Genetic polymorphisms in dopamine-related genes and smoking cessation in women: a prospective cohort study

Background  

Genes involved in dopaminergic neurotransmission have been suggested as candidates for involvement in smoking behavior. We hypothesized that alleles associated with reduced dopaminergic neurotransmission would be more common in continuing smokers than among women who quit smoking.     

Advanced primary breast cancer: assessment at mammography of response to induction chemotherapy

The response to induction chemotherapy is an important prognostic factor in patients with nonmetastatic, locally advanced breast carcinomas. Assessment at mammography of the response of 60 breast cancers in 59 women was performed between 1974 and 1986. Responses were excellent in 13 tumors, moderate in 34, and poor in 13 (excellent moderate = 78%). Assessment of response of discrete masses in a fatty breast was easiest; assessment of response of tumor areas that were poorly defined-such as a focal area of architectural distortion or mass in dense breast parenchyma-was more difficult. Of 17 patients with excellent pathologic responses-that is, minimal or no residual tumor-15 (88%) had complete responses (no residual tumor) as determined with mammography, physical examination, or both. Mammography provides information complementary to physical examination and is essential in the accurate assessment of the response to chemotherapy of locally advanced breast cancer.     

Eosinophilic infiltration in the nasal mucosa of rhinitis patients: is it affected by the presence of asthma or the allergic status of the patients?

BACKGROUND: Asthma and rhinitis often coexist, and there is evidence to suggest that they have similar histopathologic features. OBJECTIVE: To examine whether the inflammatory infiltration in the nasal mucosa in rhinitis is affected by the presence of asthma and allergy. METHODS: Nasal mucosa biopsy samples were collected from 44 individuals: 18 with rhinitis and asthma (9 allergic and 9 nonallergic), 16 with rhinitis and no asthma (8 allergic and 8 nonallergic), and 10 nonallergic control subjects. The alkaline phosphatase-anti-alkaline phosphatase method was applied to 6-microm-thick cryostat sections using monoclonal antibodies against T cells (CD4 and CD8) and eosinophils (EG2). Slides were counted blindly, and results are expressed as cells per high-power field. RESULTS: Eosinophil counts were higher in the nasal mucosa of rhinitic patients vs controls. No differences in cellular infiltration were detected between rhinitic patients with and without asthma or between allergic and nonallergic patients. A trend toward higher CD4+ T-cell counts in the nasal mucosa of rhinitic patients was observed, whereas no differences were noted in CD8+ T-cell infiltration among the groups. CONCLUSION: Inflammatory infiltration, characterized by the presence of eosinophils and CD4+ T cells, was similar in the nasal mucosa in noninfectious rhinitis irrespective of the presence of asthma or the allergic status of the patient.     

Hypo- and hypertetraploidy in a case of erythroleukemia analyzed by fluorochrome banding techniques

Chromosome studies of a case of erythroleukemia in a 57-year-old female patient were made from bone marrow aspirates using the fluorescent primary stain/counterstain methodology. The chromosome number ranged from 42 to 110. There was a high proportion of hypotetraploid cells and a few hypertetraploid and hypooctaploid ones. Structurally normal chromosomes varied in number from cell to cell, ranging from one to seven in the polyploid cells. A number of marker chromosomes were observed, some of which occurred repeatedly in two copies per hypotetraploid cell. The chromosomes involved in aberrations were tentatively identified as #3, #5, #7, #12, #13, #15, #16, #18, #19, and #21. In the abnormal chromosome #16, which was missing a normal short arm, a new kind of heterochromatin was demonstrated by sequential staining with DA-DAPI and DAPI-AMD, suggesting de novo amplification of an A-T-rich satellite DNA sequence.     

Artificial insemination and in-vitro fertilization using donor spermatozoa: a report on 15 years of experience

Donor insemination (DI) using cryopreserved semen commenced at The Royal Women's Hospital in 1976. Over the next 15 years we performed 5953 treatment cycles to achieve 816 pregnancies (13.7% per cycle) and 706 live births. In-vitro fertilization (IVF) using donor spermatozoa commenced in 1986. Over the next 5 years we performed 303 treatment cycles for 185 couples. Including subsequent transfer of cryopreserved embryos, a total of 33% of couples achieved a successful pregnancy by IVF. Statistical analysis indicated that, for DI pregnancies, the most important semen variable was the percentage post-thaw motility, whilst for normal fertilization in IVF it was the pre-freeze motility. These results may be explained by the compensatory effects of post-thaw processing of spermatozoa for IVF, but not for DI in our clinic.      

Systemic inflammation after inspiratory loading in chronic obstructive pulmonary disease

Objective

Patients with chronic obstructive pulmonary disease (COPD) present systemic inflammation. Strenuous resistive breathing induces systemic inflammation in healthy subjects. We hypothesized that the increased respiratory load that characterizes COPD can contribute to systemic inflammation in these patients.

Patients and methods

To test this hypothesis, we compared leukocyte numbers and levels of circulating cytokines (tumor necrosis factor alpha [TNFα], interleukin-1β [IL-1β], IL-6, IL-8, and IL-10), before and 1 hour after maximal incremental inspiratory loading in 13 patients with stable COPD (forced expiratory volume in one second [FEV₁] 29 ± 2.5% ref) and in 8 healthy sedentary subjects (FEV₁ 98 ± 5% ref).

Results

We found that: (1) at baseline, patients with COPD showed higher leukocyte counts and IL-8 levels than controls (p < 0.01); and, (2) one hour after maximal inspiratory loading these values were unchanged, except for IL-10, which increased in controls (p < 0.05) but not in patients with COPD.

Conclusions

This study confirms the presence of systemic inflammation in COPD, shows that maximal inspiratory loading does not increase the levels of pro-inflammatory cytokines (IL-1β, IL-8) in COPD patients or controls, but suggests that the former may be unable to mount an appropriate systemic anti-inflammatory response to exercise.     

Glucocorticoid and proteasome inhibitor impact on the leukemic lymphoblast: multiple, diverse signals converging on a few key downstream regulators

Twenty years ago a proteasome inhibitor was suggested as therapy for glucocorticoid-resistant multiple myeloma, a disease that involves terminally differentiated B cells. Since then, research has proven that it has utility on a number of tumors resistant to chemotherapy. Hematologic malignancy, however, often involves lesser differentiated cells, which have a high potential to modulate their intrinsic machinery and thereby activate alternative rescue pathways. A corresponding multiplicity of therapies is not always practical. One approach to conditions with heterogeneous physiology is to identify key biochemical mediators, thereby reducing the number of treatment targets. Results from several ongoing studies indicate convergence of genomically diverse signal pathways to a limited number of key downstream regulators of apoptosis. Convergence of pathways can be exploited to address the problem of genetic heterogeneity in acute leukemia: this would mean treating multiple molecular aberrations with fewer drugs and enhanced therapeutic benefit.