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Biomedical subjects

M Friedlander

Publications and source records attributed to M Friedlander.

At least 19 recordsLinked to original sources

Dual sequential non-cross-resistant chemotherapy for advanced stage squamous cell carcinoma of the cervix.

Forty-three patients with recurrent and metastatic squamous cell carcinoma of the cervix received a program of sequential combination chemotherapy incorporating induction with cisplatin, vinblastine, and bleomycin (PVB) and subsequent consolidation with 5-fluorouracil, doxorubicin, cyclophosphamide, and vincristine (FACV). The overall response rate was 62% and 10 patients (23%) achieved complete remission. Response status was improved in 11 patients at the completion of FACV after initial PVB therapy, including 9 complete remissions. The median survival for all patients in the study was 38 weeks and 50 weeks for the responding patients. Myelosuppression was the principal toxicity encountered and 10 episodes of neutropenic sepsis occurred, including one septic death. However, the only cumulative toxicity was peripheral neuropathy, although this was only moderate to severe in 2 patients. These results are encouraging, but will require confirmation in randomized comparison to cisplatin, presently accepted as standard single-agent therapy.

Antineoplastic Combined Chemotherapy Protocols

Preemptive analgesia. Clinical evidence of neuroplasticity contributing to postoperative pain.

Recent evidence suggests that surgical incision and other noxious perioperative events may induce prolonged changes in central neural function that later contribute to postoperative pain. The present study tested the hypothesis that patients receiving epidural fentanyl before incision would have less pain and need fewer analgesics post-operatively than patients receiving the same dose of epidural fentanyl after incision. Thirty patients (ASA physical status 2) scheduled for elective thoracic surgery through a posterolateral thoracotomy incision were randomized to one of two groups of equal size and prospectively studied in a double-blind manner. Epidural catheters were placed via the L2-L3 or L3-L4 interspaces preoperatively, and the position was confirmed with lidocaine. Group 1 received epidural fentanyl (4 micrograms/kg, in 20 ml normal saline) before surgical incision, followed by epidural normal saline (20 ml) infused 15 min after incision. Group 2 received epidural normal saline (20 ml) before surgical incision, followed by epidural fentanyl (4 micrograms/kg, in 20 ml normal saline) infused 15 min after incision. No additional analgesics were used before or during the operation. Anesthesia was induced with thiopental (3-5 mg/kg) and maintained with N2O/O2 and isoflurane. Paralysis was achieved with pancuronium (0.1 mg/kg). Postoperative analgesia consisted of patient-controlled intravenous morphine. Visual analogue scale pain scores were significantly less in group 1 (2.6 +/- 0.44) than in group 2 (4.7 +/- 0.58) 6 h after surgery (P less than 0.05), by which time plasma fentanyl concentrations had decreased to subtherapeutic levels (less than 0.15 ng/ml) in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Analgesia, Epidural

A randomized, double-blind comparison of lumbar epidural and intravenous fentanyl infusions for postthoracotomy pain relief. Analgesic, pharmacokinetic, and respiratory effects.

Although epidural opioids frequently are used to provide postoperative analgesia, several articles have suggested that the analgesia after epidural fentanyl is similar to that after an equal dose of fentanyl given intravenously. To address this issue further, 29 postthoracotomy patients were studied in a randomized, double-blinded trial comparing a lumbar epidural fentanyl infusion with an intravenous fentanyl infusion for analgesia, plasma fentanyl pharmacokinetics, and respiratory effects for 20 h postoperatively. In all patients in both groups, good analgesia was achieved (pain score less than 3, maximum 10) over a similar time course, although the patients receiving epidural infusion required a significantly larger fentanyl infusion dose than did the patients receiving intravenous infusion (group receiving epidural fentanyl infusion: 1.95 +/- 0.45 micrograms.kg-1.h-1; group receiving intravenous fentanyl infusion: 1.56 +/- 0.36 micrograms.kg-1.h-1; P = 0.0002). The time course for the plasma fentanyl concentrations was similar in the two groups, and plasma fentanyl concentrations were not significantly different at any sampling period (T7-T20; group receiving epidural fentanyl infusion: 1.8 +/- 0.5 ng/ml; group receiving intravenous fentanyl infusion: 1.6 +/- 0.6 ng/ml; P = 0.06). Similarly, calculated clearance values for the two groups were not significantly different (group receiving epidural fentanyl infusion: 0.95 +/- 0.26 l.kg-1.h-1; group receiving intravenous fentanyl infusion: 0.87 +/- 0.25 l.kg-1.h-1; P = 0.3). Both groups demonstrated a similar degree of mild to moderate respiratory depression postoperatively, which was assessed with continuous respiratory inductance plethysmography and sequential arterial blood gas analysis. Side effects (nausea, vomiting, pruritus) were mild and did not differ between groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Risk factors, epidemiology, screening, and prognostic factors in female genital cancer.

This review, which due to limitations of space cannot be exhaustive, summarizes the recent literature on risk factors and epidemiology, screening and prognostic factors in a cervical, ovarian, and endometrial cancer. There have been a large number of pertinent publications during this period and this paper summarizes and highlights recent advances in the identification of women at particularly high risk of developing gynecologic cancer, analyzes studies on early detection and screening, and reviews prognostic studies with particular reference to selection of therapy according to risk of relapse and likelihood of benefit.

Female

Frequent loss of heterozygosity on chromosome 18 in ovarian adenocarcinoma which does not always include the DCC locus.

Inactivation of the DCC gene on chromosome 18 owing to loss of heterozygosity is a common finding in colorectal cancer. Because both ovarian and colon cancer are features of Lynch syndrome II, which has been provisionally mapped to chromosome 18, we hypothesized that loss of heterozygosity at the DCC locus may also occur in ovarian neoplasia. Fifty-two sporadic ovarian adenocarcinoma tumours were analysed by Southern blotting for loss of heterozygosity (LOH) at six chromosome 18 loci. Overall, tumours from 31 patients (60%) showed allelic loss at one or more of these loci. A similarly high level of LOH, 66%, was found at D17S5 (17p13.3). In contrast, moderate levels of LOH, of 31%, 39% and 33%, were found at MYCL1 (1p32), D1S57 (1p) and D14S20 (14q32.33) respectively. However, analysis of partial chromosome deletions in 11 patients indicates that the smallest region of overlap appears to exclude the DCC gene but to be between the D18S5 and D18S11 loci. This suggests that another locus, as well as or apart from DCC, may be involved.

Adenocarcinoma

Prognostic significance of nuclear DNA content in phaeochromocytoma.

Nuclear DNA content of 27 phaeochromocytomas was measured by image analysis of thin sections and monolayer smears of nuclei extracted from thick sections (cytospins) using archival paraffin-embedded tissue blocks. Recurrence was assessed on the basis of clinical follow-up or urinary catecholamine levels. The mean follow-up was 5.0 years, with a range of 4 months to 15 years. Although it is not possible to differentiate accurately malignant tumours using DNA analysis, prediction of benign tumours is possible. Using thin sections, all tumours were benign when the percentage of cells with a DNA content of 2.5 c (2 c = diploid) was less than 40% and the DNA content of 5 c was less than 4%. Using the cytospin preparation, all diploid tumours were benign. Thus, patients with diploid tumours may be saved intensive long-term follow-up. Aneuploid and tetraploid tumours, however, continue to require careful lifelong follow-up.

Adolescent

Comparison of image analysis and flow cytometric determination of cellular DNA content.

A good correlation (r = 0.94) was obtained between the DNA indices (DI) using flow cytometry and image analysis of nuclei cytospins extracted from paraffin wax embedded tumour sections. Some of the limitations and problems associated with image analysis which came to light included an unacceptably high coefficient of variation (CV) and a "left-shift" in the DI in most DNA histograms obtained when using image analysis of 5 microns sections. In contrast, the DNA histograms generated using image analysis of cytospun nuclei from paraffin wax blocks were of good quality and similar to those obtained using flow cytometry. Variability in Feulgen staining was common and an important source of error despite rigorous control of the staining technique. This could be overcome by using internal controls such as fibroblasts rather than external controls (rat hepatocytes) to determine the diploid DI with image analysis. A thorough understanding and appreciation of the methodological problems associated with image analysis and flow cytometric determination of DNA content is required before these methods find widespread clinical application.

Adrenal Gland Neoplasms

Etoposide, carboplatin, cyclophosphamide and vincristine in previously untreated patients with small-cell lung cancer.

The efficacy and toxicity of 120 mg/m2 etoposide and 100 mg/m2 carboplatin given i.v. daily x 3 together with 750 mg/m2 cyclophosphamide and 1.4 mg/m2 vincristine given i.v. on day 1 (ECCO) in a regimen given every 28 days for 6 courses was assessed in 90 (40 limited stage, 50 extensive stage) previously untreated patients with small-cell lung cancer. Mediastinal irradiation using 50 Gy in 25 fractions was given to limited-stage patients without progression after 3 courses of chemotherapy. Cranial irradiation with 30 Gy in 10 fractions was given to all patients attaining a complete response (CR). Objective responses were seen in 83% [CR, 60%; partial response (PR), 23%] of patients with limited and 76% (CR, 22%; PR, 54%) of those with extensive disease. The median relapse-free survival for objective responders with limited disease was 13.4 months, with a median of 8.0 months for extensive-stage patients. The median relapse-free survival for patients achieving a CR was 13.4 months, with a median of 7.8 months for those undergoing a PR. The median survival was 13.3 months for patients with limited disease, with a median of 9.6 months for those with extensive disease. The median survival following a CR was 18.2 months, with a median survival of 9.9 months for those showing a PR. The combination was well tolerated, with either no nausea or nausea only (WHO grade 0 or 1) in 56% of patients and minimal mucositis, renal toxicity, neurotoxicity or ototoxicity. Neutropenia measuring less than 1.0 x 10(9) WBC/l (WHO grade 3 or 4) was seen in 74% of patients, with two deaths due to infection occurring during neutropenia. Thrombocytopenia of less than 50 x 10(9) platelets/l (WHO grade 3 or 4) occurred in 24% of patients. ECCO is a new, active, well-tolerated program for previously untreated patients with small-cell lung cancer.

Adult

Extraovarian peritoneal serous papillary carcinoma. A clinicopathologic study of 31 cases.

The rate and clinical features of patients admitted to King George V Hospital with extraovarian peritoneal serous papillary carcinoma during a 9-year period were reviewed. In this time, 31 of 236 (13%) patients with an initial diagnosis of invasive serous ovarian carcinoma fulfilled the surgicopathologic criteria for this entity. All patients had disseminated tumor equivalent to ovarian Stage III and IV disease (International Federation of Gynecology and Obstetrics [FIGO]) and with predominantly high-grade neoplasms. They were managed by surgical exploration, tumor debulking where possible, and postoperative chemotherapy. A comparison with a contemporaneous series of 139 patients with primary epithelial ovarian carcinoma matched for stage and grade of disease and managed similarly showed no difference in actuarial survival. The median survival times were 11.3 months for patients with extraovarian serous papillary carcinomas and 13.5 months for patients with equivalent primary ovarian neoplasms. The features of the disease and the treatment regimens used are discussed.

Adult

Prolonged reversible acute renal failure in focal glomerulonephritis with severe nephrotic syndrome in an elderly patient.

A clinical report of a 67-year-old woman who developed reversible acute renal failure due to focal glomerulonephritis with severe nephrotic syndrome is presented. The patient required four weeks' dialysis treatment but recovered completely. The role of temporary dialysis and diuretics on the clinical course and the reversibility of the process in old age is discussed.

Acute Kidney Injury

Meperidine to control shivering associated with platelet transfusion reaction.

Shivering may be part of a febrile non-haemolytic reaction to blood product transfusion. Shivering can increase oxygen consumption up to 500 per cent which may be detrimental to patients with decreased myocardial reserve. A case is presented of a reaction to platelet transfusion characterized by shivering, tachycardia and hypertension in a patient with a recent myocardial infarction in whom the metabolic and haemodynamic effects were considered to be potentially disastrous. Intravenous injection of meperidine was rapidly effective in treating these changes.

Adult

An evaluation of CA125, CA1 and peanut lectin immunoreactivity in epithelial ovarian neoplasms: correlation with histopathological features, prognostic variables and patient outcome.

The ability to produce monoclonal antibodies to tumour associated antigens, together with advances in immunocytochemistry, provide the potential for establishing a new functional classification of human tumours. This approach was used to investigate whether the expression of CA125, CA1 and the Thomsen-Friedenreich antigens reflected the biological behaviour of ovarian tumours and, if so, had a potential role in the clinico-pathological assessment of ovarian neoplasms. Expression of these antigens was assessed in benign, borderline and malignant ovarian epithelial tumours and attempts were made to determine if there was any correlation between immunoreactivity and tumour grade, histological subtype, FIGO Stage, tumour ploidy or patient outcome. There was no evidence that expression of these antigens had clinical significance, although it is possible that reactivity with antibody OC125 might identify patients in whom CA125 antigen levels in the sera could be used as a marker to monitor disease progress.

Antibodies

Influenza surveillance in an acute-care hospital.

The epidemiology, significance, and clinical consequences of influenza in the hospital setting were studied in a prospective surveillance of adults in an acute-care hospital during the 1986-1987 influenza season, specifically searching for cases of nosocomial influenza. A total of 43 cases of influenza A were identified; 17 cases occurred among working hospital employees, 14 cases occurred among patients in the emergency room or clinics, ten were community-acquired cases among hospitalized patients, and two cases were nosocomially acquired. The nosocomial influenza attack rate was 0.3 per 100 hospital admissions. Both cases of nosocomial influenza were associated with secondary pneumonias and prolongation of hospital stay. These cases might have gone unrecognized in the absence of an influenza surveillance program. A potential reservoir of infection was the health care providers caring for the hospitalized patients. Further systematic influenza surveillance is needed to assess the global medical and economic impact of nosocomial influenza on hospitals, rather than simply relying on reports of institutional outbreaks.

Adult

Multiple topogenic sequences in bovine opsin.

Bovine opsin, a polytopic integral membrane protein, contains seven transmembrane segments connecting eight hydrophilic domains alternating on each side of the membrane. To localize topogenic sequences that might specify the distinct topology of opsin in the membrane, we constructed various opsin mutants, each containing only one transmembrane segment. Messenger RNAs transcribed from these mutants were translated in a cell-free system supplemented with microsomal membranes. Among six of the seven transmembrane segments of opsin that were analyzed, five were able to function as signal sequences and also expressed stop-transfer sequences of variable strength. By the criteria of extractability at pH 11 and protease sensitivity, the presence of a signal sequence in combination with a "strong" stop-transfer sequence yielded integration into the lipid bilayer of the majority of chains. However, in combination with a "weak" stop-transfer sequence, we observed integration into the lipid bilayer of only some chains, with the others either completely translocated across the membrane or retained in a water-accessible space in the membrane.

Amino Acid Sequence