A comparison of efficacy of sargramostim (yeast-derived RhuGM-CSF) and filgrastim (bacteria-derived RhuG-CSF) in the therapeutic setting of chemotherapy-induced myelosuppression.

A randomized, double-blind, multicenter study in 181 afebrile cancer patients with ANC levels < 500/microL receiving myelosuppressive chemotherapy was undertaken to compare sargramostim (yeast-derived recombinant human granulocyte-macrophage colony-stimulating factor, RhuGM-CSF) and filgrastim (bacteria-derived recombinant human granulocyte colony-stimulating factor, RhuG-CSF) in the treatment of chemotherapy-induced myelosuppression. Patients received daily subcutaneous (SC) injections of either agent until ANC levels reached at least 1500/microL. There was no statistical difference between treatment groups in the mean number of days to reach an ANC of 500/microL, but the mean number of days to reach ANC levels of 1000/microL and 1500/microL was approximately one day less in patients receiving filgrastim. Fewer patients in the sargramostim arm were hospitalized, and they had a shorter mean length of hospitalization, mean duration of fever, and mean duration of i.v. antibiotic therapy compared with patients who received filgrastim. Both growth factors were well tolerated. No patient was readmitted to the hospital after growth factor was discontinued. Sargramostim and filgrastim have comparable efficacy and tolerability in the treatment of standard-dose chemotherapy-induced myelosuppression in community practice.

HTLV-I-associated myelopathy and polymyositis in a US native.

A patient who had always lived in the United States had an HTLV-I infection and a chronic myelopathy clinically mimicking amyotrophic lateral sclerosis. Needle EMG and nerve conduction studies were consistent with anterior horn cell disease but muscle biopsy showed denervation and an inflammatory myopathy. Serum HTLV-I antibody tests were positive and HTLV-I DNA was present in peripheral leukocytes. This is the 1st reported US native with HTLV-I-associated myelopathy and polymyositis.

Neuroendocrine differentiation in prostatic carcinomas. A retrospective autopsy study.

Neuroendocrine differentiation in prostatic neoplasms has in the past been considered extremely uncommon. The histologic neuroendocrine patterns reported previously vary from small cell to carcinoidlike to mixed adenocarcinoma--small cell or carcinoid. The majority of the tumors reported are of the mixed variety. We reviewed 2648 autopsies, revealing 69 prostatic carcinomas, eight with neuroendocrine differentiation (five mixed adenocarcinoma--small-cell carcinoma, two "pure" small cell, and one "pure" carcinoidlike). The mean patient age was 69.5 years. One patient presented with markedly elevated serum corticotropin and another was severely hypercalcemic with elevated serum parathyroid hormone level. Three neoplasms were incidental autopsy findings. The mean survival time, after diagnosis, was 19 months for the other patients. Three of the cases were examined ultrastructurally and showed cytoplasmic processes containing membrane-bound granules in the neuroendocrine component. The areas with neuroendocrine differentiation were positive for markers as follows: neuron-specific enolase, seven of eight; prostate-specific antigen (PSA), none of eight; chromogranin A, seven of eight; synaptophysin, four of eight; and calcitonin, four of eight. Those neoplasms mixed with an adenocarcinoma component showed well-defined PSA positivity in the glandular elements. This study suggests that neuroendocrine differentiation in prostatic neoplasms may be more common than previously thought. Often, the areas with neuroendocrine differentiation are considered to represent poorly differentiated adenocarcinoma. It is important to recognize neuroendocrine components in prostatic carcinomas owing to prognostic and potential therapeutic implications.

Identification of histopathologic risk groups in stage IB squamous cell carcinoma of the cervix.

This study was undertaken to identify histopathologic risk factors in 100 women with stage IB squamous cell carcinoma of the cervix treated surgically. Histologic factors included maximum depth of stromal invasion, presence of lymph-vascular invasion, mitotic activity, nature of the tumor-stromal borders, plasma cell-lymphocyte stromal response, histologic grade, and metastases to regional lymph nodes. Using a multifactorial analysis, the maximum depth of stromal invasion was found to be the most important prognostic indicator (P less than .0001). The depth of invasion also correlated significantly with the presence of nodal metastases (P less than .0001), lymph-vascular space invasion (P = .0003), and "spreading" versus "pushing" borders (P = .0315). The number of mitoses, grade of tumor, or plasma cell-lymphocyte stromal response did not correlate significantly with depth of stromal invasion. Lymph-vascular involvement, although present in 59% of the patients, did not significantly affect survival. Depth of stromal invasion and lesion diameter were combined to constitute three risk groups: Patients with small size cervical tumors (less than 2 cm), regardless of depth of stromal invasion, as well as patients with intermediate size lesions (2.1 to 3 cm) with stromal invasion less than or equal to 1.5 cm, constituted a low-risk group; the intermediate-risk group was comprised of those patients with cervical lesions between 2.1 and 3 cm in size and deep stromal invasion (greater than 1.5 cm), as well as those patients with large cervical lesions (greater than 3.0 cm) and stromal invasion less than or equal to 1.5 cm.2+ (greater than 3 cm) and deep stromal invasion (greater than 1.5 cm).(ABSTRACT TRUNCATED AT 250 WORDS)

A monoclonal antibody reactive with a second epitope of the 67,000-dalton human T cell antigen.

Hybridomas were produced against the T-cell CLL derived-cell line, SKW3, by the fusion of hyperimmune spleen cells with P3 myeloma cells. One clone, designated DU-SKW3-1, was shown to produce a murine IgG2b antibody reactive with an antigen expressed on normal thymocytes and peripheral blood T cells. This antigen was not detected on human B cells, erythrocytes, monocytes, granulocytes, or platelets. D-SKW3-1 also reacted with T-ALL, T-CLL, and B-CLL cells, but did not react with common ALL or acute myelocytic or monocytic leukemias. Immunoprecipitation of lactoperoxidase-iodinated, detergent-solubilized PBL demonstrated that DU-SKW3-1 reacted with a protein with an apparent mass of 67,000 daltons (p67), which had identical mobility to the antigen precipitated by L17F12, Cocapping experiments suggested that DU-SKW3-1 and L17F12 detected the same molecule: however, DU-SKW3-1 was unable to block the binding of L17F12. In addition, DU-SKW3-1 reacted with the T lymphocytes of both the great apes and old world monkeys, in contrast to L17F12 and two other p67 monoclonals, T101 and 10.2, which reacted only with the cells of the great apes. This data suggests that DU-SKW3-1 may react with a second, less phylogenetically restricted epitope on the p67 T cell-/CLL-associated molecule.

The ontogeny of thymidine kinase in tissues of man and rat.

Thymidine kinase activities, virtually all soluble in rat lung, liver, and small intestine, decreased abruptly late in gestation or immediately after birth. An injection of thyroxine delayed the fetal but not the neonatal changes in liver activity. An injection of cortisol decreased hepatic and pulmonary thymidine kinase activities in both fetal and neonatal rats but had little effect on the intestinal enzyme. Premature extrauterinization led to an earlier occurrence of the quantitative changes in thymidine kinase activity usually seen at term. Birth-associated changes included a rapid transitory increase in the hepatic enzyme and the virtual loss of intestinal thymidine kinase activity. In human tissues, the soluble thymidine kinase in liver remained high between the 11th and 22nd wk of gestation whereas the particulte enzyme, the predominant form in adult liver, rose in the second half of gestation and reached adult levels at birth. In human lung, the soluble enzyme started to decrease by the 16th gestational wk, whereas the particulate thymidine kinase reached the higher adult levels late in gestation. Thymidine kinase in adult human tissues was predominantly particulate.

Inhibition of granulocyte erythrophagocytosis by HLA antisera.

The ability of HLA antisera to inhibit granulocyte erythrophagocytosis (EP) of opsonized red blood cells (RBC) was evaluated. Human granulocytes (PMN) were separated from heparinized whole blood by the Ficoll-Isopaque technique and suspended in McCoy's medium. EP occurred when the PMN were incubated with opsonized RBC. For six HLA antibody specificities evaluated, prior incubation of PMN with HLA antisera resulted in significant inhibition of EP without cytolysis when the PMN donor was positive for the specific HLA antigen, but not when the donor was negative for the antigen. The inhibition was time- and dose-dependent. Prior absorption of HLA antisera with HLA-specific platelets reduced or abolished the inhibition. An example of anti-NB1 also inhibited EP in 4 individuals. These data suggest that HLA antibody may adversely affect granulocyte phagocytic function. Inhibition of EP might be useful in evaluating compatibility prior to granulocyte transfusion.

Gastrointestinal hemorrhage secondary to cytomegalovirus after renal transplantation. A case report and review of the problem.

Generalized cytomegalovirus infection was associated with massive and ultimately fatal upper gastrointestinal bleeding in a renal allograft recepient and persisted even after subtotal gastric resection. The surgical specimen and the remaining stomach at autopsy revealed multiple superficial ulcerations with cytomegalic inclusion bodies within the gastric mucosa. Renal failure in the terminal stages of the patient's illness required hemodialysis but did not seem to be the sole result of allograft rejection, suggesting that the renal dysfunction may be caused by the systemic viral infection.