Haplotype and genotype effects of the F7 gene on circulating factor VII,coagulation activation markers and incident coronary heart disease in UK men

Background: Evidence for the associations of single nucleotide polymorphisms (SNPs) in the F7 gene and factor (F)VII levels and with risk of coronary heart disease (CHD) is inconsistent. We examined whether F7 tagging SNPs (tSNPs) and haplotypes were associated with FVII levels, coagulation activation markers (CAMs) and CHD risk in two cohorts of UK men. Methods: Genotypes for eight SNPs and baseline levels of FVIIc, FVIIag and CAMs (including FVIIa) were determined in 2773 healthy men from the Second Northwick Park Heart Study (NPHS‐II). A second cohort, Whitehall II study (WH‐II, n = 4055), was used for replication analysis of FVIIc levels and CHD risk. Results: In NPHS‐II the minor alleles of three SNPs (rs555212, rs762635 and rs510317; haplotype H2) were associated with higher levels of FVIIag, FVIIc and FVIIa, whereas the minor allele for two SNPs (I/D323 and rs6046; haplotype H5) was associated with lower levels. Adjusted for classic risk factors, H2 carriers had a CHD hazard ratio of 1.34 [95% confidence interval (CI): 1.12–1.59; independent of FVIIc], whereas H5 carriers had a CHD risk of 1.29 (95% CI: 1.01–1.56; not independent of FVIIc) and significantly lower CAMs. Effects of haplotypes on FVIIc levels were replicated in WH‐II, as was the association of H5 with higher CHD risk [pooled‐estimate odds ratio (OR) 1.16 (1.00–1.36), P = 0.05], but surprisingly, H2 exhibited a reduced risk for CHD. Conclusion: tSNPs in the F7 gene strongly influence FVII levels. The haplotype associated with low FVIIc level, with particularly reduced functional activity, was consistently associated with increased risk for CHD, whereas the haplotype associated with high FVIIc level was not.     

Persistent pain after groin hernia surgery: a qualitative analysis of pain and its consequences for quality of life

Background: Despite a high prevalence of persistent groin pain after hernia repair, the specific nature of the pain and its clinical manifestation are poorly known. The aim of this study was to determine the type of post-herniorrhaphy pain and its influence on daily life.
Methods: In order to assess long-term pain qualitatively and to explore how it affects quality of life, 100 individuals with persisting pain, identified in a cohort study of patients operated for groin hernia, were neurologically examined, along with 100 pain-free controls matched for age, gender and type of operation. The patients were asked to answer the SF-36 questionnaire, the hospital anxiety and depression scale, the Swedish Scales of Personality (SSP) and a standardised questionnaire for assessing everyday life coping. The patients were approached approximately 4.9 years after surgery.
Results: Twenty-two patients from the pain group had become pain free by the time of examination, whereas 76 patients still had pain, of whom 47 (68%) suffered from neuropathic pain and 11 from nociceptive pain. The remaining patients suffered from mixed pain, neuropathic and nociceptive, or were found to have another reason for pain. All dimensions of SF-36 were poorer for the pain group than the control group.
Conclusion: Persistent post-herniorrhaphy pain is mainly neuropathic and has a substantial impact on health-related quality of life.     

MALIGNANT HISTIOCYTOSIS Histiocytic Medullary Reticulosis

ABSTRACT. Three cases of malignant histiocytosis occurring in children aged 2 months, 10 months and 14 years, are described. In all children the diagnosis was based on anaemia, granulocytopenia or thrombocytopenia, splenomegaly and marked erythrophagocytosis by bone marrow and lymph node atypical histiocytes. Two children aged 10 months and 14 years, underwent splenectomy after which combined chemotherapy with cyclophosphamide, vincristine and prednisone (COP) was started. In the older child a complete remission was achieved. The younger child died soon after the onset of the treatment. The youngest child was treated with bleomycin, adriamycin, cyclophosphamide, vincristine and prednisone (BACOP). He died of pneumonia and sepsis two months after the start of the treatment.     

Platelet alpha-granule secretion and its modification by SC-57101A,a GPIIb/IIIa antagonist

Platelet-agonist interaction results in aggregatory and secretory responses. While the activation of glycoprotein (GP) IIb/IIIa plays an essential role in platelet aggregation, its role in granule secretion is not clear. The present study was performed to examine the effect of 3-[[[[1-[4-(aminoiminomethyl) phenyl]-2-oxo-3S-pyrrolidinyl]amino]carbonyl]amino]-propanoate monohydrochloride salt (SC-57101A), a GPIIb/IIIa antagonist, on platelet alpha-granule secretion responses to collagen, ADP, and thrombin receptor activating peptide (TRAP). Both SC-57101A and prostaglandin E(1) (PGE(1)) inhibited collagen-, ADP-, and TRAP-induced platelet aggregation in a concentration-dependent manner. SC-57101A inhibited the collagen- and ADP-induced release of platelet-derived growth factor (PDGF) and beta-thromboglobulin (beta-TG) from platelets, but not TRAP-induced secretion of these granule contents. On the other hand, PGE(1) inhibited the release of PDGF and beta-TG from platelets activated with all the agonists used. ADP and TRAP elicited P-selectin expression in the absence of platelet aggregation, while collagen produced no such reaction. SC-57101A only moderately inhibited P-selectin expression induced by ADP and had no inhibitory effect on that induced by TRAP. The inhibition of ADP-induced secretion of alpha-granule contents by SC-57101A was abolished when platelets were pretreated with aspirin. These results suggest that GPIIb/IIIa activation plays a minor role, if any, in alpha-granule secretion in human platelets.     

Density and functioning of human lymphocytic β-adrenergic receptors during prolonged physical exercise

In order to study the regulation of β-adrenergic receptor number and function in response to prolonged physical effort, lymphocytic β-adrenoceptor density (determined by (-)[¹²⁵I]iodocyanopindolol binding), lymphocytic basal and isoproterenol-stimulated cyclic AMP (cAMP) production and concentrations of plasma catecholamines were measured before and during 3 h running exercise in eight healthy volunteers. A significant (P < 0.01) increase of the lymphocytic β-adrenoceptor density from 45±4 to 81 ± 9 fmol mg^-1 protein (mean ± SEM) took place during the first hour of exercise. As the exercise was continued for up to 2.1–3 h, the receptor densities did not change significantly any more and remained elevated (72 ± 9 fmol mg^-1 protein) in comparison to the resting levels (P < 0.02). The isoproterenol-stimulated cAMP production of the lymphocytes increased during the first hour of running from 190 ± 36 to 269 ± 56 pmol mg^-1 protein (P < 0.01) and returned to the resting level at the end of the exercise (182 ± 38 pmol mg^-1 protein). The mean levels of plasma catecholamines increased ? sixfold during the first hour of exercise and remained elevated until the end of the running. This study demonstrates that the β-adrenergic receptor system is activated in lymphocytes during prolonged aerobic physical exercise. This activated state becomes, however, attenuated within 2–3 h of exercise as indicated by a diminishing ability of β-adrenoceptors to mediate catecholamine-induced cAMP production.     

Responses of intradental nerve fibres to stimulation of dentine and pulp

In the present work responses of intradental nerve fibres to stimuli that induce fluid flow in dentinal tubules as well as to direct mechanical irritation of the exposed pulp were studied on 9 young adult beagle dogs. Under pentobarbitone anesthesia 31 single functional intradental fibre units were dissected from the mandibular nerve. Stimuli were applied to the lower left canine tooth. Exposed dentine surface was irritated by scraping, air blasts and dry absorbent paper and the pulp mechanically with a von Frey hair. Ten fibre units responded to stimulation of dentine. Six of them were also tested with mechanical irritation of the pulp and were all responsive. Fifteen of twenty fibres responded to mechanical stimulation of the pulp. The mechanosensitive nerve fibres were all A-type according to conduction velocities (mean 25.6±8.1 (SD) m/s). It is concluded that there exist mechanosensitive intradental A-nerve fibres in the dog which are activated by stimuli that induce fluid flow in dentinal tubules. Nerve fibres of this type could be responsible for dentine sensitivity in man. Consequently, the present study gives support to the hydro-dynamic hypothesis of dentine sensitivity. Moreover, mechanosensitive nerve fibres could also be responsible for the pain symptoms of pulpal inflammation, because pulpitis may also create suitable circumstances for their activation.     

Effects of PYY and PP on endocrine pancreas

Novel intestinal polypeptide YY (PYY) and pancreatic polypeptide (PP) were infused in fed anaesthetized rats. The peptides (10 and 100 pmol/kg · min) were administered during 30 min, alone, together with glucose or together with arginine. Plasma concentrations of glucose, insulin and glucagon were measured. At the dose of 10 pmol/kg · min the peptides had no effect. PP at the dose of 100 pmol/kg · min slightly augmented basal, but had no effect on stimulated insulin and glucagon release. PYY at the dose of 100 pmol/kg · min was without effect on basal insulin and glucagon levels and on glucose-induced insulin release, but exerted an inhibitory effect on arginine-induced secretion of both insulin and glucagon. It is unlikely that PYY and PP can affect secretion of insulin and glucagon via blood circulation. The potential capability of high doses of PP to affect insulin and glucagon secretion suggests that this peptide may exert direct (paracrine) effects on the pancreatic A-and B-cells     

Alkaline Phosphatase in the Developing Bursa of Fabricius

The ontogeny of alkaline phosphatase in the bursa of Fabricius was studied by histochemical and biochemical methods. According to the quantitative determinations, the activity of alkaline phosphatase increased from the 11th to 17th day of incubation--that is, during the time of the lymphoid follicle formation in the developing bursa. The activity was localized in the mesenchymal tissue surrounding the lymphoid follicles. Testosterone given in ovo prevented the appearance of alkaline phosphatase in the bursal mesenchyme but had no effect on the activity of the embryonic liver. In contrast, in ovo treatment with cyclophosphamide had no effect on the alkaline phosphatase in the bursa. By using transplantation of embryonic bursal stem cells, it was further shown that, in contrast to cyclophosphamide, testosterone destroys the capacity of the bursa to serve as a differentiation site for the B-cell lineage. The results indicate that testosterone affects the stromal cells of the bursa, whereas cyclophosphamide destroys only the lymphoid population undergoing differentiation and leaves the bursal stroma intact.     

Determinants of atrial natriuretic factor levels in coronary heart disease: significance of central pressures, heart chamber volumes and left ventricular mass

Atrial natriuretic factor (ANF) was determined in pulmonary and systemic arterial plasma during diagnostic left and right heart catheterization in twenty-three patients. In twenty of these patients ANF was subsequently measured in systemic arterial plasma during nuclear magnetic resonance (NMR) imaging of the heart with computation of left heart chamber volumes and left ventricular mass. Left ventricular end-diastolic pressure was the strongest independent predictor of pulmonary arterial plasma ANF, whereas cardiac index best predicted aortic plasma ANF. Both pulmonary and aortic plasma ANF correlated with systolic and diastolic pulmonary arterial pressure, left ventricular end-diastolic pressure and cardiac index. Left atrial volume index and left ventricular mass index did not correlate with systemic arterial plasma ANF whereas a positive linear correlation between left ventricular end-diastolic volume index and ANF could be demonstrated (r = 0.61, P less than 0.01). Left ventricular end-diastolic volume index was the most important independent predictor of systemic arterial plasma ANF. Systemic arterial plasma ANF might be a simple marker of left ventricular dilatation in patients with heart disease.     

Medical education and the corresponding professional needs of young doctors: the Finnish Junior Physician 88 Study

Summary. The Universities of Kuopio and Tampere in collaboration with the Ministry of Social Affairs and Health and Finnish Medical Association carried out the 'Junior Physician 88' study in 1988, the purpose of which was to shed further light on the life situation and future plans of young doctors and their views concerning undergraduate and postgraduate medical education. The study concerned all the doctors registered during the years 1977–1986 in Finland (   n = 5208  ). After randomization, a postal questionnaire was sent to one half (   n = 2631  ) of these doctors. After the first reminder letter, 1745 questionnaires (66.3%) were returned. According to the views of the respondents undergraduate hospital teaching was adequate but the teaching of practice in health centres, school health care, team-work, health care of the elderly, home health care, rehabilitation, environmental health care and administration did not meet the professional needs of doctors. All doctors were satisfied with the hospital teaching in their undergraduate curriculum. However, only the doctors who graduated from the two modern universities in Kuopio and Tampere were satisfied with their undergraduate health centre teaching.