Mutation of the gene encoding human TTF-2 associated with thyroid agenesis, cleft palate and choanal atresia.

Congenital hypothyroidism occurs in one of every three to four thousand newborns, owing to complete or partial failure of thyroid gland development. Although thyroid hypoplasia has recently been associated with mutations in the thyrotropin (TSH) receptor, the cause of thyroid agenesis is unknown. Proteins including thyroid transcription factors 1 (TTF-1; refs 4,5) and 2 (TTF-2; refs 6,7) and Pax8 (refs 8,9) are abundant in the developing mouse thyroid and are known to regulate genes expressed during its differentiation (for example, thyroid peroxidase and thyroglobulin genes). TTF-2 is a member of the forkhead/winged-helix domain transcription factor family, many of which are key regulators of embryogenesis. Here we report that the transcription factor FKHL15 (ref. 11) is the human homologue of mouse TTF-2 (encoded by the Titf2 gene) and that two siblings with thyroid agenesis, cleft palate and choanal atresia are homozygous for a missense mutation (Ala65Val) within its forkhead domain. The mutant protein exhibits impaired DNA binding and loss of transcriptional function. Our observations represent the first description of a genetic cause for thyroid agenesis.

Thyrotropin receptor transcripts in human adipose tissue.

Thyroid associated ophthalmopathy (TAO) is generally considered to have an autoimmune pathogenesis but the target antigen has yet to be identified. It is most frequently associated with Graves' disease and there is some logic in assuming that the same antigen, the thyrotropin receptor (TSHR), is the common link. Previous studies, mostly PCR based, aimed at investigating TSHR transcripts in the orbit, have yielded conflicting results, although there is circumstantial evidence for their presence in orbital fat. In this study, we have examined adult human adipose and muscle tissues from various locations, initially by PCR and subsequently by northern blot. We obtained the expected 610bp product in normal intestinal and orbital fat but not skeletal muscle, following two rounds of PCR amplification but only when reverse transcription used a TSHR specific primer. In northern blots, despite loading all of the RNA obtained from total normal orbital fat contents, TSHR transcripts were at the limit of detection and similarly for large samples of intestinal fat. The exception was RNA obtained from TAO orbital fat, in which TSHR transcripts of 4.6 and 1.7kb were clearly visible, as in the thyroid. We conclude that normal adult adipose tissues contain low levels of TSHR transcripts. In TAO, TSHR transcripts are elevated probably due to an increased number of cells, in particular of preadipocytes in orbital adipose tissue.

Surgical treatment of bile peritonitis in 24 dogs and 2 cats: a retrospective study (1987-1994).

OBJECTIVE: The purpose of this study was to determine the signalment, history, clinical signs, diagnosis, treatment, outcome, and factors affecting outcome of dogs and cats surgically treated for bile peritonitis. STUDY DESIGN: Retrospective study. ANIMALS OR SAMPLE POPULATION: Twenty-four dogs and two cats surgically treated for bile peritonitis. METHODS: The medical records of dogs and cats surgically treated for biliary effusions at the Ohio State University and Michigan State University between 1987 and 1994 were reviewed. Statistical analysis was performed to compare factors affecting outcome. RESULTS: The cause of the biliary effusion was determined in 24 animals, and resulted from disruption of the biliary tract secondary to trauma (n = 13) or necrotizing cholecystitis (n = 11). Determination of the bilirubin concentration of the abdominal effusion was the only diagnostic test that was 100% effective in diagnosing bile leakage before surgical intervention. The bilirubin concentration of the effusion was consistently at least two times higher than the serum bilirubin concentration. Bacteriologic culture and sensitivity revealed that a septic, biliary effusion was usually associated with multiple types of gram-negative bacteria. The overall survival rate was 50% (13 of 26). The peripheral white blood cell count was significantly lower in survivors (mean 20,608/uL) compared with nonsurvivors (mean 35,712/uL). The immature neutrophil count was also significantly lower in survivors (mean 686/uL) than in nonsurvivors (4,852/uL). Only 27% (3 of 11) of the animals with a septic biliary effusion survived. In contrast, 100% (6 of 6) of the animals in which no bacteria were isolated from the abdominal effusion survived. Open abdominal drainage was not a successful treatment for 7 of 9 animals with septic biliary effusions. Survival was not significantly affected by the distribution of the peritonitis, cause of biliary effusion, or duration of clinical signs before surgical intervention. CONCLUSIONS: Patients with sterile biliary effusions have a much lower mortality rate than those with septic biliary effusions. The successful treatment of sterile biliary effusions does not require open abdominal drainage, and is not affected by the duration of the effusion. CLINICAL RELEVANCE: This retrospective study provides information that may aid the surgeon in the diagnosis and treatment of bile peritonitis.

Peritoneal dialysis in dogs and cats: 27 cases (1976-1987).

The records of 25 dogs and 2 cats treated with peritoneal dialysis during an 11-year period were evaluated. The indications for peritoneal dialysis were acute renal failure in 21 animals, chronic renal failure in 5 animals, and azotemia of undetermined cause in 1 animal. Peritoneal dialysis resulted in a significant (P less than 0.05) decrease in serum urea nitrogen concentration in 19 of the dogs and a significant (P less than 0.05) decrease in serum creatinine in 20 dogs. The most common complication of peritoneal dialysis was hypoalbuminemia (11 animals affected). Other common complications were dialysate retention/catheter obstruction (8 animals), peritonitis (6 animals), hypochloremia (6 animals), and subcutaneous leakage of dialysate (6 animals). Twelve dogs and 2 cats died during treatment, 6 dogs were euthanatized, and 1 dog was lost to follow-up evaluation. The remaining 6 dogs survived and were discharged from the hospital after successful peritoneal dialysis. On the basis of the results of this study, the authors concluded that peritoneal dialysis, although associated with a high complication rate, was a successful technique for reducing azotemia in dogs with acute and chronic renal failure. Survival rates were poor because of the severity of the underlying renal diseases.

Pulmonary abscess caused by a Mycoplasma sp in a cat.

A Mycoplasma sp was isolated from an abscess of the right cranial lung lobe in a 6-year-old Persian cat. The cat responded well to resection of the affected lung lobe and to a 2-week course of tylosin treatment.

Cyclic hematopoiesis associated with feline leukemia virus infection in two cats.

Cyclic oscillations in the numbers of blood elements were detected in 2 cats with FeLV infection. Periodic neutropenia, followed by a return to normal neutrophil numbers, was detected in both cats. The mean cycle duration was 11.8 days, with a range of 8 to 14 days. Just before the return of normal neutrophil numbers, monocytosis developed. In 1 cat, cyclic variations in the number of reticulocytes and platelets also were detected. Bone marrow aspirates obtained during periods of neutropenia had a predominance of progranulocytes in the myeloid cell line. myeloid hyperplasia, with numerous segmented neutrophils, was seen in bone marrow aspirates obtained during periods of normal neutrophil numbers. Oral administration of prednisolone resulted in cessation of the cyclic oscillations of blood elements in 1 cat. Cyclic hematopoiesis appeared to be another non-neoplastic manifestation of FeLV infection.