Prognostic factors for myasthenia gravis treated by thymectomy: review of 61 cases.

BACKGROUND: Medical treatment for myasthenia gravis (MG) involves the use of anticholinesterase agents, immunosuppressive drugs, plasmapheresis, and gamma-globulin. However, these agents result in a complete clinical remission rate as low as 15%. As a consequence, thymectomy, preferably by transsternal approach, has become increasingly accepted as an efficacious procedure for MG, with reported complete clinical remission rates as high as 80%. METHODS: We have the clinical records of 61 patients diagnosed with MG at La Paz University Hospital, Madrid, Spain, from January 1977 to December 1994. All patients underwent thymectomy. The purpose of this investigation was to determine the major prognostic factors predicting MG outcome after operation. RESULTS: Our results indicate that patients with a length of the disease from onset to operation shorter than 8 months have the best prognosis. Ossermann stages I and III are also associated with higher complete clinical remission rates. In contrast, neither age nor sex were found to be significantly related to MG outcome after thymectomy, although female patients have better prognosis than men, and the younger the patient the more likely is complete clinical remission. Pathologic findings after the operation were not found to be of prognostic value either. CONCLUSIONS: We conclude that thymectomy is a beneficial procedure for MG patients, with a complete clinical remission rate of 46% at 5 years postoperatively in our series. Therefore we advocate thymectomy for MG patients as early as possible in the course of disease because time elapsed from diagnosis to operation is the main determinant of the outcome.

Repeated direct fetal intravascular high-dose immunoglobulin therapy for the treatment of Rh hemolytic disease.

Recently, administration of high-dose intravenous immunoglobulin (HDivIG) either to the mother or the neonate has been proposed in an effort to prevent progressive hemolysis in Rh(D) perinatal disease, but no cases have been published with direct fetal HDivIG administration. We report a case in which HDivIG was repeatedly administered by cordocentesis to a fetus affected by Rh(D) disease from 28 to 36 weeks gestation, at doses of approximately 450 mg/kg. The fetus required no transfusions, and the neonatal evolution was satisfactory. The treatment, performed at three weeks intervals, seemed to be useful in preventing fetal hemolysis. No fetal complications were present. Recurrent administration of HDivIG therapy to the fetus in cases of severe Rh(D) disease, appears to be feasible and free of serious complications to the fetus or the mother.

Effects of long-term, high-altitude hypoxemia on ovine fetal cardiac output and blood flow distribution.

OBJECTIVE: We sought to determine the effects of long-term hypoxemia on fetal cardiac output and flow distribution. STUDY DESIGN: We exposed six pregnant sheep to high altitude (3820 m) hypoxia from 30 to 135 days' gestation (term 146 days). Ten to 14 days after surgery we determined fetal cardiac output and organ blood flows by means of the radiolabeled microsphere technique during a baseline period and also during an additional 30-minute period of more severe added acute hypoxemia. RESULTS: Baseline maternal arterial PO2 was 60.7 +/- 1.7 torr and fell to 35.1 +/- 3.0 torr during the added acute hypoxemia. Fetal arterial PO2 decreased from 18.5 +/- 1.1 to 11.4 +/- 1.5 torr during added acute hypoxemia. Baseline fetal cardiac output was 351 +/- 55 ml/min/kg, which was significantly lower than previously reported values in low-altitude fetuses. Blood flow to critical organs such as the heart and brain was maintained at levels found in low-altitude fetuses, but flow to the carcass was significantly lower (-49%) than the mean value reported in the literature for low-altitude fetuses. Oxygen delivery was also maintained at normal levels to the brain and heart but was reduced in the kidneys (-31%), gastrointestinal tract (51%), and carcass (-58%). During added acute hypoxemia cardiac output did not change significantly; however, blood flow to the brain, heart, and adrenal glands increased 112%, 135%, and 156% (p < 0.05), respectively. CONCLUSION: We conclude that during long-term hypoxemia redistribution of fetal cardiac output is maintained favoring the brain and heart.

Carbohydrate metabolism during intense exercise when hyperglycemic.

The effects of hyperglycemia on muscle glycogen use and carbohydrate metabolism were evaluated in eight well-trained cyclists (average maximal O2 consumption 4.5 +/- 0.1 l/min) during 2 h of exercise at 73 +/- 2% of maximal O2 consumption. During the control trial (CT), plasma glucose concentration averaged 4.2 +/- 0.2 mM and plasma insulin remained between 6 and 9 microU/ml. During the hyperglycemic trial (HT), 20 g of glucose were infused intravenously after 8 min of exercise, after which a variable-rate infusion of 18% glucose was used to maintain plasma glucose at 10.8 +/- 0.4 mM throughout exercise. Plasma insulin remained low during the 1st h of HT, yet it increased significantly (to 16-24 microU/ml; P less than 0.05) during the 2nd h. The amount of muscle glycogen utilized in the vastus lateralis during exercise was similar during HT and CT (75 +/- 8 and 76 +/- 7 mmol/kg, respectively). As exercise duration increased, carbohydrate oxidation declined during CT but increased during HT. Consequently, after 2 h of exercise, carbohydrate oxidation was 40% higher during HT than during CT (P less than 0.01). The rate of glucose infusion required to maintain hyperglycemia (10 mM) remained very stable at 1.6 +/- 0.1 g/min during the 1st h. However, during the 2nd h of exercise, the rate of glucose infusion increased (P less than 0.01) to 2.6 +/- 0.1 g/min (37 mg.kg body wt-1.min-1) during the final 20 min of exercise. We conclude that hyperglycemia (i.e., 10 mM) in humans does not alter muscle glycogen use during 2 h of intense cycling.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of whole-body pH changes on thoracic duct lymph flow in anesthetized sheep.

Physiologic alterations of pH in vitro produce alterations of the oncotic pressure of both plasma and interstitial proteins, the effect being more marked in the latter. Therefore we postulated that by changing an animal's pH we could produce alterations in fluid distribution and affect the whole-body lymph flow rate. To test this hypothesis, we infused seven acutely nephrectomized anesthetized sheep with 2% body weight/volume isosmotic lactated Ringer's solution and bicarbonate (200 mEq) after a 30-minute control period. The fluid was infused over a 10-minute period with 20-minute recovery intervals. To another group of seven ewes, we infused the same volume of lactated Ringer's solution and hydrochloric acid (40 mEq). Throughout the experiment, we continuously measured arterial and venous pressures and lymph flow rate. Every 10 minutes we obtained samples for arterial pH, for hematocrit, and for plasma and lymph protein and osmolality. The infusion of bicarbonate was associated with a comparatively lower peak lymph flow rate (383% over baseline compared with 757% for acid infusion). Also the lymph flow rate after acid infusion started to increase approximately 5 minutes after the beginning of the infusion, as compared with approximately 10 minutes after the base infusion. Acid infusion did not increase arterial pressure, in contrast to the other infusions. The changes in pH obtained with the infusions were insignificant for the Ringer's infusion, +0.17 for the base, and -0.16 for the acid. The plasma/lymph protein concentration ratios at the end of the infusion were no different for acid or base: 112.4% +/- 4.4% and 101.9% +/- 5% (difference from control, mean +/- SEM) respectively (p greater than 0.1). In conclusion, minimal alterations of pH produced alterations in the cardiovascular and lymph flow rate responses to fluid challenge in anesthetized animals.

Cardiac function during long-term hypoxemia in fetal sheep.

To examine right ventricular function during long-term hypoxemia, we instrumented 12 fetal sheep with intravascular catheters and an electromagnetic flow probe on the pulmonary artery. In six cases, hypoxemia was induced by infusing N2 gas into the maternal trachea for 2 wk. Maternal arterial PO2 was less than 60 Torr, and fetal arterial PO2 was reduced from approximately 26 to approximately 19 Torr. Six cases served as nonhypoxic controls. We studied fetal cardiac function by increasing either preload with a volume infusion of 5% (wt/vol) dextrose or afterload by administering methoxamine (alpha-adrenergic agonist). In hypoxic animals, right ventricular output (QRV) and stroke volume (SV) were not affected on the first 2 days but fell 30% on day 3. Fetal arterial pressure (Pfa) increased 20%, hemoglobin concentration increased approximately 30%, and fetal heart rate (FHR) showed minimal changes. Within 2 wk, QRV recovered to normal values, whereas ventricular sensitivity to arterial pressure was reduced. We observed no change in plasma concentration of "cardiac enzymes" or differences in fetal growth between groups. In conclusion, during prolonged hypoxemia, right ventricular function showed a triphasic response (primary maintenance, secondary depression, and subsequent recovery), achieving a new steady state 2 wk after the start of hypoxia, characterized by decreased sensitivity to afterload, associated with polycythemia and hypertension.

Fetal responses to long-term hypoxemia in sheep.

The effect of acute or short-term hypoxia on fetal cardiovascular hemodynamics has been well known; however, little is known about the effect of long-term hypoxemia. To determine the fetal hemodynamic responses to this stress we studied two groups of animals: 1) pregnant ewes (n = 20) at 110-115 days of gestation subjected to hypoxia for up to 28 days and 2) pregnant ewes (n = 4) that served as normoxic controls. We chronically catheterized the fetal brachiocephalic artery and vein. Five to 6 days after surgery, control measurements were made of mean arterial blood pressure, heart rate, arterial PO2, O2 saturation, hemoglobin, hematocrit, blood volume, and the concentrations of erythropoietin, cortisol, epinephrine, and norepinephrine. The next day the ewes were placed in a chamber with an inspired O2 fraction of 12-13%. Within a few minutes fetal arterial PO2 decreased from control value of 29.7 +/- 2.1 to 19.1 +/- 2.1 Torr, where it remained. Hemoglobin increased from 10.0 +/- 1.0 to 12.9 +/- 1.9 g/dl by day 7, where it remained. This was associated with an increase of erythropoietin from 22.8 +/- 2.2 to 144 +/- 37 mU/ml within 24 h, but by day 7 it had returned to levels slightly above normal. Epinephrine also increased moderately and remained elevated throughout the study. However, values of mean arterial pressure and heart rate did not differ from controls. Perhaps surprisingly, these fetuses were able to compensate so that at term their body weights were normal, 3.77 +/- 0.2 kg.