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Biomedical subjects

J Lindenbaum

Publications and source records attributed to J Lindenbaum.

At least 73 records · Page 4Linked to original sources
PubMed1980

Nutritional anemia in alcoholism.

Megaloblastic anemia due to folate deficiency, the result of dietary lack and a weak antifolate action of ethanol, is the most common cause of a low hematocrit in hospitalized alcoholics. Alcoholism in the absence of significant folate depletion is more commonly responsible for macrocytosis, however. Neutrophil hypersegmentation, which typically persists or worsens during the first 1 to 2 weeks of folic acid therapy, is a useful sign of folate depletion. Serum folate concentrations, however, are often misleading. During conversion of the megaloblastic marrow following hospitalization, giant bands and metamyelocytes often persist after erythroid cells become normal. Reversible ineffective erythropoiesis due to sideroblastic anemia, often but not invariably in association with folate deficiency, is also common. In about half the patients, siderocytes in the peripheral blood smear, which may transiently increase in number during recovery, provide a useful diagnostic clue. Despite the presence of hypochromic microcytes, the erythrocyte mean corpuscular volume is typically normal or elevated. The chronic administration of alcohol along with a marginal diet has produced ringed sideroblasts in human volunteers. Inhibition of heme synthesis by ethanol and an unidentified nutritional factor probably play major roles in pathogenesis. Current evidence does not clearly implicate vitamin B6 depletion in sideroblastic anemia in alcoholics.

Alcoholism↗
PubMed1979

Persistence of neutrophil hypersegmentation during recovery from megaloblastic granulopoiesis.

We studied the rate of disappearance of neutrophil hypersegmentation in 23 patients with megaloblastic anemia during therapy with vitamin B12 and folic acid. In 14 patients with uncomplicated megaloblastic anemia, the neutrophil lobe average began to fall towards normal 11.4 +/- 0.3 (SEM) days after treatment was begun and became normal by 13.9 +/- 0.6 days. In nine patients with associated inflammatory disorders, the lobe average returned to normal more rapidly. In six initially neutropenic patients, a five-fold increase in total granulocyte count occurred by the eighth day and a seven-fold increment in the total number of circulating hypersegmented neutrophils. Granulocyte folate concentrations in five folate-deficient patients rose to normal levels within 4 to 7 days of starting therapy. Hypersegmentation thus persists for many days after correction of neutropenia and restoration of normal granulocyte folate levels have occurred. We conclude that cobalamin and folate are needed at two different steps in granulopoiesis.

Anemia, Macrocytic↗
PubMed1978

Significance of serum level of 25-hydroxycholecalciferol in gastrointestinal disease.

The serum 25-OHCC concentration was measured in 151 patients in order to evaluate the potential use of this determination in the management of gastrointestinal disorders. Patients with functional bowel disease had lower serum mean 25-OHCC levels than normals. The results were divided into normal (greater than 21 ng/ml), low normal (12-21 ng/ml), and low levels (less than 21 ng/ml). Two thirds of patients with malabsorption had low serum 25-OHCC. Most patients following jejunoileal bypass surgery for morbid obesity had low levels despite supplemental oral calciferol therapy. In patients with chronic liver disease, cholestasis more than parenchymal cell disease appeared responsible for low serum 25-OHCC levels. Measurement of serum 25-OHCC may be an ancillary screening test for fat malabsorption and in patients with intraluminal bile salt deficiency. Furthermore, repeated measurements may be useful in monitoring therapy with vitamin D products in patients with chronic malabsorption and cholestasis.

Cholestasis↗
PubMed1977

Greater bioavailability of digoxin solution in capsules. Studies in the postprandial state.

A liquid concentrate of digoxin administered as a capsule has recently been found to be better absorbed by normal subjects in the fasting state than a standard tablet or even a solution as such. It was not known whether the enchanced bioavailability of the encapsulated digoxin solution could also be demonstrated when given postprandially. In a crossover study single 0.4 mg doses of digoxin solution in a capsule, a solution in 10% ethanol as such, and a standard tablet were given to 12 normal volunteers immediately following a high-fat breakfast. The mean area under the serum concentration-time curve (AUC) and 6-day cumulative urinary glycoside excretion (CUE) were greater after the capsule than that of either the solution or the tablet. The latter two preparations appeared to be bioequivalent. Intersubject variability in the CUE was less than with the AUC, but did not differ when the three drug formulations were compared. The bioavailability of an encapsulated liquid digoxin concentrate was thus also found to be enhanced when administered postprandially.

Adult↗
PubMed1977

The mitogenic effect of the lymphocytosis promoting factor from Bordetella pertussis on human lymphocytes.

The purified lymphocytosis promoting factor (LPF) from Bordetella pertussis was found to be a potent mitogen for peripheral blood lymphocytes (PBL) from normal adults as well as for cord blood lymphocytes. Proliferation occurred in autologous plasma or fetal calf serum, regardless of previous exposure to pertussis infection or immunization. Only one adult human serum, from a physician constantly working with B. pertussis, inhibited the mitogenic response to LPF and this serum was shown to contain precipitating antibody against LPF. The proliferative effect of LPF was characteristic of a "nonspecific" mitogen and not of antigen stimulation of sensitized cells.LPF, phytohemagglutinin, and concanavalin A were approximately equal in potency although variation occurred depending upon the cell donor. Experiments with lymphocyte subpopulations obtained by rosetting techniques employing sheep erythrocytes, mouse erythrocytes, and sheep erythrocytes coated with antibody and complement suggested the requirement of a multicellular system for LPF mitogencity.PBL from most patients with chronic lymphatic leukemia and lymphosarcoma cell leukemia were even less responsive to LPF than to phytohemagglutinin, whereas PBL from patients with lymphosarcoma usually responded to both mitogens. It can be inferred from the results of experiments with both normal and leukemic cells that LPF, which is a murine thymus-derived (T)-cell mitogen, is also a T-cell mitogen for human PBL. The exact cell requirement and mode of action, however, are as yet unknown.

Adult↗
PubMed1977

The bioavailability of folic acid added to wine.

Folate deficiency is a frequent cause of anemia in alcoholics, but little attention has been paid to its prevention. Folic acid was readily soluble in wines of high ethanol content at concentrations of 10 microgram/ml. Lactobacillus casei folate activity of folic acid added to wines was well maintained during a month's storage at room temperature and fell to 61% to 66% of original activity after 3 months. Pteroylglutamic acid, 10 microgram/ml, added to wines and given in doses of the beverages (4 ml/kg body weight that caused inebriation, was well absorbed by six normal human volunteers (mean maximal increment in serum folate concentration +/- SEM, 71 +/- 8 ng/ml) and by seven recently intoxicated chronic alcoholics (mean increment, 94 +/- 4 ng/ml). Folate deficiency in alcoholics could be prevented by the fortification of alcoholic beverages with the vitamin.

Adult↗
PubMed1976

Erythroleukemia-like syndrome due to busulfan toxicity in polycythemia vera.

Over a 19-year period, a patient with polycythemia vera who had undergone a splenectomy received six courses of busulfan for recurrent thrombocytosis. The total dose of busulfan given for the sixth course was greater than that used for the previous ones. Severe pancytopenia followed, which persisted for 4 months. During this period there was marked erythroid hyperplasia in the bone marrow with striking dyserythropoiesis; PAS-positive red cell precursors, as well as moderate numbers of circulating normoblasts and evidence of chronic and acute hemolysis, were present. All of these findings reverted to normal without therapy, and the polycythemic state eventually recurred. These events are interpreted as an unusual marrow reaction following busulfan overdosage rather than a transient erythroleukemia.

Adult↗
PubMed1976

Chronic intravascular coagulation associated with chronic myelocytic leukemia. Use of heparin in connection with a surgical procedure.

A women with Philadelphia chromosome-positive chronic myelocytic leukemia lived nearly 12 years from the time of diagnosis. During most of this period she received no therapy, and marked cyclic oscillations in the white blood cell count were documented. The last two years of her illness were marked by a hemorrhagic disorder associated with hypofibrinogenemia, thrombocytopenia, increased plasma fibrinopeptide A concentration and markedly elevated serum levels of fibrin degradation products. The coagulation disorder was rapidly reversible on several occasions with heparin therapy. After treatment with heparin and platelet transfusions, the patient underwent successful resection of a large ovarian cyst with excellent hemostasis during the procedure. Postoperatively, the administration of heparin and platelets was discontinued and a large wound hematoma developed. After resumption of therapy with heparin and platelets, the remainder of her postoperative course was uneventful. The literature on the subject is reviewed and tentative guidelines are offered concerning the management of patients with intravascular coagulation who require diagnostic or therapeutic surgical procedures.

Adult↗
PubMed1976

Inhibition of digoxin absorption by neomycin.

The effect of the administration of the antibiotic neomycin sulfate on the absorption of digoxin was assessed in crossover studies in normal human volunteers. Doses of neomycin (1 and 3 g) markedly depressed serum digoxin concentrations, the areas under the serum concentration-time curves, and cumulative 6-day urinary digoxin excretion after the oral ingestion of 0.5 mg of the cardiac glycoside in tablet form. Neomycin also prolonged the mean time at which peak serum digoxin levels were attained by 1.7 to 3 hr. The inhibition of digoxin absorption was also seen: (1) when the antibiotic was given 3 or 6 hr before the cardiac glycoside, (2) with digoxin tablets of varying dissolution rate, (3) when digoxin or neomycin solutions were used instead of tablets, and (4) in a patient who had had a total gastrectomy. When neomycin was administered with maintenance doses of digoxin, steady state serum digoxin concentrations were significantly reduced. When neomycin was given after a 9-day period of digitalization, the terminal serum digoxin half-life was not significantly shortened. Single doses of neomycin did not interfere with the extent of absorption of d-xylose. In vitro, neomycin did not affect the movement of digoxin across dialysis membranes, nor did it precipitate digoxin out of human bile or intestinal fluid. Neomycin thus clearly depresses the rate and extent of digoxin absorption in man. The mechanism of this effect remains to be established.

Adult↗
PubMed1976

Pulmonary oedema associated with acidosis in patients with cholera.

Five patients with severe acidosis and pulmonary oedema complicating cholera were seen at the Cholera Research Laboratory, Dacca, in a two-year period. All had had inadequate treatment. Their disease resulted in acidosis prior to admission; only the two who subsequently survived received volumes of sodium bicarbonate solutions sufficiently large to repair completely their acidosis. Saline alone worsened pulmonary congestion, while alkali appeared to relieve it despite the accompanying volume expansion. These observations are consistent with the known redistribution of blood to the central circulation in acidosis. Timely and proper treatment of cholera will avert this syndrome, when use of isotonic sodium bicarbonate sufficient to correct acidosis may be very helpful.

Acidosis↗
PubMed1975

Bioavailability of different lots of digoxin tablets from the same manufacturer.

The bioavailability of single doses from 4 randomly selected lots of digoxin from a single manufacturer that were recently marketed in the United States was compared. In a crossover study in 6 normal volunteers, serum digoxin concentrations for 0 to 6 hr and urinary glycoside excretion for 24 hr after 0.5-mg doses were measured by radioimmunoassay. The variation in bioavailability between the 4 lots was no greater than that seen when one of them was taken twice. Intersubject variation in areas under the serum concentration-time curves and in the 24-hr urinary digoxin measurements was more than twice that of intrasubject variation. The variability of the urinary digoxin determinations was somewhat less than that of the areas under the serum concentration-time curves.

Adult↗
PubMed1975

Superior bioavailability of digoxin solution in capsules.

The bioavailability of various formulations of digoxin was assessed after single and multiple doses in a series of crossover studies in human volunteers. Digoxin tablets that were 97% dissolved in 1 hr in vitro were not significantly better absorbed than tablets with a dissolution rate of 78%. A solution given in capsule form had greater bioavailability than tablets of 97% dissolution rate; serum and urinary glycoside levels after 0.4 mg doses of the encapsulated solution were similar to those attained after 0.5 mg doses of tablets with dissolution rates of 78% and 97%. The bioavailability of the solution in capsule form exceeded that of equal doses of the same solution given as a liquid or that of a standard elixir. No increase in gastrointestinal or cardiac toxicity was detected. Inter- and intrasubject variation in bioavailability was not decreased. Above a certain level, dissolution rate is no longer the limiting factor in digoxin absorption. The mechanism of the enhanced bioavailability of concentrated liquid digoxin in capsule form remains to be determined. Such a preparation deserves further consideration as a possible replacement for digoxin tablets.

Adult↗