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Serum erythropoietin and hemoglobin affinity for oxygen in patients phlebotomized for polycythemia vera.

Serum erythropoietin (Ep) was measured by radioimmunoassay before and 24 hours after therapeutic phlebotomies in patients with polycythemia vera (PV) and in normal subjects before and after phlebotomies of comparable volumes. In addition the in vivo oxygen affinity of hemoglobin (P50) was calculated, and red cell indices and 2,3 DPG values were measured. Paired t tests determined whether the differences between pre- and post--phlebotomy values were statistically significant. Blood hemoglobin (Hb) levels declined after phlebotomy, and generally continued to be at or above normal levels. Serum Ep increased after phlebotomy in both groups of subjects. The in vivo P50 value for patients with PV (29.4 +/- 0.4 mmHg) was significantly (p less than 0.005) greater than the normal value (27.2 +/- 0.5). Seven of the PV patients (5 males, 2 females) were restudied. Their Hb and hematocrit values were either normal or slightly higher than normal. The MCV for 4 males and 1 female was below normal. The MCHC was slightly lower than normal and reticulocytosis was not present. The male PV patients had greater than normal 2,3 DPG values and most had right-shifted P50 values. There was no correlation between 2,3 DPG values and P50 values. The female patients did not have 2,3 DPG values consistently greater than normal and their P50 values were not right shifted. These results showed that serum EP increased in response to small reductions in Hb even when subnormal Hb values were not produced. The reduced affinity of Hb in PV patients may explain earlier observations that patients with PV have lower levels of urinary or plasma Ep than normals with the same hematocrits.

2,3-Diphosphoglycerate↗

Epidemiology, clinical spectrum and prognosis of hemochromatosis.

EPIDEMIOLOGY: Eleven prospective epidemiological studies from various countries have as yet evaluated the gene prevalence of HLA-linked hemochromatosis. The estimated frequency ranged from 0.027-0.107, the frequency of homozygotes from 0.00074-0.0116, and the frequency of heterozygotes from 0.052-0.191. In a meta-analysis of the eleven surveys the frequency is 0.0016 (106/64758 subjects) for homozygotes which corresponds to a gene frequency of 0.041 and a frequency of heterozygotes of 0.078. Further analyses showed that some of these studies have probably underestimated the prevalence which in reality is probably two- to threefold higher than estimated by the meta-analysis. CLINICAL SPECTRUM: In the total group of 251 patients diagnosed with hemochromatosis in the University of Düsseldorf from 1959-1992, abnormality in liver function tests (75%), weakness and lethargy (74%), skin hyperpigmentation (70%), diabetes mellitus (48%), arthralgia (44%), impotence (45% in males), and ECG abnormalities (31%) were the most frequent findings and symptoms at diagnosis. In recent years about 50% of patients were detected without having liver cirrhosis and 20% of patients did not have any symptoms and pathology except iron overload. PROGNOSIS: Survival analysis in the 251 patients showed that in the absence of cirrhosis and diabetes iron removal by phlebotomy therapy prevents further tissue damage and guarantees a normal life expectancy. Sex and presence of arthropathy did not predict prognosis. However, patients with massive and long-lasting iron overload had a worse prognosis than patients with less severe iron excess. Iron removal in general ameliorated liver disease, weakness and cardiac abnormalities, and also prevented the progression of endocrine alterations. Therapy, however, did not influence arthropathy which even got worse in several patients. Iron removal also failed to reverse insulin-dependent diabetes. During a mean followup of 13.4 years 69 deaths occurred in the 251 patients. In 19 patients death was due to liver cancer, in 14 due to liver cirrhosis, in 5 due to cardiomyopathy, and in 3 due to diabetes mellitus (all causes significantly more frequent than expected for the general population). The other causes of death were as frequent as expected including extrahepatic malignancies. All liver cancers were seen in cirrhotic livers, but often occurred many years or even decades after complete iron removal. Further strategies have to evaluate the design of screening programs in order to diagnose more patients in the precirrhotic and asymptomatic stage.

Bloodletting↗

The effect of 5-hydroxytryptamine and arterial blood withdrawal on cerebral microcirculation in the cat, arterial permeability in the rabbit.

Studies dealing with the effect of 5-HT on cerebral cortical microcirculation of cats and on permeability of femoral arteries to RISA of rabbits are presented. The effect of 5-HT on cerebral cortical microcirculation was compared to that of arterial blood withdrawal and blood reinfusion. The effect of topical administration of 5-HT was also studied. Cortical microcirculation was observed by transillumination using a microtransilluminator. Motion pictures were taken at a speed of 400 frames/sec. and a magnification of 3000X. Permeability was investigated using arterial RISA uptake in vessels perfused in vitro, with continuous recording of perfusion pressure. Microcirculatory studies revealed that arterial blood withdrawal and injection of 5-HT diminished red cell velocity, although to a different degree. With blood withdrawal and reinjection, good correlation existed between blood pressure and red cell velocity. In contrast, no correlation between blood pressure and red cell velocity was found after intracarotid injection of 5-HT. Reactive hyperemia was noted during reinfusion of blood. Both arterial blood withdrawal and 5-HT injection resulted in disappearance of red cells in individual vessels (unperfused channels). Good correlation of blood pressure with capillary red cell velocity during arterial blood withdrawal suggests absence of autoregulation in this portion of the microcirculation. Topical administration of 5-HT caused general vasoconstriction. Permeability to 5-HT to RISA followed a parabolic curve. With slight arterial vasoconstriction, permeability declined, while it rose with severe vasoconstriction.

Animals↗

Oxygen radicals in exsanguination-induced bronchoconstriction of guinea pigs.

This study investigated the relationship between oxygen radicals and exsanguination-induced bronchoconstriction using antioxidant in guinea pigs. To accomplish this, two phases of studies were carried out. In phase 1, 34 guinea pigs weighing 342 +/- 11 g were divided into five groups: control (n = 7); acute dimethylthiourea (DMTU, n = 7); chronic DMTU (n = 8); superoxide dismutase (SOD, n = 6); and catalase (n = 6). Animals in the control group were not treated. DMTU, SOD, and catalase were employed for the scavenging of hydroxyl radical, superoxide anion, and hydrogen peroxide, respectively. Ten additional guinea pigs weighing 293 +/- 6 g were divided into two groups in phase 2: sham (n = 6) and chronic apocynin (n = 4). Animals in the sham group received injections of the vehicle, whereas apocynin was used to suppress the production of superoxide anion. All animals were anesthetized, sternotomized, and artificially ventilated. Before (baseline) as well as at fixed intervals 5-30 minutes following the exsanguination, the maximal expiratory flow maneuver was performed and the dynamic compliance (Cdyn) was obtained. Decreases in the maximal expiratory flow at 50% baseline vital capacity and Cdyn were used as indicators of bronchoconstriction. Exsanguination in the control and sham groups caused a gradual increase in airway constriction with time that was significantly ameliorated by chronic DMTU and chronic apocynin pretreatments but was not affected by other acute treatments. These results indicate that chronic treatment with antioxidants ameliorates exsanguination-induced, tachykinin-mediated airway constriction.

Analysis of Variance↗

Experimental investigations on the influence of anemia on gentamicin ototoxicity.

The purpose of this study was to determine whether or not anemic patients have a higher risk of gentamicin ototoxicity. Using the laboratory rat as an animal model with auditory brain-stem response measurements and surface preparations of the organ of Corti, it could be shown that cochlear damage in anemic rats treated with gentamicin was significantly higher (P less than 0.05) than in the nonanemic ones treated with the same dosages of antibiotic. Doses of gentamicin used were 50 mg/kg for 30 days and 40 mg/kg for another 75 days.

Anemia↗

Carbon dioxide gas as a venous contrast agent to guide upper-arm insertion of central venous catheters.

PURPOSE: Evaluate in a prospective randomized study carbon dioxide (CO2) gas compared to iodinated contrast agent for image-guided placement of peripherally inserted central venous catheters (PICCs). METHODS: The upper-arm approach to the central vein was used for placement of PICCs in 74 patients requiring intermediate or long-term central venous access. Fluoroscopy was used to obtain venous access during peripheral injection of CO2 (n = 41) or low osmolar contrast material (Omnipaque 240 mgI/ml) (n = 33). RESULTS: Placement of PICCs was accomplished in 88% of the CO2 group and in 100% of the contrast group, with a mean venipuncture of two in both groups. Venous access was unsuccessful in five patients with CO2 due to a small vein, venous spasm, or technical failure. The mean and range of procedure times were 22.8 min (13-64 min) with CO2 and 23.2 min (12-60 min) with contrast material. The average and range of CO2 and nonionic contrast volumes injected during the procedure were 35.4 ml (5-300 ml) and 27.8 ml (8-120 ml), respectively. Vital signs and oxygen saturation did not change significantly during or after injection of CO2. There was no incidence of adverse reaction following CO2 injection. CONCLUSION: CO2 gas is a useful contrast agent to guide upper-arm insertion of PICCs and may be a safe alternative in patients with renal insufficiency and/or allergy to iodinated contrast material.

Adolescent↗

Effect of phlebotomy on the ferritin iron content in the rat liver as determined morphometrically with the use of electron energy loss spectroscopy.

Phlebotomy of untreated and iron-loaded rats results in a significant decrease in total liver iron. In iron-loaded rats a marked decrease in iron-containing particles is observed ultrastructurally in lysosomes and cytoplasm of hepatic sinusoidal cells but not in parenchymal cells. This remarkable phenomenon was further investigated in a morphometric study, based on element-specific (iron) distribution images made in situ in the parenchymal cell by means of electron energy loss spectroscopy. With the use of this technique it could be shown that in spite of phlebotomy the ferritin iron content of the iron-loaded liver parenchymal cell is not decreased.

Animals↗

Tunnelling of two central venous catheters inserted via a single venipuncture.

Two central venous catheters were inserted into the subclavian or internal jugular vein using a single puncture and tunnelled with two different subcutaneous pathways in 32 critically ill patients; 15 of them underwent this procedure immediately after a tracheostomy. The procedure was carried out without significant technical difficulties. Separate removal of one of the catheters was performed easily in 5 cases. Cultures were positive in 21% of 42 catheters from 21 patients; Staphylococcus epidermidis was isolated from 7 catheters. Separate tunnelling of two central venous lines inserted via a single venipuncture can be used in critically ill patients needing multiple central venous access.

Adult↗

Chorea and polycythaemia.

Two patients with chorea and polycythaemia vera are described. The literature on this rare association is reviewed and its pathophysiology discussed.

Aged↗

Iron stores in female blood donors evaluated by serum ferritin.

Iron stores were evaluated by serum ferritin determinations in 948 menstruating and 141 non-menstruating female blood donors. Blood donation was associated with a decrease in ferritin. First-time donors (n = 163) had a geometric mean ferritin of 24 micrograms/l and multiple-time donors a value of 19 micrograms/l (p less than 0.01). In the donating population 31.5% had ferritin values less than 15 micrograms/l (i.e. depleted iron stores). Menstruating donors had lower mean serum ferritin than non-menstruating donors (p less than 0.001), and a higher frequency of ferritin values less than 15 micrograms/l (p less than 0.05). There was no relationship between ferritin levels and the number of pregnancies. The frequency of donations was more predictive of ferritin levels than the number of donations. Mean ferritin displayed a moderate fall up to the 2nd donation, and was hereafter relatively constant, whereas an increase in donation frequency was accompanied by a significant decrease in ferritin. Female donors, especially when phlebotomised greater than or equal to 3 times per year, should have their iron status checked at appropriate intervals by measurement of serum ferritin and should be advised regular iron supplementation.

Adolescent↗

Peripheral arterial occlusion and amaurosis fugax as the first manifestation of polycythemia vera. A case report.

A patient with polycythemia vera, who presented digital arterial occlusion and episodic monocular blindness as the first clinical signs of the disease is described. After an early diagnosis, reduction of the cellular blood volume, and intraarterial perfusions with adenosine triphosphate (Laevadosin) followed by reserpine (Serpasil) led to adequate local tissue perfusion. No surgical intervention was required and visual disturbances disappeared. The patient has now been in a stable phase of the disease for 7 months without subsequent treatment.

Adenosine Triphosphate↗

Ferritin in erythrocytes and plasma of patients with iron overload.

Erythrocyte and plasma ferritin was followed in 13 patients with iron overload undergoing phlebotomies for at least 6 months in comparison with untreated patients and normal males. Plasma ferritin was widely scattered with an average of only twice the normal, whereas erythrocyte ferritin was highly elevated to about twelve times the normal (p less than 0.0001). - The time course of plasma and erythrocyte ferritin during phlebotomy therapy was analyzed in 3 patients with idiopathic hemochromatosis. Three stages were established: 1. plasma ferritin dropped gradually into the normal range while erythrocyte ferritin remained high, 2. appropriate phlebotomies maintained normal plasma ferritin and high erythrocyte ferritin, and indicated a monthly uptake of dietary iron of 150-200 mg at a steady state, 3. at low plasma ferritin levels, erythrocyte ferritin was rapidly decreased by further intensive phlebotomy therapy. Based on the presumed net removal of iron, 1 microgram/l plasma ferritin was equivalent to 3-6 mg of body iron and 1 microgram/l erythrocyte ferritin to somewhat less than 1 mg of body iron. - An elevated erythrocyte ferritin during phlebotomy therapy in iron overload not only depends on body iron stores like plasma ferritin but may also be regulated by the activity of erythropoiesis.

Adult↗

Development of the Clozaril Patient Management System.

The Clozaril Patient Management System (CPMS) has been developed to provide a 100% fail-safe system for monitoring white blood cell counts (WBCs) in patients being treated with clozapine (Clozaril/Leponex) in the United States and to provide comprehensive data collection on the incidence and development of agranulocytosis. CPMS provides a case administrator and a registered pharmacist. Their role is to support the physician by facilitating the determination of WBC's at a national laboratory and by distributing clozapine to the patient. Specific tasks of the case administrator include: keeping track of outpatient phlebotomy appointments, following up missed appointments, ensuring that WBCs are obtained and analyzed weekly by the national laboratory, following up the results of these tests, providing liason with the pharmacy, maintaining a data base for all patients receiving clozapine and conveying these data to the physician. Initial experience with this program in Cleveland is described in this paper. The characteristics of patients enrolled in CPMS, satisfaction with the program and its success in meeting predetermined objectives are described. Experience with 31 patients in this outpatient setting suggests that CPMS can be an effective, reliable system for assisting in blood monitoring of patients being treated with clozapine.

Adult↗

Circulatory and respiratory adaptation in man to acute withdrawal and reinfusion of blood.

In eight healthy men 950 g of blood (12.2 17.6% of the blood volume) was withdrawn and reinfused after about half an hour. Respiration and circulation were studied by analyses of expiratory gas, blood gases and data from right heart catheterization. On hemorrhage oxygen uptake and cardiac output decreased by 10 and 28%, repectively; both varied indirectly with the blood loss. The pressures in the right ventricle, pulmonary and systemic arteries fell without relation to the cardiac output. Mean heart rate did not change significantly, but a moderate positive covariation (P less than 0.05) between heart rate and arterial blood pressure was found during bleeding. This result was confirmed by the relative bradycardia noted in the period prior to reinfusion. On refilling of the bood the oxygen uptake and the pulmonary arterial pressures increased above the initial value. The heart rate varied directly with the arterial pressure also during reinfusion. The observations demonstrate a depression of the metabolism and circulation on moderate hemorrhage. Part of these effects is tentatively referred to a lowered set point of the arterial baroreflexes.

Adaptation, Physiological↗