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Biomedical subjects

R H Sills

Publications and source records attributed to R H Sills.

12 recordsLinked to original sources
PubMed1992

Protein C survival during replacement therapy in homozygous protein C deficiency.

Homozygous protein C (PC) deficiency is a rare genetic defect that usually results in fatal thrombotic complications (purpura fulminans and DIC), but it can be successfully managed with oral anticoagulants or PC replacement. The successful use of PC replacement for two individuals is described. The activity and antigen levels of PC in fresh frozen plasma (FFP) and prothrombin complex concentrate (PCC) are also reported. The concentration of PC in FFP is 87 +/- 15 units/dl. PC is present in all PCC analyzed; however, a ten-fold difference between the various brands and/or lots is noted. The PC activity and antigen correlates well with no significant levels of APC. Upon infusion of FFP into two homozygous PC-deficient children, the PC levels obtained were less than or equal to 30 units/dl post-infusion and undetectable after 12-18 hr. With infusions of PCC, plasma levels of PC obtained were 100-145 units/dl and less than 10 units/dl after 48 hr. The percent recovery and half-lives of PC from FFP and PCC were 49.8% and 7.8 hr, and 84% and 7.4 hr, respectively. One infant was treated every 48 hr for 2 years without significant purpura fulminans or DIC complications. The levels of the other PC system components did not change during the infusion of the PC-rich material. Based on this information, a specific replacement protocol has been developed using a PC-rich concentrate. However, several problems may arise with the "less pure" PC-rich concentrates: catheter-tip thrombosis, related large vessel thrombosis and blood-transmitted diseases. With a specific PC concentrate, replacement therapy is a viable alternative for the long-term management/treatment of homozygous PC deficiency.

Antigens↗
PubMed1988

Physiologic formation of intracellular vesicles in mature erythrocytes.

The ability of mature erythrocytes to spontaneously form intracellular vesicles has been implied from clinical studies but has not been examined experimentally. An in vitro model was developed to demonstrate whether mature erythrocytes are capable of spontaneously forming intracellular vesicles. Normal human erythrocytes were incubated in vitro at 37 degrees C for 144 hr in a synthetic medium. During the course of these incubations, approximately 4% of erythrocytes developed intracellular vesicles which were quantitated by using interference contrast microscopy. Electron microscopic studies confirmed the intracellular nature of these vesicles. Incubation of erythrocytes in autologous plasma produced similar results. The rate of vesicle acquisition in vivo was measured by quantitating erythrocyte vesicles immediately prior to and following splenectomy. The rates of vesicle acquisition in vivo and in vitro were comparable. This in vitro model confirms the ability of mature erythrocytes to spontaneously form intracellular vesicles and strongly supports the concept that this is a physiologic process.

Adult↗
PubMed1988

Formation of intracellular vesicles in neonatal and adult erythrocytes: evidence against the concept of neonatal hyposplenism.

Intraerythrocytic vesicles accumulate in the peripheral blood as a result of impaired clearance of these intracellular inclusions by the spleen. The observation that neonates demonstrate an increased percentage of erythrocytes containing these vesicles constitutes the primary evidence supporting the concept that the newborn is functionally hyposplenic. Neonatal erythrocytes also demonstrate an increased propensity to undergo a variety of endocytic processes. We therefore questioned whether the increase in red cell vesicles in the neonate might be the result of increased vesicle formation as opposed to impaired splenic clearance. Newborn and adult erythrocytes were incubated in vitro in synthetic medium at 37 degrees C. Several parameters confirmed the maintenance of physiologic conditions, including levels of erythrocyte phosphate metabolites monitored by nuclear magnetic resonance. The acquisition of intraerythrocytic vesicles during the course of these incubations was compared. Over a period of 144 h, 19.2% of neonatal erythrocytes acquired vesicles compared to 3.7% of the adult cells (p less than 0.001). The increase in vesicles was greater in younger density-separated erythrocytes in both the neonate (37.6%, p less than 0.0005) and the adult (10.3%, p less than 0.002), but persisted even in the oldest erythrocytes (12.2% and 2.4%, respectively). We conclude that the increase in erythrocytic vesicles in the neonate may not simply be an indication of hyposplenism, but a reflection of increased vesicle formation which overwhelms the clearance capability of the spleen.

Adult↗
PubMed1988

Studies on the vasoocclusive crisis of sickle cell disease IV. Mechanism of action of pentoxifylline (Trental).

Pentoxifylline was shown to prevent sickling induced by deoxygenation of SS-genotype blood from sickle cell disease patients. It also prevents development of cell stiffness, based on decreased membrane fluidity. This effect is related to increased red cell ATP content, decreased potassium loss during sickling and decreased attachment of hemoglobin to the red cell membrane during sickling. There was no effect on osmotic fragility or mean corpuscular volume. There was some increase in pH of blood from patients in vasoocclusive crisis of sickle cell disease under the effect of pentoxifylline. The consideration is discussed that pentoxifylline may prevent vasoocclusive crisis, but may not abort an existing process.

Adenosine Triphosphate↗
PubMed1987

Splenic function: physiology and splenic hypofunction.

A wide variety of disorders can result in diminished splenic function. The pathophysiology appears to be clearly defined in some instances, such as congenital asplenia and disorders of splenic vascular obstruction or congestion. In others, such as the autoimmune and GI disorders, the mechanism remains poorly defined. Further research is needed. The hyposplenia which occurs in many of these disorders has been associated with an increased risk of life-threatening, overwhelming bacterial sepsis. In other instances, this complication has not been reported. This certainly should not be interpreted to mean that it cannot occur. The risk of septicemia in hyposplenic disorders is rarely above 10 to 15%. In disorders with minimal inhibition of splenic function, the incidence of sepsis would presumably be less than the 1.5% incidence following surgical splenectomy for trauma. Considering these data, a very large number of patients would have to become asplenic before it would be likely that one would develop sepsis. Furthermore, the lack of awareness of the possibility of hyposplenia-related sepsis in many of these disorders may cause such occurrences to go unrecognized. Finally, since the risk of sepsis is probably less in hyposplenic adults as compared to children, studies on adults may underestimate the incidence of this complication in children. Many of the disorders reported to cause hyposplenia in adults have not been noted to do so in children. In instances such as celiac disease, it may take many years for the complication to manifest so that it would be unlikely for a child to manifest hyposplenia during childhood. However, in other instances, not enough children have been studied to be confident that the hyposplenia and its associated risk of sepsis are not complications that occur in children. Hyposplenia-related bacterial septicemia is a catastrophic complication. If a patient develops a disorder that is potentially associated with hyposplenia, the patient should be observed for signs of asplenia in the peripheral blood. If the technique is available, quantitation of red cell pits should be performed. If not, other studies of splenic function such as radionuclide scans should be considered, depending on the incidence of hyposplenia in that particular disorder. If evidence of asplenia develops, pneumococcal vaccine should be administered, penicillin prophylaxis should be considered, significant febrile episodes should be managed aggressively, and probably most importantly, the patient and family should be carefully educated about this complication. Most deaths from hyposplenia-related septicemia are preventable.

Adult↗
PubMed1987

Studies on the vasoocclusive crisis of sickle cell disease. III. In vitro and in vivo effect of the pyrimido-pyrimidine derivative, RA-233: studies on its mechanism of action.

Red cell deformability was found to be impaired in SS- and SC-genotype and to a lesser extent SA-genotype red blood cells as compared with those of AA-genotype. RA-233 in vitro improved deformability according to a bell-shaped dose-response curve. RA-233 also prevented experimental vasoocclusive crisis in Macaca arctoides. Deoxygenation of SS-genotype red cells resulted in sickle shape transformation, ATP depletion, potassium efflux, and attachment of hemoglobin molecules to the membrane. These changes were prevented by RA-233. Suspending SS-genotype red blood cells in potassium rich tris-buffer also prevented potassium efflux during deoxygenation and also decreased cellular deformability. RA-233 had no effect on osmotic fragility of SS-genotype red blood cells.

Adult↗
PubMed1979

RBC surface pits in the sickle hemoglobinopathies.

Functional asplenia develops in children with sickle cell anemia. This asplenia is related to the increased incidence of bacterial sepsis that has been documented in these patients. With the use of direct-interference contrast microscopy to quantitate splenic function, we studied children with the sickle hemoglobinopathies. A gradual increase in splenic dysfunction with increasing age was documented in children with homozygous sickle cell disease. Children with the sickle variants also seem to manifest degrees of splenic dysfunction. Direct-interference contrast microscopy is a simple quantitative technique for the evaluation of splenic function in children with the sickle hemoglobinopathies.

Adolescent↗
PubMed1978

Failure to thrive. The role of clinical and laboratory evaluation.

One hundred eighty-five patients hospitalized for evaluation to thrive were reviewed retrospectively. Eighteen percent had proven organic etiologies. The specific organic diagnosis was strongly suggested by the history and physical examination in all of these patients. Fifty percent of the patients were failing to thrive on the basis of environmental deprivation. Only 1.4% of the laboratory studies performed were of positive diagnostic assistance. No study was of positive value without a specific indication from the clinical evaluation. The history and physical examination are the most valuable tools in the evaluation of failure to thrive. Laboratory investigations are rarely helpful without a specific indication from the clinical evaluation.

Child, Preschool↗
PubMed1978

L-Asparaginase-induced coagulopathy during therapy of acute lymphocytic leukemia.

L-Asparaginase-induced coagulation abnormalities were observed in all patients receivng this drug. All patients studied demonstrated low factor IX and fibrinogen levels and most (75%) had low levels of factor XI. Disturbances in other factors were much less frequent. Despite the presence of markedly abnormal coagulation studies, clinical bleeding was not observed.

Adolescent↗
PubMed1978

Consumptive coagulopathy. A complication of therapy of solid tumors in childhood.

The association of consumptive coagulopathy and malignancy is thought to be rare in pediatrics. In one patient with Ewing's sarcoma and in two with rhabdomyosarcoma consumptive coagulopathy developed in the presence of either diffuse metastatic disease or an extensive primary tumor. The coagulopathy was a major clinical problem, developing within five days of the onset of chemotherapy. Resolution coincided with the clinical response of the tumor.

Adolescent↗