Pathology of the palatal aponeurosis in cleft palate

OBJECTIVE: The palatal aponeurosis is a controversial structure, both in terms of its anatomy and its function. This article points out a pathologic finding in the cleft palate condition that has not been previously described. DESIGN AND METHOD: By means of surgical dissections, this study demonstrates in detail that the palatal aponeurosis exists even in cleft palates, but it is disrupted, malpositioned, and folded in two layers. PATIENTS: This dissection method has been performed on more than 150 patients with cleft of the hard and soft palate, with or without cleft of the lip and alveolus. At the time of operation, the children were between 6 and 8 months of age. RESULTS: It is possible to dissect the two layers of the palatal aponeurosis, to unfold the aponeurosis, and to form a tough tendinous plane. CONCLUSION: For a functional physiologic reconstruction of the cleft palate, it is necessary not only to reconstruct the levator veli palatini and palatopharyngeus muscle slings, but also to approximate and suture the fibers of the palatal aponeurosis to the corresponding fibers of the opposite side after unfolding them in a medio-dorso-cranial direction. In this manner, a continuous palatal aponeurosis can be created, which subsequently can serve as a transmitter of the muscle forces.     

Free flap closure of recurrent palatal fistula in the cleft lip and palate patient

Recurrent palatal fistulas present a particularly vexing problem for the cleft surgeon. In this setting, the cycle of repair followed by breakdown results in increasing scar formation with associated soft tissue contracture and a resultant increase in fistula size. This pernicious cycle of events renders random local tissue transfers obsolete. As such, the cleft surgeon must look to tongue flaps or local axial pattern flaps as a means of bringing well-vascularized, pliable tissue into the defect. Although this approach has been the standard of care for the last few decades, we believe that the modern-day success rates of free tissue transfers (95%) make them a viable, one-stage means of closing these defects. In this report we present our clinical experience with recurrent palatal fistulas and highlight the effective use of the dorsalis pedis-first dorsal metatarsal artery free flap as a means of repair.     

Postpubertal growth and development of the face in unilateral cleft lip and palate as compared to the pubertal period: a longitudinal study

In adult tissues, capillary growth (angiogenesis) occurs normally during tissue repair, such as in the healing of wounds and fractures. Inappropriate capillary growth is associated with various pathological conditions, including tumour growth, retinopathies, haemangiomas, fibroses and rheumatoid arthritis in the case of rampant capillary growth, and nonhealing wounds and fractures in the case of inadequate capillary growth. The female reproductive organs exhibit marked, periodic growth and regression, accompanied by equally striking changes in their rates of blood flow. It is not surprising, therefore, that they are some of the few adult tissues in which angiogenesis occurs as a normal process. Ovarian follicles and corpora lutea have been shown to contain and produce angiogenic factors. These angiogenic factors appear to be heparin-binding and to belong to the fibroblast growth factor (FGF) and vascular endothelial growth factor (VEGF) families of proteins. In addition, factors regulating gap junctional communication may play a critical role in coordinating the interactions between luteal vascular and nonvascular tissues. Further elucidation of the specific physiological roles of these factors in follicular and luteal growth, development and function will ultimately lead to improved methods for regulating fertility in mammals.     

Development of the residual cleft in the hard palate after velar repair in a 2-stage palatal repair regimen

Delayed closure of the hard palate is believed to improve maxillary growth and facial appearance in cleft lip and palate patients. However, the cleft opening in the hard palate after velar closure might impair speech development. The aim of this investigation was to study the development of the residual cleft in the hard palate after 2-stage palatal repair (TSPR) in children born with complete cleft lip and palate (bilateral [BCLP]; n = 7 or unilateral [UCLP]; n = 22) or isolated cleft palate (CP; n = 9). Moreover, we aimed to investigate whether any morphologic factors before surgery might predict development of the residual cleft. Dental casts obtained prior to velar repair (mean age 7 months) and postoperatively at 1 1/2, 3, 4, 5 and 7 years were analyzed with a Reflex Microscope regarding the width, length and area of the cleft in the hard palate. The palatal cleft varied in size both pre- and postoperatively in all 3 types of cleft patients. The width of the cleft in the UCLP subgroup showed a marked reduction immediately after velar repair, but then, on average, remained stable until final surgical closure of the hard palate. In the BCLP subgroup the initially rather narrow width of the clefts remained unchanged postoperatively. Clefts in the CP subgroup, especially in those with a complete cleft, remained large after veloplasty. In 4 of the UCLP and 2 of the BCLP patients, the cleft width increased gradually. In some other subjects, both in the UCLP and BCLP subgroups, the residual cleft closed functionally with time, but this development could not be foreseen.     

Changes of craniofacial growth and development in males with complete unilateral cleft lip and palate between the age of 5 to 20 years

The study is based on an anthropometric assessment of X-ray films obtained in two series of males with complete unilateral cleft lip and palate. The first series was examined at the age of 5, 10 and 15 years, the second series at 15 and 20 years. The films were assessed with Jarabak's analysis. The aim of our study was to compare the amount of growth and character of developmental changes in the prepubertal, pubertal and postpubertal period of life. The highest growth rate of skeletal structures was present in the prepubertal period, it was somewhat slighter in the pubertal period and it still continued in the postpubertal period. The high growth rate in the prepubertal period was probably related to the eruption of permanent teeth. In spite of a marked deterioration of sagittal jaw relations during the prepubertal period an improvement of an overjet was attained. However during the puberty and the postpubertal period a further improvement was not recorded. The results are in agreement with facial type of growth characterized by a slight pubertal spurt.     

Speech outcome and maxillary growth in patients with unilateral complete cleft lip/palate operated on at 6 versus 12 months of age

A prospective study of speech outcome and maxillofacial growth was carried out in cleft palate patients. Seventy-six cleft palate patients were randomly selected for the study group; 41 patients were operated on at 12 months of age, and 35 patients were operated on at 6 months of age. All patients were followed until they were 4 years of age. All patients underwent a complete speech evaluation, videonasopharyngoscopy, videofluoroscopy, and maxillofacial assessment. The rate of velopharyngeal insufficiency did not differ between the two groups (17 to 19 percent; p > 0.05). However, phonologic development was significantly better (p < 0.05) in the patients operated on at 6 months of age. Furthermore, none of the patients operated on at 6 months of age showed compensatory articulation disorder. In contrast, 62 percent of the patients with postoperative velopharyngeal insufficiency operated on at 12 months of age showed compensatory articulation disorder (p < 0.05). Maxillofacial assessment showed that there were non-significant differences (p > 0.05) in maxillofacial growth in both groups of patients. All patients showed similar degrees of maxillary collapse (p > 0.05). The results of this study suggest that cleft palate repair performed at 6 months of age significantly enhances speech outcome and prevents compensatory articulation disorder.     

Maternal hyperoxia greatly reduces the incidence of phenytoin-induced cleft lip and palate in A/J mice

The A/J mouse has been used to study the teratogenic affects of phenytoin. The developmental abnormalities produced in offspring of this model are similar to some of the malformations observed in cases of human "fetal hydantoin syndrome." Placing pregnant A/J mice in a hyperoxic chamber after phenytoin injection greatly reduces the incidence of phenytoin-induced cleft lip and palate. These results suggest that phenytoin may affect embryonic development indirectly by altering maternal physiology. This maternally mediated mechanism, and the protection against it afforded by hyperoxia, has general implications for the effects of maternal toxicity on teratogenesis.     

Time-dependent vascular regression and permeability changes in established human tumor xenografts induced by an anti-vascular endothelial growth factor/vascular permeability factor antibody

The hyperpermeability of tumor vessels to macromolecules, compared with normal vessels, is presumably due to vascular endothelial growth factor/vascular permeability factor (VEGF/VPF) released by neoplastic and/or host cells. In addition, VEGF/VPF is a potent angiogenic factor. Removal of this growth factor may reduce the permeability and inhibit tumor angiogenesis. To test these hypotheses, we transplanted a human glioblastoma (U87), a human colon adenocarcinoma (LS174T), and a human melanoma (P-MEL) into two locations in immunodeficient mice: the cranial window and the dorsal skinfold chamber. The mice bearing vascularized tumors were treated with a bolus (0.2 ml) of either a neutralizing antibody (A4.6.1) (492 micrograms/ml) against VEGF/VPF or PBS (control). We found that tumor vascular permeability to albumin in antibody-treated groups was lower than in the matched controls and that the effect of the antibody was time-dependent and influenced by the mode of injection. Tumor vascular permeability did not respond to i.p. injection of the antibody until 4 days posttreatment. However, the permeability was reduced within 6 h after i.v. injection of the same amount of antibody. In addition to the reduction in vascular permeability, the tumor vessels became smaller in diameter and less tortuous after antibody injections and eventually disappeared from the surface after four consecutive treatments in U87 tumors. These results demonstrate that tumor vascular permeability can be reduced by neutralization of endogenous VEGF/ VPF and suggest that angiogenesis and the maintenance of integrity of tumor vessels require the presence of VEGF/VPF in the tissue microenvironment. The latter finding reveals a new mechanism of tumor vessel regression-i.e., blocking the interactions between VEFG/VPF and endothelial cells or inhibiting VEGF/VPF synthesis in solid tumors causes dramatic reduction in vessel diameter, which may block the passage of blood elements and thus lead to vascular regression.     

Human herpesvirus 6 infection as a risk factor for the development of severe drug-induced hypersensitivity syndrome

OBJECTIVES: To test suitability of radiographic evaluation of lung lesions as a substitute for lung lesion scores derived by examination at necropsy in challenge-exposure models of bovine pneumonia. ANIMALS: 10 calves selected by body weight from 20 multiple-source male Holstein calves approximately 1 to 2 months old enrolled in a Pasteurella multocida challenge-exposure study. PROCEDURE: Calves were paired on the basis of weight and randomly assigned within pairs to vaccine or control (saline solution) group. By use of deep tracheal cannulation, calves were challenge exposed with a culture of virulent P multocida, observed for 10 days, euthanatized, and necropsied, and the lungs were scored for pneumonic lesions. Radiographic views of the lung fields of the calves were taken before challenge exposure and before necropsy and were evaluated for alveolar disease by a veterinary radiologist. Lung lesion scores were compared with radiographic evaluations. RESULTS: There was a strong and significant correlation (R2 = 0.91, P < 0.001) between results of the evaluation of postchallenge-exposure radiographs and necropsy results. There also was also strong and significant correlation (R2 = 0.90, P < 0.001) between evaluation of the prechallenge-exposure radiographs and necropsy results. CONCLUSIONS: Radiographic evaluation of lung lesions correlates well with lung lesions found at necropsy. The findings emphasize the need for caution in interpreting the results of challenge-exposure studies of bovine respiratory tract disease in which small numbers of calves are studied.     

Regulation of ovarian follicular development by epidermal growth factor in IVF superovulation cycles

PURPOSE: The aim of this study was to evaluate the presence of IL-8, TNF-alpha, IFN-gamma in subretinal fluid of patients with rhegmatogenous retinal detachment. MATERIAL AND METHODS: We studied 15 patients operated on retinal detachment. The presence of cytokines was evaluated using immunoenzymatic assay. RESULTS: IL-8, TNF-alpha and IFN-gamma were found in all subretinal fluid samples. The concentration of cytokines in patients with retinal detachment lasting to 2 months was higher than in cases of retinal detachment over 2 months.     

Role of beta-adrenoceptors in gastric mucosal integrity and gastroprotection induced by epidermal growth factor

The central and peripheral adrenergic systems are involved in the regulation of gastric secretion but little is known about the role of alpha- and beta-adrenoceptors in gastroprotection. In this study, acute gastric lesions were produced by an intragastric (i.g.) application of 100% ethanol and gastric blood flow (GBF) was determined by H2-gas clearance technique in rats with or without i.g. or intraperitoneal (i.p.) administration of alpha- or beta-adrenoceptor agonists or antagonists. Phenylephrine, alpha1-adrenergic agonist, and clonidine, alpha2-agonist, significantly augmented the ethanol-induced lesions while decreasing the GBF and these effects were reversed by the blockade of alpha1-adrenoceptors with prazosin and alpha2-adrenoceptors with yohimbine. In contrast, isoproterenol (ISO) (0.01-10 mg/kg i.g.), beta-adrenoceptor agonist, reduced dose-dependently ethanol-induced mucosal injury and this effect was accompanied by an elevation of the GBF similarly as after epidermal growth factor (EGF) (100 microg/kg x h s.c.) or after classic protective agent, 16,16-dimethyl-PGE2 (PGE2) (10 microg/kg i.g.). The pretreatment with beta-antagonist, propranolol, diminished the protective and hyperemic effects of ISO and EGF but failed to affect those induced by PGE2. Suppression of nitric oxide (NO) synthase activity by L-NAME or sensory denervation with capsaicin attenuated significantly the ISO- and EGF-induced gastroprotection and elevation of GBF, whereas the inhibition of PG biosynthesis by indomethacin remained without any significant effect. Adrenal medullectomy or chemical sympathectomy by 6-hydroxydopamine by itself failed to influence significantly the ethanol-induced damage but completely abolished the protective and hyperemic effects of EGF being without any influence on those induced by PGE2. ISO combined with EGF, restored the protective and hyperemic effects of this peptide in medullectomized rats. We conclude that (1) local activation of beta-adrenoceptors by ISO affords protection and elevation of GBF, both these effects being mediated by arginine-NO pathway and sensory nerves and (2) sympathetic system and adrenal medulla contribute to the protective and hyperemic activity of EGF.     

Fibrinogen as an independent cardiovascular risk factor and the question of treatment with fibrinogen-lowering drugs

The atherosclerotic vascular disease is a progressive condition of multifactorial origin. Among cardiovascular risk factors alterations of lipid metabolism are of central role. But the haemostatic system, first of all the plasmatic fibrinogen is also highly implicated. Increased fibrinogen condition can be regarded as a strong and independent predictor of cardiovascular risk. Total cholesterol, LDL-cholesterol and plasma fibrinogen concentration as risk factors are compared. Fibrinogen lowering treatments are also summarized.     

Prevention of peripheral tolerance by a dendritic cell growth factor: flt3 ligand as an adjuvant

Injections of soluble proteins are poorly immunogenic, and often elicit antigen-specific tolerance. The mechanism of this phenomenon has been an enduring puzzle, but it has been speculated that tolerance induction may be due to antigen presentation by poorly stimulatory, resting B cells, which lack specific immunoglobulin receptors for the protein. In contrast, adjuvants, or infectious agents, which cause the release of proinflammatory cytokines such as tumor necrosis factor alpha and interleukin 1beta in vivo are believed to recruit and activate professional antigen-presenting cells to the site(s) of infection, thereby eliciting immunity. Here we show that administration of Flt3 ligand (FL), a cytokine capable of inducing large numbers of dendritic cells (DCs) in vivo, (a) dramatically enhances the sensitivity of antigen-specific B and T cell responses to systemic injection of a soluble protein, through a CD40-CD40 ligand-dependent mechanism; (b) influences the class of antibody produced; and (c) enables productive immune responses to otherwise tolerogenic protocols. These data support the hypothesis that the delicate balance between immunity and tolerance in vivo is pivotally controlled by DCs, and underscore the potential of FL as a vaccine adjuvant for immunotherapy in infectious disease and other clinical settings.