Perioperative management for transplant of autologous adrenal medulla to the brain for parkinsonism.
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Biomedical subjects
Publications and source records attributed to M L Berman.
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Fourteen patients with stage IB or IIA neuroendocrine small-cell cervical cancer were treated either by operation alone or operation in combination with postoperative radiotherapy at the University of California, Irvine Medical Center, and Memorial Medical Center of Long Beach, between January 1979 and February 1986. Patients were included in the study only if they met characteristic light and electron microscopic criteria for neuroendocrine small-cell cancer. Thirteen patients underwent radical hysterectomy and one a simple hysterectomy. All patients underwent pelvic lymphadenectomy, with 57% found to have nodal metastases. Twelve of 14 patients are dead of disease eight to 31 months after treatment, and the two living patients had recurrence at 38 and 44 months. One is without evidence of disease 18 months after radiation for a pelvic recurrence, and the other has survived five months after recurrence without treatment. The interval from treatment to recurrence was substantially longer in patients with tumors up to 2 cm in diameter as compared with those greater than 2 cm. Despite the early stage of cancer in these patients, the dismal outcome indicates that traditional modes of therapy for cervical cancer are not effective in cases of neuroendocrine small-cell carcinoma.
The tumoricidal activity of magnetically responsive albumin microspheres tagged with either doxorubicin or Staphylococcal protein A was tested against an induced mammary adenocarcinoma, 13762, implanted subcutaneously in the tail of female Fischer-344 rats. Magnetically responsive albumin microspheres containing Fe3O4 particles were prepared by an emulsion polymerization method incorporating either doxorubicin or protein A into the albumin matrix. Microspheres were produced with an average diameter of 1 micron (0.2 to 1.5 micron) in a concentration of 10(9) microspheres/mg. Microspheres were injected either directly into the tail artery and localized to the implanted tumor using a permanent bipolar adjustable gap magnet with a field strength of 8000 Oe, or directly into the femoral vein with no magnetic localization. Control groups consisted of animals treated with intravenously or intraarterially administered microspheres containing no active agent, and a no-treatment group. Survival was significantly greater in both the doxorubicin- and protein A-treated animals than in the control groups. First appearance of local metastases was prolonged in only the intraarterial magnetically localized doxorubicin-treated group of animals. Tumor growth rate was significantly depressed in both intraarterially magnetically localized treatment groups when compared to intravenously administered nonlocalized treatment groups. Magnetically responsive albumin microspheres appear to be an effective delivery system for cytotoxic agents and biologic response modifiers. Significant tumoricidal activity can be produced with a one-time administration of these agents utilizing this drug delivery system.
We have developed a bacteriophage lambda cloning vector, lambda ORF8, that can be used for the construction of cDNA libraries. The wild-type lambda genome contains five BamHI, five EcoRI, and seven HindIII restriction sites that have all been removed from the genome of lambda ORF8. Sites for these endonucleases are present within the multiple cloning site of lambda ORF8. We report a method for preparing cDNAs that can be cloned in a single orientation in our phage vector. The method utilizes the synthesis of double-stranded cDNA, including priming of first-strand synthesis by oligo(dT). After completion of second-strand synthesis, a bifunctional oligodeoxynucleotide linker is ligated to the cDNA fragments. This linker, which contains a BamHI restriction site, will create a HindIII restriction site when ligated to the 3' end of cDNA fragments. Subsequent treatment of methylated cDNA with HindIII and BamHI endonucleases allows these fragments to be cloned directionally into lambda ORF8. To demonstrate the utility of this cloning system, we prepared a library from 5 micrograms of mRNA isolated from phytohemagglutinin-stimulated human peripheral blood lymphocytes. The primary library contained 2 X 10(8) plaque-forming phage, at least 80% of which contain inserts. A portion of the library was examined for the presence of gamma-interferon-related clones to verify the method had generated a library that was representative of phytohemagglutinin-stimulated peripheral blood lymphocytes. This simple and efficient cDNA cloning system significantly reduces the amount of RNA and effort required for the preparation of large directionally cloned libraries.
We present a case report demonstrating that somatosensory evoked potentials (SEPs) suggested ischemia when an internal carotid aneurysm ruptured during surgical clipping. SEPs were also recorded from the contralateral cortex and subcortical and peripheral sites and remained unchanged. The use of multiple bilateral recording sites for SEP recording simplified the interpretation of acute changes.
Of 108 women treated for vulvar intraepithelial neoplasia between 1977 and 1984 at the Irvine Medical Center, University of California, and the Memorial Medical Center of Long Beach, Women's Hospital, 48 with multifocal and/or widespread lesions underwent skinning vulvectomy and split thickness skin graft reconstruction. Six women in the skinning vulvectomy sample had early stromal invasion in the vulvectomy specimen. Recurrences at intervals of four to 87 months occurred in 13 patients undergoing this procedure. The risk of recurrence did not appear to be related to the status of the surgical margins because seven of 22 patients with involved margins experienced recurrence compared with six of 26 with uninvolved margins.
Seventy-six patients with advanced ovarian cancer treated with cyclophosphamide, doxorubicin, and cisplatin (CAP) at 3-week intervals were tested for the response of their tumors to treatment with CAP in the subrenal capsule tumor implant assay. Thirty-four of the patients' tumors were assayed prospectively before clinical treatment and 33 were assayed retrospectively, after clinical treatment with CAP. Nine of the patients' tumors were assayed both prospectively and retrospectively. All of the patients underwent a tumor debulking laparotomy. Of the patients with clinically measurable residual disease, 17 had a partial response of at least 50% regression of disease, and 11 had a progression of disease. Of the patients with known residual but nonmeasureable disease, 7 had surgically verified complete responses, 8 at least 50% regression, and 23 had progression of disease: 10 had no evidence of disease clinically but had not had surgical confirmation. Twenty-six of the tumors were adenocarcinomas not otherwise specified (2 grade I, 2 grade II, and 22 grade III), 39 were serous adenocarcinomas (7 grade I, 9 grade II, and 23 grade III), 7 were endometrioid adenocarcinoma (all grade III), 3 were mucinous adenocarcinomas (1 each of grade I, II, and III) and 1 was an adenosquamous carcinoma (grade III). Thirty-four of the patients failed the therapy. The subrenal capsule (SRC) assay predicted 21 of these failures (4 prospective and 17 retrospective). Thirty-two of the patients responded to CAP chemotherapy. The SRC assay accurately predicted the clinical regression of the tumors of 22 of the patients (15 prospective and 7 retrospective). Second-look laparotomy confirmed 7 patients with no evidence of disease, 5 patients with minimal disease, and 5 patients with a greater than 50% reduction of their disease. The SRC assay predicted the response of all these patients except 2 with partial responses to chemotherapy. Thus, while the overall positive predictive value of the SRC assay in this study is 65%, it is 100% for those patients whose tumors respond completely and for those who have minimal residual disease after CAP chemotherapy.
Eight patients with advanced ovarian cancer were treated with polyinosinic-polycytidylic lysine carboxymethylcellulose (poly(ICLC]. Toxicity was substantial. No responses were seen in this small group of patients. Further clinical trials utilizing poly(ICLC) at the doses described in patients with advanced ovarian cancer do not appear to be warranted.
We describe a cloning-expression vector system for selecting DNA fragments containing open reading frames (ORFs) and expressing them as beta-galactosidase (beta Gal) hybrid fusion proteins. The plasmid vector, pWS50, utilizes the very strong and easily regulated bacteriophage lambda promoter pL, and the efficient translation initiation signals of the N-terminal segment of the lambda cII gene. Fused distally to and out of translational phase with cII is the E. coli lacZ gene, lacking its own transcriptional and translational initiating signals. A unique restriction enzyme site (NruI) is located between the upstream regulatory sequences and the lacZ gene, which provides a cloning site for the insertion of blunt ended DNA fragments. In addition, there are two other unique restriction sites (NheI and BamHI) located in this region which can also be used as closing sites. If a DNA fragment does not contain any translation termination codons (i.e., an ORF), and is inserted correctly into the vector, the translational reading frame between cII and lacZ can be restored. Colonies containing these recombinants can be easily screened as LacZ+ on lactose indicator media. The beta-galactosidase fusion proteins produced from the LacZ+ recombinants are identified on sodium dodecyl sulfate polyacrylamide gels by their large size and high level of production. To test the ORF cloning-expression system, a segment of the human T-cell lymphotrophic virus type I envelope gene was cloned and expressed at high levels. The envelope-beta Gal fusion protein was recognized by antibodies in serum from a patient with adult T-cell leukemia.
Thirty-six patients with malignant ovarian germ cell tumors were treated between 1972 and 1983, including 16 with immature teratoma, five with endodermal sinus tumor, seven with dysgerminoma, and eight with mixed germ cell tumors. The median age at presentation was 18 years and mean primary tumor diameter was 18 cm. Twenty-five of the 27 patients who were treated with multiple-agent chemotherapy underwent second-look procedures, only two of which revealed persistent malignancy. No patients have developed recurrence after a negative second-look operation. Two of the three patients with failure of initial chemotherapeutic regimens had complete remissions with second regimens. Two patients have died of malignancy, one who presented with a Stage IA mixed germ cell tumor and one noncompliant patient with a Stage IA, grade 2 immature teratoma. The other 34 patients are alive without evidence of disease from 21 to 141 months, with a median follow-up of 68 months. These data confirm that multiple-agent chemotherapy has dramatically improved the prognosis for patients with malignant nondysgerminomatous ovarian germ cell tumors.
Postoperative pain was controlled in 42 patients with either continuous intravenous (iv) or scheduled intramuscular morphine following surgery for gynecologic cancers. In this double-blind study, no statistical differences were found in pain control or rate of complications between the two methods of administration. Both routes were effective in controlling pain without producing major toxicity. Initial doses were based on the patient's weight and then adjusted every 4 hr. We conclude that both methods are safe and effective but that continuous iv infusion is the preferred route because of the ease of administration, elimination of multiple intramuscular injections, and possibly more even pain control.
Using the technique described, Hickman catheters can be inserted by a single operator at low cost and risk. The simplicity of insertion and removal with this method makes the use of this device preferable to standard temporary central venous catheters in most instances.
We have constructed a shuttle vector plasmid for studying mutagenesis in mammalian cells. The plasmid replicates in cell lines permissive for SV40 virus as well as in the bacterium Escherichia coli and carries a bacterial suppressor tRNA gene (supF) that can serve as a mutagenesis marker. The plasmid replicates as efficiently as SV40 virus in African Green Monkey kidney CV1 cells, indicating that all traces of the inhibitory sequences normally found in pBR322 and its derivatives have been removed. The design of the plasmid and the small size of the mutagenesis target gene decrease the probability of recovering spontaneous deletion mutations that have been shown to occur at high frequency during passage in mammalian cells. The frequency of spontaneous-mutant plasmids recovered after passage in CV1 cells is substantially lower than with other vectors described previously. When the plasmid DNA is treated with UV radiation before passage in CV1 cells, mutants are observed at a frequency about 20-fold above the spontaneous background.
We isolated a series of delta ompR delta envZ mutants by inducing a strain carrying a lambda prophage in the closely linked gene malP and screening the bacterial survivors for loss of the major outer membrane porins OmpF and OmpC. Characterization of these deletion strains showed that both OmpR and EnvZ were necessary for transcription of ompF and ompC and that neither gene was essential for cell viability. Moreover, the deletion strains did not exhibit the pleiotropic membrane protein deficiency observed with certain envZ mutants. The method described should allow the simple isolation of deletions in any region of the chromosome.
A skinning vulvectomy and split-thickness skin graft were used in the management of four women with benign vulvar disease after the failure of standard medical and surgical therapy. Three women remain free of the primary disease process, with a follow-up of 12-36 months. One woman with lichen sclerosus and another with "diffuse atrophy" developed recurrent disease in their skin grafts 45 and 96 months, respectively, after skinning vulvectomy. Symptomatic improvement was achieved subsequently in both women with the topical application of testosterone.
The indications for insertion of semipermanent right atrial silicone catheters and immediate and long-term complications in patients admitted to a gynecologic oncology service, are described. Eight-five catheters were inserted in 79 patients for a variety of indications. Most catheters were placed under local anesthesia, in the patient's hospital room. Immediate morbidity caused by damage to the pleura was limited to three patients (3.5%). Infectious morbidity related to catheter use was seen in five patients (5.9%). Two patients were unable to administer daily heparin boluses through the catheter, and in both of these patients catheter thrombosis was seen (2.4%). A right atrial catheter can easily be inserted at the patient's bedside or in an outpatient setting. This device should be offered to any patient in whom intermediate or long-term vascular access is desired for nutritional support, chemotherapy, pain control, or similar indications.
The effect of non-localized magnetically responsive albumin microspheres (MR-AMS) on RES phagocytic function was investigated. MR-AMS and MR-AMS containing Adriamycin (MR-AMS-ADR) were injected intravenously in rats at a dose which saturated all RES phagocytes. The ability of the RES to clear the bloodstream of a subsequent suspension of MR-AMS or streptococci was then analyzed over a three day period. MR-AMS clearance was enhanced after initial RES saturation with MR-AMS but depressed when the saturating agent was MR-AMS-ADR. Bloodstream clearance of streptococci was depressed by MR-AMS and MR-AMS-ADR. Localization of MR-AMS in the RES might depress RES phagocytosis by physical saturation of phagocytes or by a direct toxic effect of encapsulated chemotherapeutic agents.
Moxalactam was administered prior to operation to patients undergoing operation for a known or suspected gynecologic malignancy. Subsequent plasma and tissue levels demonstrated a prolonged duration of action and rapid concentration in pelvic organs after infusion.