Wound healing of canine vocal folds after phonosurgery

To develop phonosurgical techniques, the authors investigated the healing mechanisms of wounds on the vocal folds of canine larynges, and devised a method to cover the raw surfaces of such wounds. To restore the normal physiologic properties of the vocal folds, the normal mucosa should be removed as little as possible in phonosurgery. When the mucosa of the vocal folds is extensively removed by surgical intervention and the raw surface cannot be covered with the local pedicle flap, it should be covered with a free mucosal flap. We found an activated human fibrinogen concentrate, which is a biologic tissue adhesive, to be suitable for adhering a free mucosal flap to the raw surface by a laryngomicrosurgical approach.     

Frequent allelic losses and mutations of the p53 gene in human ovarian cancer.

The p53 gene on chromosome 17p is considered to be a tumor suppressor gene, and frequent mutations of the p53 gene have been found in a wide variety of human cancers. We examined 31 ovarian cancers for allelic losses and mutations of the p53 gene by polymerase chain reaction-single strand conformation polymorphism analysis as well as restriction fragment length polymorphism analysis. Allelic loss of the p53 gene was detected in 16 of 20 cases (80%). Mutations were detected in 9 of 31 cases (29%): 2 cases in exon 4; 5 cases in exons 5-6; and 2 cases in exons 7-8. In 8 of 9 cases, p53 mutations were accompanied by losses of the normal allele. These alterations of the p53 gene were commonly detected from stage I to stage IV. These results suggest that alterations of the p53 gene play an important role in the development of human ovarian cancers.     

Inhibition of the first ovulation and ovarian prostaglandin F2 alpha metabolism by danazol in rats.

The present study was conducted to investigate the mode of action of danazol by monitoring the first ovulation, serum luteinizing hormone (LH) levels and ovarian prostaglandin (PG) F2 alpha metabolism in pregnant mare serum gonadotropin (PMSG)-primed immature female rats. When danazol (750 mg/kg) was given p.o. once a day for 5 days (day 24-28), the occurrence of the first ovulation, the increase in capacity to form 13,14-dihydro-PGF2 alpha and PGF2 alpha levels induced by PMSG (5 IU) injected on day 26 were clearly inhibited on day 29. Danazol also markedly suppressed the LH surge occurring on day 28. Although the danazol-induced blockage of ovulation was restored by injection of human chorionic gonadotropin, the number of oocytes was significantly decreased as compared with that of controls. The present data indicate that the inhibitory actions of danazol on ovulation and ovarian PGF2 alpha metabolism may occur via some direct effects on the ovary in addition to the suppression of gonadotropin release from the pituitary gland.     

A case of aortoduodenal fistula following radiotherapy of retroperitoneal metastatic disease

A new case of aortoduodenal fistula was added to the five cases previously reported in the literature, in which malignancy and/or its treatments could be implicated. This 67 year-old woman, six years previously had been placed on a therapy including irradiation on the pelvis for cancer of uterine cervix. For this time she underwent a radiotherapy completed in a total dose of 55.6 Gy combined with hyperthermia and chemotherapy for retroperitoneal metastatic disease with excellent response. Three months later she had hematemesis followed by melena and deteriorated to hemorrhagic shock. Emergent aortography detected contrast extravasation from the aorta with subsequent opacification of the duodenum, and immediate intraaortic balloon occlusion was done, but she died soon thereafter. Postmortem examination revealed the fistula from the aorta just above the bifurcation to a 2 by 1.5 cm. area of the posterior wall of the third portion of the duodenum. Accentuated arteriosclerosis in locally irradiated portion of the aorta, obstruction of small arteries from organized thrombus and hyaline necrosis in the wall of the fistulous tract were defined without evidence of tumor invasion. Based upon the findings of the patient reported herein, radiation might be another possible etiologic factor in aortoduodenal fistula, as well as tumor invasion per se.     

Analysis of cefepime tissue penetration into human appendix.

Cefepime is a new extended-spectrum cephalosporin with gram-positive and gram-negative coverage including Staphylococcus aureus and Pseudomonas aeruginosa. We evaluated the drug's plasma, peritoneal fluid, and appendix tissue concentrations in patients with a postoperative diagnosis of perforated or gangrenous appendicitis. Patients 18 years of age or older were randomly assigned to receive either cefepime 2 g every 12 hours plus metronidazole 500 mg every 6 hours intravenously, or gentamicin 1.5 mg/kg plus clindamycin 900 mg every 8 hours intravenously. During surgery, appendix tissue, plasma, and peritoneal fluid samples were obtained, and frozen at -70 degrees C for high-pressure liquid chromatographic analysis. Thirty-five patients with perforated (26) or gangrenous (9) appendicitis had concentrations acceptable for analysis. The mean time between the administration of cefepime and the time of sampling (referred to as delta time) was 5.99 +/- 3.75 hours (mean +/- SD). The values for plasma (n = 34), tissue (n = 33), and peritoneal fluid (n = 25) concentrations were 16.27 +/- 21.87 micrograms/ml, 4.84 +/- 6.15 micrograms/g, and 14.4 +/- 22.84 micrograms/ml, respectively. The appendix tissue:plasma ratio was 0.66 +/- 0.52 and the peritoneal fluid:plasma ratio was 0.66 +/- 0.51. Spearman rank correlations indicated statistically significant correlations between plasma concentration (r = -0.889; p less than 0.0001), peritoneal fluid concentration (r = -0.783; p = 0.0002), and appendix tissue concentration (r = -0.704; p = 0.0016) versus delta time.(ABSTRACT TRUNCATED AT 250 WORDS)     

Relationship between Hippocampal Atrophy and Cognitive Dysfunction in Early Alzheimer-type Dementia

Background: We assessed the relationship between early cognitive dysfunction and morphologic changes in the brain, especially hippocampal atrophy, on MR images in Alzheimer‐type dementia (AID) patients to establish a technique for making an early clinical diagnosis of AID. Methods: The subjects of this study were 82 individuals who visited Kawase Neurology Clinic. They consisted of 41 ATD patients and 41 elderly individuals without dementia who visited the clinic for a neurological checkup or because of vertigo or numbness as age‐matched controls. As an index for hippocampal atrophy, the hippocampal‐intracranial ratio (HIR) was calculated. Discriminant analysis was performed using HIR results and the correct answer rate for recall and calculation items in Mini‐Mental State Examination (MMSE). Results: The mean ratio was significantly lower in the ATD patients than in the controls. This supports our previous results. The results of discriminant analysis with Mahalanobis generalized distance in the 41 controls and 22 ATD patients who scored 15 or higher. The sensitivity and specificity of HIR combined with the correct answer rate for recall and calculation items in MMSE were 95.5% and 95.1%, respectively, with an overall accuracy of 95.2%. Conclusion: HIR combined with the correct answer rate for recall and calculation items in MMSE allows for an early diagnosis of ATD.     

Coordinate phosphorylation of insulin-receptor kinase and its 175,000-Mr endogenous substrate in rat hepatocytes.

To investigate the early events in insulin signal transmission in liver, isolated rat hepatocytes were labeled with 32P, and proteins phosphorylated in response to insulin were detected by immunoprecipitation with anti-phosphotyrosine and anti-receptor antibodies and analyzed by sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis and autoradiography. In these cells, insulin rapidly stimulated tyrosine phosphorylation of the 95,000-Mr beta-subunit of the insulin receptor and a 175,000-Mr phosphoprotein (pp175). Both proteins were precipitated by anti-phosphotyrosine antibody, whereas only the insulin receptor was recognized with anti-insulin-receptor antibody. In the insulin-stimulated state, both pp175 and the receptor beta-subunit were found to be phosphorylated on tyrosine and serine residues. Based on precipitation by the two antibodies, receptor phosphorylation was biphasic with an initial increase in tyrosine phosphorylation followed by a more gradual increase in serine phosphorylation over the first 30 min of stimulation. The time course of phosphorylation of pp175 was rapid and paralleled that of the beta-subunit of the insulin receptor. The pp175 was clearly distinguished from the insulin receptor, because it was detected only when boiling SDS was used to extract cellular phosphoproteins, whereas the insulin receptor was extracted with either Triton X-100 or SDS. In addition, the tryptic peptide maps of the two proteins were distinct. The dose-response curve for insulin stimulation was shifted slightly to the left of the insulin receptor, suggesting some signal amplification at this step. These data suggest that pp175 is a major endogenous substrate of the insulin receptor in liver and may be a cytoskeletal-associated protein.(ABSTRACT TRUNCATED AT 250 WORDS)     

Variations in long- and middle-wavelength-sensitive opsin gene loci in crab-eating monkeys.

We analyzed variations in long (L)- and middle (M)-wavelength-sensitive opsin gene loci in crab-eating monkeys. Unlike humans, most monkeys have a single L and a single M gene. Two variant genotypes, one with only one opsin gene (dichromatic) and one with tandemly arrayed multiple genes, were also found in the monkeys. However, the frequency of the former was 0.47%, and that of the latter was 5% in the monkeys, while 2% and 66%, respectively, in Caucasian males. The two variants were found only in Java Island, Indonesia, and South Thailand, respectively. The data suggest that the frequency of each genotype is different among Old World primates.     

The significance of immunochemically staining calcitonin and CEA in fine-needle aspiration biopsy materials from medullary carcinoma of the thyroid

A review of ten surgical cases of medullary carcinoma of the thyroid (MCT) demonstrates the usefulness of establishing a preoperative cytological diagnosis through the immunochemical staining of calcitonin (CT) and CEA in fine-needle aspiration (FNA) biopsy smears. If MCT is suspected after routinely performing May-Grünwald-Giemsa stained cytology of an FNA biopsy in the outpatient clinic, then CT and CEA staining is recommended for confirmation of MCT. The advantages of this immunochemical staining include that it can be carried out in the outpatient clinic within one day and also that it is much less costly than measuring serum CT and CEA.