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PubMed1980

The effect of hypovolaemia on colonic blood flow in the dog.

The effects of a minor degree of hypovolaemia on colonic blood flow and on systemic haemodynamics have been studied in nine greyhound dogs. A loss in blood volume of 10 per cent over 20 min produced no change in blood pressure and only a 7 per cent rise in heart rate. Cardiac output, however, fell by 26 per cent and central venous pressure also fell significantly. Colonic blood flow fell by 28 per cent and oxygen availability by 29 per cent. All these changes were statistically highly significant. Retransfusion of shed blood resulted in a slow and incomplete return to pre-bleed status. Since colonic blood flow and oxygen availability during and after surgery may be important for colonic healing, it is suggested that even the slightest degree of hypovolaemia should be avoided in cases involving colonic anastomosis. Systemic blood pressure may be an inadequate index of the need for transfusion in these cases.

Animals↗
PubMed1988

Consequences of blood loss on growth of artificial metastases.

Previous studies have shown that lung metastases from a nonimmunogenic sarcoma (LS175) in BN (homozygous for RTln) rats were stimulated by blood transfusions. Enhanced growth was also observed after abdominal surgery combined with allogeneic blood transfusions while syngeneic blood transfusions had no effect. These experimental findings have been confirmed in retrospective clinical studies. The allogeneic blood transfusion effect may be avoided in cancer patients by autologous blood transfusions although this implies blood donation before surgery. The aim of the present study was to investigate the effect of blood loss before surgery on formation ('take') of lung colonies, and on the outgrowth of established metastases in the BN rat model. These aspects of tumour behaviour were also investigated in rats undergoing surgery, or receiving blood transfusion, or both, after blood loss. The results indicate that blood loss has a profound stimulating effect on the growth of established metastases, but not on the 'take' of tumour cells. This stimulating effect was also present when blood loss was combined with surgery, while previously surgery alone was found to have no effect. Allogeneic and syngeneic transfusions in combination with blood loss both had a strong stimulating effect on growth of established lung metastases. The results indicate that blood loss may be an important factor in determining the outcome of metastatic growth.

Animals↗
PubMed1990

Changes in cardiovascular homeostasis after injury are mediated by tissue damage and not haemorrhage.

During treatment of the injured patient it is assumed that the cardiovascular responses follow recognized physiological principles. Studies in humans have shown that injury causes a profound suppression of arterial baroreflex function which alters the normal relationship between heart rate and blood pressure and casts doubt on this assumption. To investigate the mechanism of baroreflex suppression, we have studied the effects of the two major components of injury, blood loss and tissue damage, on baroreflex function in healthy volunteers. Baroreflex function was assessed using suction stimulation of the carotid sinus. The loss of 500 ml blood had no effect on baroreflex sensitivity. A human laboratory model of tissue injury reduced the ability of the baroreflex to compensate for a rise in blood pressure (P less than 0.05, Wilcoxon signed rank test). We conclude that tissue damage, rather than hypovolaemia, appears to mediate the effect of injury on baroreflex function in the injured. Blockade of neural signals from damaged tissue may have a role in the treatment of injury.

Adolescent↗
PubMed1987

Does "physiologic" mitral valve prolapse occur with acute blood loss?

Intravascular volume changes are reported to affect the clinical and echocardiographic spectrum of patients with known mitral valve prolapse syndrome (MVPS). We tested whether acute blood loss can produce MVP in normal adults. Twenty-one subjects were studied with Doppler echocardiography before and after donating 550 ml whole blood. Two subjects demonstrated minimal (1+) prolapse postphlebotomy, but in only one echocardiographic view, and without mitral regurgitation by Doppler. Three subjects demonstrated slight, early (not late or pansystolic) mitral regurgitation after phlebotomy, but without prolapse. Left atrial dimensions decreased significantly after the blood donation but the left ventricular size was not significantly smaller. The 1+ MVP is within the range of superior systolic motion found in 35% of a normal population, free of heart disease, and without intervention. We find no evidence in our study or in the literature that pathologic degrees of MVP can be produced in normal subjects by physiologic alteration in blood volume.

Blood Volume↗
PubMedDate not supplied

Evaluation of liver iron content by computed tomography: its value in the follow-up of treatment in patients with idiopathic hemochromatosis.

The therapeutic management of patients with idiopathic hemochromatosis (IH) implies the evaluation of excess hepatic iron. This work was undertaken to confirm the value of computed tomography for the assessment of liver iron overload in such patients and to evaluate this technique during the course of treatment by phlebotomy. The study included 24 patients with initially untreated IH and 7 patients previously treated by phlebotomy for 10 months to 7 years. Follow-up was obtained in 15 subjects. In patients with untreated IH, liver attenuation coefficient (LAC) was always markedly increased (92.4 +/- 7.1 Hounsfield units) as compared with LAC of subjects with normal liver (60.2 +/- 3.1 Hounsfield units) and that of patients with chronic liver disease (53.8 +/- 4.8 Hounsfield units), and was found to be specific for liver iron overload. LAC decreased progressively during phlebotomy, and this diminution was correlated with the amount of mobilized iron (r = 0.79, p less than 0.001); it returned to normal values only after complete removal of iron overload. LAC was closely correlated with liver iron concentration (r = 0.83, p less than 0.001), better than usual biochemical parameters, especially serum ferritin (r = 0.70, p less than 0.01). This study confirms that the determination of LAC on computed tomography provides a reliable index of hepatic iron stores in patients with IH, without requiring a liver biopsy, and shows that this noninvasive method is of particular interest for the follow-up of patients treated by phlebotomy.

Adult↗
PubMedDate not supplied

Determination of iron to phosphorus ratios of iron storage compounds in patients with iron overload: a chemical and electron probe X-ray microanalysis.

The amounts of phosphorus and iron in various isolated ferritin preparations were investigated by: chemical analysis on ferritin samples and electron probe X-ray microanalysis on ferritin particles from the same preparations. A high correlation was found between iron to phosphorus ratios obtained by both methods. Further investigation by electron probe X-ray microanalysis on lysosomes of hepatic cells of patients with idiopathic and secondary hemochromatosis revealed lysosomal iron to phosphorus ratios which were very similar in all parenchymal cells but different from ratios obtained in Kupffer cells. Lysosomal iron to phosphorus ratios in hepatocytes did not change after intensive phlebotomy treatment. It is postulated therefore that, during phlebotomy, iron and phosphorus are concomitantly lost from the hepatic lysosomes.

Bloodletting↗
PubMed1992

Survival and prognostic factors in 212 Italian patients with genetic hemochromatosis.

Two hundred twelve Italian patients with genetic hemochromatosis (181 men, mean age 50 +/- 11 yr; and 31 women, mean age 49 +/- 10 yr) were followed for a median period of 44 mo (range = 3 to 218 mo). Alcohol abuse was present in 31 subjects (15%), and chronic HBV and HCV infection were seen in 19 (9%) and 35 (24%) of 145 cases tested, respectively. Twenty-four patients (11%) had concomitant beta-thalassemia trait. Liver biopsy revealed cirrhosis in 146 and a noncirrhotic pattern in the other 66. Perls' stain was degree III in 37 patients and IV in 171 patients. One hundred eighty-five patients underwent weekly venesection, and iron depletion was achieved in 122 cases after total iron removal of 3 to 41 gm. Death occurred in 44 patients after 3 to 198 mo and was due to hepatocellular carcinoma in 20 cases, liver failure in 10, extrahepatic cancer in six, heart failure in three and hemochromatosis unrelated causes in five. Cancer has developed in seven other patients still alive (hepatocellular in five and extrahepatic in two). No deaths were observed among noncirrhotic patients; cumulative survival rates in cirrhotic patients were 85%, 75%, 60% and 47% at 3, 5, 8 and 10 yr, respectively. Univariate analysis in the 146 cirrhotic patients showed that age greater than 60 yr, alcohol abuse, cardiomyopathy, skin pigmentation, portal hypertension, hypoalbuminemia, hypergammaglobulinemia and Child class B or C had significant negative prognostic value. At multivariate analysis, only alcohol abuse, gamma-globulins greater than 2.0 gm/dl and Child class B or C maintained their negative prognostic values (p less than 0.01, hazard ratio 2.7; p less than 0.001, hazard ratio 2.8; and p less than 0.001, hazard ratio 4.3, respectively).

Adult↗
PubMed1995

Kupffer cell iron overload induces intercellular adhesion molecule-1 expression on hepatocytes in genetic hemochromatosis.

The mechanisms underlying iron-induced liver fibrogenesis in patients with genetic hemochromatosis are poorly understood. We studied signs of Kupffer cell activation and inflammatory responses in liver biopsy specimens obtained from 15 patients with untreated and six patients with treated hemochromatosis. Immunohistochemistry was performed on 11 of the untreated and all treated patients. Three of the untreated patients (20%) had cirrhosis and eight (53%) had fibrosis. None had chronic active hepatitis (CAH). Immunohistochemistry indicated that 55% of the untreated patients had sparse intercellular adhesion molecule-1 (ICAM-1) expression by hepatocytes, and all of these had Kupffer cell iron overload. No ICAM-1 expression was seen by hepatocytes in treated patients or healthy controls. ICAM-1 was strongly expressed by hepatocytes from control patients with inflammatory liver disease. HLA-DR reactivity was seen on sinusoidal cells in all groups, but not on hepatocytes except for two of the control patients with CAH. Twenty-seven percent of the untreated hemochromatosis patients displayed moderate infiltration by CD3-positive lymphocytes. Electron microscopy of samples from untreated hemochromatosis patients showed hypertrophic Kupffer cells containing iron-rich remnants of phagocytosed hepatocytes. Fat-storing cells close to iron-laden hepatocytes contained multiple lipid droplets and adjacent collagen fibril bundles. Thus, in patients with untreated genetic hemochromatosis and Kupffer cell iron overload, hepatocytes occasionally express ICAM-1. In regions with heavy iron overload, Kupffer cell hypertrophy and transition of fat-storing cells are seen. Our findings indicate that release of factors from iron-loaded, activated Kupffer cells is of importance for the transformation of fat-storing cells and increased collagen deposition seen in genetic hemochromatosis.

Adult↗
PubMed1988

The effect of various postphlebotomy storage conditions on drug levels.

Monitoring drug levels in patients is standard practice in presentday critical care medicine. Clinical laboratories, however, are often unable to assay drug levels immediately following phlebotomy. This may result in blood samples being kept under a variety of storage conditions for nonuniform periods of time. The current study evaluated the stability of eight frequently monitored medications and one of their metabolities, in whole blood and plasma, at 4 degrees C or 25 degrees C, for up to 72 hours. The drugs included antibiotics, a bronchodilator, antiarrhythmics, and an anticonvulsant. Significant changes in drug levels were not identified at the time points studied. Our data suggests that meticulous postphlebotomy handling of blood samples may not be essential to obtain accurate levels of the drugs studied.

Animals↗
PubMed1991

Effects of testosterone and venesection on spinal and peripheral bone mineral in six hypogonadal men with hemochromatosis.

To measure the effect of testosterone replacement and venesection on spinal and peripheral bone mineral we prospectively studied six hypogonadal men and six eugonadal men with idiopathic hemochromatosis for 24 months. Venesections were performed every week on all patients, and intramuscular injections of testosterone were administered every 3 weeks to the hypogonadal men only. Bone mineral was measured by quantitative computed tomography in the spine and by single-photon absorptiometry in the forearm. During the 24 month period of observation serum testosterone concentrations and serum ferritin levels became normal. In the hypogonadal men mean lumbar spine bone mineral increased by 13.1 +/- 4.9% (95% CI, 0.5-25.6) and mean forearm bone mineral increased by 4.7 +/- 3.8% (95% CI, -5.1 to 14.6). In contrast in the eugonadal men treated over the same period, mean lumbar spine bone mineral decreased by 3.5 +/- 2.8% (95% CI, -10.9 to 3.8, P less than 0.01) and mean forearm bone mineral remained virtually unchanged (0.07 +/- 0.9%; 95% CI, -1.7 to 3.1, P less than 0.05). These data suggest that bone mineral increases in the lumbar spine and in the forearm in hypogonadal men with hemochromatosis treated by testosterone replacement and venesection.

Adult↗
PubMed1987

Harvesting the noncirculating pool of polymorphonuclear leukocytes in rats by hetastarch exchange transfusion (HET): yield and functional assessment.

Isolation of polymorphonuclear leukocytes (PMN) provides an opportunity to study PMN activity in vitro and to label PMN for study of in vivo kinetics. However, simple phlebotomy (SP) of a small animal frequently yields too few PMN for in vitro handling, while PMN harvested from an induced-peritonitis may not accurately reflect PMN in a less stimulated state. We report a novel method of harvesting PMN from the circulation of rats, using hetastarch exchange transfusion (HET), which is both time and animal sparing. HET harvested 8-fold more PMN than SP. In vitro cell function was examined with assays of adherence, chemotaxis, bacterial killing, and superoxide generation. No significant (p less than 0.05) difference was found between PMN obtained by HET and pooled-PMN obtained by SP. In vivo function was examined following labeling with indium111-oxine. The kinetics pattern described suggested normal migratory activity when compared to previous reports. The data demonstrate that rats possess a relatively large, noncirculating pool of PMN which is readily accessible by HET.

Animals↗
PubMed1990

Autologous transfusions for cancer patients undergoing elective ablative surgery.

Patients who have cancer are exposed to the adverse consequences of blood transfusions, such as transmissible diseases. This study presents an examination of a program of autologous blood deposit for cancer patients undergoing elective surgical procedures. Over a 3-year period, 235 patients deposited 388 units of autologous blood: 6 for head and neck tumor surgery, 8 for neurosurgical tumors, 8 for gastrointestinal and colorectal tumor surgery, 14 for adrenal tumor surgery, 16 for gynecologic tumor surgery, 23 for soft tissue and bone tumor surgery, 25 for mastectomies and reconstructive breast surgery, 42 for genitourinary tumor surgery, and 93 for bone marrow aspirations for autologous transplants. One hundred eighty-two patients (77.4%) used 278 units (71.6%) of their autologous blood units during the operations, 50/182 required additional homologous blood, and 53 did not require transfusions with autologous blood. Our study shows that a majority of these patients (132/182) underwent surgery using only autologous transfusions. Therefore, we believe that predeposited autologous blood is a viable alternative to homologous blood for cancer patients undergoing surgery.

Adolescent↗
PubMed1994

Rocking and pacifiers: two comforting interventions for heelstick pain.

The effects of behavioral interventions in reducing the stress of infant pain are not well documented. Two comfort interventions, rocking and pacifiers, were compared with routine care administered to 60 newborn infants randomly assigned to the three conditions following a neonatal screening heelstick. Heart rate, state of arousal, and crying were recorded continuously. Both pacifiers and rocking reduced crying, but pacifiers predominantly produced sleep states and rocking predominantly produced alert states. Pacifiers reduced heart rate levels significantly more than did rocking. Thus, newborns clearly benefit from both comforting methods. Several mechanisms are proposed to account for these findings.

Bloodletting↗
PubMed1991

Effect of vascular puncture on blood gases in the newborn.

Continuous monitoring methods have shown changes of oxygenation in neonates during various procedures. However, actual changes in blood gases during vascular punctures have not been reported. We studied the effect of vascular puncture on arterial blood gases during routine venipuncture in 17 neonates who had indwelling arterial catheters. Arterial blood gases were analyzed before, during, and following recovery from venipuncture. Ventilator settings were not changed during the study, though oxygen concentration (FiO2) was adjusted as indicated by continuous PO2 or saturation monitors. During venipuncture, there was a significant fall in PaCO2 from 38 +/- 5 to 32 +/- 7 mmHg (P less than 0.0001) and in PaO2 from 75 +/- 21 to 58 +/- 23 mmHg (P less than 0.0001). Following venipuncture, both values returned to baseline. The results of this study imply that blood gases obtained by intermittent arterial sticks may provide data that do not accurately reflect the neonates' respiratory status.

Blood Gas Monitoring, Transcutaneous↗
PubMed1986

Effect of absolute and relative changes of hematocrit on erythropoiesis in mice.

The serial changes of peripheral reticulocytes and marrow erythroid progenitor cells (CFU-e) in mice were monitored under the conditions of absolute or relative changes in red cell mass to study the regulatory mechanism of erythropoiesis. A decreased number of marrow CFU-e and peripheral reticulocytes was observed in the mice with relative polycythemia induced by dehydration as well as in the mice with absolute polycythemia induced by hypertransfusion. On the other hand, a transient increase in the number of marrow CFU-e followed by a gradual increase in the number of peripheral reticulocytes was seen after a considerable amount of exsanguination. Similar stimulatory effects on marrow CFU-e were also observed either by rehydrating the dehydrated mice or by overhydrating the untreated mice to relatively decrease the level of hematocrit. The results suggested that in addition to factors relating to the balance between oxygen supply and requirement, which has been well known, erythropoiesis is greatly affected by hematocrit.

Animals↗
PubMedDate not supplied

Amelioration of painful crises in sickle cell disease by venesections.

Sickle cell disease patients who acquire iron deficiency may experience a degree of amelioration from painful crises in terms of frequency, severity, and duration. This observation prompted us to identify the potential utility of iron load reduction in the management of this disease. Thirteen sickle cell patients not ameliorated by conventional treatment entered a weekly venesection protocol. Hematological values and painful crises of all degrees of severity were recorded and compared to those of the last 12 months before venesection for each case separately ("historical controls"). A decrease was noted in the frequency and intensity of several types of painful crises. Reduction of iron load by venesection seems to be a simple, safe, side-effect-free, and efficient way of preventing and ameliorating to a large extent painful crises in sickle cell disease. The biological effects of venesection on other parameters of sickle cell disease remain to be determined.

Adult↗