Predictive factors for long-term survival in patients with advanced ovarian cancer

A total of 107 patients with carcinoma of the ovary were entered in a study combining extensive primary surgery and intensive chemotherapy. Because of evidence supporting the effectiveness of both single agent platinum (P) and the combination of cyclophosphamide and doxorubicin (CA), patients were treated with alternating cycles of CA and CP. Primary surgery to remove the bulk of tumor to less than 2 cm was possible in 45% of the 85 eligible patients, and an additional 17% had similar surgery after two to four cycles of chemotherapy. Fifteen percent of patients progressed on chemotherapy. Of the 68 who were clinically and radiologically without disease at the completion of chemotherapy, 91% had second-look surgery. Forty-eight percent of these women had residual disease. All patients but one are at risk for greater than 60 months, with a median follow-up of 86 months. Overall 5-year survival is 26%, with a median survival of 33 months. Twenty patients survived over 5 years with 11 continuing to be free of disease (13% of all eligible patients). Patients with modified Broder's grade I,II tumors have not yet reached a median survival. Grade, stage, and primary mass size were the only variables with independent prognostic value in a Cox multivariate analysis.     

Wilson disease of the brain: MR imaging

Twenty-three patients with biochemically proved Wilson disease underwent magnetic resonance (MR) imaging of the brain. Positive findings, believed secondary to this condition, were found in 15 subjects. Findings varied among patients, but there were striking similarities between certain groups of patients. Areas of abnormal signal were seen in the lenticular, thalamic, caudate, and dentate nuclei, as well as in the brain stem; in these areas, the abnormalities were bilaterally symmetric. A smaller number of patients had asymmetric focal white-matter lesions. Correlation of the MR findings with clinical symptoms was generally good. Repeat imaging was performed on five patients at intervals ranging from 4 to 8 months; none showed significant interval change.     

Posttraumatic progressive myelopathy. Clinical and radiologic correlation employing MR imaging, delayed CT metrizamide myelography, and intraoperative sonography

Posttraumatic progressive myelopathy (PTPM) was studied in nine patients and grouped into three categories on the basis of characteristic radiographic findings and response to therapy: (a) myelomalacia with no cystic degeneration, which has poor response to therapy; (b) small cysts, with poor response to therapy; and (c) large cysts, which are effectively treated by decompression. One type dominated in each patient, although a mixture of types was present in each. Magnetic resonance (MR) imaging gave slightly improved resolution and specificity of type, decreased morbidity, and simplification of procedure in comparison with imaging by delayed computed tomographic metrizamide myelography (DCTM). DCTM and MR imaging results correlated nearly equally with those of intraoperative sonography (IOS) and pathologic study at surgery. IOS was superior to DCTM or MR imaging in detecting septations and small additional cysts. IOS also was helpful in myelotomy positioning, shunt placement, and verification of cyst decompression. MR imaging may replace DCTM in the preoperative evaluation of PTPM, followed by IOS imaging as indicated. Patients with nonmyelopathic signs and symptoms (e.g., radiculopathy) probably still require study with conventional and/or CT myelography.     

A new method for measurement of the electrical potential difference across the stomach wall. Clinical evaluation of the gastric mucosal integrity

PD, the electrical potential difference across the gastric mucosa, is a variable used frequently in experimental studies. Existing methods for PD measurements are, however, unstable, and variations in the pH of the gastric juice causes liquid junction potentials between gastric juice and the PD measuring probe. A new PD measuring system has been developed with high stability, easy handling, and correction for the liquid junction potentials. PD was measured between a stomach microelectrode and an intravenous reference electrode connected to a millivoltmeter. pH was measured by an intragastric microelectrode. The liquid junction potential was calculated by using the pH measured in the gastric juice and the Henderson equation and was then subtracted from the measured PD to provide a better approximation of the PD across the mucosa. The liquid junction potential calculated as stated above correlated with the liquid junction potential calculated from precise ion determinations made in gastric juice samples (y = x; r = 0.92; p less than 0.05). The reliability of the PD measuring system was tested in vitro and in vivo and was satisfactory. In conclusion, a new, reliable, and easily applied method for gastric PD measurements corrected for the liquid junction potential between gastric juice and the PD measuring probe has been developed.     

Phage display selection for cell-specific ligands: development of a screening procedure suitable for small tumor specimens

Phage display technology has been widely used for developing tumor-targeting agents. Most of the efforts were directed towards identifying phage-displayed ligands against cancer-relevant purified targets and cancer cell lines. Whole cell screening procedures typically use a relatively large sample size and are not ideally suited for complex tumor tissues. We describe here a screening protocol that is suitable for non-adherent tumor cells from biopsy specimens. It requires only approximately 20,000 cells/round for biopanning and approximately 10,000 cells/well for subsequent clone binding assessment by ELISA. We standardized the newly developed protocol using erbB2-overexpressing SKBR3 breast cancer cells and compared the results with conventional protocols employing about 10-times more plate-adhered fixed or live cells. The selection rate of SKBR3-binding clones from biopanning approximately 20,000 non-adherent SKBR3 cells by our filter cup protocol was comparable to that obtained from using approximately 200,000 plate-adhered cells. Assessment of clones selected from different phage libraries showed that clones from fixed or live cells, adherent or non-adherent cells, either biopanned in filter cup or plate share specific motifs and binding properties. Some of the clones from each biopanning protocol bound to purified erbB2 and shared motifs with erbB family of receptors and their known ligands. These results demonstrated that the protocol developed in this study was capable of selecting cell-specific ligands using relatively small numbers of cells. Screening cells from a fresh human breast cancer specimen using our protocol showed enrichment of tumor binding clones at successive rounds of selection and some of the selected clones were tumor-specific in comparison to normal breast cells. These protocols have direct application to screen for tumor-binding ligands with small tumor tissue specimens.     

Handling properties and thrombogenicity of microsutures

The thrombogenicity and handling properties of 1 polypropylene and 2 polyamide 10-0 microsuture materials were evaluated in a paired comparative study in rats. Using a sequential analysis method with significance limits corresponding to 2 α = 0.05 and β = 0.05, it was found that the handling properties of Supramide (polyamide) sutures were better than those of Prolene (polypropylene), and that the handling properties of Prolene did not differ from those of Nylon (polyamide). Also using a sequential analysis method with significance limits corresponding to 2 α = 0.05 and β = 0.02, it was found that the thrombogenicity of Prolene was significantly less than the thrombogenicity of Supramide and Nylon. It is concluded that Prolene is the microsuture of choice among the three materials tested.     

Evaluation of results of the testing of smallpox vaccines: A report on statistical methods

A report is given on the statistical methods used in the evaluation of results in the international assay of smallpox vaccines, and on special statistical problems connected with the counting of lesions (pocks and plaques).     

Gonadotropin and androgen levels in patients operated upon for cryptorchidism

53 patients previously operated upon for cryptorchidism were examined seven years (range 2-18) after the operation. We measured serum levels of sex-hormone-binding-globulin (SHBG), testosterone (T), free testosterone (free T), dihydrotestosterone (DHT), 4 androstenedione (4-AD), and dehydroepiandrosteronesulphate (DHAS), and the gonadotropin luteinizing hormone (LH) and follicular hormone stimulating (FSH). Compared to normal controls, there were decreased levels of free testosterone and DHT and increased levels of SHBG and DHAS. The FSH levels were elevated and LH values low. No relationship was found between androgen and gonadotropin levels, suggesting that the normal feed-back mechanism is malfunctioning. There were no hormonal differences between patients with previous unilateral and bilateral cryptorchidism, although SHBG levels were higher in the former. We concluded that cryptorchidism is probably due to a defect in the hypothalamic-pituitary axis and not to a primary defect in the testes.     

Endoscopic ultrasound guided biopsy performed routinely in lung cancer staging spares futile thoracotomies: preliminary results from a randomised clinical trial

BACKGROUND: Up to 45% of operations with curative intent for non-small-cell lung cancer (NSCLC) can be regarded as futile, apparently because the stage of the disease is more advanced than expected preoperatively. During the past decade several studies have evaluated the usefulness of endoscopic ultrasound guided fine needle aspiration biopsy (EUS-FNA) in lung cancer staging with promising results. However, no randomised trials have been performed, in which a staging strategy with EUS-FNA performed in all patients is compared with a conventional workup. METHODS: Before surgery (i.e. mediastinoscopy and subsequent thoracotomy) 104 patients from one hospital were randomly assigned to either a conventional workup (CWU), including EUS-FNA only for selected patients, or a strategy where all patients were offered EUS-FNA (routine EUS-FNA) in addition to CWU. Patients were followed up for a median period of 1.3 years (range 0.2-2.4 years). Thoracotomy was regarded as futile if the patient had an explorative thoracotomy without tumour resection or if a resected patient had recurrent disease or died from lung cancer during follow-up. Analysis was by intention to treat. RESULTS: Fifty-three patients were randomly assigned to routine EUS-FNA and 51 patients to CWU. EUS-FNA was performed in 50 patients (94%) in the routine EUS-FNA group and in 14 patients (27%) in the CWU group. In the routine EUS-FNA group five patients (9%) had a futile thoracotomy, compared with 13 (25%) in the CWU group, p = 0.03. CONCLUSION: Addition of routine-EUS-FNA to standard workup in routine clinical practice improved selection of surgically curable patients with NSCLC.     

International reference preparation of rheumatoid arthritis serum

The National Institute for Medical Research, London, England, was requested by the WHO Expert Committee on Biological Standardization to arrange a collaborative study of the serum pool they had obtained, to determine its suitability to serve as an international reference preparation of rheumatoid arthritis serum. A batch of this serum was assayed by 11 laboratories in 7 countries against 30 test preparations. On the basis of the results obtained, the serum has been established as the International Reference Preparation of Rheumatoid Arthritis Serum and the International Unit of Rheumatoid Arthritis Serum has been defined as the activity contained in 0.171 mg of the international reference preparation.