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.     

Myocardial scintigraphy using 99m-technetium pyrophosphate in the diagnosis of acute myocardial infarct. Comparison of planar and tomographic imaging

The aim of the study was to compare the effectiveness of planar and single photon emission computed tomography (SPECT) imaging with 99mTc-pyrophosphate in the verification of acute myocardial infarction. The study was performed on 39 patients (26 males, 13 females) aged between 41-76 years (mean 61 +/- 9) admitted to CCU for acute myocardial infarction. Patients underwent planar and SPECT imaging using a double-head-camera with a 360 degrees rotation arc within 6 days of admission. Planar images were obtained in three standard projections (anterior, LAO 45 degrees, LAO 75 degrees) with acquisitions of 500000 counts each. To obtain SPECT images ninety projections, each lasting 20 seconds, were taken; subsequently images reconstruction was performed using an iterative algorithm. Positive planar images were found in 21 out of 39 patients; SPECT images were positive in 33 patients. In "Q wave" myocardial infarctions planar images were positive in 13 out of 15 patients, whereas SPECT images were positive in all subjects; in "non-Q wave" myocardial infarctions planar images were positive in 6 out of 22 patients whereas SPECT images were positive in 16 patients (p less than 0.005); in 2 patients with left bundle branch block both planar and SPECT images were positive. A bidimensional echocardiogram was carried out on 38 patients: an alteration of left ventricular regional wall motion was present in 30 subjects; in one patient diffuse hypokinesia was present.(ABSTRACT TRUNCATED AT 250 WORDS)     

Personality and psychopathology in patients with temporomandibular joint pain-dysfunction syndrome. A controlled investigation

OBJECTIVE: Our aim was to deepen the understanding of the psychosomatic aspects of temporomandibular joint (TMJ) pain dysfunction syndrome. Patients affected by this syndrome were compared with both healthy subjects and psychiatric patients, using both self-report and physician-scored psychological measures. METHODS: Three sex- and age-matched groups were recruited: a TMJ group (n = 32), a healthy group (n = 22) and a psychiatric group (n = 22). The psychiatric group consisted of outpatients diagnosed as having a DSM-IV anxiety or depressive disorder of mild to moderate severity. Psychometric assessment included the Minnesota Multiphasic Personality Inventory (MMPI) and the Hamilton Anxiety Rating Scale (HARS). RESULTS: Psychiatric patients scored higher than both the comparison groups on all but one of the MMPI scales; the majority of the differences were significant or approached significance. TMJ patients scored higher than healthy controls on the Hs (hypochondriasis; p< or =0.01), Hy (hysteria; p< or =0.01) and D (depression; p< or =0.05) scales. Psychiatric patients scored higher than TMJ patients on the HARS psychic anxiety subscale (p< or =0.05), while TMJ patients scored higher than psychiatric patients on the somatic anxiety subscale (p< or = 0.05). CONCLUSIONS: Certain personality characteristics were associated with TMJ dysfunction. However, further longitudinal studies should be performed to properly assess causal relationships. Despite signs of neuroticism, anxiety and depression, patients with TMJ dysfunction differed from anxious and depressed patients. While the latter displayed a higher level of psychopathology, each group was characterised by a distinct pattern of anxiety symptoms. In addition, a substantial proportion of TMJ patients had little awareness of their inner states and emotions.     

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.      

High resolution ultrastructural mapping of total calcium: electron spectroscopic imaging/electron energy loss spectroscopy analysis of a physically/chemically processed nerve-muscle preparation.

We report on a procedure for tissue preparation that combines thoroughly controlled physical and chemical treatments: quick-freezing and freeze-drying followed by fixation with OsO4 vapors and embedding by direct resin infiltration. Specimens of frog cutaneous pectoris muscle thus prepared were analyzed for total calcium using electron spectroscopic imaging/electron energy loss spectroscopy (ESI/EELS) approach. The preservation of the ultrastructure was excellent, with positive K/Na ratios revealed in the fibers by x-ray microanalysis. Clear, high-resolution EELS/ESI calcium signals were recorded from the lumen of terminal cisternae of the sarcoplasmic reticulum but not from longitudinal cisternae, as expected from previous studies carried out with different techniques. In many mitochondria, calcium was below detection whereas in others it was appreciable although at variable level. Within the motor nerve terminals, synaptic vesicles as well as some cisternae of the smooth endoplasmic reticulum yielded positive signals at variance with mitochondria, that were most often below detection. Taken as a whole, the present study reveals the potential of our experimental approach to map with high spatial resolution the total calcium within individual intracellular organelles identified by their established ultrastructure, but only where the element is present at high levels.     

Ealuation of thrombolytic treatment of acute myocardial infarct using myocardial scintigraphy with Tc-99-MIBI. Immediate results and follow-up after one year

The aim of the study was to investigate Single Photon Emission Computed Tomography (SPECT) with technetium-99m esakis-2-methoxy isobutyl isonitrile (Tc-99m-MIBI) as a means of evaluating the results of intravenous thrombolytic treatment in patients with acute myocardial infarction. In addition, the evolution of myocardial perfusion pattern was studied. The study group included 15 patients (12 males and 3 females, mean age 57 +/- 8 years) with acute myocardial infarction admitted to the coronary care unit within 4 hours of the onset of symptoms. All patients were injected with 740 MBq of Tc-99m-MIBI before starting the thrombolytic therapy (rt-PA 100 mg i.v. in 3 hours); SPECT was performed 3 to 6 hours later. The tomographic study was repeated 5 days later. Ten patients were re-examined using Tc-99m-MIBI SPECT one year after the acute event. Taking into account the clinical, electrocardiographic and enzymatic data and the findings of two-dimensional echocardiography performed both on the fifth day and after one month, patients were divided into two groups: group A (8 patients) with probably effective reperfusion, group B (7 patients) probably unaffected by therapy. The infarct related vessel was patent in all group A patients and in 2 of the 7 patients of group B. The percent decrease in the perfusion defect size between the first and second scintigraphic studies showed a significant difference between the two groups: group A 61.2 +/- 6.8, group B 4.7 +/- 2.4% (p less than 0.002). A significant difference was also found when the results of the admission scintigraphy were compared with those of the control 1 year after: group A 80.8 +/- 8.7%, group B 20.8 +/- 13.8% (p less than 0.02). The percent decrease in the perfusion defect size between the 5-day and 1-year images was also significantly different in the two groups: group A 52.9 +/- 20.9%; group B 17.8 +/- 12% (p less than 0.02). The late perfusion improvement involved mainly the sub-epicardial layers. In conclusion, Single Photon Emission Computed Tomography with Tc-99m-MIBI clearly identified patients with effective reperfusion after thrombolytic treatment and distinguished them from subjects unaffected by therapy. Both, successfully and unsuccessfully treated patients showed a late perfusion improvement which was more evident in the successfully treated patients.     

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.     

"Calciosome," a cytoplasmic organelle: the inositol 1,4,5-trisphosphate-sensitive Ca2+ store of nonmuscle cells?

Calsequestrin (CS) is the protein responsible for the high-capacity, moderate affinity binding of Ca2+ within the terminal cisternae of the sarcoplasmic reticulum, believed up to now to be specific for striated muscle. The cells of two nonmuscle lines (HL-60 and PC12) and of two rat tissues (liver and pancreas) are shown here to express a protein that resembles CS in many respects (apparent mass and pH-dependent migration in NaDodSO4/PAGE; blue staining with StainsAll dye; Ca2+ binding ability) and is specifically recognized by affinity-purified antibodies against skeletal muscle CS. In these cells, the CS-like protein is shown by immunofluorescence and immunogold procedures to be localized within peculiar, heretofore unrecognized structures distributed throughout the cytoplasm. These structures appear to be discrete organelles, which we propose to be named "calciosomes." By cell fractionation (Percoll gradient and free-flow electrophoresis), the CS-like protein of HL-60 cells is shown to copurify with the markers of the inositol 1,4,5-trisphosphate (Ins-P3)-sensitive Ca2+ store, whereas the markers of other organelles (endoplasmic reticulum, Golgi complex, mitochondria, endosomes) and of the plasma membrane do not. Calciosome might thus be the intracellular target of Ins-P3--i.e., the source of the Ca2+ redistributed to the cytosol following receptor-triggered generation of the messenger.