Clinical use of selective estrogen receptor modulators and down regulators with the main focus on breast cancer.

Selective estrogen receptor modulators (SERMs) and selective estrogen down regulators (SERDs) act as estrogen receptor (ER) agonists or antagonist depending on the targeted tissue and the specific configuration of the used SERM or SERD. Effects on bone, endometrium and breast cancer are of interest. Endocrine treatments have been used in breast cancer since the end of the 19th century. In the second part of the last century different compound of SERMs and SERDs have been developed and we will discuss them mainly as used in the treatment and prevention of breast cancer. Tamoxifen is the widely investigated and most used representative of these drugs and has been introduced in the advanced disease, in the neoadjuvant and adjuvant setting and for prevention of the disease. Its role has been challenged in the last years by the introduction of third generation aromatase inhibitors that have proven a higher activity than tamoxifen and a different toxicity pattern. Several other SERMs have been investigated, but none of them was clearly superior to tamoxifen. The main interest in different SERMs has to be seen in the slightly different safety profile between the different compounds. SERDs act as pure estrogen antagonist. They have been used in the treatment of advanced breast cancers and their role in other settings still needs further investigation. The increased use of aromatase inhibitors as first line endocrine therapy raises new questions on the role that tamoxifen and other SERMs or SERDs may play in breast cancer. The sequencing of endocrine therapies and the combination of endocrine therapies with new targeted therapies in hormone sensitive breast cancer remains a very important research issue. Polymorphisms in genes coding for tamoxifen metabolizing enzymes, as for instance, the CYP2D6 genotype, have the potential of becoming clinically useful predictive marker for tamoxifen response. With this meaningful newer knowledge it is possible that the place of tamoxifen in the treatment of breast cancer will be redefined in the future.

Placental protein 14 and pregnancy-specific beta 1-glycoprotein in women with suppressed, normal and stimulated follicular maturation.

Not only the ovarian steroids but a number of proteins have an effect on the endometrium and its capability to accept an implanting embryo and to establish a pregnancy. In this study we have selected the placental protein 14 (PP14) which is, in spite of its name, produced by the glandular epithelium of the endometrium. Pregnancy-specific beta 1-glycoprotein (SP1) was also investigated. This marker is trophoblast-specific but it has been chosen since some patients repeatedly exhibit weak but detectable serum SP1 when no embryo is present. There seems to be a negative correlation between the chance of obtaining a pregnancy and the occurrence of such abnormal serum SP1 signals; they could originate from the endometrium itself or from another maternal source influencing the endometrium indirectly. The full-cycle time course was determined for these two proteins as well as for estradiol and progesterone. A total of 66 cycles were analyzed, of which 16 were from ovulating volunteers without any hormonal treatment (controls) and 13 were from women taking oral contraceptives. The remaining 37 cycles were from 32 patients undergoing conventional in vitro fertilization (IVF) treatment. Eight pregnancies were achieved in this group during the study period. We found that abnormal positive SP1 signals occurred predominantly in the unsuccessful IVF subgroup, but also in the control groups (with or without contraceptive pills), and this in a cycle-independent manner. PP14, on the other hand, exhibited cyclic patterns in the IVF and ovulating control cycles as did progesterone. However, in seven out of 13 cycles under oral contraception (and suppressed progesterone), a midcycle rise in PP14 was observed. Moreover, midcycle PP14 levels were generally higher in this group when compared to the ovulating controls as well as to the cycles under controlled ovarian stimulation for IVF. This confirms that PP14 is influenced by progesterone but only in an indirect way or under the additional effect of other hormones. It is unlikely that SP1 plays this role since it was not correlated to any of the other proteins or steroids studied. Nevertheless, SP1 did not occur randomly over the different groups.

Serum pregnancy-specific beta1-glycoprotein before embryo transfer is related to endometrial thickness and to outcome prognosis in women undergoing in-vitro fertilization treatment.

We have previously observed the repeated presence of low but detectable amounts of the trophoblast marker pregnancy-specific beta1-glycoprotein (SP1) in the serum of some women undergoing in-vitro fertilization (IVF) treatment around the time of oocyte retrieval. The occurrence of these signals seemed to be restricted to a defined group of patients which also showed a lower pregnancy success rate in a preliminary study. To test our hypothesis we have analysed 173 consecutive cycles leading to an embryo transfer. Fifty-four cycles (31%) had a serum SP1 level of at least 0.1 ng/ml between days embryo transfer -5 and embryo transfer (group A). Five pregnancies were obtained in this group (pregnancy rate = 9.3%), while in group B, defined by the absence of detectable SP1 before embryo transfer (119 cycles), 36 ongoing pregnancies were achieved (30.3%). Ten of the 41 pregnancies were achieved in 33 first-time non-pregnant patients undergoing further attempts during the study period. Again the pregnancy rate was higher in the first-time group B women (9/23 versus 1/10 for group A). Patients tended to remain in their groups A or B, the latter being associated with a better immediate as well as subsequent chance for pregnancy. Group A cycles had a significantly lower endometrial thickness two days before oocyte retrieval than group B (P = 0.0011). We postulate that the presence of an unknown, maternal and progesterone- or follicle stimulating hormone-independent factor in some patients could stimulate tonic ectopic SP1 synthesis and at the same time negatively influence endometrial development.

Multiple bilateral cerebral abscesses with hemorrhage.

Brain abscess with spontaneous hemorrhage is an uncommon illness. A rare case of multiple abscesses in both cerebral hemispheres complicated by hemorrhage is reported. Minimally invasive surgery utilizing magnetic resonance imaging (MRI) guidance was performed after extensive testing failed to yield a diagnosis. Streptococcus intermedius was isolated from cultures taken during surgery and intravenous antimicrobial therapy was instituted. Pathology other than metastatic neoplasms and subacute hemorrhage should be considered in cases of cerebral ring-enhancing masses with hemosiderin deposition.

Volumetric interstitial hyperthermia: role of the critical care nurse.

Although statistical survival of patients with malignant brain tumor is dismal and their care can be emotionally exhausting, it is hopeful and rewarding to the critical care nurse to participate in a clinical investigation that will improve the future of these patients. Each therapy cycle administered, each patient treated, and each family member is different; each is a challenge for the critical care nurse. The quality and success of a clinical investigation requires the commitment of many people working together in close team effort. With effective communication, insight, and cooperation the critical care nurse working in this research setting shares in the patient's and family's hope and determination for the future of improved medical and nursing management of malignant brain tumors.