123rc/medical_text huggingface dataset:
Effects of hydralazine and prostaglandin E1 on regional myocardial function in the ischemic canine heart. The effects of hydralazine and prostaglandin E1 on regional myocardial function were studied in dogs. Sixteen dogs were randomly assigned to one of two drug treatment groups of eight dogs each. The first group (G1) was treated with 0.4 mg/kg hydralazine administered as a bolus. The second group (G2) received prostaglandin E1 given as an infusion for a total dose of 0.8 micrograms/kg. Regional myocardial function was assessed through the measurement of myocardial segment shortening during systole. We call this index percent systolic shortening (%SS). An ischemic heart preparation was created by partial occlusion of coronary blood flow. The degree of induced ischemia was determined by following the reduction in %SS. Hydralazine reduced %SS of the ischemic myocardium while increasing the cardiac index, stroke volume index, and coronary blood flow. Prostaglandin E1 increased %SS, cardiac index, and stroke volume index in the ischemic heart preparation. Hydralazine, therefore, induced dissociation between global ventricular function and regional myocardial function whereas prostaglandin E1 did not. The present findings emphasize that evaluation of vasoactive drugs should consider their effects on regional myocardial function as well as on global hemodynamics.
Miliary tuberculosis presenting as hepatic and renal failure. A 67-year-old man developed hepatic and renal failure over a six-day period. Despite full supportive measures, he died on his 11th day of hospitalization with fulminant DIC and hepatic, renal, and respiratory failure. Postmortem examination revealed acid-fast bacilli in virtually all organ systems. Miliary tuberculosis should be considered as a potentially treatable cause of hepatic failure.
Amplification by the polymerase chain reaction of hypervariable regions of the human genome for evaluation of chimerism after bone marrow transplantation. We combined the polymerase chain reaction (PCR) with oligonucleotide hybridization as a novel and sensitive technique to evaluate posttransplant chimerism. Specific oligonucleotides for hybridization were synthesized homologous to tandemly repetitive core sequences of regions with a variable number of tandem repeats (VNTRs). Polymorphisms at such loci result from allelic differences in the number of repeats. Primers flanking the repeat region of each of the corresponding VNTRs were used for amplification. Recipient and donor pretransplant DNA and recipient posttransplant DNA were amplified. The resultant fragments were analyzed after gel electrophoresis either by hybridization in-gel or after Southern transfer. To confirm our findings, we also performed standard assays of restriction fragment length polymorphisms (RFLPs). Evaluation of 13 selected cases indicated mixed chimerism (4), complete chimerism (5), recurrence of leukemia (2), and endogenous repopulation of hematopoiesis (2) after marrow transplantation. Sensitivity of the method was determined by mixing various proportions of recipient and donor DNA; the limit of detection of the minor component in a mixture was 0.1%. PCR data correlated with RFLP data in all cases except two in which PCR proved more sensitive than RFLP. PCR amplification of VNTRs combined with oligonucleotide hybridization is a novel technique for documenting posttransplant chimerism and has advantages over RFLP analysis: high sensitivity, use of small amounts of DNA (250 ng), ease of preparation of DNA, elimination of need for restriction enzymes, and the ability to complete studies in 2 days.
Antithrombotic efficacy of continuous extradural analgesia after knee replacement. We have studied the effect of extradural analgesia on postoperative venous thrombosis in patients undergoing knee arthroplasty. Forty-eight patients were allocated randomly to receive either general anaesthesia or extradural analgesia with local anaesthetics for 3 days. All patients wore compressive elastic stockings and no anticoagulant drugs were administered. Bilateral venography was performed 10 days after surgery. Continuous extradural analgesia did not impede mobilization of the patients. One case of nonfatal pulmonary embolism occurred in a patient who received general anaesthesia. The use of continuous extradural analgesia resulted in a significant difference in the total incidence of deep vein thrombosis (18% compared with 59% after general anaesthesia (P = 0.02]. The incidence of calf vein thrombosis was 12% compared with 45% after general anaesthesia (P = 0.05).
Association between DNA ploidy pattern and cellular atypia in colorectal carcinomas. A new clinical application of DNA flow cytometric study? Fresh tissue specimens from 406 colorectal carcinomas were analyzed by DNA flow cytometric study, and the DNA ploidy pattern was compared with Dukes' stage, histologic grade, and degree of cellular atypia. Sixty-one percent of the carcinomas had a distinct aneuploid DNA pattern. The proportion of aneuploid carcinomas was significantly higher in the advanced Dukes' stages than in the localized ones. A highly significant association was found between DNA ploidy pattern and degree of cellular atypia, whereas no association was demonstrated between DNA ploidy pattern and histologic grade. This finding might indicate that cellular atypia has a stronger prognostic impact than the growth pattern of the tumor. The authors suggest that flow cytometric DNA quantification may replace assessment of cellular atypia in the histologic evaluation. Furthermore, together with earlier findings by others, these results indicate that the degree of cellular atypia may be conserved during the development from adenomas to carcinomas.
Flow cytometric analysis of DNA content in partial hydatidiform moles with persistent gestational trophoblastic tumor. Hydatidiform moles may be classified as partial or complete based on genetic and pathologic criteria. Between January 1979 and January 1990, 17 (5.5%) of 310 patients followed for partial mole developed persistent gestational trophoblastic tumor. Tissues from 14 partial moles were available for flow cytometric analysis of DNA content. Eleven partial moles (85%) were triploid, two (15%) were diploid, and one DNA histogram was uninterpretable. All patients with triploid partial moles achieved complete remission with one course of single-agent chemotherapy. The two with diploid partial mole required multiple courses of chemotherapy to achieve gonadotropin remission. Although the DNA content of most partial moles with persistent gestational trophoblastic tumor was triploid, diploid partial moles with persistent tumor were less sensitive to single-agent chemotherapy.
Renal manifestations of NaCl sensitivity in borderline hypertensive rats. Compared with the normotensive Wistar-Kyoto rat, the spontaneously hypertensive rat exhibits exaggerated alterations in renal sympathetic nerve activity and excretory function during volume expansion (exaggerated natriuresis) and environmental stress (antinatriuresis). The borderline hypertensive rat is the first filial offspring of the spontaneously hypertensive rat and the Wistar-Kyoto rat and develops hypertension with increased dietary NaCl intake. The present investigation sought to determine whether the dietary NaCl intake-induced transition from the normotensive state of the Wistar-Kyoto parent to the hypertensive state of the spontaneously hypertensive parent in the borderline hypertensive rat was accompanied by a similar transition of the renal sympathetic nerve activity and excretory responses to volume expansion and environmental stress. Borderline hypertensive rats fed a 1% NaCl diet remained normotensive and exhibited renal sympathetic nerve activity and excretory responses to volume expansion and environmental stress that were similar to those of their Wistar-Kyoto parent. Borderline hypertensive rats fed an 8% NaCl diet developed hypertension and exhibited responses that were similar to those of their spontaneously hypertensive parent. Thus, the dietary NaCl intake-induced transition from the normotensive state of the Wistar-Kyoto parent to the hypertensive state of the spontaneously hypertensive parent in the borderline hypertensive rat was accompanied by a similar transition of the renal sympathetic nerve activity and excretory responses to volume expansion and environmental stress. The results suggest that increased dietary NaCl intake is able to induce or unmask the capabilities for these responses, which are genetically conveyed to the borderline hypertensive rat by the spontaneously hypertensive rat parent in latent forms.
Subgroups of patients with atypical circadian patterns of symptom onset in acute myocardial infarction. Circadian variation of onset of acute myocardial infarction has been noted in many studies and may carry important implications. However, only a few previous studies have attempted subgroup analysis. In 4,796 patients with documented acute myocardial infarction, the time of symptom onset was recorded. As in other studies, a peak occurred in the morning hours from 6 A.M. to noon with 28% of the population (1.16 times the average percent for the other time periods) experiencing symptom onset in that period (p less than 0.001). There was a second lower peak (25%) in the evening hours between 6:01 P.M. and midnight, also observed in some previous studies. Whether the presence of subgroups with specific clinical characteristics would exhibit different patterns and thereby contribute to these peaks in the overall population was then determined. In patients with a history of congestive heart failure (n = 606) or with non-Q-wave infarction (n = 832), a pronounced peak (29%) occurred only in the evening hours. In patients greater than 70 years of age (n = 1,422), smokers (n = 2,057), diabetics (n = 767), women (n = 1,213) and patients taking beta blocking drugs (n = 847), 2 nearly equal peaks were observed. Finally, in patients with previous myocardial infarction (n = 1,104), no peaks were observed. In a subgroup of patients (n = 1,084) free from the most important modifying factors, there was a single very pronounced late morning peak (32%), 1.39 times the average percent for the other time periods (p less than 0.001), without evidence of a second evening peak.
The UCLA-University of Utah epidemiologic survey of autism: the etiologic role of rare diseases. Twelve rare diseases known to cause CNS pathology were found in 26 (11%) of 233 autistic probands identified during a recent epidemiologic survey of Utah. These 26 probands had significantly lower mean IQs than the remaining patients (43 versus 60) but similar sex distribution and prevalence of abnormal EEGs and seizures. The rarity and diversity of these 12 diseases make it highly unlikely that they randomly occurred with autism. Their presence in this epidemiologic survey is the most compelling evidence to date to support the hypothesis that different diseases producing different types of CNS pathology can play an etiologic role in autism.
Flow cytometry for clinical estimation of circulating hematopoietic progenitors for autologous transplantation in cancer patients. Optimum methods of harvesting circulating hematopoietic progenitors for autologous transplantation to support myeloablative cancer therapy are still uncertain, mostly because of the lack of an assay for marrow-repopulating stem cells. The CFU-GM assay, the commonly used indirect indicator of the quality of the graft, is poorly standardized and provides results evaluable only retrospectively. Based on the knowledge that hematopoietic progenitors express CD34 and CD33 differentiation antigens, we developed a dual-color direct immunofluorescence flow cytometry assay with the aim of replacing the CFU-GM assay advantageously. For this purpose, we applied both assays to 157 blood samples obtained daily throughout 20 different recoveries from pancytopenia induced by high-dose cyclophosphamide or etoposide cancer therapy with or without recombinant human GM colony-stimulating factor (rhGM-CSF). The appearance of CD34+ cells in the circulation indicated that hematopoietic progenitors had increased to more than 500 CFU-GM/mL, a level clinically adequate for large-scale harvest by leukapheresis. Total CD34+ cells correlated well with CFU-GM (r = .89), and data could be fitted by a linear regression line described by the equation y = 388.3 + 64.0x, where y = CFU-GM/mL and x = CD34+ cells per microliter. Moreover, in a series of six patients treated with myeloablative chemoradiotherapy, early hematopoietic recovery of marrow functions was predicted more accurately by the number of transplanted CD34+/CD33+ cells than by either total nucleated cells, CFU-GM, CD34+/CD33- cells, or CD34-/CD33+ cells. Data presented in this article favor clinical use of the CD34/CD33 flow cytometry assay to guide harvesting of circulating hematopoietic progenitors for autologous transplantation and contribute to better understanding of the role played by circulating hematopoietic progenitor cell subsets in marrow recovery after myeloablative cancer therapy.
Primary malignant melanoma in the parotid gland. Reports of primary malignant melanoma arising from the parotid salivary gland are extremely rare and, to date, have been sporadic. We report a pertinent case, and tabulate and correlate the clinical findings of the 13 cases reported thus far in the literature. The most common symptom is a progressively enlarging, asymptomatic, firm, and fixed mass. Total excision has been the established treatment of choice. The contribution of radiotherapy, chemotherapy, and immunotherapy remains unclear, and it is not possible at present to predict the outcome of treatment in individual patients. Although rare, primary malignant melanoma should be considered in the differential diagnosis of parotid tumors. The clinical significance of establishing the diagnosis of primary malignant melanoma of the parotid gland is emphasized.
Platelet-derived growth factor receptor alpha-subunit gene (Pdgfra) is deleted in the mouse patch (Ph) mutation. Platelet-derived growth factor receptors are composed of two subunits (alpha and beta) that associate with one another to form three functionally active dimeric receptor species. The two subunits are encoded by separate loci in humans and other species. In this study, we used conventional interspecific backcross mapping and an analysis of a deletional mutation to establish close linkage between the alpha-subunit gene (Pdgfra) and the dominant spotting (W) locus on mouse chromosome 5. Further, by analyzing the restriction fragment length polymorphisms in interspecific F1 hybrids, we were able to demonstrate that the closely associated patch (Ph) locus carries a deletion in Pdgfra. This observation was confirmed by both DNA and RNA analysis of 10.5-day fetuses produced from crosses between Ph heterozygotes. Out of 16 fetuses analyzed, Pdgfra genomic sequences were absent and no mRNA for the receptor was detected in 6 fetuses that were developmentally abnormal (the presumptive Ph homozygotes). We also determined that the deletion associated with the Ph mutation does not extend into the coding sequences of the adjacent Kit gene, by analysis of the genomic DNA from both the interspecific F1 hybrids and the presumptive Ph homozygotes. The absence of Pdgfra genomic sequences and the lack of detectable message associated with the Ph mutation should make this mutant a valuable asset for understanding the role of the receptor alpha subunit during mammalian development.
Circulating antibodies against human colonic extract enriched with a 40 kDa protein in patients with ulcerative colitis. We have previously described a 40 kDa colonic protein(s) which is specifically recognised by tissue-bound immunoglobulin G obtained from the colon of patients with ulcerative colitis. We now report the presence of circulating antibodies against this antigen using an enzyme-linked immunosorbent assay with a highly enriched preparation of the 40 kDa protein from normal colon extracts. Serum was collected from 79 patients with ulcerative colitis, 36 with Crohn's disease, 16 with specific diarrhoeal syndromes, and from 19 normal subjects. Twenty nine of 79 patients with ulcerative colitis, 21 of 36 with Crohn's disease, and all patients with diarrhoea were symptomatic during the collection of sera. The difference in optical density values between patients with symptomatic ulcerative colitis and each of the other groups, including patients with ulcerative colitis in remission, was highly significant (p less than 0.01). Seventy nine per cent of patients with symptomatic ulcerative colitis had optical density values above the means for all other groups. Fifty five per cent of sera from patients with symptomatic ulcerative colitis had optical densities beyond two SDs of the values for all other groups and only two of 71 sera from non-ulcerative colitis patients (one Crohn's disease and one normal subject) had values in this range. These results show the presence of anti-colon antibodies against the 40 kDa protein(s) in the sera of many patients with symptomatic ulcerative colitis.
Brief angiotensin converting enzyme inhibitor treatment in young spontaneously hypertensive rats reduces blood pressure long-term Our study examines the long-term cardiovascular effects after a brief period of angiotensin converting enzyme (ACE) inhibitor treatment in young spontaneously hypertensive rats (SHR). SHR were treated with perindopril (3 mg/kg/day) by gavage from 2 to 6, from 6 to 10, or from 2 to 10 weeks of age. Systolic blood pressure was measured in the tail weekly until 25 weeks of age. Corresponding control groups received distilled water for the same periods. In each treatment group blood pressure was reduced significantly during treatment, rose when treatment stopped, but plateaued significantly below control SHR thereafter. This difference in blood pressure at 25 weeks of age was due to reduced total peripheral resistance as determined by microsphere methods, but plasma renin activity and angiotensin II concentrations were not different. Cardiac hypertrophy was also reduced in treated SHR. In a separate experiment, perindopril treatment from 6 to 10 weeks of age resulted in a significant reduction in the media/lumen ratios of mesenteric resistance vessels at 32 weeks of age. Concomitant administration of angiotensin II with perindopril from 6 to 10 weeks of age not only prevented the long-term effects on blood pressure seen with perindopril treatment alone but was associated with cardiovascular hypertrophy in excess of untreated control SHR. Finally, perindopril given for a shorter period (6 to 7 weeks) or later in life (20 to 24 weeks) had no significant long-term effects on blood pressure. These results demonstrate that a 4-week period of ACE inhibitor treatment in young SHR is sufficient to prevent the full expression of genetic hypertension and cardiovascular hypertrophy and that angiotensin II might be important in the development of hypertension in this model, its role in later life being less important.
The opposite pupil in herniation. I serially examined the pupil opposite the one already enlarged from transtentorial herniation in 13 patients. The main abnormalities, stereotyped in most patients, were an initially diminished light reaction with a 2.5- to 4-mm-diameter pupil, followed by slight reduction in size, and then reenlargement to greater than original size, all with preserved roundness. Subsequent deterioration varied among patients, but a transitional oval shape was infrequent and oculomotor function was preserved until both pupils were enlarged and fixed. Once the pupil on the side of a mass enlarges, heralding herniation, subsequent deterioration can be appreciated through changes in reactivity and size of the opposite pupil.
Inhaled albuterol and oral prednisone therapy in hospitalized adult asthmatics. Does aminophylline add any benefit? STUDY OBJECTIVE: To determine the efficacy of intravenous aminophylline in the treatment of adult patients hospitalized for exacerbation of asthma. DESIGN: Randomized, double-blind, placebo-controlled trial throughout the study. SETTING: University Hospital Clinical Research Center. PATIENTS: Forty-four patients admitted from the emergency room with a primary diagnosis asthma; 39 patients completed the study. INTERVENTIONS: Patients received either intravenous aminophylline or placebo in addition to frequent nebulized albuterol; prednisone 0.5 mg/kg body weight every 6 h orally; and supplemental oxygen. Aminophylline infusion rates were adjusted to achieve serum theophylline concentrations of 10 to 20 micrograms/ml. Changes were made in placebo infusion rates to maintain the double blind design. MEASUREMENTS AND RESULTS: Forced expiratory volume in 1 s (FEV1) and other spirometric measurements every 8 h by a blinded investigator or trained respiratory therapist. Subjective patient response and duration of hospitalization were compared. No difference in spirometric measurements was observed between the two groups at any time point. On admission to the study, FEV1 in the placebo group was 41.5 (+/- 2.9) percent predicted and in the aminophylline group 34.7 (+/- 2.3) percent predicted (p = 0.08). At discharge, FEV1 was 70.4 (+/- 2.9) percent predicted in the placebo group and 63.7 (+/- 2.8) percent predicted in the theophylline group (p = 0.10). There was no difference in subjective patient rating or duration of hospitalization between the two groups (placebo 1.95 days and aminophylline 1.78 days, p = 0.51). CONCLUSIONS: Our results suggest that aminophylline therapy does not add significant benefit to other standard therapies in hospitalized adult asthmatic patients. Because of the risks and cost of aminophylline treatment in the hospital setting, further research is needed to determine if there are subgroups of adult asthmatics who may benefit from the addition of aminophylline to other standard optimal therapies.
Experimental intravesical therapy for superficial transitional cell carcinoma in a rat bladder tumor model. A rodent bladder cancer model that is induced by intravesical instillation of N-methyl-N-nitrosourea (MNU) was characterized. Cohorts of four to five week old female Fisher 344 rats received four biweekly 1.5 mg. doses of intravesical MNU and were sacrificed at various intervals. By week 13 all animals had flat atypia and/or papillary transitional cell tumors, and 67% of the lesions were moderately (grade II) or poorly differentiated (grade III). By week 20, 83% had gross muscle invasive tumors that eventually killed the host. A cohort of 40 MNU treated animals was subsequently treated commencing at week 17 after initiation of MNU with one of three intravesical six week regimens: 1) saline; 2) BCG (Tice strain); or 3) recombinant human tumor necrosis factor (RTNF) plus adriamycin. There was no difference in animal survival or tumor growth in any group of animals commencing therapy at week 17. A second cohort of 107 animals commenced therapy at 13 weeks after initiation of MNU with one of five intravesical six week regimens: 1) intravesical BCG (Tice strain); 2) adriamycin; 3) recombinant human tumor necrosis factor (RTNF); 4) RTNF plus adriamycin; or 5) BCG plus adriamycin. BCG, RTNF or adriamycin alone had no effect on tumor growth; however, BCG plus adriamycin and RTNF plus adriamycin commencing at week 13 significantly inhibited tumor growth and progression. In conclusion, this autochthonous intravesical rodent transitional cell carcinoma model appears useful for the following reasons: 1) it closely resembles human transitional cell carcinoma histologically and biologically in that all animals develop neoplastic changes in-situ that progress to muscle invasion and kill the host; 2) as with human bladder cancer these tumors do not respond to intravesical therapy if treated when tumor burden is large; however, tumor growth is inhibited when treated early; and 3) this model appears appropriate for screening and developing new intravesical treatments for superficial bladder cancer.