Anaphylactic reaction to recombinant human erythropoietin.
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Adult↗
Biomedical subjects
G Fernandez
Publications and source records attributed to G Fernandez.
Rapid back to back adenosine stress/rest technetium-99m teboroxime myocardial perfusion SPECT using a triple-detector camera.
Technetium-99m-teboroxime is characterized by a high extraction fraction over a wide range of blood flow rates, rapid myocardial clearance and avid hepatic uptake. This study determined the imaging parameters and examined the clinical efficacy of a rapid back to back adenosine stress/rest teboroxime myocardial perfusion SPECT protocol using a triple-detector camera. Acquisition parameters were determined using cardiac phantom studies which were then applied in SPECT studies of 51 catheterized patients (22 with prior myocardial infarction) and 20 patients with a "low" (7.9% +/- 4.3%) likelihood of coronary artery disease. Technetium-99m-teboroxime (20-25 mCi) was injected at the third minute of adenosine infusion. Teboroxime (20-25 mCi) was also injected at rest, 15 min later. Stress followed by rest SPECT were completed within 25 min using a triple-detector camera and sequential, 1-min continuous rotations in alternating directions. Summed raw data from the first to second (1-2 min), second to third (2-3 min) and second to fifth (2-5 min) minutes of imaging following stress teboroxime injection were reconstructed and compared for image quality, degree of liver interference, and accuracy for diagnostic efficacy. In a subgroup of 30 patients, 2-8-min summed images were also reconstructed to compare this more conventional imaging protocol with our rapid acquisition. Image quality was fair to good in 75% of the 1-2-min, 84% of the 2-3-min and 2-5-min studies and 53% of the 2-8-min scans. The frequency of severe liver interference appeared to increase with the duration of imaging time (1-2 min: 3%; 2-3 min: 7%; 2-5 min: 8%) and was greatest (30%, p = 0.08) with 2-8-min images. Three patients (4%) had uninterpretable studies due to intense hepatic uptake. Overall sensitivity (95%) and specificity (71%) were equal for the 2-3-min and 2-5-min stress images and appeared better than in the 1-2-min images (84% and 57%, respectively). For the 2-8-min scans, vessel sensitivity (69%) and specificity (63%) appeared poorer than with 2-3-min studies (83% and 81%, respectively). Normalcy rates were 89% for the 2-3-min and 2-5-min and 79% for 1-2-min images. The back to back adenosine stress/rest teboroxime SPECT can be performed in 30 min using a triple-detector camera. Although overall high sensitivity and normalcy rates were achieved, the protocol is technically demanding. Interference due to intense liver uptake remains problematic.
Adenosine↗
D-penicillamine therapy associated with rapidly progressive glomerulonephritis.
A 55-year-old woman with advanced rheumatoid arthritis developed rapidly progressive glomerulonephritis with epithelial crescents and pulmonary hemorrhage following treatment with D-penicillamine. D-penicillamine was then withdrawn and a pulse therapy with methylprednisolone halted the progression of kidney and lung damage. We review the other cases previously reported and discuss pathogenesis and treatment of this rare condition.
Arthritis, Rheumatoid↗
Role of locally produced growth hormone-releasing factor in somatostatin regulation by fetal rat brain cells in culture.
To determine the possible physiological role of endogenous growth hormone-releasing factor (GRF) in the neuronal content and release of cerebral somatostatin (SS), we studied the effect of endogenous GRF blockade on the immunoreactive SS (IR-SS) content of cells and media in fetal rat cerebral cortical and hypothalamic cells in culture. Cells were cultured in minimum essential medium (MEM) with 10% fetal calf serum and 10% horse serum. After 7-10 days in vitro, media were replaced with MEM without sera containing anti-GRF immunoglobulins G (IgG) for 1, 5 or 24 h. Controls were incubated with equal amounts of IgG from normal rabbit serum (NRS). In another group of experiments, cells were incubated with GRF (10(-11) to 10(-7) M) for 1 or 24 h. Long-term exposure (24 h) to anti-GRF IgG resulted in decreased media and intracellular IR-SS content, in both cerebral cortical and hypothalamic cells. 24 h treatment with GRF caused a dose-dependent increase in the IR-SS content of cells and media, the stimulatory action being abolished by the addition of anti-GRF to plates containing 10(-7) M GRF. On the contrary, when cells were exposed to anti-GRF IgG for 1 h, IR-SS increased in the media as compared to the control group. Short-term incubation (1 h) with GRF (10(-9) to 10(-7) M) resulted in a dose-dependent inhibition of IR-SS content in the cells and media. This inhibitory action was partially prevented by the addition of anti-GRF to plates containing 10(-7) M GRF.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Epidemic dermatitis due to contact with a moth in Cozumel, Mexico.
In early December 1989, an outbreak that was initially thought to be scabies was investigated among employees of tourist hotels in Cozumel, Mexico. Of 417 employees interviewed, only 19 (4.6%) met a case definition for scabies dermatitis, while 91 (21.8%) reported a nonspecific dermatitis of less than one-week's duration. Persons with nonspecific dermatitis related the onset of their dermatitis to skin contact with a moth that had been present in large numbers in November. At the time of the initial investigation in December, there were no active cases of dermatitis and the moth was no longer present. During early January 1990, numerous cases of dermatitis again began to be reported. Using a case definition for nonspecific dermatitis, a survey of Cozumel's resident population showed an attack rate of 12.1%. A case-control study revealed the only significant risk factor to be skin contact with the suspect moth (P less than 0.01), which had returned in large numbers. Six health workers volunteered to have the moth rubbed on their skin; within 5 min, five of six developed an intense pruritus followed by an erythematous rash. The moth was classified as Hylesia alinda Druce. This species has nettling hairs on its abdomen that excrete a histamine-like substance. Although this moth is normally present in small numbers in Cozumel, the passage of hurricane Gilbert killed most of its natural predators (wasps and bees), allowing its population to overgrow. No control measures were undertaken because the moth's natural predators returned that spring and dramatically reduced the moth population. No further outbreaks of dermatitis occurred.
Adolescent↗
Prenatal sonographic detection of giant parietal foramina.
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Abnormalities, Multiple↗
Effects of Carbetimer, a new antineoplastic drug, on bone metabolism.
Carbetimer is a new antineoplastic agent whose main side effects consist of neurotoxicity and long-term dose-dependent hypercalcemia. We previously showed that Carbetimer is a potent calcium chelator responsible for an acute decrease in ionized Ca levels observed in vivo. However, the mechanism of the progressive increase in serum Ca remains unknown. We have evaluated the bone-resorbing effects of Carbetimer on 45Ca-prelabelled neonatal mouse calvariae. Carbetimer induced a dose-dependent increase in 45Ca release which started at a concentration of 1 mg/ml and reached a mean of 3.3 times the control values at 10 mg/ml. This marked increase in 45Ca release was similar on previously killed bones and could not be inhibited by calcitonin. Such concentrations are probably therapeutically relevant given the known affinity of Carbetimer for bone and the large daily doses administered to cancer patients (10-15 g). Since Carbetimer could exert its antineoplastic action through immunomodulation, we also studied its effects on the production of TNF-alpha and IFN-gamma which are also known to affect bone metabolism. Carbetimer did not stimulate TNF-alpha release from isolated normal human monocytes or lymphocytes, but it markedly inhibited T-lymphocyte production of IFN-gamma, which became undetectable at a concentration of 1 mg of Carbetimer/ml. In summary, Carbetimer-induced hypercalcemia appears to be due to a direct stimulation of osteolysis, but possibly also to an inhibition of IFN-gamma production.
Animals↗
Neurosecretory and trophic action on fetal rat neuroblasts induced by an amino acid mixture.
The effects of a synthetically obtained mixture of amino acids (FACE) were investigated on the trophic and neurosecretory activity of in vitro cultures of fetal rat neuronal cells. The addition of 10(-6) M FACE to the culture medium significantly increased cell DNA content. Secretions of IR-SRIF, IR-VIP, and IR-GRF were also augmented in different proportions by the presence of FACE. Time studies demonstrated that IR-SRIF was significantly increased after 48 (P less than 0.05) and 72 (P less than 0.01) hr of exposure to FACE, and IR-VIP secretion was potentiated after only 24 hr of culture. Dose-response experiments with 10(-7) to 10(-4) M FACE indicated that concentrations of 10(-5) and 10(-4) M significantly increased both somatostatin released to the medium and cell content of IR-SRIF. FACE concentrations as low as 10(-10) M augmented the secretion of IR-GRF, and there was a dose-response correlation between 10(-10) and 10(-5) M FACE. The release and cell content of IR-VIP were also increased by FACE, with a dose-response relation at concentrations of 10(-9) to 10(-6) M. It can thus be concluded that FACE has a powerful effect on the multiplication and survival of fetal cerebrocortical cells and is also an important potentiator of IR-SRIF, IR-VIP, and IR-GRF secretion.
Amino Acids↗
Therapeutic use of right atrial pressures early after the Fontan operation.
In 334 patients undergoing the Fontan operation, the right atrial pressure was 16 +/- 36 mm Hg (mean value +/- SD) 3 h postoperatively, and was on average higher in those who died or had a takedown of the operation than in those who did not (P = 0.0001). Twenty-four hours after operation, the right atrial pressure was 18 +/- 5.5 mm Hg, was higher in those who died or had a takedown than in those who did not (P less than 0.0001); and in those who died or had takedown it was 23.5 +/- 1.66 mm Hg and higher than at 3 h postoperatively (18.7 +/- 0.52). The left atrial pressure 3 h postoperatively was 9 +/- 3.6 mm Hg, and on average was higher in the patients who died or had a Fontan takedown than in those who did not. The continuous relation between right atrial pressure and the probability of death or takedown during the first 24 postoperative hours was such as to recommend consideration of takedown whenever the right atrial pressure reaches 22 mm Hg, and when higher, the recommendation is made with greater urgency.
Adolescent↗
Outcome after a "perfect" Fontan operation.
A study was undertaken to determine the early and long-term outcomes dictated by the Fontan state per se (a state in which the force driving pulmonary blood flow is solely or largely a residue, in the systemic venous pressure, of the main ventricular chamber's contractile force) and the transition (by surgery) to it from the state of congenital heart disease under optimal conditions (after a "perfect" Fontan operation). The primary study design used a solution of a multivariate risk factor equation for death, by which survival rate under optimal conditions was predicted to be 92%, 89%, 88%, 86%, 81%, and 73% at 1 month, 6 months, and 1, 5, 10, and 15 years, respectively, after the Fontan operation. The hazard function (instantaneous risk of death at each moment in time after the operation) had an early rapidly declining phase of hazard that at about 6 months began to give way to a late hazard phase, which was rising by about 6 years after surgery. A secondary study design, using the theory of competing risks, yielded survival and hazard function information very similar to that of the primary study design. The functional capacity of the patients as expressed by New York Heart Association class was less, the longer the period of follow-up. No risk factors (other than older age at time of surgery) were found for the late decline in survival or the decline in functional status. The inference is that the premature decline in survival and functional status and the late rise in hazard function are from the Fontan state per se and that the Fontan operation is, therefore, palliative but not curative.
Adolescent↗
Calcitonin receptors on circulating normal human lymphocytes.
Circulating human lymphocytes possess specific and functional receptors for calcitriol and PTH. We sought to determine if they also possessed receptors for calcitonin (CT), the third classical calciotropic hormone. We isolated blood mononuclear cells from healthy volunteers to separate monocytes, total lymphocytes, and T-lymphocytes; the purity of the three cell populations was more than 90%, 95%, and 85%, respectively. Salmon CT (sCT) was labeled by the chloramine-T method (SA, 254 muCi/micrograms) without loss of biological activity. We found saturable (16 h at 8 C), specific, high affinity binding sites for [125I]sCT on unstimulated lymphocytes. As for CT receptors on other cells, binding of [125I]sCT was poorly reversible. Binding specificity was demonstrated by the total absence of competing effect of several unrelated hormones; human CT and CT gene-related peptide competed much less efficiently than sCT for the binding sites, whereas PDN-21 had no effect. When plotted according to the method of Scatchard, binding data on the mixed population of T- and B-lymphocytes showed an apparent Kd (mean +/- SD) of 2.9 +/- 1.0 x 10(-10) M (n = 34), with an estimation of 91-8338 (median, 1971) binding sites/cell. The data were repeatedly compatible with an aspect of positive cooperativity between the binding sites, as confirmed by a Hill coefficient greater than 1 (1.18 +/- 0.13). However, this aspect of positive cooperativity in CT binding was not observed on isolated T-lymphocytes (Hill coefficient, 0.96 +/- 0.08; n = 9; P less than 0.001 vs. the mixed population of lymphocytes). CT did not induce a significant increase in cAMP levels, but regulation of receptor concentration was demonstrated by the finding of down-regulation of CT-binding sites after sCT or human CT preincubation. In summary, we have found saturable, specific, high affinity receptors for CT on unstimulated normal human T-lymphocytes, which could, thus, be target sites for CT action on bone metabolism or on the immune system.
Animals↗
Prevalence of reoperation for pathway obstruction after Fontan operation.
Among 334 patients undergoing the Fontan operation at two institutions and followed for a long time, freedom from reoperation for Fontan pathway obstruction was 99% at 1 year after operation and 96%, 86%, and 59%, respectively, at 5, 10, and 15 years after operation. The hazard function for reoperation had an initial very rapidly declining phase and a second phase that was still rising 15 years after operation. Twelve (17%; confidence limits [CL], 13% to 23%) of 69 patients with a right atrial to right ventricular conduit (valved or nonvalved) connection underwent reoperation for pathway obstruction, whereas only 2 (4%; CL, 1% to 10%) of 45 patients with a direct connection to the right ventricle required reoperation. Five (8%; CL, 4% to 13%) of 65 patients with a right atrial to pulmonary artery conduit connection required reoperation for pathway obstruction, and only 2 (1.3%; CL, 0.4% to 3%) of 155 patients with a direct right atrial to pulmonary artery connection required reoperation. These findings have implications as to the optimal technique of the Fontan operation and also as to use of an intraatrial tunnel as part of the repair.
Adolescent↗
Long-term evaluation of direct repair of traumatic isthmic aortic transection.
Direct repair of traumatic aortic isthmic transection eliminates the late complications of prosthetic graft repair. This study evaluates the long-term fate of direct aortic repair to which little attention has been paid. Among 32 patients operated upon from 1965 to 1987, 27 (84%) underwent direct repair. The tear was circumferential in 15 patients and partial in 12. Multiple traumatic lesions were present in 26 patients, including intracranial injury in 19. Partial cardiopulmonary bypass was used in 15 patients and simple aortic cross-clamping in 12. No paraplegia was observed. There were 4 deaths from associated lesions among the 14 patients operated upon for acute traumatic isthmic transection and no deaths in the others. Among the 23 survivors, 4 were lost to follow-up; the other 19 patients have excellent clinical results. Intravenous digital aortic angiography performed in 14 patients at a mean delay of 5 years 3 months showed excellent aortic reconstruction in all cases. Technically more demanding and faster than a graft interposition, direct repair is recommended as the procedure of choice in the surgical treatment of traumatic isthmic transection, particularly in young patients, the group most at risk from this lesion.
Adolescent↗
Growth hormone-releasing factor production by fetal rat cerebrocortical and hypothalamic cells in primary culture.
Recent data from our laboratory and others have shown radioimmunoassayable GRF (IR-GRF) in the rat brain cortex. In the present study the ontogenesis of immunoreactive rat(r) GRF (IR-GRF) in long term dissociated fetal rat cerebrocortical and hypothalamic cell cultures and the regulation of its secretion by potassium depolarization and calcium channel-blocking agents were investigated. The chromatographic profiles of IR-rGRF from cell extracts were determined and compared with those from in vivo cerebrocortical and hypothalamic tissues. Mechanically dispersed cultured telencephalic and diencephalic cells from 17- to 21-day-old fetal rats showed a progressive increase in IR-rGRF, reaching maximum values (media plus cells) between 775-1020 (pg/mg protein) in hypothalamic cells on days 10-20 and between 450 and 950 pg/mg protein in cortical cells on days 25-30. IR-rGRF from acidic extracts of cells and adult cortical and hypothalamic tissues adsorbed onto octadecylsilyl-silica columns corresponds primarily to rGRF-(1-43)OH on HPLC. In gel filtration chromatography, almost all IR-rGRF from cultured cerebrocortical cells and fetal and adult cortical tissues coeluted with rGRF-(1-43)OH. IR-rGRF from cultured hypothalamic cells showed an additional component with a higher mol wt eluting in the void volume. To determine the influence of membrane depolarization of rGRF release, potassium (K+) concentrations in the medium were increased to 30 and 56 mM, inducing a marked increase in medium rGRF concentrations. Verapamil, a Ca2+ channel blocker (20 microns) reverses the effect of 56 mM potassium depolarization, suggesting that it is at least partially dependent upon Ca2+ transport. These data indicate that fetal rat cerebrocortical and hypothalamic cells in culture produce and release rGRF in response to depolarizing agents. The presence of rGRF in cortical tissue suggests that there are other physiological roles besides those implicated in the stimulation of GH secretion.
Animals↗
[Low molecular weight heparins].
The apparition in the 80's of low molecular weight heparins (LMWHs) obtained by chemical or enzymatical splitting, modified the fields of prophylactic treatment of thromboembolic diseases. These drugs present on heparin numerous advantages: equal antithrombotic activity with a smaller bleeding risk, higher bioavailability, longer pharmacokinetic, which simplify their use. The definite mode of action remains unknown, but LMWH act at different steps like coagulation (by AT III), fibrinolysis, blood cells, endothelial cells. Further, like heparin, they can be neutralized by protamine. However the right, simple, specific biological assay which presents a good correlation with the antithrombotic activity, remained to be established.
Heparin, Low-Molecular-Weight↗
[Long-term results (6 to 17 years) of 372 mitral valve replacements using the Björk-Shiley prosthesis].
From November 1970 to December 1981, an isolated mitral valve replacement was performed in 372 patients (166 males - 206 females), ranging in age from 2 months to 76 years (mean age 49 years). Eighty-nine patients (24%) had previously undergone one or two cardiac operations. Only one of the 24 hospital deaths (6.4%) was related to the prosthesis (early thrombosis). Three hundred and fourty-eight patients were discharged from the hospital, 35 were lost to follow-up, and 313 were observed with a mean follow-up of 8 years 8 months (ranging from 5 years 2 months to 16 years 3 months). Ninety-two patients (29.4%) died from 2 months to 16 years post-operatively. Thirteen late deaths were from extra cardiac causes. Cardiac failure and thromboembolic or haemorrhagic complications represent the main causes of late mortality, respectively 10 and 6.7%. Twenty-one deaths were related to the prosthesis (10 thrombo-embolic accidents, 7 haemorrhagic complications and prosthesis could be discussed in 11 cases of sudden deaths and in 12 cases of death of undetermined causes. Among the 34 thrombo-embolic complications and the 13 perivalvular leakages (6 of them related to infection), 23 patients required reoperation, for valve thrombosis (14 cases with 2 deaths) or perivalvular leakage (9 cases with 2 deaths). Four other cases of valve thrombosis were treated with fibrinolytic agents with 1 death. The actuarial survival rate, hospital mortality excluded, is 69% at 10 years and 55% at 15 years.(ABSTRACT TRUNCATED AT 250 WORDS)
Actuarial Analysis↗
The size of the pulmonary arteries and the results of the Fontan operation.
All patients (n = 334) undergoing the Fontan operation at the University of Bordeaux, France, and the University of Alabama Medical Center, Birmingham, were entered into a single data base to examine the relation, if any, between size of the pulmonary arteries and outcome. Recent follow-up was made of all patients. The time-related freedom from death or takedown of the Fontan operation was 78% at 1 month, 73% at 6 months, and 72%, 68%, 61%, and 50% at 1, 5, 10, and 15 years after the operation. The hazard function (instantaneous risk of the combined event at each moment in time after the operation) had a rapidly declining early phase that gave way at about 6 months to a late phase of hazard, which began slowly to rise about 8 years after the operation. One of the most powerful risk factors for death or takedown of the Fontan operation was the dimensions of the right and left pulmonary arteries, expressed as a McGoon ratio. By multivariate analysis, the risk of the combined event increased sharply when the McGoon ratio was less than about 1.8, and when the ratio was as low as 1.2 the probability of death or takedown within 30 days of the operation was predicted to be 55% when the right atrium was connected to the pulmonary artery and 34% when connected to the right ventricle. Other risk factors identified were age at operation, the presence of mitral atresia, the degree of main chamber hypertrophy, elevated pulmonary artery pressure, non-use of cardioplegia, global myocardial ischemic time, and attachment of the right atrium to the pulmonary artery rather than to the right ventricle.
Blood Vessel Prosthesis↗
Exclusive double outlet right ventricle with atrioventricular concordance and pulmonary stenosis. Results of reconstructive surgery.
Double outlet right ventricle associated with atrioventricular concordance, pulmonary stenosis and situs solitus of the atria is a subset of double outlet right ventricle related through the surgical treatment. From 1974 to 1985, 14 patients, 5 males, 9 females (mean age 8.9 years, range 13 months-22 years) were operated upon. All patients had infundibular stenosis and normal or large pulmonary arteries. The apex of the heart was to the right in 2 patients, the right and left ventricles were superior and inferior in 2 patients and 1 patient had both anomalies. The ventricular septal defect was subaortic in 11 patients (aorto-mitral discontinuity in 5) and non-committed in 3 patients. Three patients had 2 ventricular septal defects. The aorta was anterior in 3 patients and to the right of the pulmonary artery in 11 patients. All patients, through a transventricular and transatrial approach, had a reconstructive surgery. In 3 patients, an aortic homograft valved conduit was used. One patient had the ventricular septal defect enlarged. There was one early death (7.1%) from high residual right ventricle pressure and no late death. One patient had a transient atrioventricular block. One patient was reoperated upon for a residual ventricular septal defect. All survivors had a good clinical result. Re-evaluation in 8 patients confirmed excellent haemodynamics: the right ventricle to pulmonary artery pressure gradient decreased from 80 mm Hg (range 60-95) preoperatively to 24 mm Hg (range 3-32) postoperatively.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗