Study on the reduction of chemotherapy induced neutropenia in mice using glucosaminylmuramyl dipeptide.

Neutropenia is a common and often dose limiting side effect of some chemotherapy regimens. The aim of this study was to investigate the ability of an immunomodulator, glycosaminylmuramyl dipeptide (GMDP, CAS 78113-36-7, romurtide) to reduce chemotherapy induced neutropenia. BALB/c mice were treated with 200 mg kg-1 cyclophosphamide (CY) to induce a reversible neutropenia lasting approximately 6-7 days. There was no change in the duration or depth of neutropenia in mice treated with GMDP for 3 consecutive days (2.5 or 25 mg kg-1) starting the day after CY injection. In addition, at the doses used, the time of administration of GMDP relative to CY did not alter this response. However, a marked neutrophilia compared to controls was consistently observed in all cases. Neutrophil counts of up to 14 times the baseline value were measured 6-7 days after the induction of neutropenia. GMDP had no effect in the absence of CY. Less variation was seen in white cell counts of older non-SPF mice treated with CY. When the activity of GMDP (5 mg kg-1) was compared with G-CSF (granulocyte colony stimulating factor, 100 micrograms kg-1) in these animals, GMDP showed a consistent trend to reduce the length of neutropenia, however, under the conditions tested only G-CSF treatment resulted in a significant reduction in the duration of neutropenia. In the 12-week-old mice, the neutrophilia seen with both G-CSF and GMDP was much smaller than in the 8-week-old mice, and was not significantly different from that in control mice treated with CY alone.     

lschaemic heart disease: Non-invasive prediction of reperfusion and coronary artery patency by continuous ST segment monitoring in the GUSTO-I trial

In the GUSTO-I ECG ischaemia monitoring substudy, 1067 patientsunderwent continuous ST segment monitoring, using vector-derived12-lead (406 patients), 12-lead (373 patients) and 3-lead Holter(288 patients) ECG recording systems. Simultaneous angiogramsat 90 or 180 min following thrombolytic therapy were performedas a part of the prospective study in 302 patients. Infarct vessel patency was established as TIMI perfusion grades2 or 3 and occlusion as TIMI perfusion grades 0 or 1. Coronaryartery patency was predicted from ST trends up to the time ofangiography. Predictive values at 90 and 180 min after the startof thrombolysis were 70% and 82% for patency and 58% and 64%for occlusion, respectively. In retrospect, accuracy appearedgreatest (79–100%) in patients with extensive ST segmentelevation (400 µV), if both speed of ST recovery and extentof ST segment: elevation were taken into account. Although thethree recording systems differed considerably in signal processing,no significant difference in accuracy was demonstrated amongthese systems. We conclude that continuous ECG monitoring may help select highrisk patients without apparent reperfusion who may benefit fromadditional reperfusion therapy. As ST recovery may occur earlyafter the start of thrombolytics and accuracy of the test isrelated to peak ST levels, the use of on-line ECG monitoringdevices on emergency wards and cardiac care units is recommended.(Eur Heart J 1996; 17: 689–698)     

Familial breast cancer: report of a family pedigree

Following a report of several relatives suffering from breast cancer, the occurrence of neoplasms in 3 generations of a large family was carefully checked. Members of one out of 8 branches were found to have a high incidence of breast cancer with 6 women affected, 4 of them under the age of 40. As well as early onset, these women presented other features typical of "breast cancer families": bilateral breast cancer, other second primary tumours, ovarian cancer in the daughter of one affected patient, and benign breast disease in the sister of another.     

The psychological organization of multiple personality disordered patients as revealed in psychological testing

The reader familiar with the borderline literature may see a correspondence between certain of our MPD/DD Rorschach results and typical borderline characteristics. Most notably, both groups reason and view others in unusual but not psychotic ways and demonstrate certain difficulties in affect integration. On the other hand, the MPD/DD group exhibits many attributes that contradict predictions one would make from a borderline perspective, and which support Kluft's assertion that the majority of these patients have a more complex and structured personality system. Rather than holding oversimplified attitudes, they are attuned to the subtleties of experience. Their generally introversive personality style reflects a capacity for internalization, for ideational organization of anxiety, for taking analytic distance from themselves, and for viewing and relating to others in a complex and empathetic fashion. To return to our metaphor of the explorer, we can conclude that the borderline personality concept gives us too broad and blurred a view of the MPD/DD terrain. It lacks the level of specificity needed to describe the test phenomena that appear on these MPD/DD Rorschachs. The special test instructions, behavior ratings of extra-test dissociative phenomena, and the posttest process questions enable us to see that although at gross level certain vulnerabilities resemble borderline characteristics, the processes underlying these phenomena are quite distinct. Moreover, unexpected areas of strength and maturity also exist. These findings suggest that we are not viewing a developmental arrest, but rather, are seeing the signs of what developmental psychologists call a "strange" development i.e., an atypical developmental pathway created by unusual interactions with the world. It may well be that much of the difficulty in establishing the validity of BPD test criteria has been due to the unwitting inclusion of DD patients within these studies. If so, the distinction between borderline and dissociative test characteristics will lead to more accurate and refined studies of both groups. The concept of PTSD has been a particularly useful dimension for elucidating MPD test phenomena. As we further investigate commonalities and differences within the MPD/DD continuum, it will be interesting to examine in what way the severity of these patients' PTSD relates to their personality characteristics, symptom patterns, and treatment response. The strength of psychological assessment has long been its ability to describe the organization of psychological processes to gain a detailed knowledge of the individual. As such, in the hands of well-trained clinicians, psychological assessment has been one of the most powerful tools for predicting long-term treatment outcome.(ABSTRACT TRUNCATED AT 400 WORDS)     

Entry: a new approach

Despite all of the protections promised through grandfathering and pathways to educational mobility, the entry movement tends to be perceived by many to be "demoting" the lives and livelihoods of hundreds of thousands of RNs who do not possess the education to meet the proposed standard. Here is a proposal for a way out of the quagmire.     

Estimating the diameter of the left main bronchus

Two hundred and six standard PA chest X-rays were measured. The mean diameter of the left main bronchus (LMB) was 12.6 +/- 1.9 mm. The mean diameter of the 92 male LMB was 13.0 +/- 2.6, and for females 11.8 +/- 1.6. These data correspond closely to that reported by others. The correlation between the diameter of the LMB and that of the trachea was 0.74 but was not precise enough to be useful as an estimate for clinical use. Similarly there was good correlation between the diameter of the right main bronchus and that of the left (r = 0.75) but not precise enough to be clinically useful. In contrast to previous claims, only direct measurement of the left main bronchus has sufficient precision to define the appropriate size of left double-lumen tube to be selected for lung separation.     

Dermofasciectomy in the management of Dupuytren's disease

Dupuytren's disease may present with well-defined subcutaneous cords or as more diffuse disease with involvement of the skin. Fasciectomy is the procedure commonly carried out for the full range of disease, but is associated with rates of recurrence of up to 66%. We reviewed 143 rays in 103 patients undergoing dermofasciectomy for diffuse disease with involvement of the skin. We found recurrence in 12 rays (8.4% of rays; 11.6% of patients) during a mean follow-up of 5.8 years, eight as cords and four as nodules. We suggest that dermofasciectomy is a better method of disease control than fasciectomy for the more diffuse type of disease with involvement of the skin.     

Reduced production of interleukin 12 by interferon gamma primed alveolar macrophages from atopic asthmatic subjects

BACKGROUND: Asthma is characterised pathologically by an inflammatory pulmonary infiltrate rich in T helper (Th) 2 cells and eosinophils. Interleukin (IL)-12 is a heterodimeric cytokine critical for driving the development of uncommitted Th cells to express a Th 1 phenotype. Reduced pulmonary production of IL-12 may therefore play a role in the pathogenesis of asthma by contributing to the pulmonary cytokine imbalance seen in asthma. METHODS: IL-12 p70 protein levels in bronchoalveolar lavage fluid and p70 protein levels and IL-12 messenger RNA in alveolar macrophage cultures from normal and atopic asthmatic subjects were measured. RESULTS: There was a significant difference between the mean IL-12 p70 protein level in the bronchoalveolar lavage fluid from asthmatic subjects (37.5 pg/ml) and from normal subjects (131 pg/ml, p = 0.04). Alveolar macrophages from asthmatic subjects produced significantly less IL-12 protein (30 pg/ml) and messenger RNA than those from normal subjects (69.5 pg/ml, p<0.005). These differences were not caused by inhibition of IL-12 production by IL-10 nor to generalised hyporesponsiveness of asthmatic alveolar macrophages from subjects to the effects of interferon (IFN)-gamma. CONCLUSIONS: Pulmonary IL-12 production is lower in asthmatic subjects. This reduction is not the result of generalised hyporesponsiveness to IFN-gamma. Reduced IL-12 levels may contribute to the development of asthmatic pulmonary inflammation through dysregulation of Th cell development.     

Bioactive suture: a novel immunotherapy for head and neck cancer.

PURPOSE: We have proposed to characterize the mechanism through which bioactive surgical sutures generate a T(H)1 immune response and to define the immune-stimulating half-life of the sutures. EXPERIMENTAL DESIGN: Bioactive sutures of interferon gamma (IFNgamma), interleukin 2 (IL-2), anti-CD3/CD28, anti-CD3/CD28 + IL-2, or anti-CD3/CD28 + IFNgamma sutures were used to stimulate lymphocytes from normal donors and from head and neck cancer patients in vitro over a 24-day period. Cell supernatants were analyzed by ELISA, and T cells were phenotyped to characterize the immune response generated. Intracellular cytokine staining was performed to measure the expansion of flu-specific T cells. Electromobility shift assay and supershift assay were used to measure the intranuclear DNA binding activity of nuclear factor kappaB and its p65 subunit in T cells activated by sutures in the presence and absence of a proteasome inhibitor, MG-132. RESULTS: Anti-CD3/CD28, anti-CD3/CD28 + IL-2, or anti-CD3/CD28 + IFNgamma generated a prolonged T(H)1 immune response for 18 days in vitro. Anti-CD3/CD28 expanded flu-specific T cells. Activated T cells demonstrated enhanced CD40 ligand (CD40L) expression within 72 hours of stimulation, which stimulated other cells to secrete IL-12. Stimulated T cells demonstrated increased intranuclear expression of nuclear factor-kappaB, which was blocked by MG-132, and also reduced CD40L and IL-12 expression. CONCLUSIONS: This is the first report to demonstrate that bioactive surgical sutures can generate a prolonged T(H)1 immune response and expand flu-specific T cells. Bioactive sutures, which are primarily a T-cell stimulant, also stimulated other cells to secrete IL-12 and prolonged the immune response. Sutures may provide a novel in situ stimulating strategy for enhancing the immune system of cancer patients.     

Type I collagen promotes the malignant phenotype of pancreatic ductal adenocarcinoma.

PURPOSE: The purpose of this study was to determine the role of functional interactions between pancreatic cancer cells and pancreatic stellate cells (PSCs) in the formation of the desmoplastic reaction (DR) in pancreatic cancer and to characterize the effect of type I collagen (the predominant component of the DR) on pancreatic cancer cell phenotype. EXPERIMENTAL DESIGN: PSCs and type I collagen were identified in sections of pancreatic cancer using immunohistochemistry, and their anatomic relationship was studied. Interactions among pancreatic cancer cell lines (MIA PaCa-2, Panc-1, and AsPC-1), primary cultures of human PSCs, and type I collagen were investigated in a series of tissue culture models. RESULTS: In vivo, the DR causes gross distortion of normal pancreas, bringing cancer cells into close contact with numerous PSCs and abundant type I collagen. In tissue culture models of pancreatic cancer, conditioned media from each cell line increased PSC [3H]thymidine incorporation up to 6.3-fold that of controls, and AsPC-1 cells also increased PSC collagen synthesis 1.3-fold. Type I collagen was observed to increase long-term survival of pancreatic cancer cells treated with 5-fluorouracil, by up to 62% in clonogenic assays. This was because type I collagen increased the proliferation of cancer cells ([3H]thymidine incorporation was up to 2.8-fold that of cells cultured on tissue culture plastic) and reduced apoptosis of AsPC-1 cells in response to 5-fluorouracil (by regulating mcl-1). CONCLUSIONS: These experiments elucidate a mechanism by which the DR in pancreatic cancer may form and, via the collagen within it, promote the malignant phenotype of pancreatic cancer cells, suggesting significant detriment to the host.