shukoor65/lab-rag-model huggingface dataset:
Differential susceptibility of activated macrophage cytotoxic effector reactions to the suppressive effects of transforming growth factor-beta 1. We examined the effects of TGF-beta 1 on induction of several activated macrophage antimicrobial activities against the protozoan parasite Leishmania, and on induction of tumoricidal activity against the fibrosarcoma tumor target 1023. TGF-beta by itself did not affect the viability of either the intracellular or extracellular target in concentrations up to 200 ng/ml. As little as 1 ng/ml TGF-beta, however, suppressed more than 70% of the intracellular killing activity of macrophages treated with lymphokines. In contrast, more than 100 ng/ml TGF-beta was required to suppress intracellular killing by cells activated with an equivalent amount of recombinant IFN-gamma. Addition of TGF-beta for up to 30 min after exposure to activation factors significantly reduced macrophage killing of intracellular parasites. Pretreatment of macrophages with TGF-beta was even more effective: treatment of cells with TGF-beta for 4 h before addition of activation factors abolished all macrophage intracellular killing activity. Regardless of treatment sequence, however, TGF-beta had absolutely no effect, at any concentration tested, on activated macrophage resistance to infection induced by lymphokines or by the cooperative interaction of IFN-gamma and IL-4. Effects of TGF-beta on tumoricidal activity of activated macrophages was intermediate to that of its effects on intracellular killing or resistance to infection. Lymphokine-induced tumor cytotoxicity was marginally (25%) affected by TGF-beta; 200 ng/ml was able to suppress IFN-gamma-induced tumoricidal activity by 40%. Thus, TGF-beta dramatically suppressed certain activated macrophage cytotoxic effector reactions, but was only partially or not at all effective against others, even when the same activation agent (IFN-gamma) was used. The biochemical target for TGF-beta suppressive activity in these reactions may be the pathway for nitric oxide production from L-arginine, because TGF-beta also inhibited the generation of nitric oxide by cytokine-activated macrophages.
Central nervous system toxicity from nebulized atropine sulfate. Central anticholinergic intoxication can result from iatrogenic sources. We report the occurrence of a central anticholinergic syndrome in a patient treated with aerosolized atropine.
Noninvasive grading of musculoskeletal tumors using PET. Twenty-five patients with mass lesions involving the musculoskeletal system were studied with positron emission tomography (PET) in order to determine if a relationship exists between histologic grade and tumor uptake of [fluorine-18]2-deoxy-2-fluoro-D-glucose (FDG). There were 6 benign lesions and 19 malignant lesions of various grades. A high correlation (Rho = 0.83) was found between the normalized uptake of tracer and the NCl grade. The high-grade malignancies had significantly greater (p = 0.0091) uptake of FDG than the combination of benign lesions and low-grade malignancies. All lesions with a normalized uptake value of 1.6 or greater were high-grade, while all lesions less than 1.6 represented either benign tumors or low grade malignancies. This strong relationship between FDG uptake and grade among neoplasms from a wide variety of cell types within a single organ system suggests that the technique may be useful in predicting grade even when the cell type is unknown.
Cardiovascular causes of syncope. Identifying and controlling trigger mechanisms. Syncope usually has a cardiovascular source, so neurologic evaluation has a low diagnostic yield in these patients. Cardiac arrhythmias in persons with or without structural heart disease can produce syncope. Neurocardiogenic dysfunction that results in diminished venous return and hypercontractility is another frequent cause. Postural hypotension or left ventricular outflow obstruction may also be to blame. Careful history taking and physical examination, head-up tilt testing, echocardiography or radionuclide isotope imaging, and electrophysiologic study are often diagnostic. However, syncope remains undiagnosed in some patients, and they may require periodic reassessment. Treatment options are available for most cardiovascular disorders, among them use of pharmacologic agents; catheter, surgical, or radio-frequency modification of certain tachycardias; and permanent pacing.
Fact and fancy. What can we really tell from the placenta? Considerable interest in the clinical significance of placental abnormalities has been fueled by malpractice claims when perinatal outcome is less than optimal. The pathologist must be aware of those placental lesions that may contribute to perinatal morbidity and mortality. This article reviews the abnormalities of placentation, placental weight, maternal uteroplacental blood flow, villous histological makeup, fetoplacental blood flow, the umbilical cord, and the membranes, as well as the problems of multiple pregnancy. The important contribution of abnormal uteroplacental blood flow to adverse perinatal outcome is emphasized, as is the need to determine the extent of placental damage when evaluating the contribution thereto of particular placental abnormalities.
Pronounced reduction of aortic flow velocity and acceleration during heavy isometric exercise in coronary artery disease. Doppler-derived parameters of aortic flow were examined during heavy isometric exercise in 48 men with coronary artery disease (CAD) and in 48 gender- and age-matched healthy controls. The aim was to determine which parameters best separated the groups and to look for a possible relation between exercise-induced Doppler patterns and the extent of CAD. Isometric exercise was performed with a 2-hand bar dynamometer, and the subjects were required to perform 50% of maximal voluntary contraction for 2 minutes. Examination was performed with a pulsed Doppler transducer positioned at the suprasternal notch. Resting peak flow velocity, acceleration time, stroke volume index and cardiac index did not show significant differences between the groups. However, mean acceleration and stroke work were significantly lower in patients with CAD. In this group, exercise peak flow velocity decreased from 98 +/- 13 to 55 +/- 12 cm/s, flow velocity integral from 14 +/- 3 to 7 +/- 3 cm, mean acceleration from 11 +/- 0.9 to 4.7 +/- 1 m/s/s, and stroke volume index from 41 +/- 6 to 23 +/- 4 ml/m2 (p less than 0.001 for all). Cardiac index decreased from 2.7 +/- 0.4 to 2 +/- 0.2 liters/min/m2 (p less than 0.05). Acceleration time increased from 82 +/- 6 to 116 +/- 7 ms. In most of the indexes, the directional changes induced by isometric exercise were similar in patients with CAD and in normal control subjects. The differences compared with the rest values were significantly greater in the CAD group, and especially in patients presenting with 3-vessel disease.
Mayer-Rokitansky-Kuster-Hauser syndrome associated with endodermal sinus tumor of the ovary. Both EST and Mayer-Rokitansky-Kuster-Hauser syndrome are uncommon disorders. This report illustrates a case of these two rare conditions occurring in the same patient. Patients with Mayer-Rokitansky-Kuster-Hauser syndrome, although not appearing to be at increased risk for germ cell tumors, unlike testicular feminization patients, are not immune to ovarian cancer. Therefore, individuals with Mayer-Rokitansky-Kuster-Hauser syndrome should still be followed gynecologically because they are at least at the normal risk of developing ovarian as well as other gynecological neoplasms.
Structure-dependent dynamic mechanical behavior of fibrous caps from human atherosclerotic plaques. BACKGROUND. Although thrombosis associated with a fissured atherosclerotic plaque is believed to be the most common cause of acute coronary syndromes, the underlying factors that trigger plaque rupture are currently unknown. However, the mechanical behavior of the plaque is probably of critical importance. METHODS AND RESULTS. To test the hypothesis that the mechanical properties of a plaque are dependent on its composition and, in particular, that the stiffness of fibrous caps changes within the range of frequencies carried by a physiological pressure wave, the stress-strain relation was studied in 27 fibrous caps and related to the underlying histological structure of the fibrous cap. Fibrous caps were obtained during 14 autopsies from the abdominal aorta and were classified by histological examination as cellular (n = 7), hypocellular (n = 9), or calcified (n = 11). Hypocellular fibrous caps were 1-2 times stiffer than cellular caps (p less than 0.005), and calcified caps were 4-5 times stiffer than cellular caps (p less than 0.005). All 27 fibrous caps demonstrated an increase in stiffness with increasing frequencies of stress ranging from 0.05 to 10 Hz; the increase in stiffness was similar in all three histological classes. CONCLUSIONS. We conclude that the stiffness of fibrous caps from human atherosclerotic plaques is related to the underlying histological structure and that the stiffness increases with frequency in the range of physiological heart rates. The protective benefit of beta-adrenergic receptor blocking agents in coronary artery disease may, in part, be related to the frequency dependence of atherosclerotic plaque stiffness.
Identical orocecal transit time and serum motilin in hyperthermia and normothermia. Fever, exercise, and exposure to a hot environment can all cause symptoms of gastrointestinal dysfunction as they elevate body temperature. Nonetheless, the link between hyperthermia per se and these symptoms is unknown. To test the functional significance of increased body temperature, we investigated the influence of substantial passive hyperthermia on orocecal transit in 12 young, healthy men. Transit time was determined by a consistent rise in H2 concentration in a rebreathing apparatus after oral ingestion of 0.7 g lactulose/kg body weight. Lactulose was given in combination with a 350-ml liquid meal (360 kcal). After raising core temperature in warm water to 38.3 degrees C, orocecal transit time was identical to control (90 +/- 13 min at 38.3 degrees C, 92 +/- 13 min at 37.1 degrees C). While hyperthermia did elevate heart rate and minute ventilation, serum motilin, gastrin, and cortisol were similar in the two conditions. The failure of a passive core temperature rise to alter mouth-to-cecum transit suggests that this aspect of alimentary function is independent of body temperature.
Breslow thickness of cutaneous malignant melanoma in paraffin wax and frozen sections. Breslow tumour thickness was measured in frozen and paraffin wax sections from 21 excision biopsies of cutaneous malignant melanomas by two observers. There was no consistent variation between frozen and paraffin wax sections, with recorded differences ranging from +0.3 mm to -0.2 mm. Interobserver differences ranged from +0.4 mm to -0.2 mm. The interobserver variations exceeded the intraobserver variations, but neither were significant. These findings show conclusively that, when using high quality frozen sections, there is no significant difference between Breslow thickness measured in frozen or paraffin wax sections and therefore that frozen sections can be used to microstage melanoma. Interobserver variations seem to be a more likely source of erroneous measurements of tumour thickness.
A randomized trial evaluating leuprolide acetate before hysterectomy as treatment for leiomyomas. Fifty premenopausal patients requiring hysterectomy as treatment for symptomatic uterine leiomyomas, which were the size of 14 to 18 weeks' gestation, were randomized into two groups to determine whether preoperative gonadotropin-releasing hormone agonist would increase the feasibility of vaginal rather than abdominal hysterectomy. The control group (group A; n = 25) did not receive preoperative gonadotropin-releasing hormone agonist, but patients in Group B (n = 25) received 2 months of gonadotropin-releasing hormone agonist before undergoing hysterectomy. Patients in the two groups were similar with respect to age, gravidity, parity, pretreatment uterine size, and hemoglobin and hematocrit levels. Patients in group B had an increase in hemoglobin levels (10.75 to 12.12 gm/dl, p less than 0.05) and a decrease in uterine volume (1086.7 to 723.4 ml, p less than 0.05) after 8 weeks of agonist therapy and were more likely to undergo vaginal hysterectomy (76.0% vs 16%). Patients in group B also had shorter hospitalizations (5.2 vs 3.8 days, p less than 0.05). We conclude that the administration of gonadotropin-releasing hormone agonist for 2 months followed by vaginal hysterectomy is preferable to abdominal hysterectomy in selected patients with uterine leiomyomas.
Cleft palate fistulas: a multivariate statistical analysis of prevalence, etiology, and surgical management. A retrospective, multivariate statistical analysis of 129 consecutive nonsyndromic patients undergoing cleft palate repair was performed to document the incidence of postoperative fistulas, to determine their cause, and to review methods of surgical management. Nasal-alveolar fistulas and/or anterior palatal fistulas that were intentionally not repaired were excluded from study. Cleft palate fistulas (CPFs) occurred in 30 of 129 patients (23 percent), although nearly a half were 1 to 2 mm in size. Extent of clefting, as estimated by the Veau classification, was significantly more severe in those patients who developed cleft palate fistula. Type of palate closure also influenced the frequency of cleft palate fistula. Forty-three percent of patients undergoing Wardill-type closures developed cleft palate fistula versus 10, 22, and 0 percent for Furlow, von Langenbeck, and Dorrance style closures, respectively. The fistula rate was similar in patients with (30 percent) and without (25 percent) intravelar veloplasty. Age at palate closure did not significantly affect the rate of fistulization; however, the surgeon performing the initial closure did not have an effect. Thirty-seven percent of patients developed recurrent cleft palate fistulas following initial fistula repair. Recurrence of cleft palate fistulas was not influenced by severity of cleft or type of original palate repair. Following end-stage management, a second cleft palate fistula recurrence occurred in 25 percent of patients. Continued open discussion of results of cleft palate repair is recommended.
Deafness after bilateral midbrain contusion: a correlation of magnetic resonance imaging with auditory brain stem evoked responses. A 46-year-old woman became deaf after a closed head injury. When a computed tomographic scan failed to disclose the cause, conversion disorder was suspected. Magnetic resonance imaging, however, showed bilateral contusions of the inferior colliculi, providing objective evidence for an organic cause of hearing loss. Auditory brain stem evoked responses and stapedial reflexes also provided objective evidence of brain stem injury. This case illustrates the phenomenon of dorsal midbrain injury after head trauma. It indicates the sensitivity of magnetic resonance imaging for small focal lesions after head trauma, and it demonstrates some difficulties in the diagnosis of "hysterical" deafness.
Chronic cough in children. Chronic cough in children is a frequent complaint seen by the primary health care provider. Although many of these coughs spontaneously resolve, some are caused by a more serious process and require further attention. Selecting those patients who will benefit from a more extensive evaluation can be a difficult challenge. An overview is provided that emphasizes a systematic approach to the diagnosis and management of chronic cough.
Acute hemorrhagic diarrhea and cardiovascular collapse in a young child owing to environmentally acquired cocaine. Acute crack cocaine intoxication has become a significant problem in both adolescent and adult patients. Recently, cases of cocaine toxicity in infants and toddlers have been described. We report a four-year-old child with acute hemorrhagic diarrhea and shock after intoxication by crack cocaine. Acute cocaine intoxication should be considered in the differential for hemorrhagic diarrhea and shock. The gastrointestinal decontamination following cocaine ingestion is discussed.
Intracellular calcium and ventricular fibrillation. Studies in the aequorin-loaded isovolumic ferret heart. To elucidate the role of changes in [Ca2+]i in the induction of ventricular fibrillation (VF), Ca2+i signals, epicardial electrical potentials, and isovolumic left ventricular pressure were simultaneously recorded in isolated intact ferret hearts loaded with aequorin, a bioluminescent protein. When the preparations were perfused with 3 microM acetylstrophanthidin and 8 mM Ca2+, or with a low Na+ solution (18 mM Na+, 100 mM Li+), spontaneous transitions to the VF state were consistently observed within a short period of time. The initiation of spontaneous VF was preceded by development of a Ca2+i overload state, coincidental with the ascending phase of diastolic Ca2+i oscillations, and was followed by further elevation in Ca2+i levels, which were associated with augmented Ca2+i oscillations of a saw-toothed pattern. Pretreatment with 10 microM ryanodine, which blocked Ca2+i oscillations in the preparation, did not eliminate inducibility of VF by means of AC electrical stimulations; however, VF no longer occurred spontaneously, and the threshold for VF induction increased markedly. In the absence of a state of Ca2+i overload, spontaneous defibrillation occurred within a minute after the initiation of VF. We conclude that 1) VF can be induced in the absence of Ca2+i oscillations; however, 2) Ca2+i oscillations play a crucial role as a trigger for VF and therefore are an important determinant of the vulnerability to VF; and 3) the augmented Ca2+i oscillations after the transition to VF state may support the maintenance of this type of arrhythmia.
Urinary fibrinopeptide A in evaluation of patients with suspected acute pulmonary embolism. A prospective pilot study. This pilot study assessed the urinary fibrinopeptide A (uFPA) levels and the combination of uFPA test plus ventilation/perfusion (V/Q) scan in the diagnostic evaluation of acute pulmonary embolism (PE). One hundred consecutive patients were studied prospectively. Twenty-nine patients fulfilled diagnostic criteria defined in this study (seven with and 22 without PE). The uFPA concentration was significantly higher in patients with than without PE (41.1 +/- 2.6 vs 4.8 +/- 2.5 ng/mg of creatinine, p less than 0.0001). In all patients with PE, the uFPA levels were higher than threshold value derived by adding 2 standard deviations to the mean uFPA concentration of patients without PE. In patients without PE, the V/Q scan was negative in 16, the uFPA test was negative in 18, and at least one of the tests was negative in 21. These preliminary data suggest that a negative uFPA test may be helpful in excluding PE and that uFPA in combination with V/Q lung scans may correctly exclude PE in more patients than either test alone. Further studies in a large unselected population are needed to confirm these results.
Simian immunodeficiency virus (SIVsm) isolation from blood and brain of experimentally infected macaques. The possibility of using simian immunodeficiency virus (SIV)-infected macaques to study pathogenic events linked to HIV infection of the brain prompted us to investigate some of the virological features in SIV-infected macaques. Nine cynomolgus macaques were inoculated with SIVsm and killed at different times. We successfully isolated virus from the blood of all the animals and from the brains of eight. These results point to the early and regular spread of this lentivirus to the brain. Neutralizing activity was studied in the serum and cerebrospinal fluid specimens obtained from these macaques against a selected group of isolates. Cerebrospinal fluid did not show any neutralizing activity. Our findings integrate the observations from HIV-1 infection in man and indicate that SIV infection of macaques is a useful model for studying pathogenic events of brain infection.
Clinical relevance of tumor cell ploidy and N-myc gene amplification in childhood neuroblastoma: a Pediatric Oncology Group study. We assessed tumor cell DNA content (ploidy) and N-myc gene copy number as predictors of long-term disease-free survival in 298 children with neuroblastoma. Diploid tumor stem lines were identified in 101 patients (34%), clonal hyperdiploid abnormalities in 194 (65%), and hypodiploid stem lines in three (1%). In children with widely disseminated tumors at diagnosis (stage D), ploidy had a highly age-dependent influence on prognosis. Among infants (less than 12 months) treated with cyclophosphamide-doxorubicin, hyperdiploidy was closely associated with long-term disease-free survival (greater than 90% of cases), while diploidy invariably predicted early treatment failure (P less than .001). Similarly, in children 12 to 24 months of age who were treated with cisplatin-teniposide and cyclophosphamide-doxorubicin, diploidy uniformly predicted early failure, whereas half of the children with hyperdiploidy achieved long-term disease-free survival (P less than .001). There was no relationship between ploidy and treatment outcome in children older than 24 months with stage D tumors who had a very low probability of long-term disease-free survival (less than 10%). N-myc gene amplification was detected in 37 (25%) of the 147 tumors tested, with the remainder showing single-copy levels of the gene. N-myc gene amplification was more frequent in diploid than in hyperdiploid tumors (23 of 57 v 14 of 87, P = .001) and predicted a high likelihood of early treatment failure. In children younger than 2 years with disseminated neuroblastoma, tumor cell ploidy and N-myc gene copy number provide complementary prognostic information that will distinguish patients who can be cured on current regimens from those who require new treatment strategies.
Bradycardic responses to vagally mediated bedside maneuvers in healthy volunteers. PURPOSE: To determine the relative potency in healthy individuals of the vagally mediated reflexes used clinically to inhibit sinoatrial and atrioventricular node function. SUBJECTS AND METHODS: Twenty healthy volunteers with no history of heart disease performed face immersion in cold water and the Valsalva maneuver twice, to maximum endurance and to the subjective point of first discomfort, and face immersion in warm water and the Muller maneuver to maximum endurance only. Right and left carotid massage and left, right, and bilateral eyeball compression were each performed for 15 seconds. Change in heart rate was taken as baseline minus the rate over the slowest three consecutive QRS cycles elicited by each maneuver. Fisher's least-significant-difference multiple comparison procedure was used to analyze heart rate responses. Significance was defined as p less than or equal to 0.05. RESULTS: Maximum pulse decrements from baseline and 95% confidence intervals in beats/minute were as follows: cold-water face immersion to maximum endurance 15.5 (12.3 to 18.5), cold-water face immersion to first discomfort 10.1 (6.7 to 13.1), Valsalva maneuver to maximum endurance 9.2 (6.3 to 12.4), Valsalva maneuver to first discomfort 8.3 (5.0 to 11.3), right carotid massage 7.3 (4.3 to 10.3), left carotid massage 5.2 (2.3 to 8.4), right eyeball compression 6.0 (3.1 to 9.2), left eyeball compression 6.6 (3.6 to 9.5), bilateral eyeball compression 6.0 (3.1 to 9.2), warm-water face immersion 7.0 (3.2 to 9.8), and Muller maneuver 1.6 (-1.3 to 4.9). Bradycardia was significantly greater for cold-water immersion of the face performed to maximum endurance than for all other maneuvers. CONCLUSION: In healthy subjects, the diving reflex is the most potent of the vagally mediated reflexes utilized in clinical practice. Immersion of the face in cold water may prove effective at the bedside when other maneuvers fail to augment vagal tone adequately.