123rc/medical_text huggingface dataset:
The role of ras gene mutations in myeloproliferative disorders. Mutations in the ras genes frequently are found in myeloproliferative disorders. These abnormalities have prognostic significance in the myelodysplastic syndromes, but their clinical importance in other hematopathic states remains unclear. The study of this gene in leukemic conditions is providing insights into the genetic pathways leading to leukemic progression.
Ki67 index and S-phase fraction in human breast carcinomas. Comparison and correlations with prognostic factors. In a prospective study of 148 consecutive breast adenocarcinomas, proliferative indices of the same surgical tumor sample were performed by immunohistologic staining (Ki67 index) with the use of the Ki67 monoclonal antibody, which binds to a nuclear antigen only expressed in cycling cells, and by flow cytometry-derived S-phase fraction (SPF). Measurable Ki67 and SPF indices were obtained in 142 cases and 99 cases, respectively, and in 96 cases by both methods. In aneuploid tumors, a significant but low (P less than 0.05, r = 0.3) relationship was observed between Ki67 index and SPF. When compared with clinical, pathologic, and biochemical parameters these two proliferative indices were shown to be associated with nuclear grading and mitotic index. Additionally, correlations were observed between Ki67 index and node involvement (P less than 0.02) and between SPF and estrogen receptors (P = 0.002). These results show that (1) proliferative indices are obtained in 96% of surgical samples with Ki67 versus 67% with SPF and that (2) Ki67 index and SPF may provide complementary data with respect to prognosis.
Circadian variation in onset of acute ischemic stroke. A circadian pattern for the onset of myocardial and cerebral infarction has been identified. To evaluate this phenomenon further, we analyzed prospectively collected data from 151 patients with acute ischemic stroke. The number of strokes per 6-hour period were the following: midnight to 6 AM, 20 (13%); 6 AM to noon, 86 (57%); noon to 6 PM, 21 (14%); and 6 PM to midnight, 24 (16%). This pattern was not affected by previous use of aspirin. The most frequent time of onset was 6 AM to noon for all subgroups of ischemic stroke: small artery, 71%; cardioembolic, 62%; large artery atherothrombotic, 57%; large artery atheroembolic, 46%; and "other" or unknown cause, 40%. We also investigated the time between awakening and stroke onset in 145 patients and found that 24% of ischemic strokes occurred within the first hour after awakening. Our data demonstrate that an early morning peak exists for all subtypes of stroke. Our data also suggest that the most critical period is the first hour after awakening.
Treatment of high-risk solid tumors of childhood with intensive therapy and autologous bone marrow transplantation. Autologous bone marrow transplantation (ABMT) allows delivery of intensive, marrow-ablative chemotherapy or chemoradiotherapy to children with high-risk solid tumors. Results from several studies of neuroblastoma suggest that outcome is improved by ABMT; however, relapses can occur months to years after complete clinical remission. Other high-risk tumors including peripheral neuroepithelioma, Ewing's sarcoma, rhabdomyosarcoma, Wilms' tumor, and brain tumors also appear to be responsive to intensive marrow-ablative therapy, although few studies have been reported. For tumors that can metastasize to marrow, a sensitive method is necessary for detecting tumor cell contamination. Immunocytologic analysis with monoclonal antibodies can identify one neuroblastoma cell per 10(5) normal marrow cells; this method also is applicable to other tumors with appropriate antibodies. Ex vivo removal (purging) of tumor cells decreases the probability of infusing tumorigenic cells with the ABMT. There is considerable experience in tumor detection and purging for neuroblastoma, but little has been done for other childhood solid tumors. Future investigations of ABMT will aim to further increase disease-free survival by intensifying induction and marrow-ablative regimens and by developing therapies to be given after ABMT that are directed at minimal residual disease. As pilot investigations mature, the efficacy of ABMT and conventional chemotherapy will be compared in multi-institution randomized studies.
Penetrating trauma involving the innominate artery. Penetrating trauma involving the innominate artery is uncommon. Few surgeons have experience with this injury. A successfully managed case of penetrating innominate artery trauma is summarized and the literature reviewed.
Effects of 1.32-micron Nd-YAG laser on brain thermal and histological experimental data. Considering that the 1.32-microns Nd-YAG laser should have physicothermal properties close to those of the CO2 laser, a series of experiments were conducted on rat cortex (N = 51). Three laser wavelengths were compared: CO2 laser (10.6 microns), 1.06-microns Nd-YAG, and 1.32-microns Nd-YAG lasers. For each shot, temperature measurements were recorded with an infrared thermographic videocamera. The digitized signals were figured as thermal profiles and temperature developments. Ninety-five shots were correctly studied and analyzed: CO2, N = 29; 1.06-microns Nd-YAG, N = 20; 1.32-microns Nd-YAG, N = 46. The histological lesions produced by these three lasers were compared on animals killed 24 hours (N = 20), 8 days (N = 20), and 30 days (N = 5) after the laser impacts. For equivalent densities of energy, the depth of cortical necrosis was comparable for the CO2 laser (200-250 microns) and the 1.32-microns Nd-YAG laser (210-260 microns) whatever the date of death; the 1.06-microns Nd-YAG laser shots were responsible for much more important damage (400-550 microns). Because of its important absorption in water and nervous tissue, the authors consider the 1.32-microns Nd-YAG laser most suitable for neurosurgery, particularly because it is conducted through optic fibers, and therefore is easy to handle during neurosurgical procedures.
Evaluation of hepatocellular carcinoma aggressiveness by a panel of extracellular matrix antigens. Invasion and metastasis requires a series of interactions between malignant cells and the extracellular matrix (ECM). Antigen markers that relate to these interactions were evaluated for prognostic correlation in human hepatocellular carcinoma. Basement membrane type IV collagen (cIV), type IV collagenase (cIVase), laminin, and laminin receptors (LRs)--all ECM antigens previously proposed to be modulated in association with tumor aggressiveness--were immunohistochemically investigated in 30 cases of hepatocellular carcinomas (HCCs). The pattern of antigen expression was correlated with 1) 36 months' clinical follow-up and 2) the pathologic grade. As a means of estimating the proliferation fraction, an additional antigen, Ki67, was also studied in this series. There were major differences in the distribution of cIV and laminin, and in the quantity of cIVase-, LR-, and Ki67-positive cells associated with grade and prognosis. A smaller quantity of cIV and laminin and a higher number of cIVase-, LR-, and Ki67-positive cells were detected in the poorly differentiated compared with the well-differentiated HCCs. The tumors with lower immunoreactivity for cIV and laminin components accompanied by a higher number of cIVase-, LR-, and Ki67-positive cells fall into a group with the poorest overall survival (P less than 0.006). The panel of antigens is proposed as a useful prognostic tool for evaluating HCC tumor aggressiveness.
Screening of nineteen unrelated families with generalized resistance to thyroid hormone for known point mutations in the thyroid hormone receptor beta gene and the detection of a new mutation. Generalized resistance to thyroid hormone (GRTH) is a syndrome characterized by impaired tissue responsiveness to thyroid hormone. Two distinct point mutations in the hormone binding domain of the thyroid hormone receptor (TR) beta have recently been identified in two unrelated families with GRTH. One, Mf, involves a replacement of the normal glycine-345 for arginine in exon 7 and another, Mh, replaces the normal proline-453 for histidine in exon 8. To probe for the presence of the Mf and Mh defect in 19 unrelated families with GRTH, we applied separate polymerase chain reactions using allele-specific oligonucleotide primers containing the normal and each of the two mutant nucleotides at the 3'-position. A total of 24 affected subjects and 13 normal family members were studied. The mode of inheritance was dominant in 13 families, was unknown in 5 families, and was clearly recessive in 1 family in which only the consanguineous subjects were affected. Primers containing the substitutions specific for Mf and Mh amplified exons 7 and 8, respectively, only in affected members of each of the two index families. Primers containing the normal sequences amplified exons 7 and 8 of the TR beta gene in all subjects except affected members of one family. In this family with recessively inherited GRTH, neither exon could be amplified using any combinations of primers and DNA blot revealed absence of all coding exons. These results indicate a major deletion of the TR beta gene, including both DNA and hormone binding domains. Since heterozygous members of this family are not affected, the presence of a single normal allele is sufficient for normal function of the TR beta. These data also support the hypothesis that in the dominant mode of GRTH inheritance the presence of an abnormal TR beta interferes with the function of the normal TR beta. Distinct mutations are probably responsible for GRTH in unrelated families.
Stressful events and life satisfaction among elderly men and women. The purpose of this study was to examine the interrelationships among stressful events, domain-specific assessments of life satisfaction, and global evaluations of life satisfaction. This research was guided by two competing theoretical formulations. According to bottom-up theory, older adults first assess feelings of satisfaction within specific life domains that are based in part on the experiences (i.e., stressors) they encounter in these areas. The domain-specific views are subsequently synthesized to form an overall sense of satisfaction with life as a whole. In contrast, the top-down theory suggests that a person's ongoing sense of satisfaction with life as a whole predisposes him or her to assess satisfaction with specific domains in ways that are congruent with his or her initial sense of global life satisfaction. Analysis of data provided by older participants in a nationwide survey tends to support the bottom-up perspective.
Intrahepatic cholestasis due to hypersensitivity reaction to procainamide. Hypersensitivity reactions to procainamide involving liver dysfunction are rare. We describe a patient who developed liver dysfunction after procainamide administration, manifested by fever, jaundice, elevated bilirubin concentration, and alkaline phosphatase concentration. Hepatobiliary scintigraphy demonstrated good hepatic uptake of the radionuclide without movement from hepatic parenchyma. To our knowledge, this is the first reported case of procainamide-induced intrahepatic cholestasis as demonstrated by radionuclide hepatobiliary scintigraphy.
Local recurrence following abdominoperineal excision and anterior resection for rectal carcinoma. The aim of this retrospective study is to compare the outcome of abdominoperineal excision (APE) and anterior resection (AR) for rectal cancer in terms of local tumor recurrence. A further comparison has been carried out between hand-sewn and stapled anastomosis; 147 patients have been followed for at least 2 years: 69 after APE and 78 after AR, 40 being stapled. The following variables potentially related to the risk of recurrence were evaluated: age, grading, staging, and site of the tumor. An overall 2-year local recurrence rate of 11 percent after APE and 12 percent after AR was observed, whereas it was 13 and 11 percent following stapled and hand-sewn sutures, respectively. Both differences were not statistically significant. A similar local recurrence rate was noted after APE and AR when the patients were matched for Dukes' stage and grading of the lesion. A trend toward an increased risk of recurrence following AR (P = 0.07) was shown when comparing the two procedures if mid and upper rectal cancers were grouped together. In the patients with anastomotic leaks after AR, no increase of local recurrence was observed. In conclusion, AR is unlikely to be followed by an increased risk of local recurrence and, therefore, when oncologically indicated, may be considered the operation of choice in the treatment of rectal cancer, although the possible risk of its overuse should be taken into account.
Why does somatostatin cause gallstones? Long-term administration of the somatostatin analogue, octreotide, is complicated by gallstone formation. Somatostatin is known to inhibit hepatic bile secretion and gallbladder emptying. However, the effect of octreotide on gallbladder bile composition remains unknown. Therefore, we tested the hypothesis that octretide would alter hepatic bile composition and cause gallbladder stasis, thereby increasing gallbladder bile solute concentrations. Fourteen control prairie dogs received daily saline injections, whereas 10 animals received 1 micrograms of octreotide subcutaneously three times per day for 5 days. Cholecystectomy and common bile duct cannulation were then performed. Octreotide increased hepatic bile concentrations of bilirubin monoglucuronide (p less than 0.05), total bilirubin (p less than 0.05), and total protein (p less than 0.01). Rsa, an index of gallbladder stasis, was decreased (p less than 0.01) in the octreotide group. Gallbladder bile total calcium (p less than 0.05), bilirubin monoglucuronide (p less than 0.05), total bilirubin (p less than 0.01), total protein (p less than 0.05), and total lipids (p less than 0.05) were increased in the octreotide group. Animals receiving octreotide also had decreased hepatic (p less than 0.05) and gallbladder (p less than 0.001) bile pH. No differences in cholesterol saturation index were observed. These data suggest that in the prairie dog, octreotide (1) alters hepatic bile composition, (2) causes gallbladder stasis, and (3) increases gallbladder bile calcium, bilirubin, protein, lipid, and hydrogen ion concentrations. We conclude that octreotide causes alterations in gallbladder bile composition that increase the likelihood of cholesterol and calcium bilirubinate precipitation.
The growth inhibition of human breast cancer cells by a novel synthetic progestin involves the induction of transforming growth factor beta. Recent experimental work has identified a novel intracellular binding site for the synthetic progestin, Gestodene, that appears to be uniquely expressed in human breast cancer cells. Gestodene is shown here to inhibit the growth of human breast cancer cells in a dose-dependent fashion, but has no effect on endocrine-responsive human endometrial cancer cells. Gestodene induced a 90-fold increase in the secretion of transforming growth factor-beta (TGF-beta) by T47D human breast cancer cells. Other synthetic progestins had no effect, indicating that this induction is mediated by the novel Gestodene binding site and not by the conventional progesterone receptor. Furthermore, in four breast cancer cell lines, the extent of induction of TGF-beta correlated with intracellular levels of Gestodene binding site. No induction of TGF-beta was observed with the endometrial cancer line, HECl-B, which lacks the Gestodene binding site, but which expresses high levels of progesterone receptor. The inhibition of growth of T47D cells by Gestodene is partly reversible by a polyclonal antiserum to TGF-beta. These data indicate that the growth-inhibitory action of Gestodene may be mediated in part by an autocrine induction of TGF-beta.
Sensitivity of urinary quantitative immunocytology with monoclonal antibody 486 P3/12 in 241 unselected patients with bladder carcinoma. We investigated the sensitivity of quantitative immunocytology with our monoclonal antibody 486 P3/12 in 241 unselected patients with transitional cell carcinoma. Immunocytology yielded a sensitivity of 91.8%, 89.4% and 92.9% for grade 1, 2 and 3 tumors, respectively. Standard cytology was positive in 59.2%, 63.8% and 84.7%, respectively. Deoxyribonucleic acid flow cytometry, used in the first 69 patients, was positive in only 27.7%, 48.6% and 57.1%, respectively.
A study of the seasonal variation of migraine. Available evidence supports the contention that migraine involves a disturbance in serotonin function. Several parameters of serotonin function in humans have been found to vary seasonally and may underlie the seasonal fluctuations observed in many clinical neuropsychiatric phenomena that are thought to involve serotonin dysfunction. We therefore postulated that migraine headaches might also vary seasonally and examined the admissions to our hospital over a 20-year period with a primary diagnosis of migraine. Peak admissions were found to occur most frequently in the spring for females in comparison to males (p less than or equal to 0.04, chi-square). The implications of these findings are discussed.
Respiratory failure and unilateral caudal brainstem infarction. We report clinicotopographic correlations in 2 patients with central hypoventilation and unilateral infarct in the caudal brainstem. One patient had nearly complete loss of ventilation involving both automatic and voluntary components. He showed no ventilator response during a CO2 retention test (PaCO2 62 mm Hg, PaO2 82 mm Hg), while consciousness was preserved until death. The infarct involved the reticular formation, nucleus tractus solitarius, nucleus ambiguus, and nucleus retroambiguus on the right but spared the dorsal motor nucleus of the tenth cranial nerve, and sensory and corticospinal tracts. The second patient showed hypoventilation more selectively involving automatic responses (Ondine's curse). The infarct involved the medullary reticular formation and nucleus ambiguus but spared the nucleus tractus solitarius. We suggest that unilateral involvement of pontomedullary reticular formation and nucleus ambiguus is sufficient for generating loss of automatic respiration, while associated lesion of the nucleus tractus solitarius may lead to more severe respiratory failure involving both automatic and voluntary responses.
Castanospermine vs. its 6-O-butanoyl analog: a comparison of toxicity and antiviral activity in vitro and in vivo. Inhibitors of glycoprotein processing, such as castanospermine (1,6,7,8-tetrahydroxyoctahydroindolizine), have been shown previously to inhibit human immunodeficiency virus type 1 (HIV-1) with acceptable toxicity in cultured human cells. In prior experiments, we have tested the toxicity and antiviral efficacy of castanospermine in mice infected with the Rauscher murine leukemia virus (RLV). When compared with 3'-azido-3'-deoxythymidine (AZT, zidovudine), castanospermine was less effective and more toxic. Since the 6-O-butanoyl analog of castanospermine was previously found to have a more favorable activity profile than the parent compound against HIV-1 in cultured cells, we compared the antiviral efficacy of both compounds in parallel in vitro and in vivo in the RLV system. Plaque formation in the XC assay was inhibited with a 50% inhibitory concentration (IC50) of 2.4 microM for the 6-O-butanoyl analog of castanospermine, as compared to 9 microM for castanospermine. For both compounds, concentrations resulting in significant cytotoxicity were about ten times higher. Both compounds significantly decreased HIV-1 env-induced syncytium formation in a novel in vitro assay. In RLV-exposed mice, the 6-O-butanoyl analog showed no advantage over the parent compound: both curves for toxicity as well as antiviral efficacy were super-imposable. We conclude that the 6-O-butanoyl analog of castanospermine as well as castanospermine itself are active antiviral agents in mice and that prolonged oral administration is tolerable. However, in comparison to AZT, their antiviral activity profiles are less favorable.
Prevalence of carcinoma in situ and other histopathological abnormalities in testes from 399 men who died suddenly and unexpectedly. To determine the prevalence of carcinoma in situ of the testis and other testicular histopathological abnormalities in the general male population, we examined gonads from 399 men 18 to 50 years old who died suddenly and unexpectedly. No sign of malignancy was found in any of these gonads. However, 3 of the 399 men had been previously treated for testicular tumor or carcinoma in situ. Thus, the over-all prevalence of testicular neoplasia in the population studied was 0.8% (95% confidence limits 0.2 to 2.2%). This frequency is of the same magnitude as the lifetime risk of testicular cancer in the Danish male population. The median weights of the left and right testes were 19.3 and 19.7 gm., respectively. This difference was statistically significant (p = 0.00003). Thus, our study confirmed that on average the left testis is smaller than the right testis. The median weight of the gonads collected in our study was 0.9 gm. lower than the weight of testes examined 40 years earlier at the same department of forensic medicine. However, this difference was not statistically significant (p = 0.17). Microscopic examination of the gonadal specimens revealed that 83% of the men exhibited complete spermatogenesis, including late spermatids in all tubules. In the age group studied we found no age-related changes in testicular weight or in the proportion of tubules with degenerative changes, such as spermatogenic arrest, the Sertoli-cell-only syndrome or hyalinization.
Preoperative cytology and mammography in patients with single-duct nipple discharge treated by surgery. Microdochectomy has been the routine management for single-duct nipple discharge. Our review of 176 consecutive patients surgically treated between 1975 and 1988 revealed eight patients with in situ carcinomas and seven with infiltrative carcinomas. Seventeen patients had multiple papillomas, two had atypical hyperplasia and two had atypical epitheliosis. Case selection for surgery has recently been advocated. In our study, nipple discharge cytology was helpful in 67 per cent of cases with underlying malignant pathology. Mammography was found to be unreliable, alerting suspicion in only two of 15 cases.