Sequential Granulocyte Colony-Stimulating Factor Increases Cisplatin Cytotoxicity in Human Epithelial Ovarian Cancer Cell Lines

Background: To determine the effect of granulocyte colony-stimulating factor (G-CSF) on tumor growth and cisplatin cytotoxicity in human epithelial ovarian cancer. Methods: Six human epithelial ovarian cancer cell lines were treated with media (control) for 24 hr, G-CSF for 24 hr, cisplatin for 24 hr, simultaneous cisplatin and G-CSF for 24 hr, media (control) for 48 hr, cisplatin for 24 hr and sequential media for 24 hr, cisplatin for 24 hr, and sequential G-CSF for 24 hr. Following incubation, the percentage cell lysis was determined by particle concentration fluorescein immunoassay chemosensitivity assay. Results: G-CSF resulted in tumor cell growth (7–19%) in three cell lines. Simultaneous G-CSF decreased cisplatin cytotoxicity in five cell lines (7–45%). Sequential G-CSF increased cisplatin cytotoxicity in all six cell lines (5–108%). Conclusions: G-CSF may result in ovarian cancer proliferation. Simultaneous G-CSF may decrease cisplatin cytotoxicity, while sequential G-CSF appears to increase cisplatin cytotoxicity.     

Urinary albumin excretion rate and puberty in non-diabetic children and adolescents

Slightly elevated urinary albumin excretion rate (microalbuminuria) is a marker of early diabetic nephropathy, but it is unclear if the established definition of microalbuminuria (20–200 μg/min) is correct for children and adolescents. We investigated the albumin excretion rate, albumin/creatinine ratio and urinary albumin concentration in 150 healthy schoolchildren and adolescents to (a) obtain a reference value for albumin excretion rate, (b) relate albumin excretion to pubertal stages and (c) evaluate albumin/creatinine ratio and morning albumin concentration as screening methods for elevatcd albumin excretion rate. Albumin concentration was measured by immunoturbidimetry in timed overnight urine samples. The albumin excretion showed a skewed distribution (geometric mean 3.2 μg/min, 95 percentile 15.1 μg/min). In girls, a peak in the albumin excretion rate was found at the pubertal stage 4 (Tanner) and in boys at stage 5. Albumin/creatinine ratio of 2.5 mg/mmol as a scrccning level for elevatcd albumin cxcrction (15 μg/min) showed a high positivc (0.88) and negative (0.99) predictive value.     

Pulmonary function pre- and post-total laryngectomy

Pulmonary function pre- and post-total laryngectomy was assessed in 16 patients without overt inspiratory stridor preoperatively. It could be shown that total laryngectomy is associated with a significant decrease in vital capacity and in an increase in inspiratory flow-volume values 9 days postoperatively. The inspiratory values tended to increase slightly over the next half year. The measured expiratory flow-volume values were preoperatively already significantly lower than the predicted values, and no significant changes could be observed immediately after the operation nor after 6 months. These alterations have to be taken into account when judging the pulmonary function after total laryngectomy.     

Late effects of radiotherapy on hearing

Summary The effect of radiotherapy on hearing was studied in 30 patients who were treated by surgery and radiotherapy for a parotid neoplasm. Functions of the irradiated ear were compared with those of the non-irradiated ear in the same patient. Tympanometry showed a small but significant reduction of static compliance on the irradiated side when compared with the non-irradiated side. Audiometry showed a significant increase in hearing loss in the 1–2, 4–8 and 10–20 kHz ranges that increased with frequency. This hearing loss was mainly sensorineural in contrast to hearing loss at 250–500 Hz, where it was more of a conductive type. There appeared to be a significant dose-effect relation in sound perception at 4–8 kHz. Doses to the cochlea of less than 55 Gy seldom caused a hearing loss, in contrast to doses exceeding 65 Gy. Overall, radiotherapy was found to cause significant, mainly sensorineural hearing losses, which were partly dose-dependent.     

H-2-dependent regulation of the high level of expression of ecotropic murine leukemia virus.

Adult B10.Y mice, which are congenic with C57BL/10ScSn ((B10) mice for the H-2 region, expressed a high titer of infectious ecotropic virus in the spleen. F1 hybrids between B10.Y and B10 mice were negative or had very low levels of virus expression. In (B10.Y x B10)F2 segregant mice, the high virus phenotype segregated with the H-2pa haplotype of B10.Y, whereas the virus-negative phenotype was associated with the H-2b haplotype of B10. Molecular hybridization experiments with a selected ecotropic AKR murine leukemia virus cyclic DNA probe indicated that both partner strains possessed ecotropic virus sequences and that the number of sequences present was the same in B10.Y mice as in B10 mice. This finding excluded the possibility that the H-2-related effect might be due to the presence of additional viral structural genes within or close to the H-2 region of B10.Y mice. The level of expression of this endogenous ecotropic virus was therefore affected by regulatory genes of the H-2 region.     

Phase II and pharmacokinetic study of high-dose methotrexate in the treatment of advanced gynecologic malignancy: A Southwest Oncology Group trial

Fifteen patients with advanced or recurrent gynecologic malignancy were treated with high-dose methotrexate (HDMTX) (1–8 g/M²) and citrovorum factor rescue (10–100 mg/ M²). One complete response (13%) and two improved responses occurred in eight patients (25%) with squamous cell carcinoma and one of seven patients (14%) with nonsquamous nontrophoblastic carcinoma had stable disease for 7 months. The median duration of survival in the squamous group was 9 months and in the nonsquamous groups 6.5 months. Mean serum MTX concentrations were proportional to the doses administered and typical two compartment plasma disappearance curves were seen. Adverse toxic reactions were not observed at serum MTX levels less than 7.8 × 10^?7, M at 24 hr and 1 × 10^?7 M at 48 hr post-MTX. Hematopoietic toxicity occurred most frequently with leukopenia observed in 19.5% of courses. Hepatic, renal, gastrointestinal, and dermatologic toxicities were observed infrequently. Drug-induced nephrotoxicity occurred in one patient and possibly related leukoencephalopathy occurred in another patient. On the basis of the relatively low response rate observed in this trial and the high expense of HDMTX therapy, the value of such therapy may be limited in advanced nontrophoblastic gynecologic cancer.     

Compliance, quality of life and quantitative voice quality aspects of hands-free speech

CONCLUSIONS: With the use of a new automatic stoma valve (ASV) it appears possible to rehabilitate patients who have previously been unsuccessful in acquiring hands-free speech. As well as making daily ASV use possible for an additional group of patients, this new device was also appreciated by many patients as an additional rehabilitation tool for specific occasions. Despite statistically significant improvements in aspects of voice and breathing using this novel ASV, improvement of peristomal adhesion is probably the main factor needed to further increase success rates. Nevertheless, our results show that it makes sense to keep trying to achieve hands-free speech, even if previous attempts have failed. OBJECTIVE: To make a long-term (6 months) assessment of compliance and aspects of voice, breathing and quality of life using a new ASV: the Provox FreeHands heat and moisture exchanger (HME). MATERIAL AND METHODS: This was a prospective clinical multicentre trial in 79 laryngectomized patients (8 regular ASV users, 58 previously unsuccessful users and 13 new users). Data were collected at baseline and after 1 and 6 months by means of European Organization for Research and Treatment of Cancer Quality of Life questionnaires and specific structured questionnaires concerning compliance, skin adhesion, voicing and pulmonary aspects. An objective assessment of voice parameters (maximum phonation time, maximum phonation time while counting, dynamic loudness range and number of pauses in a standard read-aloud text) was made for comparison of different stoma occlusion methods (digital occlusion via an HME and two different ASVs). A subjective assessment of overall voice quality was made. RESULTS: After 6 months, 19% of patients used the new ASV on a daily basis (mean 5 h/day), while 57% used it on an irregular basis as an additional rehabilitation tool for special occasions. Two-thirds of the study group indicated that they would continue to use the new ASV after the study period. With respect to the objective parameters, statistically significantly better maximum phonation times and dynamic loudness ranges were observed with the new ASV compared to the Blom-Singer ASV. However, the best results for all the objective parameters were obtained with digital occlusion via the Provox HME.