Severe pre-eclampsia and HELLP syndrome after massive fetomaternal hemorrhage following blunt abdominal trauma.

Severe pre-eclampsia and HELLP syndrome developed within 24h after a 31year old nulliparous woman suffered a blunt abdominal trauma with massive fetomaternal hemorrhage and fetal intracranial bleeding. This is the first case reported of fulminating pre-eclampsia and HELLP syndrome following maternal exposure to a large amount of fetal cells and/or fetal cell debris as DNA or microparticles.

Dealing with difficult sexual questions during consultations: a new training program.

For over 30 years gynecological teaching associates have made a valuable contribution to undergraduate and postgraduate medical education, by allowing medical students to perform a pelvic examination on them. These women are skilled in giving detailed feedback to the medical students about their examination performance. In this study we describe a new training program: gynecological teaching associates act as simulated patients portraying a gynecological/sexual problem, in addition to allowing themselves to be examined by the students. This creates the opportunity of immediate feedback on the entire process of the consultation. Conditions are addressed that should be met to ensure the feasibility of this method.

Microcephaly is not mandatory for the diagnosis of mosaic variegated aneuploidy syndrome.

The phenotype of mosaic variegated aneuploidy (MVA) syndrome is characterized by severe microcephaly, growth deficiency, mental retardation, and mild physical anomalies. The MVA syndrome is associated with mosaicism for several different aneuploidies involving many different chromosomes with or without premature centromere division (PCD). To date 28 cases of MVA syndrome have been reported. We report the first case of MVA syndrome without microcephaly. The clinical features in our patient included craniofacial dysmorphic features, growth retardation, and developmental delay. Cytogenetics analyses and FISH studies showed multiple aneuploidy with trisomy 18, 19, and 8, respectively in blood lymphocyte and fibroblasts without PCD. This case is compared with the other of MVA syndrome previously reported in literature. From this case report, we suggest that microcephaly is not mandatory for the diagnosis of MVA syndrome.

[Bullous cutaneous mastocytosis revealed by acute disease secondary to morphine administration]. / Mastocytose cutanée bulleuse révélée par un malaise grave secondaire à la prise de morphinique.

UNLABELLED: Mastocytosis in children shows in three clinical forms. The rarest is the diffuse or bullous form. CASE REPORT: Since one month of age an infant showed a diffuse erythema and vesicle rash. At four months of age, serious discomfort after morphinic absorption led to the diagnosis of bullous cutaneous mastocytosis. Histologic examination confirmed this diagnosis. The clinical severity led to intravenous corticosteroid and antihistamine therapy. COMMENTS: Bullous cutaneous mastocytosis is unusual in children. However, it should be considered if there are any doubts because of its serious complications and iatrogenic therapeutic risks. Some serious cases require intravenous corticosteroid therapy. Appropriate care enables a normal development with a disappearance of the disease before the teenage years.

Effects of Radix Angelicae sinensis and shuanghuanglian on a rat model of chronic Pseudomonas aeruginosa pneumonia.

OBJECTIVE: To study the effect of two kinds of Chinese herbal medicine, Radix angelicae sinensis (RAS) ([Chinese characters: see text]) and Shuanghuanglian (SHL) ([Chinese characters: see text]) on chronic Pseudomonas aeruginosa (PA) lung infection in a rat model mimicking cystic fibrosis (CF). METHODS: Rats were divided into RAS, SHL and control groups. All rats were challenged intratracheally with alginate embedded PA and the treatments with herbal medicine started on the same day of challenge. The drugs were administered subcutaneously once a day for ten days and the control group was treated with sterile saline. The rats were sacrificed two weeks after challenge. RESULTS: Significantly improved lung bacterial clearance (P < 0.05, P < 0.01) and milder macroscopic lung pathology (P < 0.005) were found in the two treated groups compared to the control group. In the SH treated group, the neutrophil percent in the peripheral blood leukocytes (P < 0.05), the anti-PA IgG level in serum (P < 0.05), the incidence of lung abcesses (P < 0.005) and the incidence of acute lung inflammation (P < 0.05) were significantly lower than in the control group. The RAS treatment reduced fever (P < 0.05), decreased the incidence of lung abcesses (P < 0.005) and lung mast cell number (P < 0.05), and lowered anti-PA IgG1 level in serum (P < 0.05) when compared to the control group. The anti-PA bacterial activity test in SHL was weakly positive whereas in RAS it was negative. CONCLUSION: The treatment with both herbal medicines could increase the resistance of the rats against PA lung infection and they therefore might be potential promising drugs for stimulation of the immnune system in CF patients with chronic PA lung infection.

Effects of ginseng treatment on neutrophil chemiluminescence and immunoglobulin G subclasses in a rat model of chronic Pseudomonas aeruginosa pneumonia.

Chronic Pseudomonas aeruginosa lung infection in cystic fibrosis (CF) patients is almost impossible to eradicate with antibiotic treatment. In the present study, the effects of treatment with the Chinese herbal medicine ginseng on blood polymorphonuclear leukocyte (PMN) chemiluminescence and serum specific antibody responses were studied in a rat model of chronic P. aeruginosa pneumonia mimicking CF. An aqueous extract of ginseng was administered by subcutaneous injection at a dosage of 25 mg/kg of body weight/day for 2 weeks. Saline was used as a control. Two weeks after the start of ginseng treatment, significantly increased PMN chemiluminescence (P

[Effects of subcutaneous injection with different doses of ginseng on the rat model of chronic Pseudomonas aeruginosa pneumonia].

OBJECTIVE: To observe the effect of ginseng extracts on a rat model of chronic Pseudomonas aeruginosa (PA) pneumonia. METHODS: Subcutaneous injection with four different doses of ginseng aqueous extracts to the model rats for two weeks. RESULTS: Milder macroscopic lung pathology and lower incidence of lung abscesses were found in all the four groups received different doses of ginseng treatment compared to the control group (P < 0.05). Histopathology of the lungs was negatively correlated with the ginseng doses (r = -0.95, P < 0.01). The mast cell number in the lung foci in group I, II and IV was significantly lower than that in the control group (P < 0.05). Bacterial clearance in group II and group III was enhanced significantly (P < 0.05) compared with that in the control group. The specific antibody responses were down-regulated in group II, III and IV (P < 0.01), and IgM level in group I was lower compared to the control group (P < 0.01). Serum IgM level was positively correlated with the ginseng doses (r = 0.93, P < 0.05). IgG2a titer in group I was higher than that in the control group (P < 0.05). Serum IgG2a level was positively correlated with the ginseng doses (r = 0.90, P < 0.02). Two weeks after PA lung infection, the serum level of IgG against PA, aeruginosa alginate in group I, II, and III was higher than that in the control and group IV (P < 0.05), and the anti-alginate IgA level in group I, III and IV was lower than that in the control (P < 0.05). CONCLUSIONS: The ginseng dose of 2.5 mg/kg was the best dosage in the present study, and it showed an effect of stimulating T helper type I response.

Ginseng treatment enhances bacterial clearance and decreases lung pathology in athymic rats with chronic P. aeruginosa pneumonia.

In an athymic rat model of chronic Pseudomonas aeruginosa lung infection mimicking cystic fibrosis (CF), we studied the effects of the Chinese herb ginseng. Rats were treated subcutaneously with ginseng extracts (25 mg/kg) once a day for 10 days after challenge with P. aeruginosa embedded in alginate beads. We found that ginseng treatment significantly reduced bacterial load (p < 0.02) and the number of mast cells in the lungs (p < 0.01). Furthermore, it decreased the severity of lung pathology (p < 0.02) and lowered serum anti-P. aeruginosa IgM and IgA antibody levels (p < 0.004, p < 0.04) compared to the control group. The down-regulated specific humoral immunity in the ginseng-treated group and the fact that athymic rats have a severely compromised T-cell-mediated immune reactivity due to the absence of thymus might suggest an activation of innate immunity after ginseng treatment. Our findings indicate that ginseng treatment increases the resistance of the athymic rats to P. aeruginosa lung infection. We therefore think that ginseng has promising potential as a natural medicine for stimulation of the immune system in CF patients with chronic P. aeruginosa lung infections.

Ginseng treatment reduces bacterial load and lung pathology in chronic Pseudomonas aeruginosa pneumonia in rats.

The predominant pathogen in patients with cystic fibrosis (CF) is Pseudomonas aeruginosa, which results in a chronic lung infection associated with progressive pulmonary insufficiency. In a rat model of chronic P. aeruginosa pneumonia mimicking that in patients with CF, we studied whether the inflammation and antibody responses could be changed by treatment with the Chinese herbal medicine ginseng. An aqueous extract of ginseng was injected subcutaneously, and cortisone and saline were used as controls. Two weeks after challenge with P. aeruginosa, the ginseng-treated group showed a significantly improved bacterial clearance from the lungs (P < 0.04), less severe lung pathology (P = 0.05), lower lung abscess incidence (P < 0.01), and fewer mast cell numbers in the lung foci (P < 0.005). Furthermore, lower total immunoglobulin G (IgG) levels (P < 0.01) and higher IgG2a levels (P < 0.025) in serum against P. aeruginosa sonicate and a shift from an acute type to a chronic type of lung inflammation compared to those in the control and cortisone-treated groups were observed. These findings indicate that ginseng treatment of an experimental P. aeruginosa pneumonia in rats promotes a cellular response resembling a TH1-like response. On the basis of these results it is suggested that ginseng may have the potential to be a promising natural medicine, in conjunction with other forms of treatment, for CF patients with chronic P. aeruginosa lung infection.

Differentiation of primary and secondary cutaneous B-cell lymphoma by Southern blot analysis.

Malignant B-cell lymphomas represent a heterogenous group of lymphoreticular disorders that involve the skin in about 20% of reported cases. Skin involvement may be primary or secondary (ie, the result of hematogenous spread). Primary cutaneous B-cell lymphomas (PCBCLs) are thought to take a comparatively favorable course, respond readily to nonaggressive treatment, and lack evidence of extracutaneous spread. Nine primary B-cell lymphomas (7 centrocytic or centroblastic follicular, 1 immunoblastic, 1 centroblastic), three secondary (follicular) cutaneous B-cell lymphomas (SCBCLs) and two pseudolymphomas were studied. Staging revealed that bone marrow was involved only in SCBCLs. Centrocytes were detected in blood smear preparations of all SCBCLs. All lymphomas were treated with local irradiation. Patients with primary centroblastic and immunoblastic cutaneous lymphomas and those with secondary lymphomas received additional chemotherapy. Pseudolymphomas were treated by simple excision. Patients were monitored on average for 55 months. During this period, no patients with PCBCLs exhibited cutaneous relapses or hematogenous spread. In contrast, all patients with SCBCLs experienced cutaneous relapses. Peripheral blood, bone marrow, and skin samples from all patients were subjected to Southern blot analysis using a JH probe. Clonal rearrangement was found in all skin samples investigated except specimens from pseudolymphomas. Peripheral blood and bone marrow samples were positive in SCBCLs (the rearrangement pattern was different from that of the skin samples for two of the three patients), whereas it was negative in all PCBCLs and pseudolymphomas. In conclusion, Southern blot analysis of peripheral blood may be useful in differential diagnosis of PCBCLs and SCBCLs and a prognostic marker. Furthermore, these data confirm the comparatively favorable clinical course of PCBCLs and suggest that in these cases, local irradiation can be considered adequate treatment, whereas SCBCLs require additional systemic therapy.

The efficacy and safety of zidovudine alone or as cotherapy with acyclovir for the treatment of patients with AIDS and AIDS-related complex: a double-blind randomized trial. European-Australian Collaborative Group.

OBJECTIVE: To evaluate the efficacy and safety of zidovudine (ZDV) at a maintenance dose of 250 mg every 6 h alone or as cotherapy with acyclovir (ACV; 800 mg every 6 h) as treatment for AIDS and AIDS-related complex (ARC). DESIGN: Double-blind, randomized, placebo-controlled clinical trial of up to 1 year's therapy. SETTING: Teaching hospital ambulatory clinics in eight European countries and Australia. SUBJECTS: A total of 131 patients with AIDS and 134 with ARC were enrolled and followed from 1986 to 1988. MAIN OUTCOME MEASURES: Time to development of AIDS-defining opportunistic infections and AIDS-associated neoplasms, survival assessed at 1 year after entry, performance status, body weight, CD4+ cell counts. RESULTS: During the study period, 46 (36%) ZDV recipients and 37 (27%) cotherapy recipients developed opportunistic infections. The probability of an ARC patient progressing to AIDS (1982 Centers for Disease Control criteria) was 0.18 and 0.15 [95% confidence interval (CI) for difference, -0.17 to 0.11] for the ZDV alone and cotherapy recipients, respectively. After excluding patients who experienced an opportunistic infection during the first 4 weeks of therapy, the probability was 0.13 and 0.099 (95% CI for difference, -0.16 to 0.10) for the ZDV and cotherapy recipients, respectively. Thirty-six patients treated with single-agent therapy [28 (41%) AIDS and eight (12%) ARC patients] and 15 cotherapy recipients [13 (21%) AIDS and two (3%) ARC patients] died during the study. There was a significant difference in time to death between the cotherapy and ZDV alone groups for both AIDS (P = 0.014) and ARC (P = 0.045) patients, with cotherapy patients surviving longer. Infections related to herpesviruses, but not cytomegalovirus, were reduced in patients receiving ACV therapy. CD4+ cell counts in both arms generally increased initially and then declined. Forty-six per cent of patients in the ZDV group (59% of AIDS and 31% of ARC patients) and 52% of patients in the cotherapy group (69% of AIDS and 34% of ARC patients) experienced bone-marrow suppression. Red cell transfusions were administered to 33% of ZDV alone recipients and 34% of cotherapy recipients. CONCLUSION: These data show that the addition of high-dose ACV cotherapy to ZDV for patients with AIDS and advanced ARC results in a statistically significant improvement in survival with minimal increase in the risk of toxicity.

Cell-associated proteoheparan sulfate mediates binding and uptake of thrombospondin in cultured porcine vascular endothelial cells.

[125I]Thrombospondin (TSP) binds to porcine endothelial cells in a specific, saturable and time-dependent fashion and is endocytosed by a receptor-mediated process. The N-terminal heparin-binding domain is necessary for the interaction with the cell surface. Binding and uptake is inhibited by heparin and to a much smaller extent by other vascular glycosaminoglycans. Chemical modification of lysine and arginine residues of TSP, but not treatment of the molecule with neuraminidase, resulted in a pronounced loss of binding at the cell surface. Treatment of cells with heparitinase but not with chondroitin ABC lyase caused inhibition of binding and uptake of TSP. Inhibition of sulfation of proteoglycans on the cell surface by chlorate leads to a dose and time-dependent inhibition of binding and degradation of TSP. In the presence of chlorate, newly synthesized TSP is not incorporated into the cell matrix but mainly released into the culture medium, whereas localization and incorporation of newly synthesized fibronectin is not altered. A cell surface proteoheparan sulfate was identified as TSP binding macromolecule by affinity chromatography. The data emphasize the role of heparan sulfate proteoglycan as a receptor-like molecule for the specific interaction with thrombospondin.

Colocalization of a large heterodimeric proteoglycan with basement membrane proteins in cultured cells.

A novel large heterodimeric dermatan sulfate proteoglycan with core proteins of 460 and 300 kDa, respectively, had been described as a secretory product of human fetal skin fibroblasts (Breuer et al., J. Biol. Chem. 266, 13224-13232 (1991)). Pulse-chase experiments showed a preferential association of the proteoglycan with the cell membrane. Immunogold labeling indicated its localization in fibrils on the cell surface as well as in fibrillar extensions from the cell body. Immunofluorescence studies yielded a fibrillar and punctate staining pattern which was also seen in cultured human and porcine endothelial cells. Dot-like structures were observed in transformed human keratinocytes. Various immunocytochemical double-labeling experiments indicated a remarkable colocalization of the proteoglycan with fibronectin, laminin, perlecan, and type IV collagen whereas only occasionally a colocalization with chondroitin-6-sulfate was found. No evidence for an enrichment of the proteoglycan in vinculin-containing structures was obtained. These results suggest that the proteoglycan is a widely distributed macromolecule which can associate with basement membrane components. Preliminary findings in rat cornea supported this conclusion.

Susceptibility of strains of the Mycobacterium tuberculosis complex to fusidic acid.

The activity of fusidic acid was studied in 40 strains of M. tuberculosis (of which 20 strains were mono- or multiresistant to standard antituberculosis drugs) and 10 strains of M. bovis. Minimum inhibitory concentration (MIC) was determined by the radiometric (BACTEC) broth method. The MIC for the 50 strains varied between 8 and 32 mg/l, with a MIC90 of 16 mg/l for M. tuberculosis and a MIC90 of 32 mg/l for M. bovis. Minimal bactericidal concentration (MBC, defined as the lowest concentration of fusidic acid which killed 99% or more of the population) varied between 32 mg/l and 500 mg/l, with a MBC90 of 250 mg/l for M. tuberculosis and 500 mg/l for M. bovis. No cross-resistance to other antituberculosis drugs (ethambutol, isoniazid, rifampicin, streptomycin, pyrazinamide, ofloxacin, ciprofloxacin) was observed as strains resistant to one or more standard antituberculosis drugs were as susceptible to fusidin as sensitive strains of M. tuberculosis. No synergism or antagonism could be demonstrated when fusidic acid was combined with either ethambutol, isoniazid, rifampicin or streptomycin against strains of M. tuberculosis resistant to one or more standard antituberculosis drugs. Addition of pooled human serum to the medium increased both MIC and MBC by factors of 4 and 8 at serum concentrations of 10% and 50%, respectively. Single-step mutation to high-level resistance to fusidic acid at a frequency of less than 1.7 x 10(-8) could be readily selected at four times the MIC. These fusidic acid-resistant organisms had a generation time 2.0-2.7 x longer than their parent organisms.

Stimulation of the biosynthesis of lactosamine repeats in glycoproteins in differentiating U937 cells and its suppression in the presence of NH4Cl.

We prepared a mouse monoclonal antibody, 2D5, which recognized a highly glycosylated human lysosomal membrane antigen. The apparent molecular mass of this antigen was cell type dependent and ranged between 100 kDa and 130 kDa. The difference was due to a variation in the carbohydrate moiety, since upon removal of the N-linked oligosaccharides the size of the glycoprotein was reduced to approximately 50 kDa in all cases. The high carbohydrate contents, subcellular localization and N-terminal sequence indicated a high similarity or identity of this antigen with the lamp-2 protein. In U937 cells several agents known to elicit differentiation induced synthesis of a larger form of the lamp antigen. Thus, treatment of cells with calcitriol resulted in a shift in its average molecular mass from 115 kDa to 130 kDa. The difference was due to an increase in the contents of lactosamine repeats. In subcellular membranes from calcitriol-treated cells the specific activity of the UDP-N-acetylglucosamine: N-acetyllactosamine N-acetylglucosaminyltransferase was enhanced 3-fold. The enhancement was accompanied with an elongation of lactosamine repeats in N-linked oligosaccharides in the 46 kDa mannose 6-phosphate receptor and the homing receptor, the leucocyte antigen CD44. In contrast, the apparent size of the leucocyte antigen CD43 which bears numerous O-linked oligosaccharides was not changed indicating a selectivity in the modulation of the formation of lactosamine repeats in N- and O-linked carbohydrates. It is shown further that the synthesis of lactosamine repeats in U937 cells is impeded in the presence of NH4Cl.

[Adrenal cortex function in patients with AIDS and healthy HIV-positive persons]. / Binyrebarkfunktionen hos AIDS-patienter og raske HIV1-positive personer.

Adrenal function was estimated by synthetic ACTH test in 18 men with AIDS (or AIDS-related complex) and compared with that of 10 HIV positive but otherwise healthy men. According to this test none fulfilled the criteria for adrenal insufficiency defined as plasma cortisol concentration less than 500 nmol/l 30 minutes after ACTH stimulation. Seven of eighteen AIDS patients had baseline cortisol concentrations above 0.5 mumol/l compared to none in the HIV-positive group. Three of eighteen AIDS patients had a limited response to synthetic ACTH injection compared to none in the HIV-positive group. Two of these three AIDS patients had lowered serum Na+ concentration; they survived for two and three weeks, respectively. Otherwise the basal cortisol level and response to synthetic ACTH was uncorrelated with survival time, other signs of adrenal insufficiency, treatment with ketokonazole, CMV-infection, T-helper cell count or Th/Ts-ratio. The pituitary-adrenal axis was estimated by measuring the diurnal rhythm of serum ACTH and cortisol in eight patients and was found intact and normal in all of them. Thus, absolute adrenal insufficiency is uncommon in AIDS-patients. Relative adrenal insufficiency may occur in severely ill preterminal patients as a result of primary target organ failure, but the pituitary-adrenal axis generally appears to be undisturbed.

Aspirin reduces the growth of medial and neointimal thickenings in balloon-injured rat carotid arteries.

We analyzed the effect of Aspirin on the growth of experimentally induced vascular thickenings in rat carotid arteries. Vascular thickenings were induced by denudation of the endothelium in the left carotid artery with a balloon catheter. Administration of Aspirin-rich food (17.4 g/kg body wt/day) was started 1 week before and continued 2 weeks after injury. Nine rats were used. A control group of equal size received normal food. Sizes of the tunica media, the neointima, and the open vessel lumen were measured on cross sections of carotid segments with the aid of a videomorphometry system. The results show that in the Aspirin group, neointimal lesions are significantly smaller than in the control group (0.14 mm2 versus 0.23 mm2; p less than 0.5). Thickenings of the tunica media are also reduced (0.11 mm2 versus 0.12 mm2; p less than 0.5). It is suggested that Aspirin reduces both medial hypertrophy and neointimal outgrowth in injury-induced atherosclerosis.

Fusidic acid, an immunosuppressive drug with functions similar to cyclosporin A.

Fusidic acid, a tetracyclic triterpenoic acid, is used for local and systemic treatment of bacterial infections. Its in vitro effects on the human immune response were tested. Activated blood mononuclear cells released lower levels of interleukin (IL) 1 in the presence of nontoxic and clinically attainable levels of fuscidic acid (15 to 50 micrograms/mL). In contrast, the drug failed to affect the production of two other monocyte-derived cytokines, tumor necrosis factor (TNF)-alpha and IL 6. The production of the T-cell-derived cytokines, IL 2 and interferon-gamma (IFN-gamma), were also suppressed (IC50: 5 to 15 micrograms/mL). The early costimulatory effects of IL 1 and IL 6 on mouse thymocytes and human T cells were suppressed by similar levels of the drug, as was the hybridoma growth-promoting function of IL 6. T-cell proliferation induced by phytohemagglutinin or allogeneic cells was reversibly inhibited (IC50: 15 micrograms/mL). These functions of fusidic acid were strikingly similar to those of cyclosporin A. Because of the low toxicity of the former, it may have a role as a clinically useful suppressor of immunoinflammatory processes.