Biomedical subjects
Publications and source records attributed to M H Kroll.
Some cephalosporin-like antibiotics have been shown to interfere with creatinine assays performed by the commonly used Jaffe methods. The authors show that four new drugs of this type--moxalactam, cefoperazone, cefotaxime, and ceftazidime--do not interfere with this test. A table is presented summarizing all literature data regarding interference with creatinine assays of cephalosporin-like drugs.
Anemia, frequently hypochromic and microcytic, occurs in approximately one third of patients with renal cell carcinoma. We have described a patient with classic iron deficiency anemia and renal cell carcinoma whose blood picture reverted to normal after removal of the tumor. Abundant hemosiderin in the tumor cells is evidence that tumor cells removed iron from the circulation, causing the iron deficiency anemia.
A 16-year old girl with insulin-dependent diabetes mellitus (8 years' duration) developed tropic malaria 7 weeks after her return from Kenya despite a longtime prophylaxis using pyrimethamine and sulfadoxine (Fansidar). The disease was detected during an episode of ketoacidosis which proved exceptionally difficult to manage. Adequate chloroquine therapy resulted in temporary recovery. A recurrence of malaria four weeks later was successfully treated with quinine and doxycycline. Intraleucocytary parasites were found during both these episodes. Already prior to antimalarial drug therapy the girls' preexisting retinopathy was found to have deteriorated.
The concentration of creatinine in serum, which is used to estimate glomerular filtration rate, is measured by reaction with alkaline picrate, but this reaction is not specific for creatinine. Although several other cephalosporin antibiotics have been reported not to react with picrate, we reacted picrate with creatinine, cefoxitin, penicillin, and eight different cephalosporins, and found that all compounds reacted with picrate and showed superimposable spectrophotograms with absorption maxima at 485 nm. From these results we conclude that the color-absorbing moiety of the product is the picrate molecule. Further, the structure common to creatinine and the cephalosporins, cefoxitin, or penicillin is the carbonyl group attached to a nitrogen and a carbon atom. We postulate that the carbonyl group with the adjacent carbon and nitrogen atoms is probably the chemical moiety that reacts with picrate to absorb energy at 485 nm.
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Interference by cefoxitin with determination of creatinine is less with the Technicon SMAC than with other commercial analytical systems. The SMAC assay involves a single-point kinetic method with dialysis, whereas most other commercial methods are multipoint kinetic without dialysis. The apparent creatinine concentration measured for aqueous solutions of cefoxitin was 73 mmol of creatinine per mole of cefoxitin with the SMAC, 135 mmol/mol with a manual method. Furthermore, we determined for the SMAC that the average fraction of creatinine dialyzed was 0.128 and for cefoxitin, 0.064. Thus, the concentration of and interference by cefoxitin in the reaction mixture for SMAC are reduced by half (i.e., the apparent creatinine concentration for cefoxitin with the manual system multiplied by 0.5 is essentially that noted with the SMAC: 68 vs 73). Thus we conclude that the diminished interference be cefoxitin with determination of creatinine by SMAC is primarily ascribable to the dialysis step.
Some cepha antibiotics interfere positively in the Jaffé method for determining creatinine. The extent of this interference differs with the modification used, and its mechanism is unknown. We studied the spectrophotometric and thermodynamic properties of the reaction of picrate with creatinine and two cepha antibiotics, cefoxitin and cephalothin. The absorbance spectra of the chromophore produced by each of the three compounds when reacted with picrate were essentially identical, with an absorbance maximum at 485 nm. We determined the molar absorptivity, rate constant, and equilibrium constant for the reaction of the three compounds with picrate. The molar absorptivity was similar for creatinine and cefoxitin but about fourfold smaller for cephalothin. The rate constant and equilibrium constant for the reaction with picrate were respectively 20- and 10-fold greater for creatinine than for either of the two cepha antibiotics. Thus, these differences indicate the mechanism by which these two cepha antibiotics interfere with the Jaffé procedure for creatinine, and explain why the degree of interference depends on details of the procedure.
We studied the clinical aspects of 30 cases of trabecular carcinoma of the skin. Twenty-three patients were followed up for more than one year. Trabecular carcinoma of the skin is often misdiagnosed as a metastatic malignant tumor. The average age at the time of diagnosis was 68 years; most tumors occurred during the seventh and eighth decades of life. Most initial lesions were located in the head, neck, and upper extremities. Lymph node metastases developed in 13 patients, three of whom eventually died of the disease. Local recurrence developed in ten patients, four of whom died of metastatic trabecular carcinoma. The overall mortality was five of the 30 patients. Three of the patients in whom generalized metastases developed also suffered from some other severe systemic disorder. Nearly half of the 23 patients are free of disease. Sweat gland differentiation was observed in two cases, which indicates that the cell of origin is a multipotential unit capable of both neuroendocrine and sudoriferous differentiation.
In this study it is demonstrated for the first time that shear stress induces the binding of exogenous von Willebrand factor (vWF) multimers to platelets. The vWF preparations used were: 125I-vWF purified from human cryoprecipitate (and including all vWF multimers present in normal plasma); and 35S-cysteine-vWF secreted by human umbilical vein endothelial cells (HUVECs) (and containing unusually large vWF forms, as well as all plasma-type vWF multimers). Direct shear-induced binding to washed platelets (300-360 x 10(3)/microliters) of radiolabeled vWF was maximum at 60-120 dynes/cm2 evaluated at 30 sec and was in extent about one-quarter of the binding stimulated by ristocetin after 3 min of incubation. The shear-induced binding of only a small percentage of added radiolabeled vWF was sufficient to initiate aggregation. Radiolabeled vWF attached to both glycoprotein (GP) Ib and GPIIb-IIIa receptors in the shear field, with complete inhibition of binding occurring with simultaneous blockade of both receptors. Binding was potentiated by ADP released from sheared platelets.
Elevated shear stress levels in pathologically stenosed vessels induce platelet activation and aggregation, and may play a role in the pathogenesis of arterial disease. Increased plasma catecholamine concentrations have also been implicated in the onset of acute coronary ischemic syndromes. This study was designed to examine the synergistic interaction of shear stress and epinephrine in the activation of platelets. Platelets (in PRP) sheared at 60 dyn/cm2 showed little or no aggregation unless pretreated with epinephrine. Pretreatment with 250 nM epinephrine followed by shear at 60 dyn/cm2 induced > 60% platelet aggregation. The specific alpha 2-adrenergic receptor antagonist yohimbine inhibited the synergistic aggregation, as did the ADP scavenging system phosphocreatine/creatine phosphokinase, indicating a three-way synergism with ADP. Chemical or monoclonal antibody blockade of von Willebrand factor (vWF) interactions with either platelet glycoprotein (Gp) Ib or Gp IIb/IIIa completely inhibited platelet aggregation induced by activating levels of shear stress alone. However, the combination of epinephrine and shear stress induced platelet aggregation that was blocked by 10E5, a monoclonal antibody that inhibits vWF binding to Gp IIb/IIIa, but not by aurin tricarboxylic acid or the monoclonal antibody 6D1, both of which inhibit vWF binding to Gp Ib. Synergistic platelet aggregation in response to epinephrine and shear stress was observed in washed platelets, platelet-rich plasma and whole blood in vitro, and also ex vivo following exercise to elevate endogenous levels of catecholamines. These results indicate that epinephrine synergizes with shear stress to induce platelet aggregation. This synergistic response requires functional Gp IIb/IIIa complexes, but is at least partially independent of vWF-Gp Ib interactions.