New gene for autosomal recessive non-syndromic hearing loss maps to either chromosome 3q or 19p.

Autosomal recessive non-syndromic hearing loss (ARNSHL) is the most common form of prelingual inherited hearing impairment. A small consanguineous family with this disorder was ascertained through the Institute of Basic Medical Sciences in Madras, India. Conditions such as rubella, prematurity, drug use during pregnancy, perinatal trauma, and meningitis were eliminated by history. Audiometry was performed to confirm severe-to-profound hearing impairment in affected persons. After excluding linkage to known DFNB genes, two genomic DNA pools, one from the affected persons and the other from their non-affected siblings and the parents, were used to screen 165 polymorphic markers evenly spaced across the autosomal human genome. Two regions showing homozygosity-by-descent in the affected siblings were identified on chromosomes 3q21.3-q25.2 and 19p13.3-p13.1, identifying one (or possibly both) as the site of a novel ARNSHL gene.

Localization of a novel gene for nonsyndromic hearing loss (DFNB17) to chromosome region 7q31.

Autosomal recessive nonsyndromic hearing loss (ARNSHL) is the most common form of hereditary hearing impairment (HHI). To date, 16 different loci have been reported, making ARNSHL an extremely heterogeneous disorder. One of these loci, DFNB4, was mapped to a 5-cM interval of 7q31 in a large Middle-Eastern Druze family. This interval also includes the gene for Pendred syndrome. We report on three new families with HHI from the Madras region of southern India that demonstrate linkage to 7q. Their pedigrees are compatible with autosomal recessive inheritance. Furthermore, the largest family identifies a novel locus (DFNB17) telomeric to the DFNB4 and Pendred intervals. A 3-cM region of homozygosity by descent between markers D7S486 and D7S2529 is present in all affected individuals in this family and generates a multipoint LOD score of 4.24. The two other families map to the previously reported DFNB4 region but have insufficient power to attain significant LOD scores. However, mutations in the Pendred syndrome gene are present in one of these families.

Incidence of vocal fold paralysis in infants undergoing ligation of patent ductus arteriosus.

BACKGROUND: Left-sided, iatrogenic vocal fold paralysis (IVFP) secondary to recurrent laryngeal nerve injury is a potential complication of ligation of patent ductus arteriosus (PDA). This study investigates specific risk factors associated with IVFP. METHODS: A retrospective chart review was performed for all infants 12 months of age or younger who underwent operative PDA closure at the University of Iowa from January 1, 1991, to January 1, 1994. RESULTS: Six cases of IVFP were diagnosed in 68 infants who underwent PDA ligation using clips (52.9%), suture ligatures (41.2%) or both (5.9%). Compared with infants without postoperative IVFP, infants with IVFP were smaller at birth (0.9 versus 2.3 kg; p < 0.001) and more premature (gestational age, 26.3 versus 33.8 weeks; p < 0.001), and were smaller (1.1 versus 3.4 kg; p < 0.001) and younger (31.9 versus 88.4 days; p < 0.001) at operation. Weight gain from birth to operation was significant only in infants without postoperative IVFP (p < 0.05). Although the overall incidence of IVFP in all infants undergoing PDA closure was 8.8%, five of the six cases (83.3%) of IVFP occurred in extremely low birth weight infants, ie, those weighing 1 kg or less at birth. Among the cohort of extremely low birth weight babies undergoing operation, the incidence of IVFP was 22.7%. Iatrogenic vocal fold paralysis was associated only with the use of surgical clips; however, because clips were used in 90.9% of the premature infants requiring PDA ligation, it was not possible to establish whether suture ligature is a safer technique. CONCLUSIONS: This study demonstrates that the single major risk factor for IVFP after ligation of PDA is birth weight less than 1 kg.

Vocal fold paralysis in infants twelve months of age and younger.

Seventeen cases of unilateral or bilateral vocal fold paralysis were diagnosed in infants younger than 12 months from 1991 to 1994 at the University of Iowa Hospitals and Clinics. Eight (47%) children with left vocal fold paralysis had a history of prior thoracic surgery--two to repair complex congenital anomalies and six to ligate a patent ductus arteriosus. During the study period, a total of 81 patent ductus arteriosus ligations were performed, yielding a 7.4% postoperative incidence of vocal fold paralysis. Seven (41%) children had idiopathic vocal fold paralysis (3 right, 1 left, 3 bilateral). Two (12%) children had VFP caused by central nervous system pathology (1 right, 1 bilateral). Tracheotomy was not required in any case. Prognosis for vocal fold paralysis varied with cause. With left vocal fold paralysis caused by thoracic surgery, no improvement was noted after an average follow-up of 6 months; with idiopathic vocal fold paralysis infants improved within an average of 6 weeks of diagnosis; with vocal fold paralysis caused by central nervous system pathology, treatment of the underlying condition was followed by return of vocal cord function. Irrespective of cause, the morbidity associated with vocal fold paralysis is minimal. Although tracheotomy is not required, careful airway observation is important. Differences and similarities of these results with other studies are discussed.

Appropriateness of magnetic resonance imaging in sudden sensorineural hearing loss.

Idiopathic sudden sensorineural hearing loss is an enigmatic condition of unknown cause. Although the treatment for sudden sensorineural hearing loss is controversial, the evaluation for a cause should not be. All patients are evaluated with a complete history, physical examination, audiologic examination, and blood draw to evaluate complete blood count, general chemistry screen, thyroid function test results, erythrocyte sedimentation rate, and fluorescent treponemal antibody absorbance. Magnetic resonance imaging with gadolinium contrast is essential in the evaluation of idiopathic sudden sensorineural hearing loss, even if there is a complete response to either treatment or no treatment. During the last year we treated 16 patients for idiopathic sudden sensorineural hearing loss with our protocol of intravenous dextran/Hypaque or oral high-dose steroids. Fifteen patients were evaluated immediately before treatment with a magnetic resonance imaging scan. An additional patient had been treated successfully with high-dose steroids at an outside institution and came in for an evaluation. Of these 16 patients, 3 (18.75%) were found to have significant pathologic conditions on magnetic resonance imaging scan. The patient who had been treated successfully on the outside was noted to have a 5-mm intracanalicular acoustic neuroma, the second patient was found to have a multiple sclerosis lesion at the level of the superior olive, and the third patient, who had had a normal magnetic resonance imaging scan 18 months previously, was now found to have a large 4- to 5-cm meningioma in the cerebellopontine angle. We believe it is essential that all patients with idiopathic sudden sensorineural hearing loss be evaluated at some point during their treatment with a magnetic resonance imaging scan with gadolinium contrast.

Passage to India: the search for genes causing autosomal recessive nonsyndromic hearing loss.

Hereditary hearing impairment affects approximately 0.05% of all children born in the United States. It is most commonly autosomal recessive, nonsyndromic, and monogenic [autosomal recessive nonsyndromic hearing loss (ARNSHL)]. Although the number of disease loci is not known, some estimates exceed 100. Using a strategy of homozygosity mapping to localize ARNSHL genes by screening consanguineous families for chromosomal regions that are homozygous by descent, we have mapped several genes in multiplex, nuclear, consanguineous families in Tamil Nadu, India. From the mean frequency of the ARNSHL genes in this population, the total number of disease genes is estimated to be 57.

The evolution of the Hughes tarsoconjunctival flap for the lower eyelid reconstruction.

The Hughes tarsoconjunctival flap was initially described in 1937. This flap is best used for reconstructing full-thickness defects involving the central portion of the lower eyelid. The evolution of this flap over the last 60 years is outlined. Several important modifications are presented; these modifications lead to decreased donor-site morbidity and improved recipient site outcome.

A simplified algorithm for the use of Z-plasty.

For the neophyte, the Z-plasty maneuver can be a surgical procedure veiled in intrigue. The theoretical mechanics of Z-plasty geometry are described, establishing that the new length of the central limb in a 60-degree Z-plasty is square root(3) of its original length. Factors such as skin tension, flap thickness, and flap location can, in application, distort the desired outcome. An algorithm is established that describes the indications and simplifies the execution of this technique.

Establishing cleft malformation surgery in developing nations: a model for the new millennium.

This three-stage model outlines a safe and effective method for achieving a local cleft board in a developing region. Maintaining local culture and guaranteeing patient safety are paramount concerns. Success is rooted in the constant assessment and recognition of negative forces, including misdirection and stagnation. The key factors are the identification of an interested local host and a source of funding as the site evolves toward independence. As of June 30, 2000, 501 cases had been performed independently and free of charge by the host healthcare provider in Nepal. There had been no major morbidities or mortalities.

Web-based medicine as a means to establish centers of surgical excellence in the developing world.

The growth of the Internet has provided a unique opportunity for rapid, global communication. Web-based medicine uses this technology to help surgeons in developing regions of the world gain direct access to recognized experts. This serves to empower local surgeons in the developing world through direct skill-transfer and encouraging academic pursuit. Web-based medicine follows the paradigm of a university without borders, therefore requiring exacting patient record keeping, monthly peer review, and continuing medical education of all its participants. All those who participate in Web-based medicine have undergone a credentialing process to guarantee that they possess adequate credentials. Patient confidentiality is strictly maintained. Web-based medicine also provides a follow-up strategy for medical volunteer groups who provide overseas services. Interplast, Inc., has administered a Web-based medicine site at http://www.wiredmd.com since July of 1999. A total of 767 cleft malformation cases performed locally by participating host surgeons in the developing world have been reviewed through the site. Additionally, 16 consultations have been posted and discussed by participating surgeons worldwide. Financing remains the major impediment to the globalization of this technology.

A classification schema for the vomeronasal organ in humans.

The vomeronasal organ is a chemoreceptive structure located at the base of the nasal septum with direct axonal connections to the accessory olfactory bulb in many terrestrial vertebrates. Pheromones presumably bind to the vomeronasal organ and exert behavioral or physiologic responses, thereby allowing chemical communication between animals of the same species. The presence and function of the vomeronasal organ in humans is debated. A phenotypic classification schema for the human vomeronasal organ is described and applied to 253 human subjects who underwent nasal examination. Of these subjects, only 6 percent possessed a vomeronasal organ with 64 percent unilateral and 36 percent bilateral in appearance. No difference existed in gender, age, or race between those subjects with or without a vomeronasal organ. There is no evidence supporting involutional senescence of this structure. Future investigations should use this phenotypic schema for the vomeronasal organ to allow accurate comparisons of study populations.

Invisible culprit: intralabyrinthine schwannomas that do not appear on enhanced magnetic resonance imaging.

Intralabyrinthine schwannoma (ILS) is an infrequent tumor that arises in isolation within the periphery of the temporal bone. Only 32 cases have been reported to date in the literature, of which 12 were discovered at autopsy. Prior to the advent of gadolinium-enhanced magnetic resonance imaging (Gd-MRI), only 1 ILS had been diagnosed preoperatively. However, after Gd-MRI became a common modality, 5 ILSs were imaged. Two additional cases are reported that were discovered during labyrinth-destructive surgery despite normal Gd-MRI findings. Possible explanations for and potential ramifications of nonenhancing ILS are discussed.

The postoperative incidence of small bowel obstruction following standard, open appendectomy and cholecystectomy: a six-year retrospective cohort study at Yale-New Haven Hospital.

The incidence of postoperative small bowel obstruction (SBO) after standard, open appendectomy and cholecystectomy was calculated during a six-year period at a university medical center hospital, which is the larger of two local, community hospitals. A cohort of 567 patients who underwent either a standard, open appendectomy or cholecystectomy from 1 October 1985 through 30 September 1986 was assembled. Of these patients, 182 (32.1%) were readmitted to the hospital prior to 1 October 1991 and thereby received follow-up. The time-related incidence of readmission to the hospital with a specific diagnosis of SBO as estimated by the Kaplan-Meier method was tabulated. This analysis revealed the following incidence rates of postoperative SBO: 10.7% following appendectomy during 64 months of follow-up (n = 41) and 6.4% following cholecystectomy during 67 months (n = 141). The Kaplan-Meier product-limit incidence of postoperative SBO was significantly different for standard appendectomy versus standard cholecystectomy (Breslow-Cox P value < 0.0277). This implies that the anatomical position and/or the likelihood of perioperative infection associated with open, abdominal surgery plays a significant role in subsequent adhesion formation and development of SBO. These data may be compared to laparoscopic techniques in future studies.

A five-residue sequence near the carboxyl terminus of the polytopic membrane protein lac permease is required for stability within the membrane.

The lac permease (lacY gene product) of Escherichia coli contains 417 amino acid residues and is predicted to have a short hydrophilic amino terminus on the inner surface of the cytoplasmic membrane, multiple transmembrane hydrophobic segments in alpha-helical conformation, and a 17-amino acid residue hydrophilic carboxyl-terminal tail on the inner surface of the membrane. To assess the importance of the carboxyl terminus, the properties of several truncation mutants were studied. The mutants were constructed by site-directed mutagenesis such that stop codons were placed at specified positions, and the altered lacY genes were expressed at a relatively low rate from plasmid pACYC184. Permease truncated at position 407 or 401 retains full activity, and a normal complement of molecules is present in the membrane, as judged by immunoblot analyses. Thus, it is apparent that the carboxyl-terminal tail plays no direct role in membrane insertion of the permease, its stability, or in the mechanism of lactose/H+ symport. In marked contrast, when truncations are made at residues 396 (i.e., 4 amino acid residues from the carboxyl terminus of putative helix XII), 389, 372, or 346, the permease is no longer found in the membrane. Remarkably, however, when each of the mutated lacY genes is expressed at a high rate by means of the T7 RNA polymerase system [Tabor, S. & Richardson, C. C. (1985) Proc. Natl. Acad. Sci. USA 82, 1074-1079], all of the truncated permeases are present in the membrane, as indicated by [35S]methionine incorporation studies; however, permease truncated at residue 396, 389, 372, or 346 is defective with respect to lactose/H+ symport. Finally, pulse-chase experiments indicate that wild-type permease or permease truncated at residue 401 is stable, whereas permease truncated at or prior to residue 396 is degraded at a significant rate. The results are consistent with the notion that residues 396-401 in putative helix XII are important for protection against proteolytic degradation and suggest that this region of the permease may be necessary for proper folding.

Pectoralis major myofascial flap: a valuable tool in contemporary head and neck reconstruction.

BACKGROUND: The pectoralis major myofascial (PMMF) unit is rapidly mobilized, reliable, and extremely useful in a number of clinical situations calling for vascularized soft-tissue coverage in the head and neck. Although free-tissue transfer has emerged as the preferred method of reconstruction for a large variety of defects in the head and neck, the pectoralis major muscle should be considered when vascularized soft-tissue coverage is required in this area. METHODS: A retrospective chart review of 24 PMMF flaps performed at the University of Iowa Hospitals and Clinics between January 1, 1991, and May 1, 1996, was undertaken. Outcomes were evaluated relative to accomplishing the established preoperative surgical goals. RESULTS: Utilization of the PMMF flap was grouped according to four primary indications: (1) protection of threatened great vessels or free flap vascular pedicles in situations of wound breakdown due to fistula or infection (7 cases); (2) vascularized soft-tissue coverage of great vessels or free-flap vascular pedicles and prevention of potential wound breakdown in surgical defects in which compromised healing was anticipated (7 cases); (3) closure of small pharyngeal defects (2 cases); or (4) vascularized coverage of the mandible following debridement for osteoradionecrosis (8 cases). The PMMF flap was 100% successful when the surgical goal was to protect exposed vascular structures and promote wound healing in the presence of fistula or infection. The PMMF flap was 100% successful in the protection of vascular structures and prevention of wound breakdown in cases where compromised wound healing was anticipated. The PMMF flap provided closure, and a vascularized surface for mucosalization, when used to primarily reconstruct small pharyngeal defects. The PMMF flap provided definitive closure in 5 of 8 (62.5%) cases of osteoradionecrosis of the mandible when it was used to invest the remaining mandibular bone. Three of 8 cases (37.5%) required further surgical management and were considered failures. An acceptable cosmetic outcome was obtained in women undergoing this procedure by using an inframammary incision. The preoperative goal of the PMMF flap procedure was met in 21 of 24 (87.5%) cases. There was a major complication rate of 12.5% as well as a minor complication rate of 12.5%. CONCLUSION: In cases requiring the protection of vital vascular structures from infection, salivary secretions or skin flap breakdown, the PMMF flap should be considered. The PMMF flap is an excellent reconstructive option in selected clinical situations, where vascularized soft-tissue coverage is required in the head and neck.

Localization of a gene for otosclerosis to chromosome 15q25-q26.

Among white adults otosclerosis is the single most common cause of hearing impairment. Although the genetics of this disease are controversial, the majority of studies indicate autosomal dominant inheritance with reduced penetrance. We studied a large multi-generational family in which otosclerosis has been inherited in an autosomal dominant pattern. Five of16 affected persons have surgically confirmed otosclerosis; the remaining nine have a conductive hearing loss but have not undergone corrective surgery. To locate the disease-causing gene we completed genetic linkage analysis using short tandem repeat polymorphisms (STRPs) distributed over the entire genome. Multipoint linkage analysis showed that only one genomic region, on chromosome 15q, generated a lod score >2.0. Additional STRPs were typed in this area, resulting in a lod score of 3.4. STRPs FES (centromeric) and D15S657 (telomeric) flank the 14. 5 cM region that contains an otosclerosis gene.

Construction of P1-derived artificial chromosome and yeast artificial chromosome contigs encompassing the DFNB7 and DFNB11 region of chromosome 9q13-21.

DFNB7 and DFNB11, two loci for autosomal recessive nonsyndromic hearing loss (ARNSHL), have been mapped to chromosome 9q13-21 in separate consanguineous families. Using a radiation hybrid map, we have determined the correct marker order in the DFNB7/11 region and have demonstrated that the DFNB11 locus resides within a redefined DFNB7 interval. The gene(s) responsible for ARNSHL at these loci resides within an approximately 1 cM interval bounded by markers D9S1806 (centromeric) and D9S769 (telomeric). A recently discovered Indian family confirms the new telomeric boundary. To assist in the identification and cloning of candidate genes, YAC and PAC contigs were constructed. A total of 19 YAC and 23 PAC clones were utilized to span the affected region and ensure double coverage throughout. Twenty-two previously published STSs and 21 new STSs were used to determine marker order and confirm the integrity of the contig. Using a positional cloning strategy we have identified three cochlear expressed genes that map to the DFNB7/11 interval.

An autosomal recessive nonsyndromic form of sensorineural hearing loss maps to 3p-DFNB6.

Autosomal recessive nonsyndromic hearing loss (ARNSHL) is the most common form of congenitally acquired inherited hearing impairment. Although numerous loci are believed to exist, only five have been identified. Using a pooled genomic DNA screening strategy, we have identified a sixth locus, DFNB6, on 3p in the interval bounded by D3S1619 and D3S1766.