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Biomedical subjects

P A Kirby

Publications and source records attributed to P A Kirby.

15 recordsLinked to original sources
PubMed2001

Intraoperative diagnosis of tanycytic ependymoma: pitfalls and differential diagnosis.

Smear preparations have become increasingly popular in the intraoperative assessment of central nervous system pathology. The cytological features of a histologically proven tanycytic ependymoma are presented with the pitfalls and differential diagnosis. The smear preparation showed a glial neoplasm composed of cells with long, bipolar glial processes and oval to spindle-shaped nuclei resembling those seen in pilocytic astrocytoma smears. The smear characteristics of an ependymoma usually show remarkably uniform round-to-oval nuclei, fluffy glial processes, and a perivascular nuclear-free zone (pseudorosetting). None of these features were present in our case. The accompanying frozen section showed a fascicular spindle-cell tumor that resembled a schwanomma, a commonly reported misinterpretation of the histology of tanycytic ependymomas on frozen sections. Careful attention to the radiological findings, the surgeon's impression, and the intraoperative smear preparation details should allow one to include this uncommon entity in the differential diagnosis of spinal neoplasms.

Adult↗
PubMed2001

p53 Mutations and microsatellite instability in ovarian cancer: Yin and yang.

OBJECTIVE: We tested the hypothesis that p53 frameshift mutations in ovarian cancer occur as a result of genomic instability rather than as a proximal cause of this process. STUDY DESIGN: Sequencing of the p53 tumor suppressor gene has been carried out on 305 ovarian, fallopian tube, and peritoneal cancers. Two groups of p53 null mutations were identified: (1) those caused by frameshift insertion or deletion mutations (n = 31) and (2) those caused by nonsense mutations (n = 28). As a control group 59 tumors with p53 missense mutations were selected by matching with the p53 null tumors on the basis of patient age at diagnosis, stage and grade of cancer, cancer site, and year of diagnosis. Microsatellite instability was determined from paired normal and tumor tissue deoxyribonucleic acid by means of the following different markers: D2S123, D5S346, D17S250, BAT25, and BAT26. Amplimers from polymerase chain reactions were evaluated on 7% polyacrylamide gels. RESULTS: The p53 null tumors were more likely to be of higher stage and grade. Fallopian tube cancers were more common (P =.02) in the p53 frameshift group. The overall incidence of microsatellite instability was 39%, 36%, and 25% for tumors with p53 frameshift nonsense and missense mutations (P =.30). Microsatellite instability was seen almost exclusively with ovarian cancer (P =.04). CONCLUSIONS: Microsatellite instability is a relatively common event in ovarian cancer and is dependent on marker selection. The p53 frameshift mutations do not appear to occur as a consequence of genomic instability.

Adult↗
PubMed2001

The p53 mutational spectrum associated with BRCA1 mutant ovarian cancer.

PURPOSE: Cancer-specific p53 mutational spectra have been identified. Data from murine models and human BRCA1-related hereditary breast cancers suggest that both unique and specific BRCA1-associated p53 mutations may be found in BRCA1-related ovarian cancers. EXPERIMENTAL DESIGN: The p53 mutational spectrum from ovarian cancers containing either somatic or germ-line BRCA1 mutations was compared with that of sporadic ovarian cancers defined as those diagnosed with a negative family history for breast/ovarian cancer in a three-generation pedigree. Tumor DNA was screened over exons 2-11 of the p53 gene by the PCR and single-strand confirmation polymorphism analysis of the amplimers. Cycle-based DNA sequencing from separate reactions was used to confirm p53 mutations. RESULTS: p53 gene mutations were detected in 42 of 86 sporadic ovarian cancers, compared with 13 of 15 cancers with somatic BRCA1 mutations (P = 0.007) and 16 of 20 cancers with germ-line BRCA1 mutations (P = 0.01). p53 null mutations were found in 31.4% of BRCA1 mutant cancers, compared with only 9.3% of the sporadic cancers (P = 0.002). The p53 mutational spectrum of germ-line BRCA1-related cancers was shifted toward transversions, frameshifts, and non-CpG transitions relative to the spectrum of sporadic ovarian cancers. Thirty-three unique ovarian cancer p53 mutations were sequenced. However, the specific p53 mutations in the BRCA1 mutant cancers were no more unique to this cohort than the p53 mutations of the sporadic cancers. CONCLUSIONS: Ovarian cancers containing somatic or germ-line BRCA1 mutations are uniformly accompanied by p53 dysfunction. This finding offers additional support to observations regarding the importance of p53/BRCA1 interactions in ovarian carcinogenesis.

BRCA1 Protein↗
PubMed2000

Defects of blastogenesis: counseling dilemmas in two families.

Three patients are described with defects of blastogenesis and predominantly midline defects. Two were sibs of whom the firstborn were female cephalothoracopagus-conjoined twins with multiple predominantly midline defects initially thought to be a sporadic occurrence. A subsequent brother presented with severe hydrocephalus, rhombencephalosynapsis, conotruncal defect, ambiguous genitalia, and unilateral pre-axial polydactyly; an autosomal recessive defect is postulated in this case. Patient 3 had hydrocephalus, small cerebellum, cleft lip and palate, and a large sacrococcygeal teratoma, the better differentiated part of which included ovarian tissue with primordial follicles. The latter may occur in incomplete twinning as a defect of blastogenesis. The mother had had a previous termination of a fetus with hydrocephalus from a different relationship. Counseling was difficult since no examinations were done on the previous fetus and no further investigations of this family could be obtained, but a genetic origin is suspected. Most defects of blastogenesis are sporadic; however, some cases have a genetic cause and ultrasound examinations should be offered in subsequent pregnancies.

Abnormalities, Multiple↗
PubMed2000

Hepatitis C virus (HCV) infection and cryoglobulinemia: analysis of whole blood and plasma HCV-RNA concentrations and correlation with liver histology.

The influence of cryoprecipitate (CP) on liver histology and peripheral titers of hepatitis C virus (HCV) RNA was evaluated for 115 patients with chronic hepatitis. Fifty-four patients had measurable CP levels whereas 61 did not. Assessment of liver biopsies for grade of fibrosis revealed that patients with CP had increased fibrosis (P <.001) and incidence of cirrhosis (P =.001) compared with those without CP. In contrast, there was not a significant difference in the inflammatory activity score between the 2 groups. HCV RNA in whole blood (WB) and plasma (Pl) was evaluated in patients with or without CP by end-point-limiting dilution titer. Among patients with CP, WB titers were significantly higher than Pl titers (P <.001); however, there was no difference in WB or Pl titers in patients without CP (P =.068). Histological activity and fibrosis scores of patients from either group were compared with peripheral viral titers of WB and Pl, percentage of CP, rheumatoid factor (RF) titer, and serum alanine transaminase (ALT). There were significant correlations between the amount of fibrosis and the percentage of CP and rheumatoid factor titer, yet neither of the latter parameters was correlated with inflammatory activity. These data suggest that patients with CP and chronic hepatitis owing to HCV are more likely to have progressive disease than patients without CP. Furthermore, the presence of CP in patients infected with HCV appears to influence the amount of virus detected in patient Pl, suggesting that WB assays may be more reliable for HCV-RNA quantitation in patients with CP.

Adult↗
PubMed1999

Spindle epithelial tumor with thymus-like differentiation (SETTLE) of the thyroid with prominent mitotic activity and focal necrosis.

Spindle epithelial tumor with thymus-like differentiation (SETTLE) is a rare, apparently low-grade spindle cell tumor of the thyroid gland occurring in young individuals and thought to be derived from thymic or branchial pouch remnants. Spindle epithelial tumor with thymus-like differentiation has little to no mitotic activity, and focal necrosis has been reported in one case. We present a case of SETTLE in a 29-year-old man that was initially evaluated by fine-needle aspirate biopsy and ultimately found to be consistent histologically with SETTLE. In this case, there were numerous mitotic figures among the spindle cells and focal necrosis. Spindle epithelial tumor with thymus-like differentiation has been considered to be a tumor of low malignant potential with metastases developing some years after diagnosis. This is the first case in which prominent mitotic activity and necrosis is reported perhaps representing an aggressive variant.

Adult↗
PubMed1998

RSH (Smith-Lemli-Opitz) syndrome: "severe" phenotype with ectrodactyly.

We describe the antenatal ultrasound findings of growth retardation, oligohydramnios, mesomelic limb shortness, and cardiac, renal, and hand defects in a fetus who was postnatally diagnosed as having RSH ("Smith-Lemli-Opitz") syndrome. An unusual finding was ectrodactyly of both hands.

Brain↗
PubMed1992

Systemic calciphylaxis presenting as a painful, proximal myopathy.

A renal transplant patient who presented with a painful, proximal myopathy due to systemic calciphylaxis is described. The myopathy preceded the characteristic skin and soft tissue necrosis. Systemic calciphylaxis should be considered in a dialysis or a renal transplant patient presenting with a painful proximal myopathy even in the absence of necrotic skin lesions.

Calciphylaxis↗
PubMed1983

Mineral content of the forearms of babies born to Asian and white mothers.

Vitamin D deficiency is common in pregnant Asian women. The effect of maternal vitamin D deficiency on fetal skeletal mineralisation was assessed by measuring the bone mineral content of babies born to 45 Asian women, 19 Asian women who had received 1000 units of vitamin D during the last trimester, and 12 white women. The mean cord blood concentrations of 25-hydroxy vitamin D in the three groups were 5.9 +/- SE 0.9 nmol/l (2.4 +/- SE 0.4 ng/ml), 15.2 +/- 3.2 nmol/l (6.1 +/- 1.3 ng/ml), and 33.4 +/- 3.6 nmol/l (13.4 ng/ml), respectively. Despite this wide variation in values there was no significant difference in the bone mineral content (as assessed by photon absorptiometry) of the forearms of babies born to these women. This suggests that mineralization of the fetal skeleton is not impaired in maternal vitamin D deficiency. Craniotabes (skull softening) was present in seven of the 64 Asian babies. The bone mineral content in these babies was not significantly different from that of babies without this sign, and craniotabes should not therefore be taken as an indication of a generalized impairment in skeletal mineralization.

Adult↗
PubMed1977

Non-linear bone loss in oophorectomized women.

Sequential bone loss in 37 women with bilateral oophorectomy was monitored by radiographic morphometry. The changes in mean width of the cortices of the 2nd, 3rd and 4th metacarpals of both hands were determined using a semiautomated computer-controlled morphometer. It was found that a significantly greater rate of decrease of mean cortical width occurred in those women first observed within three years of the artificial menopause than in the other members of the group.

Castration↗