Australian Cattle Dogs with Neuronal Ceroid Lipofuscinosis are Homozygous for a CLN5 Nonsense Mutation Previously Identified in Border Collies.

BACKGROUND: Neuronal ceroid lipofuscinosis (NCL), a fatal neurodegenerative disease, has been diagnosed in young adult Australian Cattle Dogs. OBJECTIVE: Characterize the Australian Cattle Dog form of NCL and determine its molecular genetic cause. ANIMALS: Tissues from 4 Australian Cattle Dogs with NCL-like signs and buccal swabs from both parents of a fifth affected breed member. Archived DNA samples from 712 individual dogs were genotyped. METHODS: Tissues were examined by fluorescence, electron, and immunohistochemical microscopy. A whole-genome sequence was generated for 1 affected dog. A TaqMan allelic discrimination assay was used for genotyping. RESULTS: The accumulation of autofluorescent cytoplasmic storage material with characteristic ultrastructure in tissues from the 4 affected dogs supported a diagnosis of NCL. The whole-genome sequence contained a homozygous nonsense mutation: CLN5:c.619C>T. All 4 DNA samples from clinically affected dogs tested homozygous for the variant allele. Both parents of the fifth affected dog were heterozygotes. Archived DNA samples from 346 Australian Cattle Dogs, 188 Border Collies, and 177 dogs of other breeds were homozygous for the reference allele. One archived Australian Cattle Dog sample was from a heterozygote. CONCLUSIONS AND CLINICAL IMPORTANCE: The homozygous CLN5 nonsense is almost certainly causal because the same mutation previously had been reported to cause a similar form of NCL in Border Collies. Identification of the molecular genetic cause of Australian Cattle Dog NCL will allow the use of DNA tests to confirm the diagnosis of NCL in this breed.

Characterization of the thyroid Na+/I- symporter with an anti-COOH terminus antibody.

The Na+/I- symporter (NIS) is the plasma membrane protein that catalyzes active I- transport in the thyroid, the first step in thyroid hormone biogenesis. The cDNA encoding NIS was recently cloned in our laboratory and a secondary structure model proposed, suggesting that NIS is an intrinsic membrane protein (618 amino acids; approximately 65.2 kDa predicted molecular mass) with 12 putative transmembrane domains. Here we report the generation of a site-directed polyclonal anti-COOH terminus NIS antibody (Ab) that immunoreacts with a approximately 87 kDa-polypeptide present in membrane fractions from a rat thyroid cell line (FRTL-5). The model-predicted cytosolic-side location of the COOH terminus was confirmed by indirect immunofluorescence experiments using anti-COOH terminus NIS Ab in permeabilized FRTL-5 cells. Immunoreactivity was competitively blocked by the presence of excess synthetic peptide. Treatment of membrane fractions from FRTL-5 cells, Xenopus laevis oocytes, and COS cells expressing NIS with peptidyl N-glycanase F converted the approximately 87 kDa-polypeptide into a approximately 50 kDa-species, the same relative molecular weight exhibited by NIS expressed in E. coli. Anti-NIS Ab immunoprecipitated both the NIS precursor molecule (approximately 56 kDa) and the mature approximately 87 kDa form. Furthermore, a direct correlation between circulating levels of thyroid-stimulating hormone and NIS expression in vivo was demonstrated.

Streptococcal gangrene of the head and neck: a case report and review of the literature.

Necrotizing bacterial infections that occur in the head and neck are exceedingly rare and are often associated with a group A beta-hemolytic streptococcus (Streptococcus pyogenes). The disease is associated with soft tissue necrosis and vascular thrombosis. There appears to be an increasing incidence of hyperaggressive beta hemolytic streptococcal infections associated with high mortality rates. We report the survival of an otherwise healthy patient who developed a flu-like illness followed by a rapidly progressive toxic systemic illness associated with subtotal facial soft tissue necrosis down to bone. The recent literature related to this necrotizing bacterial infection is reviewed. Otolaryngologists must be aware of this entity since survival depends upon aggressive early wound management and high-dose intravenous antibiotics.

Staphylococcus aureus nasal carriage in patients with rhinosinusitis.

Toxic shock syndrome has been associated with rhinologic surgery and medical devices, and it has been linked to a circulating exotoxin of a toxogenic strain of Staphylococcus aureus. One hundred forty patients with rhinosinusitis were studied. Nasal cultures were obtained. The microbiological characteristics are described. The carrier rate for Staphylococcus aureus was 35%. Thirty percent of patients selected for surgery were Staphylococcus aureus carriers. Toxin-capable isolates were identified in 40% of those tested. Users of cocaine, topical decongestants, and steroid sprays had a statistically higher rate of Staphylococcus aureus carriage compared to nonusers. It is hoped that by identifying the population at risk and defining the factors associated with the development of toxic shock syndrome, a cogent policy of prevention can be established.

Otogenic Münchausen syndrome.

Münchausen syndrome is uncommon in otolaryngology. Self-induced otitis externa has rarely been reported, and nothing is known concerning the true incidence of feigned vertigo. We present a patient who has been hospitalized several times and who has undergone ear surgery and treatment at different institutions along the eastern seaboard. She has suffered complications of therapy, including a profound sensorineural hearing loss, and was referred to us for surgical treatment of bizarre intractable otitis externa. The infection failed to respond to medical treatment and was ultimately found to be self-inflicted. Despite psychotherapy, the patient continues to seek further treatment at still other hospitals. This entity must be considered whenever a thorough evaluation fails to yield a reasonable organic diagnosis.

Antibiotic prophylaxis in vascular and interventional radiology: a rational approach.

The current medical and surgical literature was reviewed to determine the rationale for the use of prophylactic antibiotics during surgical procedures. Specifically, the experimental basis for the timing and duration of administration of the antibiotics was considered, and the expected pathogens in each type of surgery were cataloged. High-risk patient groups were identified. The risk of infectious complications during interventional radiologic procedures was reviewed, and appropriate choices of drugs were determined by analogy to the corresponding surgical procedures.

Toxic shock syndrome in nasal surgery: a physiochemical and microbiologic evaluation of Merocel and NuGauze nasal packing.

A prospective comparison of the microbiologic safety of Merocel versus NuGauze nasal packing in 119 surgical patients is presented. Presurgical and postsurgical nasal cultures were obtained, analyzed, and compared. The importance of a preoperative nasal culture isolate of Toxic Shock Syndrome Toxin Number 1 (TSST-1) producing Staphylococcus aureus in predicting postoperative toxigenic S. aureus isolation and Toxic Shock Syndrome symptomatology is demonstrated. An in vitro comparison of the ability of NuGauze and Merocel to amplify TSST-1 production was performed.

Reversible doxorubicin-induced congestive heart failure.

Doxorubicin hydrochloride is a chemotherapeutic agent highly effective against a wide range of neoplasms. A prime limiting factor to the administration of this drug is cardiotoxicity, which frequently develops when the cumulative dose exceeds 500 mg/sq m. Late cardiomyopathy, which may develop up to a year after therapy has been discontinued, was thought to be rapidly progressive and unresponsive to standard cardiac therapy. An adult who received 475 mg/sq m of doxorubicin hydrochloride experienced a cardiotoxic reaction one year after the completion of therapy. The patient responded to standard cardiac therapy. Resolution of left ventricular dysfunction was verified by echocardiography and radionuclide angiocardiography.

Erythropoietin-dependent primary pure erythrocytosis.

We investigated the pathogenesis of isolated erythrocytosis of 14 yr duration in a 28-yr-old man. The increase in red cell mass was attributed to increased erythropoietin production. An extensive search for recognized causes of secondary erythrocytosis was unrevealing. Family members were found to be hematologically normal. After reduction of the circulating red cell mass by 20%, erythropoietin activity nearly quadrupled, thus suggesting a normal erythropoietin response to phlebotomy. When bone marrow cells of the patient were cultured in plasma clots in the absence of added erythropoietin, endogenous erythroid colony formation was observed, a pattern previously believed to be specific for polycythemia vera bone marrow cells. Our observations suggest that the erythrocytosis in this individual is best explained by an abnormal "servoregulatory" mechanism of erythropoietin production. In addition, this is the first instance in which the rule that endogenous erythroid colony formation is correlated with the diagnosis of polycythemia vera has not held.