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.     

The use of cranial bone grafts in the closure of alveolar and anterior palatal clefts

A method is described for harvesting cancellous bone from the diploic space. In our opinion, this is the material of choice for bone grafting alveolar clefts in the 7- to 11-year age group. The procedure could be performed at an earlier age if the maxillary segments are under orthopedic control and in proper alignment. Success of the procedure depends on proper orthodontic preparation of the maxillary segments and careful, complete closure of the soft tissues across the anterior palatal cleft, the nasal lining defect, and the anterior alveolus. Results have been encouraging in terms of bone formation, and tooth migration into the bone graft can be expected if there has been no damage to the dental sac. Closure of the alveolar defect at the time of the primary lip closure would preclude the eventual need for a bone graft, but it cannot be accomplished without early, precise alignment of the maxillary segments if extensive periosteal denudation is to be avoided. The age beyond which periosteal closure alone will be inadequate to provide sufficient bone formation and should be supplemented by a bone graft remains to be established.     

Long-term results following the repair of palatal clefts: a comparison of three different techniques

A series of 109 patients was divided according to type of palatal defect, technique of repair (pushback, von Langenbeck, or pushback with island flap), results of standardized multifactorial speech analyses, and effectiveness of primary and secondary operations. Sixty-five patients (60 percent) showed improved speech after the initial repair, with 49 of these rated as "good." Forty-five percent improved after the von Langenbeck operation, 57 percent improved after the pushback procedure, and 53 percent improved after the pushback/island flap repair. Persistent hypernasal speech was treated with superiorly based pharyngeal flaps in 18 patients with uniform success (p less than or equal to 0.001). The worst results (after all three techniques) followed the repair of bilateral complete clefts. This experience has tempered our expectations in dealing with cleft palate patients, especially those having bilateral defects.     

Levator advancement technique for eyelid ptosis

There have been many procedures advocated for the treatment of eyelid ptosis. The technique advocated in this paper consists of careful dissection and identification of anatomic landmarks, including preaponeurotic fat, Whitnall's superior transverse ligament, and the vertically oriented blood supply of the levator muscle. The attachment of the levator muscle into the cephalad portion of the levator muscle into the cephalad portion of the levator aponeurosis can be identified and easily dissected in order to perform the procedure of detachment and advancement to the tarsal plate. This procedure for ptosis has been successful in management in moderate to severe ptosis and in some cases has actually increased the muscle function, thereby enhancing the result. In this technique, the full length of levator muscle remains, so maximum excursion is achieved postoperatively. In addition, this surgical approach may be utilized for levator-lengthening procedures in cases of thyroid exophthalmus or overcorrected ptosis simply by performing the reverse procedure of detachment and insertion of a spacer based on the same ratio. Good results have been achieved in over 20 patients, with the exception of two patients who had absent to poor function and in whom undercorrection was present postoperatively.     

Drug repositioning for orphan diseases

The need and opportunity to discover therapeutics for rare or orphan diseases are enormous. Due to limited prevalence and/or commercial potential, of the approximately 6000 orphan diseases (defined by the FDA Orphan Drug Act as <200 000 US prevalence), only a small fraction (5%) is of interest to the biopharmaceutical industry. The fact that drug development is complicated, time-consuming and expensive with extremely low success rates only adds to the low rate of therapeutics available for orphan diseases. An alternative and efficient strategy to boost the discovery of orphan disease therapeutics is to find connections between an existing drug product and orphan disease. Drug Repositioning or Drug Repurposing--finding a new indication for a drug--is one way to maximize the potential of a drug. The advantages of this approach are manifold, but rational drug repositioning for orphan diseases is not trivial and poses several formidable challenges--pharmacologically and computationally. Most of the repositioned drugs currently in the market are the result of serendipity. One reason the connection between drug candidates and their potential new applications are not identified in an earlier or more systematic fashion is that the underlying mechanism 'connecting' them is either very intricate and unknown or indirect or dispersed and buried in an ever-increasing sea of information, much of which is emerging only recently and therefore is not well organized. In this study, we will review some of these issues and the current methodologies adopted or proposed to overcome them and translate chemical and biological discoveries into safe and effective orphan disease therapeutics.     

Exploiting drug-disease relationships for computational drug repositioning

Finding new uses for existing drugs, or drug repositioning, has been used as a strategy for decades to get drugs to more patients. As the ability to measure molecules in high-throughput ways has improved over the past decade, it is logical that such data might be useful for enabling drug repositioning through computational methods. Many computational predictions for new indications have been borne out in cellular model systems, though extensive animal model and clinical trial-based validation are still pending. In this review, we show that computational methods for drug repositioning can be classified in two axes: drug based, where discovery initiates from the chemical perspective, or disease based, where discovery initiates from the clinical perspective of disease or its pathology. Newer algorithms for computational drug repositioning will likely span these two axes, will take advantage of newer types of molecular measurements, and will certainly play a role in reducing the global burden of disease.     

A method for repositioning the external ear

The malposition of an otherwise normal-appearing external ear is not uncommon in certain craniofacial syndromes. This paper presents a 10-year experience of 14 patients who underwent external ear repositioning. In this technique, a posterior incision is used to mobilize surrounding soft tissues circumferentially around the external auditory canal, which then serves as an axis for anterior rotation and elevation. Elevation of up to 8 mm and rotation up to 30 degrees can be achieved. Further elevation is limited by the ensuing constriction and resistance of the external auditory canal. More rotation can be achieved with a Z-plasty transposition of an inferiorly based postauricular skin flap.     

Levator veli palatini muscle and eustachian tube function

Thirty previously unoperated patients with submucous cleft palate, occult submucous cleft palate, and unilateral congenital paralysis of the levator veli palatini muscle were examined. All patients were subjected to a comprehensive otoscopic, endoscopic, audiologic, and tympanometric evaluation. A correlation was made between levator veli palatini muscle anomalies, eustachian tube orifice anomalies, and middle ear ventilation and disorders. Normal middle ear ventilation was found in 23 patients. Negative middle ear pressure that consequently normalized following treatment of coexisting sinusitis was found in 3 patients. Only in 4 patients was chronic middle ear disease found. In one of them, middle ear effusion disappeared following successful treatment of sinusitis. Our conclusion is that the levator veli palatini muscle has no significant function in the opening mechanism of the eustachian tube and must be considered as a velopharyngeal valve muscle only.