Effects of parenteral recombinant human macrophage colony-stimulating factor on monocyte number, phenotype, and antitumor cytotoxicity in nonhuman primates

Recombinant human macrophage colony-stimulating factor (rhM-CSF) was given to cynomolgus monkeys by continuous intravenous infusion or subcutaneous injection, at a dose of 50 to 100 micrograms/kg/d in repetitive 14-day cycles. Starting within 24 to 48 hours of initiation of rhM-CSF, there was a progressive increase in the number of circulating monocytes, from a baseline of 811 +/- 253 cells/microL to a peak of 3,495 +/- 712 cells/microL on day 5 to 7. Many of these cells were large, granular, and extensively vacuolated. The expanded cell population expressed HLA-DR, LFA3, CD11b (904), and CD14 (MY4), and was 77% CD16 (FcRIII) positive by two-color cytofluorometry. In functional assays, fresh monocytes showed little cytotoxicity against cultured human melanoma cells (SKMel-1), with or without prior rhM-CSF treatment. However, after 3 days of in vitro culture in rhM-CSF, monocytes from treated animals mediated efficient antibody-dependent cytotoxicity (ADCC) against SKMel-1 using the murine monoclonal antibody 3F8 (IgG3, anti-ganglioside GD2). Under the same conditions, monocytes from control animals showed little ADCC (17% versus 82%, P less than .05). Antitumor cytotoxicity in the absence of antibody was less efficient and was not significantly different between the two groups. There was a mild decrease in platelet count during rhM-CSF treatment, without clinical symptoms. No abnormalities of serum biochemical parameters were seen. We conclude that parenteral rhM-CSF increases the number of circulating monocytes in nonhuman primates, and that these monocytes mediate increased antitumor ADCC after a brief period of in vitro differentiation. This study has implications for the design of possible future clinical trials combining antitumor monoclonal antibodies and rhM-CSF.     

Therapy of severe aplastic anemia in young adults and children with allogeneic bone marrow transplantation

During an 8-year period, 28 young adults (median age 27 years) and 30 children (median age 10 years) with severe aplastic anemia have received allogeneic bone marrow transplantation (BMT) from major histocompatibility locimatched sibling donors after preparation with cyclophosphamide and total lymphoid irradiation (TLI). All recipients were previously transfused. Comparison of post-bone marrow transplantation events in adults and children reveals equivalent median time to engraftment, median duration of hospitalization, median Karnofsky assessment of activity, and equivalent low rejection rate. Although the incidence of moderate and severe acute graft-v-host disease (GVHD) and of extensive chronic GVHD was greater in adults than in children, the projected survival at 4 years of adults (67%; 95% confidence interval [CI] 49% to 85%) and of children (73%; 95% CI 57% to 89%) was equivalent. All survivors are transfusion-free and have normal peripheral blood counts. One of 28 adults and 2 of 30 children have experienced rejection, and 1 of these patients survives after a second transplant. No malignancies have been identified following transplantation. An unexpectedly high incidence of hypothyroidism has been detected and may be attributable to preparation of recipients with TLI. Therapy of severe aplastic anemia with allogeneic BMT after preparation with cyclophosphamide and TLI offers a high rate of transfusion-free survival and a low rejection rate in previously transfused young adults and children.     

Immunologic abnormalities in myelofibrosis with activation of the complement system

Eighteen patients with agnogenic myeloid metaplasia with myelofibrosis were studied for clinical and laboratory evidence of immunologic dysfunction. Clinical findings included the presence of arthritis, vasculitis, and erythema nodosum. Laboratory abnormalities included the presence of circulating immune complexes, antinuclear antibodies, positive direct Coombs tests, elevated latex fixations, and a circulating lupus type anticoagulant. Total hemolytic complement was markedly depressed in four patients. Analysis of complement (C) components C1-C9 and factor B demonstrated significant reduction of only C3 and factor B. By crossed-immunoelectrophoresis, both C3 and factor B, but not C4, were cleaved, indicating that C activation was occurring predominantly via the alternative pathway. The control proteins beta 1H and C3b inactivator were decreased in three of four patients with hypocomplementemia. These data suggest that immunologic mechanisms associated with activation of the complement system play an important role in the disease process of some patients with agnogenic myeloid metaplasia with myelofibrosis.     

Summer-type relapsing fever (hypersensitivity pneumonitis) secondary to Cladosporium herbarum in the domestic environment

‘Summer-type relapsing fever’ is the most prevalent form of hypersensitivity pneumonitis in Japan. It is usually caused by hypersensitivity to Trichosporon cutaneum – a seasonal mould which thrives in homes with damp, decayed wood, damp mats and bedclothes. The disease has been rarely described outside Japan. We report the first documented case of summer-type hypersensitivity pneumonitis in Europe – in this case caused by hypersensitivity to the mould Cladosporium herbarum.     

Evaluation of the association of serum levels of hyaluronic acid,sICAM-1, sVCAM-1, and VEGF-A with mortality and prognosis in patients with Crimean-Congo hemorrhagic fever

BackgroundCrimean-Congo hemorrhagic fever (CCHF) is a tick-borne viral hemorrhagic disease. Pathogenesis of the disease has not been well described yet. A well-known pathogenic feature of CCHF virus is its capability to damage endothelium. Increased hyaluronic acid (HA) levels indicate liver sinusoidal endothelial damage. Soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1) and vascular endothelial growth factor-A (VEGF-A) play a role in the inflammatory process, vascular damage and plasma leakage.ObjectivesTo investigate whether or not there is a relationship between HA, sICAM-1, sVCAM-1 and VEGF-A serum levels and fatality in CCHF.Study designSixty-one patients who were confirmed by RT-PCR and serological tests for CCHF, included in the current study. HA, sICAM-1, sVCAM-1, VEGF-A levels in serum samples were analyzed by ELISA.ResultsThere were statistically significant differences between fatal and non-fatal CCHF patients in terms of HA, sICAM-1, sVCAM-1, and VEGF-A levels. In addition, AST and ALT levels were positively correlated with HA, sICAM-1, sVCAM-1, and VEGF-A levels.ConclusionHA, sICAM-1, sVCAM-1, and VEGF-A levels of the patients that died during hospitalization were statistically significantly higher than the patients that survived, and this finding suggests that the level of these molecules could be used as a prognostic marker in CCHF.     

Management of advanced-stage primary carcinoma of the fallopian tube: case report and literature review

Primary carcinoma of the fallopian tube is a very unusual gynecologic malignancy that accounts for less than 1% of all malignancies of the female genitalia. A 55-year-old, gravida 7, para 3 woman presented with no gynecologic complaints other than backache. TVS demonstrated a 35 x 25 mm heterogeneous mass that was not clearly separated from the left ovary, and another 31 x 14 mm cystic septated lesion in the left ovary region. Pelvic MRI demonstrated a 35 x 35 x 20 mm left adnexal mass that enhanced with contrast and a neighboring tubular-cystic mass. Upper and lower gastrointestinal endoscopy revealed no malignancy. Serum CA 125-level was merkedly elevated at 369 U/ml (normal < 35 U/ml). Laparotomy revealed left hydrosalpinx and a papillary-fimbrial mass. Pelvic lymph node metastases were observed. Frozen-section analysis identified the mass as a serous adenocarcinoma. Total abdominal hysterectomy, bilateral salpingo-oophorectomy, appendectomy, omentectomy, pelvic and para-aortic lymph node dissection, and peritoneal washing were performed. The definitive histopathological diagnosis was primary serous adenocarcinoma of the fallopian tube with six of 25 lymph node biopsies showing metastasis. Six cycles of paclitaxel (175 mg/m2) plus cisplatin (75 mg/m2) combinatin chemotherapy were administered with 3-week intervals between cycles. Second-look laparotomy was performed; there was no evidence of disease. At the time of writing 12 months after the second-look laparotomy, she was still disease-free.     

Interleukin-6 levels in hyperemesis gravidarum

INTRODUCTION. Hyperemesis gravidarum (HG) is associated with higher levels of serum beta-hCG levels and hyperthyroidism. Interleukin-6 (IL-6), a pro-inflammatory cytokine, is reported to enhance secretion of beta-hCG from trophoblastic cell line. METHODS. We measured serum levels of IL-6, thyroid hormones and beta-hCG of hyperemetic patients and gestational age-matched controls to search for a difference between the two groups. RESULTS. There was a significant difference in beta-hCG ( p=0.028), though IL-6 levels were higher in the hyperemetic group, it did not reach a significant level. Interleukin-6 positively correlated with beta-hCG ( r=0.38 and p=0.13).     

A STUDY OF METHODS USED FOR DISINFECTION OF ANAESTHETIC EQUIPMENT BETWEEN TWO SURGICAL OPERATIONS AT A LARGE TEACHING HOSPITAL

A prospective study on the growth of bacteria on certain commonly used anaesthetic equipment was undertaken in a large teaching hospital with a view to assess the effectiveness of disinfection/sterilization procedures. Samples for microbiological assessment were drawn by the worker using standardised procedures and tested in the laboratory by a microbiologist, blinded to the type of sample. Criteria for growth positivity was taken as > 25 colony forming units. A total of 90 observations were taken. 30 each for ’before use’, ’after use’ and ’after disinfection’. Overall 54.6% of the equipment showed growth “before use” with maximum growth being seen in Suction catheters (66.6%) and Guedal airways (60.0%). On the other hand, the proportion of equipment showing growth “after use” was quite high (84.6%), with suction catheters and endotracheal tubes showing 90.0% growth each. There was significant difference as regards “before” and “after” use growth on Endotracheal tubes, Guedel airways and Face masks (p < 0.05). Analysis of growth “after” disinfection” revealed that the probability of growth remains as high as 70% in suction catheters (95% CI=54% to 86%) and 60% in laryngoscopes (95% CI=43% to 78%). The study revealed gross inadequacies in methods of disinfection being followed at present.KEY WORDS: Anaesthetic equipment, Disinfection     

Close mapping of the focal non-epidermolytic palmoplantar keratoderma (PPK) locus associated with oesophageal cancer (TOC)

Focal non-epidermolytic palmoplantar keratoderma (PPK or palmoplantar ectodermal dysplasia type III) is associated with oesophageal cancer in three families: two large pedigrees located in Liverpool, UK and in the midwestern American states and one smaller family from Germany. In these families, the PPK is inherited as autosomal dominant and has a late onset, usually manifesting between 7 and 8 years of age. The disease is characterised by thickening of the pressure areas of the soles, but is not restricted to the feet and also presents with oral leukokeratosis and follicular hyperkeratosis. The disease locus [previously termed the "tylosis oesophageal cancer gene' (TOC) locus] has been mapped to 17q23-qter by linkage analysis. This region is located telomeric to the keratin 16 gene, in which mutations have been identified in focal PPK families who show no increased cancer risk. We describe the close mapping of this locus to the interval between AFMb054zf9 and D17S1603 using haplotype analysis of additional Genethon markers in the region and show that although the American family is unlikely to be related to either of the other two, the UK and German pedigrees may share a common descent. This work provides a basis for positional cloning and candidate gene analysis in order to identify a gene that may be involved in familial oesophageal cancer.