Identities, frequencies and origins of TMC1 mutations causing DFNB7/B11 deafness in Pakistan.

Non-syndromic deafness is genetically heterogeneous. We previously reported that mutations of transmembrane channel-like gene 1 (TMC1) cause non-syndromic recessive deafness at the DFNB7/B11 locus on chromosome 9q13-q21 in nine Pakistani families. The goal of this study was to define the identities, origins and frequencies of TMC1 mutations in an expanded cohort of 557 large Pakistani families segregating recessive deafness. We screened affected family members for homozygosity at short-tandem repeats flanking known autosomal recessive (DFNB) deafness loci, followed by TMC1 sequence analysis in families segregating deafness linked to DFNB7/B11. We identified 10 new families segregating DFNB7/B11 deafness and TMC1 mutations, including three novel alleles. Overall, 9 different TMC1 mutations account for deafness in 19 (3.4%) of the 557 Pakistani families. A single mutation, p.R34X, causes deafness in 10 (1.8%) of the families. Genotype analysis of p.R34X-linked markers indicates that it arose from a common founder. We also detected p.R34X among normal control samples of African-American and northern European origins, raising the possibility that p.R34X and other mutations of TMC1 are prevalent contributors to the genetic load of deafness across a variety of populations and continents.

A novel mutation at the DFNA36 hearing loss locus reveals a critical function and potential genotype-phenotype correlation for amino acid-572 of TMC1.

We ascertained a North American Caucasian family (LMG248) segregating autosomal dominant, non-syndromic, post-lingual, progressive sensorineural hearing loss. The hearing loss begins in the second decade of life and initially affects high frequencies. It progresses to profound deafness at all frequencies by the fourth or fifth decade. The phenotype co-segregates with short-tandem repeat markers flanking the TMC1 gene at the DFNA36 locus on chromosome 9q31-q21. The affected individuals carry a novel missense substitution, p.D572H (c.G1714C), of the TMC1 gene. This mutation is at the same nucleotide and amino acid position as the only other reported DFNA36 mutation, p.D572N (c.G1714A). Our observations implicate a critical function for amino acid-572 for wild-type TMC1 function or the pathogenesis of DFNA36 hearing loss. The slower progression of hearing loss associated with p.D572H, in comparison with that caused by p.D572N, may reflect a correlation of DFNA36 phenotype with TMC1 genotype.

Transnasal bamboo foreign body lodged in the sphenoid sinus.

Transnasal sphenoid sinus foreign body is a rare condition. We report a very rare case of transnasal bamboo foreign body lodged in the sphenoid sinus without damages to the orbital wall or skull base. A 69-year-old man fell down onto a bamboo stick, which snapped after penetrating his face through the right nostril. CT demonstrated that the bamboo stick stuck into the middle meatus, penetrated the ethmoid sinus just medial to the lamina papyracea and reached to the sphenoid sinus. No abnormal findings were detected in the orbit or skull base. The foreign body was removed from the nasal cavity without any complication. The endoscope was useful for evaluating possible injuries in the orbit and skull base and confirming the absence of residual foreign bodies.

Relief of post-tonsillectomy pain by release of lidocaine from fibrin glue.

OBJECTIVES: Pain inevitably develops after resection of the palatine tonsil (tonsillectomy). Therefore, we applied a mixture of lidocaine and fibrin glue to the tonsillar fossae immediately after tonsillectomy and evaluated its analgesic effects. STUDY DESIGN: A prospective randomized trial. METHODS: Seventy-four consecutive patients who had undergone tonsillectomy by the same surgeon (S.K.) were allocated by the sealed envelope method into three groups. After routine tonsillectomy, the operation was terminated in group A (control group), but the bilateral tonsillar fossae were covered with 1 mL fibrin glue using CaCl2 as solution to dissolve thrombin in group B and using 4% lidocaine chloride instead of CaCl2 in group C. No significant difference was observed in age or sex among the three groups. Analgesic effects were evaluated in terms of the postoperative days required until the patient began to eat normally and the postoperative days on which the patient desired analgesic administration. RESULTS: The mean postoperative days until the patient began to eat normally were 4.22 in group A and 3.78 in group B, showing no significant difference, but 2.83 in group C, being significantly shorter (P <.05). The mean postoperative days on which analgesic administration was necessary were 4.56 in group A and 4.91 in group B, showing no significant difference, but 2.88 in group C, being significantly shorter (P <.05). CONCLUSION: This method can be readily performed, requires no special treatment, and appears to have adequate pain-relieving effects.

[Fatal pulmonary embolism developing after tympanoplasty: a case report and incidence of pulmonary embolism at Toyooka Hospital].

We report a case of fatal pulmonary embolism (PE) developing after tympanoplasty. A 69-year-old woman underwent type III tympanoplasty for a middle ear cholesteatoma under general anesthesia. Operating time was 3 hours 27 minutes and anesthesia lasted 5 hours 9 minutes. The next morning, 14 hours 5 minutes after returning to the recovery room, the patient lost consciousness while getting out of bed. Although consciousness recovered transiently, she went into shock with cardiopulmonary arrest. Heart beat was regained after resuscitation with artificial respiration and cardiac massage, but her blood pressure was unstable. Echocardiography revealed right ventricular overload and pulmonary hypertension. Because PE was suspected, thrombolytic therapy was conducted to stabilize hemodynamics. Enhanced computed tomography (CT) of the chest showed bilateral pulmonary thromboembolism. The patient died of hypoxic encephalopathy 23 days after PE onset. We have seen 40 cases of PE at our hospital in the last 70 months. Five patients developed PE after surgery with a postoperative occurrence rate of 0.03% (5/16, 277), and 3 of them died. Enhanced CT in 19 of 21 cases (90.5%) before or just after the start of therapy for PE was useful in establishing the diagnosis. Although PE is rare in the field of otolaryngology and head and neck surgery, it may develop rapidly after any type of surgery resulting in a fatal outcome. It is thus important to establish diagnosis early and prevent such serious complications.

A case report of FSH-producing nasal ectopic pituitary adenoma extending to the frontal cranial fossa.

We report the first case of an ectopic pituitary adenoma in the nasal cavity that produced follicle-stimulating hormone (FSH). A 60-year-old man complaining of left nasal bleeding had a polypoid tumor in the left nasal cavity. Findings of computed tomographic scanning and magnetic resonance imaging showed that the tumor originated from the olfactory cleft, occupied the nasal cavity, and extended to the frontal cranial fossa. Results of histologic examination suggested ectopic pituitary adenoma. Magnetic resonance imaging results showed the pituitary gland to be normal. Electron microscopy findings demonstrated a large number of secretory granules in the tumor cells that were positive for FSH on immunohistochemical analyses. Serum gonadotropin levels were normal, and no clinical signs of hypersecretory syndrome were noted. The above findings led us to establish the diagnosis of FSH-producing ectopic pituitary adenoma. The patient underwent craniofacial resection of the tumor followed by an uneventful recovery. The pathologic findings and clinical course of the case were comparable to those of FSH-producing adenomas arising from the pituitary gland.

Methanol stimulates the colony-formation rate in a human hepatoma cell line (HLE).

Effects of methanol on colony-formation of human hepatoma cells were investigated. Among five human hepatoma cell lines (Hep G2, HLE, HuH-6, HuH-7, and PLC/PRF/5), only HLE cells showed enhanced colony formation due to methanol. The effective concentrations of methanol were around 1%. The enhancement occurred in a greater degree when the cells were seeded in the culture medium containing methanol than when methanol was added 24h after the cells were seeded. Methanol itself, however, did not enhance the cell proliferation.