shukoor65/lab-rag-model huggingface dataset:
Compound heterozygosity in nonphenylketonuria hyperphenylalanemia: the contribution of mutations for classical phenylketonuria. Hyperphenylalaninemia (HPA) results from defective hydroxylation of phenylalanine in the liver, in most cases because of defective phenylalanine hydroxylase. HPA is highly variable, ranging from moderate elevation of plasma phenylalanine with no clinical consequences to a severe disease, classical phenylketonuria (PKU). Non-PKU HPA was found in excess of PKU in Israel, while the opposite is true in Europe. To study the genetic basis of non-PKU HPA, we performed haplotype analysis at the phenylalanine hydroxylase locus in 27 families with non-PKU HPA. All individuals with this condition were compound heterozygotes. In six of these families, in which both PKU and non-PKU HPA were segregating, haplotype analysis showed that non-PKU HPA resulted from compound heterozygosity for a PKU mutation and a second mutation, with milder effect, which is probably expressed only when it interacts with the severe mutation. The involvement of PKU mutations in non-PKU HPA was further demonstrated in Jewish Yemenite families with non-PKU HPA, in which the individuals with this condition were carriers of the single PKU allele which exists in this community. In addition, two previously known PKU point mutations (R261Q and R408W) were found in individuals with non-PKU HPA. These mutations are associated, in our population, with the same haplotypes as those with which it is associated in Europe. Based on the above-mentioned genetic model for non-PKU HPA, successful prenatal diagnosis of this condition was performed in one family.
In vivo pharmacology of DuP 753. A review of the in vivo pharmacology of DuP 753 (2-n-butyl-4-chloro-5-hydroxymethyl-1-[2'-(1H-tetrazol-5-yl)biphen yl-4- yl)methyl]imidazole, potassium salt) is presented. In the pithed rat, DuP 753 exerted a selective and competitive inhibition of the pressor response to angiotensin II (AII). In conscious normotensive rats, DuP 753 inhibited the AII-induced aldosterone secretion and drinking response. DuP 753 lowered blood pressure in conscious normotensive rats pretreated with furosemide but not in untreated normotensive rats. Unlike saralasin, DuP 753 given intravenously did not cause pressor response. In conscious renal hypertensive rats (RHRs), a high renin model, DuP 753 decreased blood pressure with an intravenous ED30 of 0.78 mg/kg and an oral ED30 of 0.59 mg/kg. The antihypertensive efficacy of DuP 753 in RHRs was similar to that of captopril. In DOCA hypertensive rats, a low renin model, DuP 753 did not lower blood pressure. In conscious 18- to 21-week-old spontaneously hypertensive rats (SHRs), DuP 753 given orally or intravenously reduced blood pressure dose-dependently and did not alter heart rate at these doses. The acute antihypertensive efficacy of DuP 753 was greater than that of captopril in SHRs. In contrast, DuP 753 and captopril given orally at 10 mg/kg/day for 15 days in SHRs caused a similar decrease in blood pressure. Bilateral nephrectomy but not inhibition of prostaglandin synthesis abolished the antihypertensive effect of DuP 753 in SHRs. Our study, therefore, indicates that DuP 753 is an orally active, nonpeptide, selective, and competitive AII receptor antagonist lacking agonism. It appears that there is a relationship between basal renin level and the acute antihypertensive effect of DuP 753 in rats. Further, our results suggest that the renin-angiotensin system plays a significant role in the control of blood pressure in conscious SHRs.
Intermediate term results of infant orthotopic cardiac transplantation from two centers. Orthotopic cardiac transplantation has become established for selected infants with severe forms of congenital heart disease. This study reviews the combined experience and intermediate term results of infants undergoing orthotopic cardiac transplantation from Children's Memorial Hospital, Chicago, and Kosair Children's Hospital, Louisville. From June 1986 through December 1989, 20 orthotopic cardiac transplantations were performed in 19 patients. Sixteen patients had variants of hypoplastic left heart syndrome. One infant had anomalous origin of the left coronary artery with severe ischemic cardiomyopathy. Two infants had aortic stenosis with endocardial fibroelastosis, and one had extracorporeal membrane oxygenation as a bridge to transplantation. Immunosuppression included cyclosporine, azathioprine (Imuran), and corticosteroids with an effort to wean the patients from steroids by 6 months to 2 years. Three early deaths resulted--from technical errors in two patients and from hyperacute rejection in one patient at 3 days. Four late deaths have occurred. Two patients died at 2 and 13 months of acute rejection. One patient died at 15 months of acute rejection after retransplantation. One patient died at 7 months of respiratory syncytial viral pneumonia. The remaining 12 patients are surviving 5 to 47 months (means 20 months) after orthotopic cardiac transplantation. Rejection surveillance in the first 6 months is by clinical signs supplemented by echocardiography, electrocardiography, and cell cycle analysis; endomyocardial biopsy is used after 6 months of age. For the cumulative series, 24 episodes of suspected rejection have been treated during 277 at-risk patient months with intravenous methylprednisolone (Solu-Medrol) (n = 18) and monoclonal antibody (OKT3) (n = 6), for an incidence of 1.04 episodes of rejection per patient per year. Serious posttransplantation infections including endocarditis, catheter sepsis, meningitis, and colonic perforation were successfully treated in four patients. Subjectively, their quality of life is excellent as shown by normal growth and developmental milestones and a low hospital readmission rate (1.4 episodes per patient per year). These encouraging intermediate term results warrant continued application of infant orthotopic cardiac transplantation for severe forms of congenital heart disease.
Urinary tract calculi that form on surgical staples: a characteristic radiologic appearance. An autostapler is frequently used when bowel is interposed in the urinary tract during reconstructive urologic surgery in children. Usually the metallic staples are buried beneath the intestinal mucosa. However, if a portion of a staple is unintentionally left exposed or becomes exposed through migration and is then bathed by urine, it can become the nidus for formation of a calculus. The radiologic studies of 30 patients having surgery of this type in our hospital from 1980 to 1990 were reviewed prospectively, and stones were found to have developed on staples in eight patients. None of the patients had metabolic abnormalities. The stones were easily visible on plain radiographs because they were calcified. They formed in the lumen of the bladder or the bowel segment on the exposed portion of the staple. Thus, the staple was eccentric in the calculus and not central, as is usually the case with a stone forming on a foreign body. This experience suggests that stones forming on surgical staples during reconstructive urologic surgery have a characteristic radiologic appearance that may aid in their identification.
Sleep-induced periodic breathing and apnea: a theoretical study. To elucidate the mechanisms that lead to sleep-disordered breathing, we have developed a mathematical model that allows for dynamic interactions among the chemical control of respiration, changes in sleep-waking state, and changes in upper airway patency. The increase in steady-state arterial PCO2 accompanying sleep is shown to be inversely related to the ventilatory response to CO2. Chemical control of respiration becomes less stable during the light stage of sleep, despite a reduction in chemoresponsiveness, due to a concomitant increase in "plant gain" (i.e., responsiveness of blood gases to ventilatory changes). The withdrawal of the "wakefulness drive" during sleep onset represents a strong perturbation to respiratory control: higher magnitudes and rates of withdrawal of this drive favor instability. These results may account for the higher incidence of periodic breathing observed during light sleep and sleep onset. Periodic ventilation can also result from repetitive alternations between sleep onset and arousal. The potential for instability is further compounded if the possibility of upper airway occlusion is also included. In systems with high controller gains, instability is mediated primarily through chemoreflex overcompensation. However, in systems with depressed chemoresponsiveness, rapid sleep onset and large blood gas fluctuations trigger repetitive episodes of arousal and hyperpnea alternating with apneas that may or may not be obstructive. Between these extremes, more complex patterns can arise from the interaction between chemoreflex-mediated oscillations of shorter-cycle-duration (approximately 36 s) and longer-wavelength (approximately 60-80 s) state-driven oscillations.
Neuroeffector functions of sensory fibres: implications for headache mechanisms and drug actions. The results of recent investigations designed to elucidate the neuroeffector functions of sensory fibres, the cause of migraine headache and the mechanism of action of antimigraine drugs are reviewed and discussed. Neurogenic inflammation (vasodilatation and neurogenic plasma extravasation) is one explanation for the development of headaches and the blood flow changes which occur during migraine headache. Numerous studies have recently been carried out on rats and guinea-pigs into the effects of antimigraine agents, including ergot alkaloids, sumatriptan and non-steroidal anti-inflammatory drugs (NSAIDs), on neurogenic plasma protein extravasation in the dura mater induced by electrical stimulation of trigeminal ganglia or systemic administration of capsaicin. It is known that the dura mater is able to produce headaches in man. Ergot alkaloids have been shown to block neurogenic inflammation via a C-fibre dependent neuronal mechanism. Sumatriptan appears to act fairly similarly although, whereas the ergot alkaloids are non-selective for either 5-hydroxytryptamine (5-HT; serotonin) receptors or 5-HT1, sumatriptan is selective for 5-HT1 receptors. The antimigraine action of NSAIDs may be via either an effect on blood vessels or an effect on the nerve fibre. The antimigraine effects of ergot alkaloids, sumatriptan and NSAIDs are discussed in the light of the common vasoconstrictor actions of these agents and knowledge that vasodilatation is apparently not responsible for migraine headache pain in most cases.
Degree of coronary artery disease predicted by exercise testing. The ability of exercise testing to predict the extent of coronary artery disease was examined in 268 male patients undergoing both coronary angiography and bicycle testing with electrocardiography before coronary artery bypass surgery. When maximal ST-depressions limited by symptoms increased from 0 to 4 mm or more, the percentage of patients with 'serious' coronary disease, defined as either triple vessel disease or left main stem stenosis, increased from 50% to 80% (P = 0.0001). The patients in the lowest third of physical work capacity showed only a slightly increased risk of serious disease. This tendency was abolished in patients who were using beta-blockers, whereas the relationship between ST-depression and disease was not affected by this medication. The probability of finding left main stem stenosis in a patient increased from 5 to 30% with increasing ST-depression: beta-blockers did not affect this relationship, but there was no additional predictive effect of implicating the level of physical work capacity. It is concluded that traditional electrocardiography during exercise is of value when selecting patients for angiography, but that the physical work level obtained during the test does not predict the degree of coronary pathology.
Mechanism of shock associated with right ventricular infarction. Various mechanisms have been proposed to explain the shock sometimes associated with right ventricular infarction, but only small numbers of patients with clinical shock have been studied. The haemodynamic profiles of seven patients with clinical cardiogenic shock after right ventricular myocardial infarction were studied prospectively. They were selected because all had a stable cardiac rhythm and none had absolute hypovolaemia during the study period. In all of them the mean right atrial pressure exceeded the pulmonary artery occlusion pressure. After treatment with varying combinations of dopamine, dobutamine, and glyceryl trinitrate (titrated to achieve the optimum haemodynamic response) the mean systemic arterial pressure increased, as did the cardiac index. There was an associated increase in the left ventricular stroke work index but the right ventricular stroke work index was unchanged. There was no significant change in heart rate, mean right atrial pressure, or pulmonary artery occlusion pressure. This suggests that the probable mechanism of the shock associated with right ventricular infarction is concomitant severe left ventricular dysfunction.
Cost-effectiveness analysis of paramedic emergency medical services in the treatment of prehospital cardiopulmonary arrest. STUDY OBJECTIVES: 1) Identification of marginal costs associated with prehospital resuscitation of cardiopulmonary arrest; 2) Determination of cost effectiveness for such resuscitation; and 3) Comparison of cost effectiveness of paramedic care with selected other medical interventions. DESIGN: Retrospective review of 190 cases of out-of-hospital cardiac arrest. SETTING: City limits of a midsized southwestern city. The events studied took place outside of medical facilities. TYPE OF PARTICIPANTS: Victims of out-of-hospital cardiac arrest for whom the EMS system was activated by a 911 telephone request for emergency medical assistance. MEASUREMENTS AND MAIN RESULTS: The cost, including training, personnel, equipment, and response time maintenance, per year of life saved was found to be $8,886.00 for paramedic care. This result was compared with published cost-effectiveness figures for heart transplantation, liver transplantation, bone marrow transplantation, and chemotherapy for acute leukemia. Paramedic care was more cost effective, as measured by cost per year of life saved, than organ transplantation and chemotherapy for acute leukemia. CONCLUSION: Out-of-hospital treatment by paramedics of cardiopulmonary arrest is more cost effective than heart, liver, bone marrow transplantation, or curative chemotherapy for acute leukemia.
Effective treatment of small-noncleaved-cell lymphoma with high-intensity, brief-duration chemotherapy. Small-noncleaved-cell (SNC) lymphoma is a high-grade, biologically aggressive neoplasm notable for poor response to therapy, high relapse rate, and less than a 20% long-term survival. We treated 20 patients with SNC lymphoma with a novel chemotherapeutic regimen using intensive doses of chemotherapy at frequent intervals in the inpatient setting. All patients were previously untreated. Sixteen patients (80%) had stage IV disease. Most patients (95%) had at least one other characteristic associated with poor prognosis (bulky [greater than 10 cm] disease, multiple extranodal sites, poor performance status), and 85% had two or more characteristics associated with poor prognosis. Seventeen patients (85%) achieved a complete response (CR) to therapy, including all three patients with human immunodeficiency virus (HIV)-associated disease. There have been three relapses, all occurring less than 18 months after treatment, and two of three relapses occurred in patients who were unable to complete therapy. At a median follow-up of 29 months, 13 patients (65%) remain disease-free; the calculated 5-year actuarial disease-free survival is 60%. Toxicity, chiefly myelosuppression, was severe but manageable. There were two treatment-related deaths, both in elderly patients with poor performance status and advanced-stage disease. These data suggest that such a dose-intensive approach improves the response and survival of patients with SNC lymphoma.
The transient appearance of small blastoid cells in the marrow after bone marrow transplantation. Of 14 patients who underwent allogeneic or syngeneic bone marrow transplantation, 6 had a transient appearance of small blastoid cells in the bone marrow after transplantation. Most of these patients (11) had leukemia, although 3 had severe aplastic anemia. The cells were 8-18 micron in diameter and had scant cytoplasm and dense nuclei with smooth, homogeneous chromatin. They often had distinct nuclear clefts. These cells constituted 4.0-21.3% of the total number of bone marrow cells. They were not reactive with peroxidase, alpha-naphtyl butylate esterase, naphthol AS-D chloroacetate esterase, or periodic acid-Schiff stains. Immunocytochemical analysis revealed that the small blastoid cells expressed terminal deoxynucleotidyl transferase, Ia-like, CD19, and CD10 antigens and cytoplasmic mu heavy chains, indicating a precursor B-cell phenotype. CD20 antigen was not expressed on these cells. The data suggest that cytoplasmic mu may be expressed earlier than CD20 antigen in the differentiation of B-cell lineage. The morphologic, cytochemical, and immunophenotypic characteristics did not distinguish these nonneoplastic cells distinctly from leukemic lymphoblastic cells. The increase of small blastoid cells was a transient and self-limited phenomenon, in contrast to that of neoplastic blasts. These cells should be recognized as a common component of the bone marrow of marrow transplant recipients. The significance and role of these cells in immune recovery and hematopoiesis remain uncertain.
Mitral valve replacement in idiopathic hypereosinophilic syndrome. Idiopathic hypereosinophilic syndrome is an eosinophil-mediated tissue injury causing multiple organ failure. Cardiac manifestations include subendocardial fibrosis, thrombus leading to peripheral emboli, restrictive cardiomyopathy, and valvar dysfunction. This article describes a patient with the syndrome and reviews surgical experience with valve replacement and long-term prognosis.
Pulse oximetry monitoring outside the intensive care unit: progress or problem? OBJECTIVE: To evaluate the use of continuous pulse oximetry monitoring in general care units. DESIGN: Hemoglobin oxygen saturation data collected prospectively by use of pulse oximetry with concurrent review of the medical record. SETTING: General medical-surgical nursing units in a large, tertiary care university hospital. PATIENTS: Forty patients on two nursing units monitored with continuous, bedside pulse oximetry at the request of their primary physicians. MEASUREMENTS: All patients had continuous pulse oximetry monitoring. A research associate visited the bedside two or three times daily and recorded saturation compared with time data from the previous 8.75 hours. Patients were studied for 36 hours or until pulse oximetry monitoring was discontinued. Episodes of desaturation were counted. Patient charts were reviewed for documentation of desaturation in either nursing or physician notes. Orders adjusting oxygen therapy or other respiratory therapy within 12 hours of any desaturation episode were also recorded. MAIN RESULTS: Thirty of the 40 patients (75%) had at least one episode of desaturation to less than 90%; 23 (58%) had at least one episode to less than 85%. Desaturation episodes were documented in nursing notes for only 33% of those patients who desaturated to less than 90% and in physician notes in only 7% of cases. Changes in respiratory therapy were ordered in 20% of patients who desaturated to less than 90% and in only 26% who desaturated to less than 85%. CONCLUSIONS: Despite their repeated occurrence, episodes of hypoxemia were rarely documented in either nursing or physician notes. Further, even in patients who had episodic desaturation, pulse oximetry monitoring had little effect on changes in physician-directed respiratory care.
Peripheral neuropathy after chronic endoneurial ischemia. We have developed a method for producing chronic regional nerve ischemia in rats by creating proximal limb arteriovenous shunts. This procedure results in a 50 to 75% reduction in endoneurial blood flow within the distal sciatic nerve as measured by the iodoantipyrine method. Nerve conduction velocities in sciatic nerves ipsilateral to the shunt fell by 25 to 30% within 2 weeks after creation of the shunt and did not recover for up to 10 months after the procedure. Morphological studies of the ischemic nerves showed structural abnormalities at nodes of Ranvier and mild axonal atrophy. Neither segmental demyelination nor axonal degeneration were evident. These results indicate that reduced endoneurial blood flow, insufficient to cause infarction, may result in measurable functional and morphological abnormalities in peripheral nerves.
Clinical comparison of polyglactic acid (Vicryl) and polytrimethylene carbonate (Maxon) suture material. Over a 1-year period, 584 repairs of surgical defects were completed using two different synthetic absorbable sutures, polyglactic acid (Vicryl) and polytrimethylene carbonate (Maxon). No difference in scar width or postoperative complications were found between the two sutures, but polytrimethylene carbonate (Maxon) demonstrated preferable handling and tying characteristics.
Low energy catheter ablation of right ventricular outflow tract tachycardia. A 38 year old woman with a structurally normal heart presented with near syncope and had right ventricular outflow tract tachycardia. She was intolerant of antiarrhythmic medication and underwent low energy catheter ablation. Six non-arcing shocks of 25 J were delivered to the right ventricular outflow tract. No further ventricular tachycardia occurred during a follow up of seven months without antiarrhythmic treatment.
Fixed subaortic stenosis: anatomical spectrum and nature of progression. Retrospective echocardiographic review identified 58 consecutive infants and children with fixed subaortic stenosis. Mean (SD) age at diagnosis was 4.8 (3.6) years (range two days to 14.7 years), and diagnosis occurred in infancy in eight. Associated cardiac abnormalities were present in 41 (71%) whereas fixed subaortic stenosis was an isolated lesion in 17 (29%). Four types of fixed subaortic stenosis were identified: short segment (47 (81%)), long segment (7 (12%)), posterior displacement of the infundibular septum with additional discrete narrowing of the left ventricular outflow tract (3 (5%)), and redundant tissue arising from the membranous septum (1 (2%)). Echocardiographic studies had been performed before the diagnosis of fixed subaortic stenosis in nine patients, all with associated abnormalities. These were performed in infancy in each and showed a "normal" left ventricular outflow tract in six and posterior deviation of the infundibular septum in three. In 16 patients serial echocardiographic studies had been performed after the diagnosis of fixed subaortic stenosis but before surgery of the left ventricular outflow tract. Rapid evolution of short segment to long segment narrowing was seen in one patient, and tethering of the aortic valve or mitral valve developed in a further four patients. Aortic valve or mitral valve involvement was not seen before the age of three years but was common thereafter (10/40 patients, 25%). Fixed subaortic stenosis may be an "acquired" lesion with the potential for changes in form as well as progression in severity of left ventricular outflow tract obstruction.