Parotid and central nervous system relapse during complete hematologic remission in acute promyelocytic leukemia.
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Adolescent↗
Biomedical subjects
C Hernandez
Publications and source records attributed to C Hernandez.
Male-specific transcription initiation of the C4-Slp gene in mouse liver follows activation of STAT5.
The mouse genes encoding the constitutively expressed complement component C4 and its closely related isoform C4-Slp (sex-limited protein), which is expressed only in male animals of several strains, provide a unique model to study sequence elements and trans-acting factors responsible for androgen responsiveness. Our previous studies have shown that hormonal induction of C4-Slp is mediated by a sex-specific pattern of growth hormone secretion. Promoter analyses in vitro have led to contradictory conclusions concerning the significance of C4-Slp-specific sequences in the 5' flanking region. Mutant mice carrying the H-2(aw18) haplotype, which is characterized by a large deletion in the S region covering the C4 and 21-OHase A genes, permit the direct in vivo analysis of C4-Slp transcription, unhindered by the presence of C4. Run-on analysis of transcription in liver nuclei of males and females of this strain demonstrated a 100-fold higher transcriptional activity in males, essentially determined at the transcription initiation level. The androgen dependence of transcription initiation was confirmed by run-on analysis of testosterone-treated females, where transcriptional activity started after 6 days of androgen treatment and reached male levels after 20 days. Conversely, the growth hormone-regulated activity of transcription factor STAT5 was already detected in liver nuclei after 48 hr of androgen treatment. Furthermore, we demonstrate that activated STAT5 recognizes in vitro two upstream gamma interferon-activated sequence (GAS) elements of the C4-Slp gene, centered at positions -1969 and -1831. We postulate that binding of STAT5 to these C4-Slp-specific GAS elements plays a crucial role in the chromatin remodelings that lead to transcriptional competence of the C4-Slp gene in the liver.
Animals↗
Intracavernous methoxamine in the treatment of priapism.
Methoxamine is an alpha-adrenergic drug, its unique pharmacokinetics and mechanism of action on alpha-1 receptors lead to consider it, similarly to phenylephrine, as a first-choice drug for treating drug-induced or veno-occlusive priapism. The experience obtained with its use in the management of three cases of priapism lasting over 7 h and one case of sustained rigid erection caused during anesthetic induction are reported.
Adrenergic alpha-Agonists↗
Bronchial microbial patterns in severe exacerbations of chronic obstructive pulmonary disease (COPD) requiring mechanical ventilation.
We carried out a comprehensive microbiological study of the upper and lower airways in patients with severe exacerbations of chronic obstructive pulmonary disease (COPD) requiring mechanical ventilation in order to describe microbial patterns and analyze their clinical significance. Quantitative cultures of tracheobronchial aspirates (TBAs), bronchoscopically retrieved protected specimen brush (PSB) and bronchoalveolar lavage fluid (BALF) at admission to the ICU and after 72 h, as well as serology for bacteria and respiratory viruses were performed. Fifty patients (mean age 68 +/- 8, 46 males) were studied prospectively. Potentially pathogenic microorganisms (PPMs) and/or a positive serology were present in 36 of 50 (72%) patients, including 12 (33%) polymicrobial cases. Only six (12%) had no pathogen in any sample in the absence of antimicrobial pretreatment. Microbial patterns corresponded to community-acquired pathogens (Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis) in 19 of 34 (56%) and to gram-negative enteric bacilli (GNEB), Pseudomonas, and Stenotrophomonas spp. in 15 of 34 (44%) of isolates. Chlamydia pneumoniae and respiratory viruses were found in 18% and 16% of investigations, respectively. Repeated investigation after 72 h in 19 patients with PPMs in the initial investigation revealed eradication of virtually all isolates of community-acquired pathogens and GNEB but persistence of three of five Pseudomonas spp. and both Stenotrophomonas spp. as well as the emergence of new GNEB, Pseudomonas and Stenotrophomonas spp. Clinical parameters neither predicted the presence of PPMs nor of GNEB and Pseudomonas/Stenotrophomonas spp. Nevertheless, severe pneumonia attributable to initially isolated pathogens occurred in two patients with severe COPD exacerbation. We conclude that pathogens were more frequently present than previously reported. The rate of GNEB and Pseudomonas/Stenotrophomonas spp. isolates was high. The presence of pathogens was clinically unpredictable. Thus, in this population of patients with severe exacerbations of COPD, it may be advisable to obtain respiratory samples and to treat according to diagnostic results. Further studies are warranted to clarify this issue.
Aged↗
A genetic deficiency that spans the flightin gene of Drosophila melanogaster affects the ultrastructure and function of the flight muscles.
We have developed a reverse-genetic approach to study the function of flightin, a unique protein of the flight muscle myofibril of Drosophila melanogaster. We describe the generation and characterization of Df(3L)fln1, a lethal genetic deficiency in the 76BE region of the third chromosome which deletes several genes, including the gene for flightin. We show that heterozygous flies harboring the Df(3L)fln1 mutation exhibit both impaired flight and ultrastructural defects in their flight muscle myofibrils. We found that the mutation does not interfere with assembly of the myofibril but leads to disorganization of peripheral myofilaments in adult myofibrils. Most myofibrils, nevertheless, retain an intact core that represents approximately 80 % of the normal lattice diameter. Mechanical analysis of single skinned flight muscle fibers demonstrates that the mutation has no significant effect on net power output but increases the frequency at which maximum power is delivered to the wings, potentially reducing the overall performance of the flight system. The results suggest that flightin is an indispensable part of the flight muscle contractile mechanism.
Animals↗
Kinins mediate the inhibition of atrial natriuretic peptide diuretic effect induced by pepsanurin.
Pepsanurin is a peptidic fraction resulting from pepsin digestion of plasma globulins, that inhibits ANP renal excretory actions. We studied whether kinin-like peptides mediate the anti-ANP effect by testing if pepsanurin: 1) was blocked by the kinin B2 receptor antagonist HOE-140, 2) was produced from kininogen, and 3) was mimicked by bradykinin. Anti-ANP activity was assessed in anesthetized female rats by comparing the excretory response to two ANP boluses (0.5 microgram i.v.) given before and after i.p. injection of test samples. Pepsanurin from human or rat plasma (1-5 mL/kg), and bradykinin (5-20 micrograms/kg), dose-relatedly inhibited ANP-induced water, sodium, potassium and cyclic GMP urinary excretion, without affecting arterial blood pressure. The same effect was exerted by pepsin hydrolysates of purified kininogen, whereas hydrolysates of kininogen-free plasma had no effect. HOE-140 (5 micrograms, i.v.) did not alter baseline, or ANP-induced excretion, but blocked the anti-ANP effects of pepsanurin. Histamine (15 micrograms/kg) plus seroalbumin hydrolysates did not affect ANP response, despite inducing larger peritoneal fluid accumulation as compared with pepsanurin or bradykinin. We concluded that kinins cleaved from kininogen mediate the anti-ANP effects of pepsanurin by activation of kinin B2 receptors, independently of changes in systemic arterial pressure or peritoneal fluid sequestration.
Adrenergic beta-Antagonists↗
Fetal laceration injury at cesarean delivery.
OBJECTIVE: To investigate the incidence of fetal laceration injury in cesarean delivery. METHODS: A retrospective review was conducted using a computer-based data coding system. All neonatal records were reviewed for infants delivered by cesarean during a 2-year period. Maternal records were reviewed in those cases of documented fetal laceration injury. The Fisher exact test was used when indicated. RESULTS: There were 904 cesarean deliveries performed during the study period; of these, 896 neonatal records (98.4%) were available for review. Seventeen laceration injuries were recorded (1.9%). The incidence of laceration appeared higher when the indication for cesarean was nonvertex (6.0% versus 1.4%, P = .02). One of 17 (5.9%) maternal records indicated the presence of the laceration of the fetus. CONCLUSION: Fetal laceration injury at cesarean delivery is not rare, especially when it is performed for nonvertex presentation. The minority of obstetric records show documentation of such lacerations, suggesting that this complication often may not be recognized by obstetricians.
Cesarean Section↗
In vitro effects of Celiptium and MR 14504 on mature rat Leydig cell testosterone production.
Percoll-purified mature rat Leydig cells have been used to evaluate the testicular toxicity of two highly potent intercalating agents (Celiptium and MR 14505). Testosterone secretion in the absence and in the presence of human chorionic gonadotropin (hCG) was measured to assess Leydig cell function. Celiptium and MR 14504 induce time- and dose-related inhibitory effects on the production of testosterone by Leydig cells, both in the presence and in the absence of hCG, whatever the concentration of hCG used. We have observed that MR 14504 is about 5 times more potent as an inhibitor of rat Leydig cell steroidogenesis than Celiptium without inducing any cell toxicity. The present study indicates that the Leydig cell is an additional potential site for the primary toxic effects of these drugs in the adult rat testis.
Animals↗
Pemphigus foliaceus: preferential binding of IgG1 and C3 at the upper epidermis.
The immunopathological mechanism of pemphigus foliaceus acantholysis remains controversial. Previous workers have found that IgG autoantibodies are reactive with the epidermal surface and capable of blister induction. The presence of complement components in lesions also suggests their potential role in this disease. Complement participation, however, has not been clearly demonstrated. We describe a case of pemphigus foliaceus (PF) in a 58-year old woman which was confirmed by histopathological and immunopathological studies, and by ELISA assay on recombinant PF antigen. Unusual features of this case include the predominance of IgG1 anti-epithelial antibody in both the deposits and circulation, and the preferential binding of IgG and complement component 3 at the upper epidermis. We believe that this pattern of co-localized deposition suggests a location-specific, non-random complement activation.
Autoantibodies↗
Earth-Based Observations of the Galileo Probe Entry Site
Earth-based observations of Jupiter indicate that the Galileo probe probably entered Jupiter's atmosphere just inside a region that has less cloud cover and drier conditions than more than 99 percent of the rest of the planet. The visual appearance of the clouds at the site was generally dark at longer wavelengths. The tropospheric and stratospheric temperature fields have a strong longitudinal wave structure that is expected to manifest itself in the vertical temperature profile.
Journal Article↗
Genetic analysis of seven Mediterranean families with multiple endocrine neoplasia type 2A.
OBJECTIVE: Genetic analysis is now essential for the accurate screening of families with multiple endocrine neoplasia type 2 (MEN2). We present the genetic analyses by both haplotype and direct RET proto-oncogene mutation analysis in seven Mediterranean MEN 2A families and have compared these results with biochemical screening tests and pathological examinations. DESIGN: Total DNA was extracted from leucocytes. Linkage analysis was performed using five RFLP systems from three loci that flank the MEN2A locus (FNRB, RBP3, D10S15). RET proto-oncogene analysis was carried out by automatic DNA sequencing and adequate digestion of PCR amplified products for exons 10 and 11. Screening for medullary thyroid carcinoma or C-cell hyperplasia was performed by the pentagastrin provocation test. Adrenal medullary function was assessed by measurements of 24-hour urinary excretion of catecholamines and their metabolites. Serum calcium and phosphate measurements were the initial screen for hyperparathyroidism. Serum PTH was determined only if hyperparathyroidism was suggested by the former determinations. PATIENT: Genetic study was performed in 59 individuals (39 at risk) from seven kindreds of Mediterranean origin with MEN 2A. RESULTS: Diagnosis by linkage analysis was not possible in 30% of individuals at risk, but RET proto-oncogene analysis identified all these individuals. Mutations of the RET proto-oncogene were detected in exon 10 (codon 618) in one MEN 2A kindred and in exon 11 (codon 634) in the others. The results of direct analysis were concordant with linkage studies in each case. Three individuals from different MEN 2A kindreds, who were subsequently shown not to be gene carriers, had false positive pentagastrin stimulation tests. CONCLUSION: Biochemical tests can be replaced by direct DNA mutation analysis as the first line screening test in order to identify gene carriers of MEN 2A.
Base Sequence↗
Serial passage of tobacco rattle virus under different selection conditions results in deletion of structural and nonstructural genes in RNA 2.
The RNA genome of tobacco rattle virus (TRV) is bipartite. RNA 2 of the nematode-transmissible TRV isolate PPK20 encodes the viral coat protein (cp) and proteins with molecular weights of 29,400 and 32,800 (29.4K and 32.8K proteins). When this isolate was serially passaged in tobacco by using phenol-extracted RNA as the inoculum in each transfer, defective interfering (DI) RNAs rapidly accumulated. A number of these DI RNAs were cloned. Six DI RNAs had single internal deletions in RNA 2 that removed most of the cp gene, the 29.4K gene, and the 5' half of the 32.8K gene. The borders of the deletions in these DI RNAs were found to be flanked in the genomic RNA 2 by short nucleotide repeats or sequences resembling the 5' end of TRV genomic and subgenomic RNAs. Two DI RNAs were found to be recombinants containing a 5' sequence derived from RNA 2 and a 3' sequence derived from RNA 1. When serial passage of TRV isolate PPK20 was carried out by using leaf homogenates as inocula in each transfer, accumulation of a DI RNA (designated D7) with a functional cp gene was observed. The deletion in D7 covered the 3' end of the cp gene, the 29.4K gene, and the 5' half of the 32.8K gene. An infectious cDNA clone of D7 RNA was made. In mixed infections, D7 RNA rapidly outcompeted RNA 2 but did not compete with RNA 1. The deletion in D7 RNA abolished the nematode transmissibility of the PPK20 isolate. These results may explain the observation that many laboratory isolates of tobraviruses have lost their nematode transmissibility and contain RNA 2 molecules of widely different lengths.
Culture Media↗
Protection from the nephrotoxicity of contrast dye.
Previous studies have reported a 4%-50% incidence of acute renal failure (ARF) following the use of radiocontrast media in patients with preexisting chronic renal insufficiency. In these studies, ARF was defined as a rise of the serum creatinine of at least 1 mg/dl above baseline. Using the same criteria, we studied 214 patients undergoing various intravascular radiocontrast media procedures. Patients were infused with a specially prepared cocktail solution (NSMF) containing 1000 ml half-normal saline, 12.5 g of mannitol (M), I ampule NaHCO3, and 200 mg of furosemide (F) at 100 ml/h from one hour prior to two hours after the procedure. Urinary output was replaced with normal saline for at least 6 h after the procedure. Seven percent of the patients developed acute renal insufficiency. Only 3% of the patients had a rise in serum creatinine greater than 2 mg/dl. No patient required dialysis therapy after the procedure. There was one unrelated death caused by acute myocardial infarction postangioplasty. Risk factors for development of ARF despite cocktail administration included the presence of diabetes mellitus and angiotensin converting enzyme (ACE) inhibitor therapy. We concluded that the properly administered NSMF solution protects against radiocontrast dye induced renal failure. In select patients with chronic renal insufficiency, consideration should be given to withholding ACE inhibitor therapy for 24-48 h prior to administration of intravenous radiocontrast dye. A large controlled trial will be required to establish whether the NSMF solution offers benefit beyond that of saline hydration alone.
Acute Kidney Injury↗
High-risk coronary angioplasty assisted by active hemoperfusion. A feasibility study.
We assessed the effectiveness of distal hemoperfusion support during gradual, prolonged balloon inflation during percutaneous transluminal coronary angioplasty in high-risk patients. The patients were identified as having a poor left ventricular ejection fraction ( < 35%), > 50% of viable myocardium at risk percutaneous coronary balloon angioplasty, or both. A total of 64 procedures were performed in 61 patients. Angiographic success was achieved in 83 of 86 (96.5%) lesions treated with hemoperfusion support. Hospital complications included 1 patient who had a non-Q-wave infarction, 1 who had to undergo redo percutaneous coronary balloon angioplasty, and 5 who required coronary artery bypass operations. The hospital mortality was 7.8% (5 patients). This preliminary study indicates that hemoperfusion support can enable expeditious, simple, economical, and effective percutaneous transluminal coronary balloon angioplasty in a subset of labile patients in whom procedural failure frequently leads to sudden death.
Angioplasty, Balloon, Coronary↗
Early and late mortality of patients undergoing aortic valve replacement after previous coronary artery bypass graft surgery.
BACKGROUND: In a small number of patients who undergo coronary artery bypass graft surgery (CABG), a hemodynamically significant aortic valve lesion requiring aortic valve replacement (AVR) develops as they grow older. In a limited number of studies in small patient groups, high mortality has been shown in patients undergoing AVR after CABG. We undertook this study to determine the mortality risk factors for patients who undergo AVR after CABG procedures. METHODS AND RESULTS: The outcome of 104 patients treated at our institution between January 1983 and December 1993 was retrospectively reviewed. The initial surgery was CABG in all patients. The patient population included 86 men (83%) and 18 women (17%); their mean age was 67 years. Overall, 70% of patients had congestive heart failure, and 96% had multivessel coronary artery disease. The diagnosis was aortic stenosis in 68% of patients, aortic insufficiency in 16%, and combined aortic stenosis and aortic insufficiency in 16%. Postoperative complications included worsening congestive heart failure (35%), perioperative myocardial infarction (13%), and bleeding (28%). The early mortality was 14%, and the late mortality was 17% (mean follow-up, 35 months). The risk factors for early mortality were number of diseased vessels (P = .028), renal failure (0.000), and prior myocardial infarction (P = .028). A perioperative predictor of early mortality was cardiopulmonary bypass time (P = .000). The risk factors for late mortality included preoperative diabetes mellitus (P = .007), postoperative acute respiratory distress syndrome (P = .011), and ventricular arrhythmias (P = .0001). The survival at 1, 5, and 10 years was 96%, 75%, and 49%, respectively. CONCLUSIONS: Risk factors were identified for early and late mortality in patients undergoing AVR after previous CABG. Although early morbidity and mortality were high, the longterm outcome of the survivors was favorable.
Aged↗
Blindness associated with preeclampsia and eclampsia.
OBJECTIVE: Over a 14-year period at Parkland Hospital, the clinical courses of 15 women with severe preeclampsia or eclampsia were further complicated by blindness. Our purpose is to describe their management and outcome, as well as to offer insight to the pathophysiologic characteristics of blindness complicating pregnancy-induced hypertension. STUDY DESIGN: Prospective ascertainment of women with blindness and pregnancy-induced hypertension was done. These cases were managed according to the standardized preeclampsia-eclampsia regimen used at our hospital since 1955. Briefly, this regimen includes magnesium sulfate given intramuscularly to prevent or control seizures, hydralazine to lower dangerously elevated blood pressure, intravenous fluid restriction, and delivery. RESULTS: There were 15 women with blindness that persisted from 4 hours to 8 days; it subsequently resolved completely in all. Of the 13 women who underwent computed tomography, 8 had low-density areas localized predominantly in the occipital lobes. Five of these 13 subsequently underwent magnetic resonance imaging and 2 showed corresponding hyperintense lesions in the occipital areas. CONCLUSIONS: On the basis of previously published experiences with computed tomography in women with eclampsia, as well as the experiences described here, we conclude that cortical blindness associated with preeclampsia-eclampsia results from petechial hemorrhages and focal edema in the occipital cortex. These lesions are likely stimulated by disparity in cerebral regional blood flow that is characterized by vasospasm and diminished flow primarily affecting the posterior circulation.
Adolescent↗
A comparative study on the return to ovulation following chronic use of once-a-month injectable contraceptives.
A comparative study was undertaken involving 21 Mexican women who discontinued the use of medroxyprogesterone acetate 25 mg plus oestradiol cypionate 5 mg (Cyclofem) and norethisterone enanthate 50 mg plus oestradiol valerate 5 mg (Mesigyna) to assess the time required for the return to menses and ovulation. All subjects were exposed to once-a-month injectable contraceptives for two years and were followed for 120 days after the last injection. The urinary concentration of oestrone glucuronide and pregnanediol glucuronide was determined daily in all subjects beginning one month after the last injection. The results disclosed that ovulatory cycles were documented after 120 days of the last injection in six women of each studied group. Similar endometrial bleeding patterns were observed in both groups, indicating that the two drugs have alike pharmacokinetic and pharmacodynamic effects.
Adult↗
Obstetric clavicular fracture: the enigma of normal birth.
OBJECTIVE: To determine the main risk factors involved in neonatal clavicular fracture, the most common injury to the neonate. METHODS: Two hundred fifteen cases of clavicular fracture of 65,091 vaginal deliveries (0.4%) occurring between January 1983 and December 1988 were pair-matched with controls based on mode and date of delivery, race, and maternal age. Incidences, odds ratios, and stratified analysis were used to identify and control for confounding between risk factors. RESULTS: Shoulder dystocia, increasing birth weight, and increasing gestational age were identified as risk factors. Within the range of normal birth weights, there is a biologic gradient of increasing risk for clavicular fracture. Although shoulder dystocia is the strongest risk factor identified, the magnitude of its point estimate is probably affected to a large extent by differential ascertainment. The use of forceps, prolonged second stage of labor, and nulliparity status were not significantly associated with neonatal clavicular fracture. CONCLUSIONS: Neonatal clavicular fracture occurs commonly in an obstetric population. Obstetric clavicular fracture is an unpredictable, unavoidable complication of normal birth.
Adolescent↗