Acute ischaemic lesions in death due to ischaemic heart disease. An autopsy study of 333 cases of out-of-hospital death

The frequency of acute coronary artery thrombus and myocardial infarction in subjects dying suddenly or unexpectedly from ischaemic heart disease (IHD) is still unclear, with previous autopsy studies reporting an incidence between 4% and 100%. In this study of 333 randomly selected out-of-hospital deaths, detailed autopsy showed IHD as the sole cause of death in 206 (62%). One hundred and seventeen acute coronary thrombi were present in 96 cases whilst four had an established acute infarct without an identifiable coronary thrombus. Thus 100 (48.5%) IHD deaths had evidence of an acute ischaemic lesion. Acute lesions were equally prevalent among males and females, but the incidence declined with increasing age and they were less frequent among those with a prior clinical history of heart disease. One hundred and forty-seven IHD deaths were witnessed. The proportion of cases with an acute ischaemic lesion increased with the duration of pre-morbid symptoms. Of those with an acute lesion, only 17% died without symptoms compared to 63% of those without an acute lesion. All cases with symptoms lasting more than 3.5 h had an acute lesion. Overall, almost half out-of-hospital IHD deaths in this study were related to an acute ischaemic lesion. Differences in the detail of the pathological examination and examination of differing sub-groups of the out-of-hospital death population probably account for the differing results of previous studies.     

Effects of muscarinic agents on cultured human trabecular meshwork cells

Intracellular calcium measurements were performed in cultured human trabecular meshwork cells preloaded with the cell permeant dye fura 2-AM. Fluctuations in calcium levels were then monitored with microscope-based ratio fluorometry. Carbachol increased intracellular calcium in a dose-dependent manner; as did oxotremorine-M, aceclidine, and pilocarpine. Carbachol's effect was blocked by the non-selective muscarinic antagonist atropine, as well as by muscarinic receptor subtype-selective antagonists such as pirenzepine (M1-selective), p-fHHSiD (M3-selective), and 4-DAMP (M1, M3 subtypes). Rank order of potencies for the antagonists' effects was atropine = 4-DAMP > p-fHHSiD > pirenzepine, a profile suggesting that the M3 receptor subtype is essential in the carbachol effect. Phospholipase C activity was estimated via measurement of total production of inositol phosphates in cultured human trabecular meshwork cells pre-exposed to 3H-myoinositol. In these cells, carbachol also stimulated phosphoinositide production in a dose-dependent manner, and an antagonist profile similar to that seen for calcium response was obtained when carbachol was used as the effector. The data indicate that muscarinic effects on cultured human trabecular meshwork calcium mobilization and phospholipase C activity are mediated by an M3-like receptor subtype. Therefore, the muscarinic M3 receptor may play a role in trabecular meshwork cell function(s).     

Prolonged immunodepression after trauma and hemorrhagic shock

OBJECTIVE: To define and discuss the cytologic findings in six cases of nodular pseudoangiomatous stromal hyperplasia (PASH) of the breast. STUDY DESIGN: Retrospective evaluation of the medical records, cytologic and histologic material from six patients with palpable mammary PASH. Cases in which PASH was associated with other predominant mammary lesions were not included in the study. RESULTS: A total of six patients with histologically proven PASH underwent aspiration in nine occasions (three patients studied twice). Clinically, five patients were diagnosed as having fibroadenoma or another benign lesion, and in one patient carcinoma was suspected. In two patients, mammography disclosed rapid growth of the lesion. Seven aspirations, performed on five patients, were diagnosed as fibroadenoma (n = 5) or fibroadenomatous lesion (n = 2). An eighth aspiration was cystic and reported as fibrocystic disease. The last case was erroneously diagnosed as suspicious for carcinoma. Even after revision, the cytologic similarities of PASH with fibroadenoma were remarkable. Most smears were less cellular than those of conventional fibroadenomas. Epithelial clusters showed variable size, with a predominance of medium to small groups. Stromal elements were minimal or absent. Background cellularity was composed of round to oval naked nuclei and others with spindle shapes. Occasional epithelial clusters showed cellular dissociation and slight atypia. CONCLUSION: Due to the absence of specific cytologic features and similarities to fibroadenoma, a precise diagnosis of PASH cannot be made on cytologic material. However, the majority of cases can be diagnosed correctly as benign, allowing appropiate treatment.     

Private practitioners in the slums of Karachi: what quality of care do they offer?

Private health services have expanded in many developing countries over the last 10 yr. Qualified private practitioners provide basic health care for poorer groups in urban areas, although health care planners frequently criticize them for providing poor quality of care, charging high fees and failing to provide preventive health advice. In Karachi, a large city with more than 400 slums, private practitioners are important providers of care to the poor. This study assessed the nature and quality of care provided by 201 practitioners selected from four districts of the city. Vignettes of specific medical problems were used to assess their knowledge and their practice was measured by observing 658 doctor-patient contacts. The results show that knowledge was closer to accepted medical management than was their actual prescribing practice. On the other hand, their manners and interpersonal behaviour were good. Thus poor prescribing practice, which might equally stem from market influences as lack of knowledge, is the cause of low standards of care. In these circumstances, didactic in-service training to improve prescribing practice is unlikely to be successful.     

The use of antiadhesins--a new prospective trend in preventing and treating infectious diseases (a foundation for the technologies for creating drugs in the 21st century)

The state and prospects of research on creation of antiadhesins--new generation drugs for preventing and treatment of infectious diseases, are analyzed in the paper. The elaboration of such drugs is based on the profound knowledge about the nature of viral, bacterial, fungal and other infectious agents of diseases, molecular mechanisms of their interactions with the affected organs and tissues which are based on the processes of carbohydrate-protein recognizing. Rapid development of such fields of science as glycobiology and lectinology has created the preconditions for artificial synthesis of oligosaccharides which mimicked the receptors and can interact with adhesive structures of the disease agents more intensively than their natural analogs and block them. This makes the interaction of the latter with the affected organs impossible. The intensive work on elaboration of natural drugs: antiadhesins, is carried out in most countries. Adhesins are not harmful for people and cannot provoke the development of resistance to them in the disease agents. Till recently Ukraine belonged to the number of countries where the fields of science mentioned above were intensively developed but, in connection with the present stagnation of science and even the artificial hindering of its development, the country gradually losses the position of a leader. Hence, one can conclude that when 10-15 years later the market of pharmaceutical products will be filled with antiadhesins, our country will not be on the list of their producers, if the authorities will spend funds to buy foreign drugs as before instead of stimulating the development and production of the home ones.     

HAH1 is a copper-binding protein with distinct amino acid residues mediating copper homeostasis and antioxidant defense

HAH1 is a 68-amino acid protein originally identified as a human homologue of Atx1p, a multi-copy suppressor of oxidative injury in sod1 delta yeast. Molecular modeling of HAH1 predicts a protein structure of two alpha-helices overlaying a four-stranded antiparallel beta-sheet with a potential metal binding site involving two conserved cysteine residues. Consistent with this model, in vitro studies with recombinant HAH1 directly demonstrated binding of Cu(I), and site-directed mutagenesis identified these cysteine residues as copper ligands. Expression of wild type and mutant HAH1 in atx1 delta yeast revealed the essential role of these cysteine residues in copper trafficking to the secretory compartment in vivo, as expression of a Cys-12/Cys-15 double mutant abrogated copper incorporation into the multicopper oxidase Fet3p. In contrast, mutation of the highly conserved lysine residues in the carboxyl terminus of HAH1 had no effect on copper trafficking to the secretory pathway but eliminated the antioxidant function of HAH1 in sod1 delta yeast. Taken together, these data support the concept of a unique copper coordination environment in HAH1 that permits this protein to function as an intracellular copper chaperone mediating distinct biological processes in eucaryotic cells.     

Psychosocial factors in children with idiopathic musculoskeletal pain: a prospective, longitudinal study

To explore the role of psychosocial factors in the development and persistence of idiopathic musculoskeletal pain (IMP) in children, 23 children with IMP and 52 children with juvenile chronic arthritis (JCA) were compared at first admission to hospital and at 9 y follow-up. Semistructured interviews were performed at both assessments. At first admission, the prevalence of psychiatric diagnoses was high both in patients with IMP and patients with JCA, but patients with IMP more often had pain models, reported more school stress and more often lived with one biological parent. At follow-up, overall psychosocial functioning and level of chronic family difficulties were improved in both groups, but patients with IMP had a higher prevalence of psychiatric diagnoses and more chronic family difficulties and life events than patients with JCA. The persistence of IMP at follow-up was related to pain models, school stress, less parental education and more chronic family difficulties at first admission. Findings support the association between psychosocial factors and childhood IMP.     

In vitro expression of the diphtheria toxin A-chain gene under the control of human chorionic gonadotropin gene promoters as a means of directing toxicity to ovarian cancer cell lines

OBJECTIVE: Our goal was to determine whether toxicity of the diphtheria toxin A-chain gene regulated by the human chorionic gonadotropin promoter can be directed to malignant ovarian cell lines. STUDY DESIGN: Plasmids containing diphtheria toxin A-chain gene linked to the regulatory elements of the metalloergothioneine and human chorionic gonadotropin promoters were transfected into the cell lines. Expression of diphtheria toxin A-chain gene was determined by the inhibition of a cotransfected luciferase reporter gene. RESULTS: Cytotoxicity of the diphtheria toxin A-chain gene is shown in a dose-responsive manner. Transfection of a plasmid expressing the diphtheria toxin A-chain gene controlled by a constitutive promoter readily inhibits protein synthesis. Specific inhibition of luciferase protein synthesis occurs in ovarian cancer cells transfected with the diphtheria toxin A-chain gene under the control of the human chorionic gonadotropin promoters when compared with normal ovarian epithelial cells or fibroblasts. CONCLUSIONS: These data demonstrate the preferential expression of the diphtheria toxin A-chain gene, regulated by the human chorionic gonadotropin promoter, to ovarian cancer cell lines. This provides an avenue for targeting such cells for suicide, toxin, or cytokine genes.     

Hodgkin's disease in patients older than 70 years of age: a registry-based analysis

Between 1973 and 1993, 529 patients aged 15 years and over with Hodgkin's disease (HD) were entered into a lymphoma registry. Twenty-eight cases (1 only diagnosed at autopsy) of histologically proven HD in patients aged 70 years or older were identified. The distribution of sex, 'B' symptoms, histology and stage was not significantly different from that of younger patients, except for the fact that there were no patients aged 70 years or older with lymphocyte predominant HD. Nineteen patients were treated radically, 5 patients palliatively and 4 patients received no radiotherapy or chemotherapy. Three of the 14 patients treated with chemotherapy achieved the planned dose intensity. The cause-specific 5-year survival was 75% for patients aged 15-69 years and 28% for patients aged 70 years and over (logrank chi(2) = 43.7, P < 0.00001). The younger and older groups treated with radical intent had complete response rates of 97% and 74%, respectively (logrank chi(2) = 17.91, P < 0.00001) and relapse rates at 5 years of 27% and 56%, respectively (logrank chi(2) = 4.86, P = 0.0275). The main reason for the poorer prognosis of patients aged 70 years and over was the increasing difficulty of chemotherapy delivery associated with advancing age.