In last ten years or more, the term pharmacovigilance has been often used instead of post-marketing surveillance (PMS) or drug monitoring. However, this term, pharmacovigilance, is not just another term for PMS but should be understood as a new discipline, namely, science for the benefit-risk evaluation of medicinal products on humans with the final aim of individualization of medical therapy. It will be more clearly understood why nowadays this term pharmacovigilance has been used, when one considers the historical development of the safety issue of medicinal products. Pharmacovigilance as a new discipline should evaluate constantly safety and efficacy of medicinal products in daily practice considering all available data from non-clinical data, clinical data, pharmacoepidemiological data, post-marketing clinical data, risk-benefit evaluation and applied pharmacologies such as gender-specific pharmacology, pharmacogenetics, graviduspharmacology etc. in order to collect, evaluate and disseminate systematically necessary information and data on the safety and efficacy of medicinal products.
In addition, one should realize the presence of two different aspects of pharmacovigilance, namely obligatory duty of care and voluntary duty of care. The former aspect is defined by regulatory authorities and each pharmaceutical industry should carry out all necessary countermeasures and studies defined by regulatory authorities in order to keep the optimal standard on the efficacy, safety and effectiveness of the company's medicinal products. The latter aspect can also be considered as ethical duty of care for pharmaceutical industries, and refers to more detailed studies in particular patients such as children, pregnant women, aged patients, ethnically different patients, etc.

To detect essential hypertension and eventually to prevent cerebral apoplexy, we have measured blood pressureof the inhabitants in the Kamigo Section of Kisakata Town, Akita Prefecture (no. of households- 515 ; pop.- 2, 489) by making house-to-house calls once every three years since 1971.
The ratio of those having their blood pressure taken to the total population was 49% in 1971, 79% in 1974 and54% in 1977.
The average systolic pressure reading was 138.7mm/Hg for man and 136.5mm/Hg for woman, while the averagediastolic pressure was 84.9mm/Hg for man and 82.0mm/Hg for woman.
Twenty-six percent of the hypertensives were taking anti-hypertensive drugs regularly in 1971. The percentagewent up to 51% in 1974 and 56% in 1977.
Over the past six years, the patients with cerebrovascular attacks (CVA) dropped from 60 to 53 persons (changesin population adjusted). The deaths from cerebral apoplexy also decreased from 84 to 64.
The peak age of the persons who were seized with and died of cerebral apoplexy advanced from 65 to 75. Only4% of the CVA patients aged below 70 took anti-hypertensive drugs regularly. Seventy-nine percent did not takethe medicine at all.
All this suggests that taking anti-hypertensive drugs is effective to the prevention of cerebral apoplexy.

A 44-year-old man underwent implantation of a DDD pacemaker for third degree heart block at age 20. The cutaneous pocket for the pulse generator was situated in the left pectoral region. He visited our hospital because of skin ulcer over the pacemaker without any other complaint such as fever or pain. The patient received a new DDD pacemaker system in the right pectoral region and old pacing leads were translocated under the pectoral muscle. However, right pectoral skin ulcer appeared 1 month later. Patch tests revealed a positive reaction to silicon. Wrapping of the pacemaker with a polytetrafluoroethylene (PTFE) sheet proved to be effective.

We report 4 cases of delayed hypersensitivity reaction to Vancomycin (VCM) after cardiac surgery. Case 1: A patient developed sepsis and mediastinitis after aortic valve replacement (AVR) for aortic valve insufficiency. Case 2: A patient developed mediastinitis after coronary artery bypass grafting (CABG) for effort angina pectoris. Case 3: A patient developed pneumonia after AVR for aortic valve infective endocarditis. Case 4: A patient developed sepsis after CABG for acute myocardial infarction. All of them received VCM intravenously and their infections improved. However, sudden high fever, skin rush and eosinophilia occurred 12 or 13 days after the initiation of therapy. These symptoms resolved after halting VCM administration. We need to take examine eosinophils when considering further administration of VCM.

A 62-year-old man suddenly felt severe back pain. An enhanced computed tomography (CT) demonstrated an acute Stanford type B dissection and the true lumen was severely compressed by the false lumen. We started conservative therapy because there was no sign of organ ischemia. A 23 days from onset, he developed bilateral limb ischemia and renal failure because the compression of the true lumen increased. After bilateral axillo-femoral bypass the organ ischemia disappeared. Four months later, CT showed the dilatation of the true lumen and occlusion of the bilateral grafts. In spite of graft occlusion, there was no sign of organ ischemia.

Fatal intestinal necrosis developed following off-pump CABG and implantation of a bifurcated vascular prosthesis in a 70-year-old man with unstable angina pectoris and abdominal aortic aneurysm. A CT scan with three-dimensional reconstruction (3D-CT), showed no narrowing or obstruction of the SMA. The patient was scheduled to undergo an extensive resection of the intestine on the 23rd postoperative day. The pathological diagnosis was nonocclusive mesenteric ischemia (NOMI). He died of multiple organ failure on the 38th postoperative day. Early diagnosis of NOMI is essential to lower mortality and postoperative morbidity. Invasive angiography is the gold standard in diagnosis. 3D-CT, a non-invasive method, is an increasingly useful technique, which may allow identification of vascular anatomy and pathology with sufficient detail for diagnosis. Several other causes of acute abdomen, other than mesenteric ischemia, can be ruled out. Therefore, 3D-CT might be useful in screening for NOMI.

A 56-year-old man was admitted with fever of unknown origin and congestive heart failure. Blood cultures grew Streptococcus gordonii. An echocardiographic examination showed vegetation attached to the bicuspid aortic valve and severe aortic regurgitation. Despite the aggressive therapy, an emergency operation had to be performed because it was otherwise impossible to control heart failure. Vegetation was attached to the aortic valve leaflets. There was no noticeable lesion on the aortic annulus, but a myocardial abscess was noted in the left atrial wall. Aortic valve replacement was performed after the myocardial abscess was drained. It was assumed that the myocardial abscess was due to the septic state from Infective endocarditis because it was recognized at a distant zone from the active valvular infection.

A 64-year-old man who underwent aortic valve replacement with a 25mm Bjork-Shiley valve in 1993 began to have severe anemia and required repeated transfusions by November 2003. Doppler echocardiography showed only mild aortic regurgitation, but revealed turbulent flow around the mechanical valve. Autoimmune hemolytic anemia (AIHA) was diagnosed and he was treated with prednisolone (PSL) starting May 2004. Because of unremitting hemolysis requiring multiple transfusions and the occurrence of renal dysfunction, he underwent rereplacement of the aortic valve with a 25-mm Freestyle valve. His hemolysis and general condition immediately improved. This case suggests the possibility that mild regurgitant jet and turbulent jet stress can cause severe hemolysis when AIHA develops.

To demonstrate delayed neuro-toxicity of organophosphate, we administered 13 types of organophosphorous pesticide to hens. Initially, a screening test was performed with nine varieties of the chemical product. Later, four types were given to the fowls. Those hens dosed with S-Seven and Surecide developed ataxia and other neurophatic symptoms in the lower limbs.
After 50 days of observation, all the hens were killed and anatomized. Phathohistological examination revealed various changes in the hens that developed neuropathic symptoms: atrophy, diminution and disappearance of nerve cells in the anterior horn of the spinal cord ; edematous changes in the myelin; swelling of the neuroglia ; atrophy and vaculolar degeneration of liver cells; and necrobiosis of nepaticlobures.
It was found that these changes are closely related with the development of ataxia and doses of the chemical.
It was also found that the pathotistological changes occurred to a less extent in those hens which did not develop toxicoses.

We investigated the content of NO₃-N in the well water of the eastern, middle and nothern districts of Nagano Prefecture. The NO₃-N content seasonally changes and takes on the pattern of a high in summer and a low in winter.
Rain is considered to dilute the contaminated well water, but it lets NO₃-N flow from the soil into the.well water, when the rain is poured by a typhoon. As a result, a high content of NO₃-N is measured in the well water.
The water sample of 25 out of 85 wells in Matsukawa Town exceeded the tolerance level of NO₃-N (10 ppm, but 44.3 ppm in terms of NO₃^-).
By crop area, the amount of NO₃-N was highest in the fruitgrowing area, which was followed in order of the vegetable-growing area, the flower-growing and the rice planting area.
We consider that the contamination of well water is caused both by chemical fertilizers and the less absorbility of the soil.