Efficacy of epidural blood patches for spontaneous low-pressure headaches: a case series.

Patients with a spontaneous cerebrospinal fluid leak, normally at a spinal level, typically present with low-pressure headache. In refractory cases, an epidural blood patch may be attempted. We aimed to assess the efficacy of lumbar epidural blood patching in spontaneous, low-pressure headaches. Methods We retrospectively analysed notes of patients who had an epidural blood patch performed for spontaneous low-pressure headaches in a single centre. Information regarding demographics, radiology and clinic follow-up was extracted from an electronic patient record system. Questionnaires regarding outcome were sent to patients a minimum of 6 months post-procedure. All patients received an epidural blood patch in the lumbar region irrespective of the site of cerebrospinal fluid leak. Results Sixteen patients who underwent lumbar epidural blood patching were analysed (11 female; mean age 43 years). The site of cerebrospinal fluid leak was evident in only 3/16 patients. Thirteen patients attended clinic follow-up; three reported complete headache resolution, four reported improvement in intensity or frequency and six described no change. Five of eight questionnaire respondents reported reduction in pain, and in these responders, mean headache severity improved from 9/10 to 3/10. Five of eight patients returning follow-up questionnaires reported sustained improvement in headache symptoms. Conclusion Epidural blood patch procedures can provide sustained improvement in headache symptoms in selected patients with spontaneous intracranial hypotension, but an untargeted approach has a lower success rate than reported in other case series.

In vivo induction of tumor-specific immunity by glycolipid extracts of SV40-transformed cells.

Glycolipid extracts were prepared from various Syrian golden hamster cell lines, either SV40-transformed or spontaneously transformed. To detect possible SV40-TSTA activity of the glycolipid preparations, normal hamsters were inoculated with different glycolipid extracts and were subsequently challenged with an SV40 tumor-cell line. Significant immunoprotection against SV40 tumor challenge was induced with glycolipids obtained from SV40-transformed cell lines. This was expressed as complete tumor rejection or as a decrease in tumor growth rate, when compared to controls. No protective effects were induced with glycolipid extracts from spontaneously transformed cells. Results suggest that tumor-specific glycolipids synthesized in cells transformed by SV40 virus could act as tumor transplantation antigens responsible for specific tumor rejection in syngeneic hosts.

In vitro induction of tumor-specific immunity by highly purified VSV grown in SV40-transformed cells and tumor glycolipids incorporated into liposomes.

Cytotoxic effector lymphocytes (CL) were induced by in vitro immunization of spleen cells from normal Syrian hamsters to syngeneic tumor cells, either SV40-transformed (EH-SV) or spontaneously transformed (EH-N). The lymphocyte reactivity was measured in a direct 51Cr release cytotoxicity assay performed with EH-SV- and EH-N-labelled targets. A specific cytotoxic effect against tumor cells carrying the sensitizing antigens was observed. Cytotoxic effector lymphocytes were also induced by in vitro immunization of hamster spleen cells to highly purified vesicular stomatitis virus (VSV) grown either in syngeneic SV40-transformed fibroblasts or in "normal" fibroblasts. Purified virus possessing an intact envelope or virus subparticles devoid of their glycoprotein spikes stimulated the cellular immune responses against host tumor antigens present within the viral envelope. Cytotoxicity assays have revealed two tumor-specific antigens (TSA), one induced by SV40 and present in SV40-transformed cell lines and the other present in "normal" cells. CL were also induced by in vitro sensitization of spleen cells from normal hamsters to liposomes containing the polar glycolipid fraction from EH-SV and/or EH-N cells. A specific cytotoxic effect against tumor cells that have supplied the glycolipid extract was observed, suggesting specific recognition of glycolipid antigens characteristic for each tumor line. This study supports the view that surface glycolipids act as tumor-specific antigens implicated in the destruction of SV40-induced tumors in Syrian hamsters.

Specific glycolipid antigen(s) in SV40-transformed cell membranes.

A glycolipid extract was prepared from an SV40-transformed hamster cell line (EH-SV) according to the Folch partition procedure. The glycolipids from the aqueous layer were incorporated in liposomal membranes composed of lecithin/sphingomyelin/cholesterol (1:1:2 by weight). This liposomal preparation was inoculated in Syrian hamsters to raise immune sera. The sera were absorbed with trypsinized "normal" hamster cells (EH-N) and tested on various cell lines by the indirect immunofluorescence technique. When used for staining living cells, the immune serum produced a distinct cell-surface fluorescence with SV40-transformed cell lines regardless of the cell origin (e.g., rat or hamster). No reaction was observed with heterologous Py-transformed cell lines, spontaneously transformed cells, or sera from non-immunized hamsters. When used for staining acetone-fixed cells, the antiglycolipid serum reacted specifically with a thermostable antigen in the nuclear envelope and the cytoplasm of SV40-transformed cells. The sera lack interfering SV40 T reactivity. The results indicate the presence of related SV40-specific glycolipid antigen(s) in the plasma membrane, the nuclear membrane and probably other endomembranes of SV40-transformed cells.

SV40 tumor rejection induced by vesicular stomatitis virus bearing SV40 tumor-specific transplantation antigen (SV40-TSTA). I. Specificity of immunoprotection and effect of enzyme treatment on TSTA activity.

Highly purified vesicular stomatitis virus (VSV) was obtained from VSV-infected SV40-transformed hamster cell lines. Immunization with this virus protected hamsters against challenge with SV40-transformed cells (TSV5-cl2). This protection was obtained regardless of the source of the SV40-transformed cells (e.g. cat, rat, hamster) used to produce VSV, and was therefore associated with the SV40 tumor-specific transplantation antigen (SV40-TSTA). Furthermore, when grown on spontaneously transformed cell lines or on cells transformed by a different oncogenic DNA virus, such as polyoma virus, the VSV failed to protect against the SV40-induced tumor. It was concluded that the SV40-TSTA activity of purified VSV is due to the incorporation of SV40-TSTA within the viral envelope. When VSV was treated with proteolytic enzymes (bromelain, trypsin) no loss of TSTA-induced tumor rejection was observed, although VSV had lost its ability to induce virus-neutralizing antibody. This clearly demonstrates that the TSTA activity is not related to the viral spikes. Phospholipase C suppressed the TSTA activity but neutralizing activity was still detectable in the anti-VSV sera. The results presented here demonstrate that the protection afforded by VSV is highly specific. It is particularly interesting that SV40-TSTA activity may be conveyed by the lipid core of the viral envelope.

SV40 tumor rejection induced by vesicular stomatitis virus bearing SV40 tumor-specific transplantation antigen (SV40-TSTA). II. Association of SV40-TSTA activity with liposomes containing VSV glycolipids.

Highly purified vesicular stomatitis virus (VSV) was obtained from VSV-infected SV40-transformed and from "normal" hamster cell lines. A glycolipid extract was prepared from these VSV preparations according to the Folch partition procedure. These glycolipids were rendered immunogenic to the Syrian hamsters when incorporated within liposomal membranes composed of lecithin/sphingomyelin/cholesterol (1/1/2 by weight). When the glycolipids were extracted from VSV grown on cell lines (TSV5-cl2 and EHSVi-cl1) which contained the SV40 tumor-specific transplantation antigen (SV40-TSTA), it was possible either to induce a tumor rejection or at least to slow the growth of the tumor in Syrian hamsters challenged with TSV5-cl2 cells. No protection was obtained in animals treated with liposomes containing glycolipids extracted from purified VSV grown on SV40-TSTA-negative cells (EHB). The SV40-TSTA could be a glycolipid of the transformed cell membrane which is incorporated within the VSV envelope.