measured using BIACORE technology) which represents a significant part of the affinity of the complete Tg 10 antibody (K(D) in the 10(-9) M range). The synthetic peptide also elicited anti-idiotypic antibodies in rabbits that recognized specifically the Ab1 antibody in an Ab1- and antigen-inhibitable manner. The peptide idiotope was further characterized chemically by the identification of residues important for binding to the Ab2 and by modelization of its structure. Our approach makes it readily possible to map and characterize functional, continuous-type idiotopes that could be further used to manipulate the immune response by peptide technologies.

Amino Acid Sequence↗

Electrolytic lesions of the pedunculopontine nucleus disrupt concurrent learned aversion induced by NaCl.

Bilateral electrolytic lesions in the pedunculopontine nucleus (PPN) impair acquisition of short-term, or concurrent, Taste Aversion Learning (TAL) in rats. This type of TAL is characterized by the daily presentation of two different flavor stimuli at the same time, one associated with simultaneous intragastric administration of an aversive product (hypertonic NaCl) and the other with physiological saline. Sham-lesioned control animals learn this taste discrimination task, but both lesioned animals and control animals learn a long-term, or delayed, TAL task in which each gustatory stimulus is presented individually every other day and the intragastric products, LiCl (0.15 M) and physiological saline, are administered after a 15-min delay. These results are analyzed in the context of the cerebellar circuits involved in learning and in relation to the two TAL modalities described above.

Animals↗

The role of the lateral parabrachial nuclei in concurrent and sequential taste aversion learning in rats.

The purpose of this study was to examine the role of the external lateral parabrachial subnucleus (PBNLe) in two different taste aversion learning (TAL) procedures. For the first, short-term (concurrent) TAL, two different-flavored stimuli were presented at the same time, one associated with simultaneous intragastric administration of an aversive product, hypertonic NaCl, and the other with saline. In the second, long-term (sequential/delayed) TAL, each gustatory stimulus was presented every other day and the intragastric products LiCl and saline were administered after a 15-min delay. Electrolytic lesions in the PBNLe blocked acquisition of concurrent TAL, in which the vagal visceral information is critical. But the same lesions failed to interrupt sequential TAL. This result was independent of the order in which the two tasks (concurrent and sequential) were presented. However, as found by other authors, the latter type of learning was impaired in the presence of larger lesions in this same area. This supports the existence of sensory information needed to establish sequential TAL in other subnuclei of the parabrachial complex. The results of these experiments suggest that the different modalities of TAL are anatomically specific.

Animals↗

Craniofacial shortening by contraction osteogenesis: an experimental model.

Application of gradual external forces to correct craniofacial deformities challenges many procedures in conventional craniomaxillofacial surgery. Distraction osteogenesis is replacing traditional osteotomies for correction of patients with craniomaxillofacial deficiencies. However, the reverse concept, contraction osteogenesis, has yet to be established for patients with craniomaxillofacial excesses. The purpose of this investigation is to demonstrate the contraction osteogenesis phenomenon applied in a controlled animal model during the craniofacial growth period. Twenty-six 26-day-old rabbits were assigned to one of four groups: 0, control; 1, pin control (pin insertion); 2, no contraction (pins and contraction device application, without active contraction); and 3, contraction (pin insertion, contraction device application, and active contraction). An external fixator was placed across the incisive-maxillary suture, and the effects after 4.5 weeks of contraction at a rate of 0.5 mm twice a week were compared with control groups. The results were assessed by craniometric and cephalometric measurements and by histologic examination. Gross alterations were evident in the contraction group, characterized by midface anteroposterior shortening, maxillary regression, snout deviation, and anterior crossbite. Histologic examination of the contraction group demonstrated a significant increase in osteoblastic activity. Contraction osteogenesis is a new treatment concept in craniofacial development and may offer therapeutic opportunities for shortening skeletal structures without the need of osteotomies, thus taking advantage of the potential of craniofacial growth and remodeling.

Animals↗

An iterative structure-assisted approach to sequence alignment and comparative modeling.

Correct alignment of the sequence of a target protein with those of homologues of known three-dimensional structure is a key step in comparative modeling. Usually an iterative approach that takes account of the local and overall structural features is required. We describe such an approach that exploits databases of structural alignments of homologous proteins (HOMSTRAD, http:/(/)www-cryst.bioc.cam.ac.uk/ approximately homstrad) and protein superfamilies (CAMPASS, http:/(/)www-cryst.bioc.cam.ac.uk/ approximately campass), in which structure-based alignments are analyzed and formatted with the program JOY (http:/(/)www-cryst.bioc.cam.ac.uk/ approximately joy) to reveal conserved local structural features. The databases facilitate the recognition of a family or superfamily, they assist in the selection of useful parent structures, they are helpful in alignment of the target sequences with the parent set, and are useful for deriving relationships that can be used in validating models. In the iterative approach, a model is constructed on the basis of the proposed sequence alignment and this is then reexpressed in the JOY format and realigned with the parent set. This is repeated until the model and sequence alignment is optimized. We examine the case for comparison and use of multiple structures of family members, rather than a single parent structure. We use the targets attempted by our group in CASP3 to assess the value of such procedures.

Algorithms↗

Inferior olive lesions impair concurrent taste aversion learning in rats.

Taste aversion learning can be established according to two different procedures, concurrent and sequential. For the concurrent task, two different taste stimuli are offered at the same time, one associated with simultaneous intragastric administration of an aversive stimulus and the other associated with physiological saline. This discrimination is learned by sham-lesioned control animals and by animals with lesions in the cerebellar cortex but not by rats lesioned in the inferior olive. At the same time, animals with lesions in the inferior olive and sham-lesioned animals achieve sequential learning when the gustatory stimuli are offered individually during each daily session. The results obtained show that electrolytic lesions in the inferior olive impair acquisition of concurrent learning and are analyzed in terms of an anatomical system consisting of the vagus nerve, inferior olive, and cerebellum, which differentiates between the two modalities of taste aversion learning, concurrent and sequential.

Analysis of Variance↗

Combined maxillary and mandibular distraction osteogenesis.

Mandibular elongation by gradual distraction in patients with hemifacial microsomia is a simple and effective procedure to correct facial asymmetry. The changes in mandibular dimension result in changes in dental occlusion. These are minimal in children because of the rapid growth of the maxilla and can be corrected easily with minor orthodontic treatment. Mandibular distraction in adults with hemifacial microsomia produces good aesthetic results but leaves the patient with a severe alteration in the occlusion requiring complex orthodontic treatment over a long period of time. To avoid this problem, an incomplete Le Fort I osteotomy is performed simultaneously with the mandibular corticotomy. Intermaxillary fixation is placed on the fifth postoperative day, and distraction is initiated. This technique preserves the preexisting stable occlusion. After distraction, both the maxillary and mandibular occlusal planes become horizontal, and facial asymmetry is corrected.

Adolescent↗

Velopharyngeal motion after sphincter pharyngoplasty: a videonasopharyngoscopic and electromyographic study.

Sphincter pharyngoplasty is a surgical procedure for managing velopharyngeal insufficiency after palatal closure. This procedure is intended to create an active diaphragm for velopharyngeal closure. The purpose of this study was to evaluate velopharyngeal motion after sphincter pharyngoplasty, by using selective electromyography and simultaneous videonasopharyngoscopy. Twenty-five patients who were subjected to sphincter pharyngoplasty from 1985 to 1996 were reviewed. All conditions were evaluated by using electromyography with simultaneous videonasopharyngoscopy. The following velopharyngeal muscles were examined: superior constrictor pharyngeus, palatopharyngeus, and levator veli palatini. The palatopharyngeus was included in the superiorly based surgical flaps inserted at the posterior pharyngeal wall. Twenty-three patients (92 percent) showed complete velopharyngeal closure. The two patients with residual velopharyngeal insufficiency showed a defect size of 20 and 25 percent. None of the patients showed electromyographic activity at the superiorly based flaps, indicating absence of activity of the palatopharyngeus muscles. However, all patients showed normal electromyographic activity at the superior constrictor pharyngeus and the levator veli palatini. Videonasopharyngoscopy demonstrated that lateral pharyngeal wall movements, which ranged from 25 to 40 percent, were related to strong electromyographic activity at the superior constrictor pharyngeus. It is concluded that the superiorly based pharyngeal flaps of the sphincter pharyngoplasty do not seem to create an active diaphragm for velopharyngeal closure. Moreover, the observed sphinctering seems to be passive, caused by the contraction of the superior constrictor pharyngeus.

Adolescent↗

Analysis of 1930 bedridden patients in the internal medical sector of the emergency department of a large city hospital: appropriate and non-appropriate admission.

This paper discusses criterion for the appropriateness of admission to the hospitalization ward in the internal medical sector of the emergency department, and analyses the bedridden patients in the emergency department of the major hospital in the city of Genoa. The analysis covers 1930 patients, for which considerations are made, globally and separately in two different age groups, as to the appropriateness of admission to the hospitalization ward of the emergency department, the occurrence of subjective urgencies and objective instabilities, and progression subsequent to hospitalization (discharge, transfer into other hospital wards, decease). The most significant results of the analysis were the following: (1) no significant difference was found between younger and older patients regarding appropriateness of admission; (2) in cases of appropriate admission subjective urgency was clearly prevalent in relation to objective instability, the latter being much more frequent in the older age group; (3) a lack of self-sufficiency and the absence of adequate family support were important factors regarding inappropriate admission of older patients; (4) the greater frequency of objective instability in the older patients-as well as a lack of self-sufficiency-was the major factor in their greater length of stay in the emergency department. These results challenge the misconceived but diffused conviction that there is widespread mishandling of the elderly regarding admission to the emergency department, while at the same time stresses the need for alternative services and structures concerning hospital admission of older patients.

Adult↗

Bilateral lesions in the cerebellar interpositus-dentate region impair taste aversion learning in rats.

Taste Aversion Learning (TAL) has been induced through two different behavioral procedures: a short-term o concurrent (two-daily flavors) and a long-term (one-daily flavor) procedure. For the first, two gustatory/olfactory stimuli are presented separately but at the same time on a daily basis. One of the flavors is paired with simultaneous intragastric administration of hypertonic NaCl and the other is paired with physiological saline. In the long-term procedure, the two stimuli are presented on alternate days, one of them followed by intragastric injection of the aversive stimulus, and the other by saline. The subjects for both types of tests were animals that had been lesioned in the interpositus-dentate region of the cerebellum. The experiments show that the lesions disrupt short-term TAL, but have no effect on long-term TAL. The results are discussed in terms of the role of the cerebellum in relation to TAL and the different anatomical substrates of both learning modalities.

Animals↗

Maxillary distraction: aesthetic and functional benefits in cleft lip-palate and prognathic patients during mixed dentition.

In the last few years, distraction techniques have been used successfully to correct the hypoplastic human mandible. In patients with cleft lip and palate, normal growth of the maxilla may be impaired by early cleft repair, and many of them do not respond to orthodontic procedures alone. Maxillary distraction is an alternative technique to correct maxillary hypoplasia during mixed dentition. In the last 3 years, the procedure was performed in 38 patients aged between 6 and 12 years; 18 patients had unilateral cleft lip and palate, 9 patients had bilateral cleft lip and palate, 7 patients had unilateral cleft palate, 2 patients had prognathism, and 2 patients had nasomaxillary dysplasia. Photographs, posteroanterior and lateral cephalograms, and dental models are obtained preoperatively (as well as an orthopantomogram) to locate the tooth buds. A subperiosteal dissection is performed exposing the anterior and lateral aspects of the maxilla, and an incomplete horizontal osteotomy is done above the tooth buds. Using a facial mask and an intraoral fixed appliance system as an anchorage, we initiate on the fifth postoperative day the application of distraction forces. Maxillary advancement between 4 and 12 mm is achieved during 3 to 4 weeks, and a satisfactory class I or II molar relationship is also obtained. A combination of forward and downward distraction forces can be used to achieve simultaneous advancement and elongation of the hypoplasic maxilla. The aesthetic results are excellent, and the nasolabial angle is increased, including a more anterior projection of the upper lip. Nasal breathing is improved as well as the air flow and patency of the nasal airway. Velopharyngeal function remains unchanged after the procedure. The follow-up in this series varied from 6 months to 3 years. No relapses have been observed.

Child↗

Determining the optimal thymidine concentration for growing Thy- Escherichia coli strains.

Changes of thymidine concentration in the growth medium affect the chromosome replication time of Thy- strains without at the same time causing a detectable difference in the growth rate (R. H. Pritchard and A. Zaritsky, Nature 226:126-131, 1970). Consequently, the optimal thymidine concentration cannot be determined by ascertaining which concentration produces the highest growth rate. Here we present a method for determining the optimal thymidine concentration of any Thy- Escherichia coli strain. Using this method, we found that the E. coli "wild-type" strain MG1655 has a partial Thy- phenotype.

Bacteriological Techniques↗

[Bone substitute with growth factor. Preliminary clinical cases for cranio- and maxillo-facial indications].

Several biological materials have been analyzed in combination with osteo-inductive growths factors to determine whether such a system can replace bone grafting in surgical practice. Efforts have been aimed at the discovery of the best carriers and delivery systems. We present the results of the surgical treatment of 11 cranio-maxillo-facial defects in 9 patients using a combination of natural coral skeleton (NCS in blocks or granules), human fibrin glue and transforming growth factor beta-1 (TGF-beta 1) as a composite bone substitute. Three patients were initially excluded because of early extrusion of the materials due to a technical error. Clinical and radiological evaluation was performed in all cases, with the patient acting as his own control. Clinical firmness and radiological mineralization occurred in three quarters of cases. New bone formation was confirmed histologically in two of these patients. Clinically the initial results remained stable over a three years follow-up with staged surgical procedures performed on a number of patients. None of the patients suffered any detrimental effect from implantation of the bone substitute. Although the numbers in these series are limited, the association of TGF-beta 1, human fibrin glue and NCS represented an interesting step, although the clinical results could be improved. Important factors in the success of this technique appeared to be stabilisation of the biological materials, quality and asepsis of the surrounding tissue and the dose of growth factor.

Acrocephalosyndactylia↗

Systematic exploration of the antigen binding activity of synthetic peptides isolated from the variable regions of immunoglobulins.

Sets of short (12 residues) cellulose-bound synthetic overlapping peptides derived from the sequences of the variable regions of the heavy and light chains of three different antibodies (an anti-thyroglobulin antibody, the HyHEL-5 anti-lysozyme antibody, and an anti-angiotensin II antibody) were used to systematically assess the antigen binding capacity of peptides from the antibody paratope outside their natural molecular context. Peptides enclosing one or several of the complementarity determining region (CDR) residues had antigen binding activity, although the most active peptides were not necessarily those bearing the greatest number of CDR residues. Several residues from the framework region, preceding or following the CDR, were found to play a role in binding. Affinity constants from 4.1 x 10(-7) to 6.7 x 10(-8) M-1 for the soluble form of 9 lysozyme-binding dodecapeptides were measured by BIAcore analysis. Alanine scanning of lysozyme-binding hexapeptides from the HyHEL-5 sequence identified 38 residues important for binding, of which 22 corresponded to residues that had been shown by x-ray crystallography to be at the interface between HyHEL-5 and lysozyme. Our results could be of interest for the rational identification of biologically active peptides derived from antibody sequences and in providing an experimental basis for mutagenesis of the antibody paratope.

Amino Acid Sequence↗

Radical chemoradiotherapy for elderly patients with bladder carcinoma invading muscle.

BACKGROUND: Chemoradiotherapy is becoming an alternative to radical cystectomy among patients with bladder carcinoma invading muscle. In 1988, the authors began a protocol with methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC regimen) and radiotherapy for these patients. Traditionally, age has been considered a determinant factor thereby excluding the older patients from the oncologic protocols that are considered to be more aggressive. The authors analyzed 20 patients (age > 70 years) who were treated during this period with the same protocol as the authors' other patients. METHODS: The study included 20 patients (age range, 70-78 years; median age, 74 years) including 4 patients with T2 disease, 9 with T3 disease, and 7 with T4 disease. All patients had a Karnofsky performance status of > 60. Treatment protocol included cytoreductive transurethral resection, 2 cycles of M-VAC chemotherapy, and radiotherapy (45 grays [Gy] on pelvic volume) with concurrent cisplatin (20 mg/m2 on Days 1-5. Response was determined by cystoscopic evaluation. If there was a complete response, radiotherapy continued until a total dose of 65 Gy; if there was not a complete response, cystectomy was performed. RESULTS: Tumor response after a dose of 45 Gy included 11 complete responses (55%), 5 partial responses (25%), and 4 nonresponses (20%). Overall survival was 75%, 34%, and 27% in the 2nd, 3rd, and 5th years of follow-up, respectively. Cause specific survival was 79%, 54%, and 38%, respectively. Survival for patients with complete response was 100%, 60%, and 48%, respectively. Severe toxicity was uncommon, with the most frequent toxicities being leukopenia and cystitis. No treatment-related death occurred with either treatment protocol. CONCLUSIONS: The age of the individual must not become a strict exclusion criterion for the radical treatment of old patients with invasive bladder carcinoma.

Aged↗