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Biomedical subjects

G Rothstein

Publications and source records attributed to G Rothstein.

At least 55 records · Page 3Linked to original sources
PubMed1980

Neutropenia and thrombocytopenia in renal allograft recipients treated with trimethoprim-sulfamethoxazole.

Hematologic toxicity occurred when trimethoprim-sulfamethoxazole was given for prolonged periods to renal allograft subjects also treated with azathioprine. In six such patients, the incidences and duration of neutropenia and thrombocytopenia were greater than in 25 similar allograft recipients treated with azathioprine alone. In bone marrow culture, the antifolate action of trimethoprim-sulfamethoxazole enhanced the marrow-suppressive effect of 6-mercaptopurine, the active moiety cleaved from azathioprine. These studies show that in renal allograft recipients treated with azathioprine, the prolonged use of trimethoprim-sulfamethoxazole may result in life-threatening hematotoxicity.

Adult↗
PubMed1980

Defective opsonization in multiple myeloma.

The mechanisms responsible for the unusual susceptibility of multiple myeloma (MM) patients to infections are incompletely defined. Since MM is associated with decreased production of normal serum proteins, we investigated the possibility that the production of opsonins might also be impaired. The neutrophil chemiluminescence assay of opsonization was used to evaluate the ability of serum from patients with MM to opsonize zymosan. It was found that sera from 18 MM patients exerted only 50% +/- 2.5% (mean +/- SEM) of the opsonic activity found in 18 control sera (p less than 0.001). In mixture experiments, untreated normal serum completely restored the opsonic activity of MM serum, suggesting a deficiency of opsonic factors rather than an inhibitor. In other mixture experiments, heat-inactivated normal serum only partially corrected the opsonic defect in MM serum. Serum from three patients had low C3 levels, and treatment of particles with these resulted in a greater opsonic defect than the patient population as a whole (p less than 0.02). No correlation between the opsonic defect and infections was established over an 18-mo period. These data suggest that MM serum lacks both heat-stable and heat-labile opsonic activity, the direct clinical significance of which remains to be clarified. However, these studies support the concept that defective host resistance in MM may be multifactoral, combining opsonic abnormalities with other defects previously described.

Complement C3↗
PubMed1979

Pitfalls in the interpretation of leukocyte counts of newborn infants.

Some pitfalls in the interpretation of neonatal leukocyte counts are identified. The well-known variability in neonatal leukocyte counts was investigated by simultaneously sampling arterial, venous and capillary blood, and during periods of rest and mild and violent exercise. Venous blood leukocyte counts were 82% +/- 3.5 (mean +/- SE, P = less than .001) of counts in simultaneously drawn capillary blood from heel punctures; arterial blood counts were 77% +/- 5.3 (P less than .001) of capillary blood values. Following violent crying, capillary blood leukocyte counts increased to 146% +/- 6.1 (P less than .001) of baseline values, and a shift to the left occurred. Milder exercise induced an increase to 113% +/- 5.2 (P less than .05), without a leftward shift. Thus, counts from different vascular sources cannot be considered equivalent. Also, counts from vigorously crying babies may show leukocytosis and a leftward shift, and erroneously suggest bacterial infection. It is recommended that serial counts be obtained from a consistent vascular source in resting babies.

Arteries↗
PubMed1978

Effect of lithium on neutrophil mass and production.

We measured the effect of lithium on the blood neutrophil mass and neutrophil production, using standard di-isopropylfluorophosphate (DF32P) methods. In 12 lithium-treated patients the total blood neutrophil pool was 105 (42 to 270) x 10(7) cells per kilogram (median and 95 per cent limits) as compared with 61 (27 to 138 x 10(7) in 71 controls (P less than 0.001). The neutrophil turnover rate, a measure of effective neutrophil production, was 230 (108 to 380) x 10(7) cells per kilogram per day in the lithium-treated group and 160 (62 to 400) x 10(7) in the controls (P less than 0.05). Neutrophil migration into skin lesions ranged from 34 to 469 x 10(5) cells per day in the lithium-treated patients, as compared with 1.7 to 68 x 10(5) in 10 controls. Lithium causes enlargement of the total circulating neutrophil mass and accelerates neutrophil production without impairing neutrophil migration into skin lesions.

Cell Movement↗
PubMed1977

cGMP stimulation of stem cell proliferation.

The process by which resting hemopoietic stem cells become activated is poorly understood, but it has been suggested that cyclic nucleotide levels in the cell may play an important role. In the present study, the effect of various, nucleotides and stimulators of nucleotide synthesis upon the formation of in vitro granulocyte colonies has been examined. It was found that physiologic concentrations of 3', 5'-cyclic guanosine monophosphate enhanced the formation of granulocyte-macrophage colonies in the presence of colony-stimulating activity. The cells sensitive to cGMP activation were resistant to thymidine suicide and could not be activated by colony-stimulating activity alone. Therefore it was suggested that the cGMP sensitive stem cell was an ordinarily resting stem cell which was triggered into a proliferative state by cGMP.

Animals↗
PubMed1977

Enhancement of colony-stimulating activity production by lithium.

Since lithium causes granulocytosis in some patients, its effect upon granulocyte production was investigated using mouse marrow in the agar culture system. When lithium was added to semisolid cultures of mouse marrow, there was no stimulation of colony formation in the absence of colony-stimulating activity (CSA). In addition, lithium did not potentiate the action of already formed CSA. However, lithium did stimulate the production of CSA by lung tissue. Lithium enhancement of CSA production was blocked by puromycin, indicating that lithium action required active new protein synthesis. It was concluded that lithium promoted enhanced granulocyte production in vitro by stimulating the synthesis of CSA.

Animals↗
PubMed1975

Preleukemia.

Explore the source record for details and available documents.

Anemia↗
PubMed1971

Leukokinetic studies. XIV. Blood neutrophil kinetics in chronic, steady-state neutropenia.

The kinetics of blood neutrophils was investigated by means of the in vitro radioactive diisopropyl fluorophosphate method in 35 patients with a chronic, steady-state neutropenia. There were 17 patients in whom the half disappearance time of neutrophils was normal. In 10 of these patients, the production of neutrophils was low and in 7, production was normal. In 18 patients the half disappearance time of neutrophilic granulocytes was shorter than normal. The production of neutrophilic granulocytes was low in five of these patients, normal in eight patients, and increased in five. An attempt was made to correlate other laboratory measurements with the kinetic picture, but no relationship was found; the marrow neutrophil reserve as measured by endotoxin or cortisol injection; marrow cellularity on aspiration or biopsy; in vitro-labeling index with (3)HTdR; or serum lysozyme concentration proved of no value in identifying the various kinetic groups. The only finding that seemed to correlate with the kinetic picture was the presence or absence of splenomegaly. In 12 of the 18 patients with a short half disappearance time, splenomegaly was present whereas in 15 of 17 patients with a normal half disappearance time, there was no splenomegaly. Of 20 patients with greater than 1000 neutrophils per mm(3), 17 were found to have a normal total-blood neutrophil pool. Thus these patients, with many of their cells marginated, agree to have a "shift neutropenia."Myelocyte to blood transit time and myelocyte generation time, as measured in seven patients by in vivo labeling with diisopropy fluorophosphate, proved to be essentially normal. Thus, it appears that in chronic neutropenia, increased or decreased production of neutrophils is accomplished by increasing or decreasing early precursor input into the system.

Agranulocytosis↗
PubMed1971

STimulation of granulocytopoiesis by a diffusible factor in vivo.

A millipore diffusion chamber system was used to cultivate mouse marrow in the abdomens of irradiated and unirradiated host mice for 24 hr. When the irradiated hosts were 72, 96, or 120 hr postirradiation, the number of blasts and promyelocytes in the implanted chambers after cultivation was greater than those in the same marrow cultivated in unirradiated hosts. These data indicate that in vivo, there is stimulation of granulocytopoiesis by a diffusible factor or factors.

Animals↗
PubMedDate not supplied

Neutrophil transfusion on septic neutropenic neonates.

Depletion of the mature marrow neutrophil stores occurs commonly in neonates with bacterial sepsis and correlates with a fatal outcome. This report discusses the feasibility and efficacy of neutrophil transfusions in such patients and describes two who received neutrophil transfusions and survived without adverse sequelae.

Adolescent↗
PubMedDate not supplied

Use of whole blood exchange transfusion to supply neutrophils to septic, neutropenic neonates.

When neutropenia due to exhaustion of the marrow neutrophil reserve, develops in a neonate with bacterial sepsis the likelihood of survival is very small. We report such a case who was treated with a double-volume exchange transfusion using fresh unstored whole blood. We were able to determine a net gain of 5 x 10(8) neutrophils per kg. Then, in neutropenic neonatal animals, neutrophil transfusion by double-volume exchange transfusion with unstored blood was investigated.

Agranulocytosis↗
PubMedDate not supplied

Effect of intravenous immunoglobulin G on neutrophil kinetics during experimental group B streptococcal infection in neonatal rats.

A modified form of serum immunoglobulin G (pH 4.25) was tested for its effect on neutrophil kinetics and survival rates in neonatal rats with type III, group B streptococcal pneumonia and sepsis. Each of 30 animals received a transthoracic inoculation of 10(5) organisms/g of body weight; all died within 48 hr. When 100, 1,000, or 2,000 mg of immunoglobulin G/kg was administered intraperitoneally at the time of bacterial inoculation, survival rates rose to 20%, 90%, and 100%, respectively. Even when the immunoglobulin preparation was administered intraperitoneally 2 hr after transthoracic inoculation of bacteria, all 19 animals survived. Only seven of 15 animals survived when immunoglobulin administration was delayed for 22 hr. Immunoglobulin facilitated the neutrophil inflammatory response: when immunoglobulin (rather than an albumin control) was administered, neutrophils were released more rapidly from the storage pool and accumulated more quickly at the site of bacterial inoculation. Unlike infected control animals, immunoglobulin recipients did not develop neutropenia or depletion of the neutrophil storage pool.

Animals↗