Collagen deposition in a non-fibrotic lung granuloma model after nitric oxide inhibition

Recent studies support the concept that pulmonary granulomatous inflammation directed by interferon (IFN)-gamma, interleukin (IL)-12, and nitric oxide usually resolves in the absence of fibrosis. To determine whether nitric oxide participates in modulating the fibrotic response during the development of pulmonary granulomas in response to purified protein derivative (PPD), mice presensitized to PPD received daily intraperitoneal injections of N(G)-nitro-D-arginine-methyl ester (D-NAME), N(G)-nitro-L-arginine-methyl ester (L-NAME), or aminoguanidine after delivery of PPD-coated beads to the lungs. Eight days later, morphometric analysis of lung granulomas revealed that L-NAME-treated mice when challenged with PPD in vitro for 36 hours had the largest pulmonary granulomas and the greatest collagen deposition among the treated groups. In addition, equivalent numbers of dispersed lung cells from L-NAME- and aminoguanidine-treated mice produced significantly higher levels of IL-4, monocyte chemoattractant protein (MCP)-1, and macrophage inflammatory protein (MIP)-1alpha and significantly lower levels of eotaxin compared with D-NAME-treated mice. Cultures of dispersed lung cells from L-NAME-treated mice also produced significantly more IL-10 and less IL-12 compared with similar numbers of dispersed lung cells from D-NAME-treated mice. Cultures of isolated lung fibroblasts from L-NAME-treated mice expressed higher levels of C-C chemokine receptor 2 (CCR2) and CCR3 mRNA and contained less MCP-1 and eotaxin protein than a similar number of fibroblasts from D-NAME-treated mice. Thus, nitric oxide appears to regulate the deposition of extracellular matrix in lung granulomas through the modulation of the cytokine and chemokine profile of these lesions. Alterations in the cytokine, chemokine, and procollagen profile of this lesion may be a direct effect of nitric oxide on the pulmonary fibroblast and provide an important signal for regulating fibroblast activity during the evolution of chronic lung disease.     

Attachment relationships in infant twins: the effect of co-twin presence during separation from mother

In this study the roles of the mother and the co-twin in inhibiting emotional arousal and reducing manifest distress of a twin who had been isolated in a modified strange situation were compared. The subjects were 15 children, each a member of a twin pair. The subjects were placed in a playroom under three conditions in the following order: (a) mother and twins present; (b) twins together, mother absent; (c) subject isolated from both co-twin and mother. The episodes in which all partners were together were alternated with brief separations. The subjects' distress was minimal when they were separated from the mother with the co-twin present. Upon reunion, stable social behavior was quickly restored. However, separation from the mother and co-twin produced a high level of distress for the subjects. When reunited, the isolated twin initiated physical contact with the mother, soliciting and receiving comfort from her. Furthermore, the distress of the isolated twin was transmitted to the co-twin who had remained with the mother during the isolation period. The nonisolated twin also solicited comfort from the mother. The presence of the co-twin during the reunion following isolation had little effect in reducing the subject twin's distress.     

Alteration of the cytokine phenotype in an experimental lung granuloma model by inhibiting nitric oxide

Pulmonary granulomatous inflammation modulated by IFN-gamma and IL-12 is also associated with augmented inducible nitric oxide synthase (NOS II). To address the role of increased nitric oxide synthesis in this model, mice received daily i.p. injections of NG-nitro-L-arginine-methyl ester (L-NAME; 8 mg/kg) during both the 2-wk immunization period with purified protein-derivative (PPD) and the subsequent lung challenge with PPD-coated Sepharose beads. Other groups of animals received saline, L-NAME or NG-nitro-D-arginine-methyl ester (D-NAME; 8 mg/kg) during the pulmonary embolization period and not the PPD sensitization period. On day 4 post-PPD bead challenge, PCR analysis of the whole lung revealed that NOS II expression appeared to be similar in both of the L-NAME treatment protocols. L-NAME-treated mice in both dosing protocols had lung lesions that were significantly larger than granuloma lesions measured in mice that received saline or D-NAME. The enlarged lesions from L-NAME-treated mice contained markedly greater numbers of neutrophils and eosinophils. Equivalent numbers of PPD-activated dispersed cells from whole lungs of L-NAME-treated mice produced significantly higher levels of IL-4 and IL-10 and smaller amounts of IL-12 and IFN-gamma compared with similar lung cultures derived from control or D-NAME-treated mice. Levels of C-C chemokines such as monocyte chemoattractant protein-1 (MCP-1), C10, and macrophage inflammatory protein-1alpha (MIP-1alpha) were also significantly elevated in lung cultures from L-NAME-treated mice compared with controls. Thus, nitric oxide regulates the size and cellular composition of the Th1-type lung granuloma, possibly through its effects on the cytokine and chemokine profile associated with this lesion.     

Acute and relapsing experimental autoimmune encephalomyelitis are regulated by differential expression of the CC chemokines macrophage inflammatory protein-1alpha and monocyte chemotactic protein-1

Myasthenia gravis (MG) patients develop autoantibodies primarily against the acetylcholine receptor in the motor endplate, but also against intracellular striated muscle proteins, notably titin, the giant elastic protein of the myofibrillar cytoskeleton. Titin antibodies have previously been shown to be directed against a single epitope on the molecule, located at the A-band/I-band junction and referred to as the main immunogenic region (MIR) of titin. By using immunofluorescence microscopy on stretched single myofibrils, we now report that approximately 40% of the sera from 18 MG/thymoma patients and 8 late-onset MG patients with thymus atrophy contain antibodies that bind to a more central I-band titin region. This region consists of homologous immunoglobulin domains and is known to be differentially spliced dependent on muscle type. All patients with I-band titin antibodies also had antibodies against the MIR. Although a statistically significant correlation between the occurrence of I-band titin antibodies and MG severity was not apparent, the results could hint at an initial immunoreactivity to titin's MIR, followed by reactivity along the titin molecule in the course of the disease.     

Ovarian blood flow in conscious and anaesthetized pregnant rabbits near term and the influence of arterial blood gas tensions

Total ovarian, luteal and stromal blood flows were measured with radioactive microspheres (25 mum diameter) in 7 rabbits anaesthetized with sodium pentobarbitone and 23 conscious rabbits at Day 28 of gestation. Despite major differences in cardiac output, arterial PO2, PCO2, pH and base status, ovarian tissue blood flows were similar in both groups. In the conscious rabbits total ovarian blood flow was negatively related to arterial pressure, and luteal blood flow was negatively related to pressure and arterial pH. In the anaesthetized rabbits ovarian stromal blood flow was positively related to arterial PO2.     

Reactivity of trypsin in reverse micelles: pH-effects on the W0 versus enzyme activity profiles

We have adapted the new MxA gene-induction bioassay to measure neutralizing antibodies to interferon-beta1b (IFN-beta1b, the active ingredient in Betaseron) in sera from patients treated with Betaseron. This antibody assay has been validated to quantify neutralizing titers of 1:20 and above, with a precision of +/- 0.20 in log10. We have used this MxA gene-induction antibody assay to reinvestigate serum samples from multiple sclerosis (MS) patients treated with Betaseron. The titers measured were closely comparable to those obtained in antiviral assays. Data obtained by both methods show that neutralizing antibodies may appear and subsequently disappear over time in the sera of some patients treated with Betaseron. Sera from some patients contain binding antibodies to IFN-beta1b. It was shown that binding antibody titers do not correlate quantitatively or qualitatively with neutralizing antibody titers, and indeed, a number of patients develop high levels of binding antibodies but never form measurable levels of neutralizing antibodies.     

Sensitivity of fluorochrome microscopy for detection of Mycobacterium tuberculosis versus nontuberculous mycobacteria

BACKGROUND: Sternal wound infection is a relatively rare but potentially devastating complication of open heart operations. The most common treatments after debridement are rewiring with antibiotic irrigation and muscle flaps. Here we present the results of a prospective trial to determine the appropriate roles of closed-chest catheter irrigation and muscle flap closure for sternotomy infection and to assess the effect of internal mammary artery bypass grafting on the outcome of each treatment modality. METHODS: Between 1990 and 1994, 5,658 sternotomies were performed at the University of Washington Medical Center. Sternal dehiscence occurred in 43 patients, 25 of whom had infection (overall incidence, 0.44%). Because of the infrequency of this complication, a prospective, randomized trial was developed in which the initial approach to sternal dehiscence was rewiring and catheter irrigation. Muscle flaps were used as the primary treatment if the sternum could not be restabilized or as secondary treatment if catheter irrigation failed. Wound resolution, length of hospital stay, and complications were evaluated. RESULTS: Sterile dehiscences were successfully closed with irrigation in 17 of 18 patients; the other patient required flap closure. Of the 25 patients with infection, 19 had irrigation and 6, closure with flaps primarily. In the group of infected patients, 17 of the 19 who received irrigation also had internal mammary artery bypass grafting. Irrigation failed in 15 (88.2%) of these 17 patients, and salvage was accomplished with muscle flap closure. All 6 patients with infection who were closed primarily with muscle flaps had a successful outcome. Hospitalization averaged 10.2 days when muscle flaps were used primarily and 14.3 additional days for unsuccessful irrigation. When irrigation was successful, the hospital stay averaged 11.2 days. CONCLUSIONS: Catheter irrigation should be reserved for patients without infection or patients with infection but without internal mammary artery bypass grafts in whom dehiscence occurs less than 1 month after sternotomy. All others should have closure with muscle flaps.     

Serial measurement of arterial plasma progesterone levels throughout gestation and parturition in individual rats

Daily blood samples were taken from 6, chronically cannulated, fully conscious rats to measure plasma progesterone levels throughout gestation. Progesterone levels in individual rats fluctuated by up to 28 ng/ml per day, but tended to be consistently higher or lower than the group mean. The accuracy of predicting progesterone levels in individual rats from previous values was examined. Progesterone levels on day 7 of gestation were negatively correlated with foetal weights near term. There was little indication that high progesterone levels at any stage of gestation lead to increased foetal or placental weights. Progesterone levels on day 17 were positively correlated with the number of corpura lutea but there was little relationship between progesterone and either the number or total mass of the placentas. Serial blood samples taken from a second group of 6 rats at 2 hourly intervals showed that the time between the major fall in progesterone levels to below 12 ng/ml and the onset of parturition was relatively constant (varying by only 8 h) despite a 29 h range in the total length of gestation.     

Etomidate in urological outpatient anaesthesia. A clinical evaluation

Induction of anaesthesia with the new short acting agent etomidate has been studied in 200 patients undergoing urological outpatient procedures. These patients exhibited a similar pattern of recovery to those receiving 7 mg/kg propanidid but had greater cardiac and respiratory stability. However, there was a 25% incidence of pain which was reduced to 13-9% by increasing the rate of injection from 30 to 15 seconds. The incidence of involuntary movements was 29-7% which was reduced to 15% by the faster rate of injection. The omission of atropine premedication did not affect cardiac stability. Etomidate appears to have many desirable features as an induction agent except for a high incidence of pain on injection which is reduced by rapid injection.