Ifosfamide has single agent activity in advanced breast cancer and may potentiate the activity of doxorubicin. The combination of ifosfamide 5 g/m2 and doxorubicin 40 mg/m2 every 3 weeks for 4 cycles was used to treat 77 patients with advanced breast cancer. Fifty three patients had not received prior chemotherapy. All patients had one or more poor prognostic features, including tumor expression of epidermal growth factor receptor in 11/12 tested. The overall response rate was 74% (95% confidence intervals 62%-83%). The median survival was 9.4 months. The principal toxicities were febrile neutropenia and ifosfamide encephalopathy each in 6% of patients. A high percentage of the projected dose intensity was administered. This is a highly active combination with acceptable toxicity in advanced breast cancer, although the long term survival remains poor. Further exploration of ifosfamide in combination chemotherapy for advanced breast cancer is warranted.

Adult↗

PubMed1994

Release of chicken luteinising hormone-releasing hormone-I (cLHRH-I) by mediobasal hypothalamus in the cockerel: validation of an incubation system and effect of excitatory amino acids.

An in vitro system for the incubation of mediobasal hypothalami (MBH) of cockerels and a radioimmunoassay for chicken luteinising hormone-releasing hormone-I (cLHRH-I) were developed. The size of the hypothalamic fragment (MBH including the median eminence) and the incubation conditions used (40 degrees C, under constant shaking and gassing) preserved the physiological properties of the tissue. It was possible to maintain the MBH in vitro and to study the LHRH release for several hours. The assay proved sensitive enough (ED80 = 0.794 pmol/tube, ie 4.59 pg/ml) and sufficiently precise (within-assay coefficient of variation = 4.4% and between-assay coefficient of variation = 10.2%) to measure the amounts of peptide released in the incubation medium. The use of this incubation system provided the first evidence of the stimulating effect of the excitatory amino acids glutamate, NMDA and kainate on the secretion of cLHRH-I in birds. Our results suggest that the effect on the NMDA receptor is predominant.

Amino Acids↗

PubMed1994

The effect of topical ceftazidime on pseudomonas keratitis in rabbits.

Ceftazidime is a beta-lactam antibiotic highly effective against Pseudomonas aeruginosa infection. Using a rabbit model of Pseudomonas keratitis, 10(3) bacteria (in 20 microliters) were injected unilaterally into the corneal stroma of albino rabbits. Twenty-six hours after inoculation, topical Ceftazidime (50 mg/ml) drops were administered for 48 h, following which the corneal tissue was cultured. Eighteen of 20 corneal cultures (90%) from rabbits treated with Ceftazidime drops were negative. In comparison, all untreated control group cultures showed florid bacterial growth. These results suggest that topical Ceftazidime may be a useful agent in the treatment of P. aeruginosa keratitis.

Administration, Topical↗

PubMed1994

Spirituality and risk: toward an understanding.

To be fully healthy is to risk encountering and embracing the complex substrate of mysterious life-giving and life-denying spiritual forces, the hidden wholeness of God. Risky health behavior may paradoxically arise from the psychospiritual need to both probe and avoid probing the deeper understandings of health reflected in the tensions between good and evil. Avoidance of the painful truths of poverty, racism, sexism, and classism among other evils in our society results in the prevalence of high-risk life styles, addictions, and violent behaviors. Spiritual paradigms from holistic community care are needed to enable communities to more fully respond to the health empowering potential of the hidden wholeness rather than hiding from it.

Health Behavior↗

PubMed1994

Localization of antigenic domains on the major subunits of Bordetella pertussis serotype 2 and 3 fimbriae.

Antibody-binding domains on the major subunits of Bordetella pertussis serotype 2 (Fim2) and 3 fimbriae (Fim3) have been identified using synthetic peptides which were screened for recognition by anti-protein monoclonal antibodies (mAbs). The presence of non-contiguous fimbrial epitopes was demonstrated by both anti-Fim2 and anti-Fim3 mAbs, several of which recognized at least two peptides that were discontinuous in the amino acid sequence of the corresponding subunits. The specificity of one mAb, 51/24, directed against Fim2, was investigated by replacement-set analysis of a 10-residue peptide, and revealed that antibody binding to the peptide was dependent on the sequence N94PQ96 which is non-conserved in Fim3. Furthermore, proline at residue 95 was found to be essential for mAb 51/24 binding. The specific anti-Fim3 mAb, AG3A, was found to recognize the 10-residue carboxy-terminal peptide from both Fim3 and, unexpectedly, from Fim2. This result suggests that mAb AG3A serospecificity at the protein level is determined by a conformational constraint which prevents mAb AG3A binding to the Fim2 C-terminal domain. Several free peptides containing amino acid residues which comprise part of the Fim2 and Fim3 epitopic domains were prepared as immunogens. One of these peptides was immunogenic in the mouse, indicating the location of a T-helper cell epitope within the peptide sequence, and induced a strong anti-peptide antibody response. The other peptides each required immunization as a conjugate with a carrier protein for anti-peptide antibody stimulation. All four anti-peptide antibody preparations only weakly recognized fimbriae-coated ELISA plates.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗