Rifampicin and dapsone in superficial pustular folliculitis

Fifty male patients diagnosed to have superficial pustular folliculitis (SPF) were included in an open trial to study the effects of rifampicin vs dapsone. Rifampicin, in a dose of 10mg/kg body weight for a period of 8 weeks was given for 25 patients in phase I and the drug cleared the lesions in 72%. Dapsone in a dose of 100 mg/day produced moderate response in 20% only. 17 patients who did not clear with dapsone were started on rifampicin (phase II) and 7/17 showed marked improvement. Remissions with rifampicin ranged from 3-9 months or longer. In patients who relapsed, a second course of the drug was effective.     

Distribution of bratton-marshall-positive material in mice following intravenous injections of nitrosoureas

Summary As determined by a colorimetric assay measuring parent compounds plus ether-extractable, nitroso-containing metabolites, N,N-bis(2-chloroethyl)-N-nitrosourea (BCNU) disappeared more rapidly than N-(2-chloroethyl)-N cyclohexyl-N-nitrosourea (CCNU) and N-(2-chloroethyl)-N-(4-transmethylcyclohexyl)-N-nitrosourea (MeCCNU) and their products from the tissues of mice injected IV. Assay of selected samples by high-pressure liquid chromatography revealed that the colorimetric assay for BCNU was specific in that the two assays gave equivalent results. Following IV-injections of CCNU and MeCCNU, however, levels of the parent compounds decreased much more rapidly than the total, color-producing material.Of seven tissues, the largest Cxt values for BCNU, as determined by the colorimetric assay, were noted for blood (442 g-min/ml) and large intestine (285 g-min/g). Liver (29 g-min/g) had the lowest Cxt value, reflecting rapid metabolism of the compound by this organ. Color-producing material related to CCNU disappeared from the solid tissues of mice in a manner generally parallel to that for blood. Of the Cxt values for this compound and its products, those for lung (1753 g-equivalents-min/g), kidney (1633 g-equivalents-min/g), and small intestine (1557 g-equivalents-min/g) were highest. Consistent with its slower rate of metabolism, MeCCNU and its color-producing metabolites remained in most tissues of mice for 12 h following injection. Except for brain (1434 g-equivalents-min/g), Cxt values for this nitrosourea and its metabolites in tissues were higher than those of blood (5485 g-equivalents-min/ml), with kidney (15,324 g-equivalents-min/g), liver (12,921 g-equivalents-min/g), and large intestine (11,501 g-equivalents-min/g) being highest. For each nitrosourea, a fair correlation was observed between the Cxt values for tissues and the toxic and/or antitumor effects at those sites.     

Radiographic findings in tuberculosis of the calvarium

We reviewed the pattern of involvement of the calvarium by tuberculosis (TB) in five patients and the role of imaging in its management. Four patients presented with localised scalp swelling and one with generalized seizures. Radiographs revealed lucent lesions with minimal surrounding sclerosis in the frontal (2), parietal (2) and occipital (1) bones. CT showed lesions involving the entire thickness of the calvarium and accompanying contrast-enhancing soft tissue. The patient presenting with seizures had a ring-enhancing lesion in the parietal lobe in addition to the extra-axial lesions. Although radiographs in all cases demonstrated calvarial TB, CT showed the extent of the defect, involvement of adjacent soft tissues, and in one case an intra-axial lesion. Radiographs suffice for follow-up of these patients. Received: 23 July 1999 Accepted: 20 September 1999     

Infection with oncolytic herpes simplex virus-1 induces apoptosis in neighboring human cancer cells: a potential target to increase anticancer activity.

PURPOSE: The antitumor efficacy of a herpes simplex virus (HSV)-1 oncolytic virus depends on the cytotoxic effect of the virus, but also on viral replication and spread within the tumor. Apoptosis is considered a defense mechanism of infected cells that minimizes the spread of viral progeny by limiting cellular production of virus. We sought to determine whether oncolytic HSV-1 infection induces apoptosis in neighboring, uninfected cells and whether manipulation of apoptosis can increase viral replication and cytotoxicity. EXPERIMENTAL DESIGN: NV1066 is an oncolytic HSV-1 mutant that contains the marker gene for enhanced green fluorescent protein. OCUM human gastric cancer cells were infected with NV1066 in vitro and inspected for apoptosis by Hoechst and terminal deoxynucleotidyltransferase-mediated nick end labeling staining and for infection by expression of green fluorescence. RESULTS: A significant increase in apoptosis was seen in cells infected by NV1066. More interestingly, a significant percentage (10%) of uninfected cells also proceeded to apoptosis. After NV1066 infection, cells were also treated with N-acetylcysteine (NAC), an inhibitor of apoptosis. By day 4 after infection, 2.7x more NV1066 was produced in cells exposed to NAC than in those not exposed to NV1066 (P = 0.04). NAC also increased tumor kill when administered with virus. CONCLUSIONS: These data suggest that NV1066 induces apoptosis in uninfected cocultured cells, potentially hindering propagation of viral progeny and concomitant tumor kill. Inhibition of apoptosis may improve the efficacy of oncolytic HSV-1 therapy.     

Angiogenesis inhibition by an oncolytic herpes virus expressing interleukin 12.

PURPOSE: Oncolytic herpes simplex viruses (HSVs) may have significant antitumor effects resulting from the direct lysis of cancer cells. HSVs may also be used to express inserted transgenes to exploit additional therapeutic strategies. The ability of an interleukin (IL)-12-expressing HSV to treat squamous cell carcinoma (SCC) by inhibition of tumor angiogenesis is investigated in this study. EXPERIMENTAL DESIGN: A replication-competent, attenuated, oncolytic HSV carrying the murine IL-12 gene (NV1042), its non-cytokine-carrying analog (NV1023), or saline was used to treat established murine SCC flank tumors by intratumoral injection. The expression of secondary antiangiogenic mediators was measured. Angiogenesis inhibition was assessed by in vivo Matrigel plug assays, flank tumor subdermal vascularity, and in vitro endothelial cell tubule formation assay. RESULTS: Intratumoral injections of NV1042 (2 x 10(7) plaque-forming units) into murine SCC VII flank tumors resulted in smaller tumor volumes as compared with NV1023 or saline. IL-12 and IFN-gamma expression in tumors was 440 and 2.2 pg/mg, respectively, at 24 h after NV1042 injection, but both IL-12 and IFN-gamma were undetectable (<0.2 pg/mg) after NV1023 or saline injections. Expression of two antiangiogenesis mediators, monokine induced by IFN-gamma and IFN-inducible protein 10, was elevated after NV1042 treatment. Matrigel plug assays of NV1042-transfected SCC VII tumor cells demonstrated significantly decreased hemoglobin content and microvessel density as compared with NV1023 and PBS. Excised murine flank tumors treated with NV1042 had decreased subdermal vascularity as compared with NV1023 and PBS. Both splenocytes and IL-12 expression by NV1042 were required for in vitro inhibition of endothelial tubule formation. CONCLUSIONS: IL-12 expression by an oncolytic herpes virus enhances therapy of SCC through antiangiogenic mechanisms. Strategies combining HSV oncolysis with angiogenesis inhibition merit further investigation for potential clinical application.     

Tendon-to-bone healing of a semitendinosus tendon autograft used for ACL reconstruction in a sheep model

Anterior cruciate ligament (ACL) reconstruction was performed in a single hind limb of 30 sheep using a doubled semitendinosus tendon graft. Three additional animals were used as controls. Histologic and biomechanical analysis was performed from 4-52 weeks postoperatively. Perpendicular collagen fibers were found connecting the tendon graft to the bone tunnels at 8 weeks. These fibers were seen circumferentially at 12 weeks. By 24 weeks, the bone tunnel was well-defined, and no further changes were observed at 52 weeks. Tendon incorporation within the femoral and tibial tunnels was similar at each interval. Although the small sample size did not permit statistical testing, the reconstruction strength was similar up to 12 weeks (15%-19% of controls). This increased at 24 (28%) and 52 (40%) weeks. The stiffness primarily increased from 4-8 weeks (18%-39%) and 24-52 weeks (52%-82%). Up to 12 weeks, failures occurred by graft pull-out from the bone tunnel. All 24- and 52-week specimens ruptured through the intra-articular portion of the graft, further indicating sufficient graft incorporation within the bone tunnels.