Is blood pressure variability related to activity of the sympathetic system?

1. In 70 patients with untreated essential hypertension, blood pressure variability was correlated to plasma catecholamines and to the response of blood pressure and peripheral flow to cold pressure and handgrip tests. 2. Supine blood pressure was recorded every 5 min, during 3 h. Variability was defined as the standard deviation of the mean of the readings in that period. 3. Blood pressure variability is positively and significantly correlated to the level of pressure and to age. 4. No significant correlation could be found with plasma catecholamines and sympathetic function tests. 5. It is concluded that blood pressure variability is related to the level of pressure but not to activity of the sympathetic nerves.


Uptake and efflux of noradrenaline from platelets; a model system for neurogenic mechanisms in essential hypertension.

1. The rate (k) of initial efflux of noradrenaline from platelets was determined in 63 individuals. A highly significant correlation was found between diastolic blood pressure and efflux rate. 2. When platelets are incubated in buffers with various Na+ concentrations in the range 110-170 mmol/l a higher Na+ concentration will give a faster efflux of noradrenaline for each concentration tested. 3. The value for k was determined in 41 normotensive first-degree relatives of hypertensive individuals and 21 persons with no family history of hypertension. Efflux rate of noradrenaline was significantly higher in the relatives and within this group was a subgroup with very high k values.


Constriction-distension relationships of resistance vessels in normo- and hyper-tension.

A haemodynamic analysis of resistance vessel behaviour in normo- and hyper-tension has been performed, relating vessel design, degree of contraction, wall distensibility and transmural pressure to each other in a way which allows a semiquantitative prediction of their respective influences in various situations.


Enhanced release of noradrenaline in the kidney of the young spontaneously hypertensive rat.

1. Vascular reactivity and noradrenaline overflow were studied in Tyrode solution-perfused kidneys from young (6 weeks) normotensive and spontaneously hypertensive (SH) rats. 2. The vasoconstrictor response to nerve stimulation was greater in the kidneys from young SH rats than in those from young control rats. 3. Nerve stimulation evoked a greater release of noradrenaline in the kidneys from young SH rats than in those from normotensive animals. 4. The results demonstrate that the renal sympathetic nerves release more noradrenaline than normal in the young SH rats, which could be an important factor in causing hypertension.


Modulation of sympathetic vascular tone by prostaglandins in corticosterone-induced hypertension in rats.

1. In corticosterone-induced hypertension in rats the activity of the peripheral sympathetic nervous system and its modulation by prostaglandins was studied. 2. Plasma concentrations of noradrenaline were reduced if compared with those in normotensive control rats. 3. The sensitivity of the isolated perfused hind-limb preparation to noradrenaline was enhanced before blood pressure rose and increased further with the development of hypertension. 4. Arachidonic acid, prostacyclin (prostaglandin I2), but not 6-keto-prostaglandin F1 alpha, reversed the supersensitivity to noradrenaline. 5. These results suggest that corticosterone induces a supersensitivity to noradrenaline by inhibiting the biosynthesis of prostaglandins. Changes in the sensitivity of the vascular smooth muscle may play a role in the development of glucocorticoid hypertension.


Effects of high salt intake and meclofenamate on arterial pressure and renal function in the spontaneously hypertensive rat.

1. The effects of prolonged high sodium intake (duration 3 months) and meclofenamate were studied in two groups of male spontaneously hypertensive (SH) rats. 2. Group 1 (eight rats) received 1% NaCl in water and served as controls, and group 2 received 1% NaCl in water plus meclofenamate (3.5-4.0 mg daily). 3. Group 2 rats developed higher arterial pressure, renal vascular resistance and left ventricular weight and greater renal histological changes, with lower effective renal plasma flow, renal blood flow and glomerular filtration rate, than group 1. No differences were observed between the two groups in heart rate, body weight, fluid intake, urine volume, UNaV, UKV and right ventricular weight. 4. The results suggest that the combination of high sodium intake and meclofenamate exerts a greater damaging effect on the arterial presssure and renal function of SH rats than salt alone.


The ratio between thickness of media and internal radius in cerebral, mesenteric and renal arterial vessels in spontaneously hypertensive rats.

1. Larger arterial vessels of 15-day-old spontaneously hypertensive (SH) rats showed significantly greater media/internal radius ratio than those of Wistar-Kyoto rats in the brain, kidney and mesentery. 2. Since larger cerebral and renal arteries of adult SH rats did not differ from controls the above results indicate the presence of a non-pressure-dependent vascular abnormality in young SH rats. 3. There were marked differences between the vascular beds of adult SH rats in the increase of media/radius ratio. Thus the changes were evident in all sizes of mesenteric arteries but only in the smallest cerebral arteries.


The effect of mental stress on prostaglandin F2 alpha in patients with essential hypertension and in healthy subjects.

1. The influence of mental stress, 30 min Kraepelin's arithmetic test under noise on the plasma concentration and urinary excretion of prostaglandin (PG) F2 alpha was studied in patients with essential hypertension and in healthy subjects. 2. Before the arithmetic test the plasma PGF2 alpha in hypertensive patients was significantly higher than in healthy subjects. The mental stress produced a significant increased in plasm PGF2 alpha in healthy subjects but not in patients with essential hypertension. 3. Three hour urine excretion of PGF2 alpha before stress was about two times lower in hypertensive patients than in healthy subjects. After exposure to stress a significant decrease in urinary excretion of PGF2 alpha was found in healthy subjects, but not in hypertensive patients. 4. The stress-induced increase in plasma PGF2 alpha of healthy subjects may reflect elevated brain PGF2 alpha synthesis. The individual differences in response to stress in hypertensive patients may result from specific impairments in synthesis and/or prostaglandin turnover.


Familial resemblance in casual blood pressure--a maternal effect?

1. The familial resemblance in causal blood pressure was studied in material derived from an ophthalmic population survey. The population consisted of 1078 individuals forming 373 families and 1410 pairs divided into groups with different relationships. In order to adjust for age, the difference between the logarithm of the systolic blood pressure and that of the value expected from a linear regression on age was used instead of the observed pressure. 2. There was no significant correlation between spouses. Children did not resemble their fathers at all. Sons and daughters were significantly correlated with their mothers. The resemblance between siblings was even greater and highly significant. The familial resemblance was not dependent on synchronized pressure readings or on a common household and was not related to the time available for cumulation of effects. 3. Together these findings formed a pattern strongly suggesting long-lasting maternal effects on the systolic blood pressure.


Autoantibodies in untreated and treated essential hypertension: relationship to histocompatability leucocyte antigen-B15 and vascular complications.

1. The presence of autoantibodies and the histocompatibility leucocyte antigen (HLA) antigen B15 was studied in relation to vascular complications (WHO III) in 148 patients with essential hypertension. 2. Nine of 36 patients with WHO stage III hypertension had autoantibodies, compared with seven out of 78 normotensive controls. 3. The frequency of B15 was 36.1% in hypertensive patients with stage III hypertension and 14.8% in controls. Nine of 18 patients with cerebral complications had B15 and four out of 18 with cardiac complications had B15. 4. The relative risk of vascular complications was 3.4 times higher in B15-positive patients with essential hypertension compared with B15-negative patients. 5. This study suggests that B15-positive patients with essential hypertension represent a subgroup with a higher risk of vascular complications. Long-term studies are needed to determine whether B15 might serve as predictor for vascular complications. 6. The study adds further support to suggestions of a genetic and possibly HLA-linked connection between essential hypertension, diabetes and autoimmunity.


Physical activity and the circadian rhythm of blood pressure.

1. Ambulatory blood pressure monitoring was carried out in 10 subjects for a period of 48 h, the first or second 24 h part of which was selected randomly to be a period of complete bed rest. 2. Heart rate was significantly lower throughout the period of bed rest except for the period 04.00-08.00 hours, when there was little difference. 3. The circadian variation of blood pressure was reduced during the day of bed rest but this was mainly due to higher night-time pressures.


Factors influencing blood pressure in chronic alcoholics.

1. Of 96 alcoholics admitted for detoxification, 48% were hypertensive (systolic blood pressure greater than 140 mmHg and/or diastolic pressure greater than 90 mmHg). 2. Elevation of both systolic and diastolic blood pressures was related to the severity of alcohol-withdrawal symptoms. 3. After these symptoms had abated only 9% of patients remained hypertensive. 4. Blood pressure remained normal if patients abstained from alcohol after discharge but rose in those who started drinking again. 5. Hypertension was not consistently related to the presence or severity of alcoholic liver disease. 6. Alcohol-related hypertension may be the result of the alcohol-withdrawal syndrome; increased noradrenergic activity is suggested as the likely mechanism.


Effect of isometric exercise on the renal excretion of sodium and potassium in mild hypertension.

1. Basal levels of pulse rate, blood pressure and rates of sodium and potassium excretion were observed in eight white male patients with mild hypertension and eight age-, sex- and colour-matched controls during an initial rest period of 90 min and then for 5 h after a 1 h period of isometric exercise involving all four limbs in rotation. The studies were repeated on another day with the subjects resting instead of exercising for 1 h. 2. Changes in systolic pressure after exercise were similar in the hypertensive and control groups, whereas the rise in diastolic pressure was higher and the rise in pulse rate lower after exercise in the hypertensive group compared with the control group. 3. The changes in the rate of salt excretion were significantly different in the two groups, the hypertensive group retaining proportionately more sodium and potassium over several hours.


Abnormal whole-body and cellular (erythrocytes) turnover of 22Na+ in normotensive relatives of probands with established essential hypertension.

1. Whole-body elimination rate of 22Na+ was decreased in normotensive or borderline first-degree relatives of hypertensive probands. 2. Whole-body potassium, exchangeable sodium and urine excretion of sodium, potassium and creatinine were similar in relatives and controls. 3. Erythrocyte net influx of 22Na+ was significantly increased in normotensive relatives. 4. Abnormal whole-body and cellular handling of sodium (22Na+) demonstrated in relatives indicates that this abnormality may have an important role in the development of essential hypertension in man.


Intralymphocytic sodium in hypertensive patients: a significant correlation.

1. Intralymphocytic sodium concentration was measured in 50 patients with essential stable hypertension, 44 patients with labile hypertension and 40 subjects with normal blood pressure. 2. Intralymphocytic sodium concentration in normotensive subjects was significantly lower than in the other two groups. 3. The concentration was significantly correlated with mean blood pressure in the group as a whole and in the groups with stable and with labile hypertension. No correlation was found in normal subjects.


Clinical and pathological relevance of erythrocyte cation fluxes measurement in hypertension.

1. The clinical applications of a simple laboratory test for the diagnosis of essential hypertension were further investigated on a large number of patients (124 individuals). 2. The reduced erythrocyte ratio of Na+/K+ net fluxes observed in essential hypertensives might be secondary to a functional defect in a Na+-K+ cotransport system. 3. A similar reduction in the ratio of Na+/K+ net fluxes was also observed in erythrocytes of some normotensive subjects born of hypertensive parents and of genetically hypertensive rats. This suggests that the erythrocyte membrane defect follows the genetic transmission of hypertension.


Circulatory changes during pregnancy in spontaneously and renal hypertensive rats.

1. Mean arterial pressure, heart rate, cardiac output (dye-dilution technique), stroke volume, total peripheral resistance (TPR), utero-placental blood supply (microsphere technique) and foetal weights were determined 2 days before expected birth in normotensive control (NC) rats, spontaneously hypertensive (SH) rats, rats with short-standing renal hypertension induced early in pregnancy and rats with established renal hypertension induced 4 weeks before pregnancy. Non-pregnant rats in comparable states served as controls. 2. In normal pregnancy cardiac output increased by 33% and blood pressure and TPR decreased by 17 and 38% respectively. The same principal changes were noted in SH rats and those with short-standing renal hypertension, but no changes were found in rats with established renal hypertension during pregnancy. 3. Myometrial and placental blood supply was lower in all hypertensive groups compared with NC rats, the reduction being 46 and 36% in SH rats and in rats with established renal hypertension as much as 74 and 68% respectively. 4. In SH rats foetal weights were reduced compared with NC rats, but despite the 68% reduction of placental blood flow in rats with established renal hypertension foetal weights were here unchanged.


A circulating humoral pressor agent in Dahl S rats with salt hypertension.

1. In Dahl S rats becoming hypertensive while on a diet of high NaCl content there appears to be a blood-borne humoral agent which produces vasoconstriction in a bioassay using the isolated hindquarters of rats. 2. This vasoconstrictor effect strongly suggests the presence of a humoral pressor agent or the lack of a vasodilator agent in the blood of hypertensive S rats. 3. The vasoconstrictor effect is not due to high renin concentrations. 4. This humoral vasoconstrictor action could partly account for the high vascular resistance in the hypertensive S rat.


Biochemical alterations of connective tissue metabolism in the arterial walls of stroke-prone spontaneously hypertensive rats.

1. The chemical characteristics of the vascular connective tissue components were determined in stroke-prone (SP), stroke-resistant (SR) spontaneously hypertensive (SH) rats and normotensive Wistar-Kyoto (WK) rats. 2. The ratio of hydroxylysine to hydroxylsine plus lysine in the vascular collagen was increased in 6-month-old SP-SH rats and SR-SH rats as compared with WK rats. 3. An age-related increase in uronic acid and hexose content of the aorta was noted in SP-SH, SR-SH and WK rats. However, the increase was more prominent in SH rats, especially SP-SH rats at the stages examined (11 weeks and over 8 months of age). 4. The ratio of galactosyl-hydroxylysine to glucosyl-galactosyl-hydroxylysine in the aortic collagen was decreased in 6-month-old SH rats, especially SP-SH rats as compared with WK rats. 5. A relative increase in beta and gamma components in aortic collagen was noted in 6-month-old SP-SH rats when compared with SR-SH rats. 6. The increased content of uronic acid and hexose and the structural changes of vascular collagen as demonstrated in SP-SH rats might be related to the fragility of the arterial wall and/or to the pathogenesis of stroke-proneness.


The effects of metoprolol on ambulatory blood pressure.

1. Continuous monitoring of arterial pressure was performed via an indwelling cannula over 24 h in 12 hypertensive patients before treatment and again 2-4 months after starting metoprolol (100 mg twice daily). 2. During treatment, heart rate and systolic and diastolic pressures were significantly reduced. 3. The circadian patterns of heart rate and blood pressure changes were similar before and during therapy.


Responsiveness to prazosin in renal failure.

1. The fall in blood pressure produced by a test dose of prazosin was greater in a group of patients with chronic renal failure than in a group with normal renal function. 2. This difference could not be attributed to increased reactivity, measured as the slope of the regression line relating mean blood pressure and plasma prazosin concentration, nor to retarded elimination of the drug. 3. The enhanced antihypertensive effect of prazosin in renal failure appears to reflect changes in the bioavailability or distribution of the drug, which result in higher drug concentrations for a given dose.


Assessment of the antihypertensive effect of atenolol with 24 h ambulatory monitoring of blood pressure.

1. Twenty-four hour intra-arterial blood pressure measurements and electrocardiograms were obtained from 12 subjects with untreated essential hypertension. 2. The patients kept records of their activity, paying particular attention to times of retiring to bed, and times of waking in the morning. 3. All subjects were treated with a single daily dose of atenolol (50 to 200 mg) for between 2 and 9 months, and then underwent a second 24 h blood pressure study. 4. Arterial blood pressure was lowered significantly throughout the 24 h period with a single daily dose of atenolol.


Protein synthesis and composition of cardiac and vascular tissue in spontaneously hypertensive rats and the effects of beta-adrenergic antagonist treatment.

1. Propranolol and metoprolol were given in the diet of spontaneously hypertensive (SH) rats during the development of hypertension. 2. At the early established phase of hypertension, protein synthesis and protein composition of the left ventricle, aorta, mesenteric artery and vena cava were measured. 3. The left ventricle, aorta and mesenteric artery from the SH rats were hypertrophied compared with control Wistar-Kyoto rats, and protein composition was not dramatically changed. The increased protein content could only in a few cases be assigned to an increased protein synthesis at this age. 4. Both beta-adrenergic antagonists prevented the hypertrophy of aorta and mesenteric artery but not in heart.


Effect of exercise in hypertension controlled with metoprolol or methyldopa.

1. The adequacy of the control of essential hypertension during exercise was studied in patients whose resting blood pressure had been controlled for 1 year with either metoprolol or methyldopa. 2. Systolic blood pressure increased with exercise in both groups, the increase being significantly less in the metoprolol group than in the methyldopa group.


Observations on some properties of a long-acting preparation of propranolol.

1. The effects of 160 mg of propranolol and 160 mg of a long-acting (LA) formulation of propranolol were studied in healthy subjects. 2. Both drugs reduced an exercise tachycardia but the peak was less and the 24 h effect greater after long-acting propranolol than after propranolol. 3. These differences were maintained on repeated dosing for 8 days. 4. In contrast to single doses of 400 mg of sotalol, 160 mg of oxprenolol and 160 mg of slow-release oxprenolol, the peak effect of long-acting propranolol was less and that at 24 h was greater.


Objective measurement of performance during acute stress in patients with essential hypertension: assessment of the effects of propranolol and metoprolol.

1. A standardized method of objectively measuring performance during simulated car driving is described. 2. The effect of a single dose of propranolol and metoprolol were compared with placebo in two groups of patients with untreated essential hypertension. 3. Performance was similar after beta-adrenoreceptor-blocking agents or placebo. 4. Blood pressure response to stress persisted after administration of the blocking agents.


The pathogenesis of propranolol-withdrawal syndrome in essential hypertension.

1. In hypertension, the beta-adrenoreceptor-blocker-withdrawal syndrome comprises tachycardia, sweating, tremor and general malaise, symptoms resembling thyrotoxicosis. 2. The effect of abrupt cessation of propranolol on serum concentrations of thyroxine (T4) and triiodothyronine (T3) was therefore investigated in five patients with uncomplicated essential hypertension, treated with propranolol in doses from 160 to 480 mg/day. 3. Four of the five patients developed one or more of the above-mentioned symptoms within 2-6 days after withdrawal of propranolol. 4. A mean relative increase in serum free T3 of 51% (range 22-74%) was found in these four patients on the day of onset of symptoms. 5. The increase in free T3 in the five patients correlated positively with total serum propranolol on the last day the drug was given (r = 0.91, 2P = 0.03). 6. As an increase in T3 was found only in patients suffering the withdrawal syndrome, and was maximal the day the symptoms appeared, despite a variation in time of onset from 2 to 6 days, it is suggested that the beta-adrenoreceptor-blocker-withdrawal syndrome, at least partially, is caused by rebound increased production of T3, induced by the well-known inhibition of the monodeiodination of T4 to T3 during beta-adrenoreceptor blockade. 7. This assumption may explain the clinical symptoms and the reported transient increased beta-adrenoreceptor sensitivity with unchanged serum concentrations of catecholamines.


Antihypertensive effects of clonidine in tetraplegic subjects devoid of central sympathetic control.

1. The effects of 300 microgram of oral clonidine on blood pressure, heart rate, plasma noradrenaline and adrenaline concentrations were studied in seven tetraplegic subjects with physiologically complete cervical spinal cord transections. 2. Clonidine did not significantly change resting blood pressure during the 8 h of the study. Resting heart rate fell. Resting plasma noradrenaline and adrenaline concentrations, when measured 2 h after clonidine, were not significantly lower. 3. Urinary bladder stimulation resulted in a marked rise in blood pressure accompanied by an elevation in plasma noradrenaline but not adrenaline. The hypertensive response to bladder stimulation was substantially reduced by clonidine, the maximum suppression occurring 2-4 h after administration of the drug. The plasma noradrenaline response to bladder stimulation, when measured 2 h after clonidine, was significantly lower than the response before clonidine. In two tetraplegic subjects with indwelling catheters the rise in intravesical pressure caused by bladder stimulation was unchanged by clonidine. 4. The pressor response to intravenous noradrenaline in two tetraplegic subjects and to intravenous phenylephrine in a further two tetraplegic subjects was unchanged by clonidine. 5. Clonidine may have additional antihypertensive effects which occur independently of actions in the brain. These effects may be exerted by an action either on sympathetic neurones in the spinal cord or on presynaptic alpha-adrenoreceptors in the periphery.


Action of clonidine on centrally evoked salivation in anaesthetized cats.

1. Clonidine (4 microgram/kg) given intracisternally to anaesthetized cats inhibited brain stem-evoked parasympathetic submaxillary or parotid salivation by 62% at 5 Hz and 44% at 15 Hz. 2. The inhibitory action of clonidine on salivation was equally prevented by pretreatment with either intracisternal yohimbine (175 microgram/kg) or phentolamine (250 microgram/kg), used as preferential pre- and post-synaptic alpha-adrenoreceptor-blocking drugs respectively. 3. the inhibition of centrally evoked salivation by clonidine is due to an action on alpha-adrenoreceptors but no clear evidence was obtained to indicate whether these were located pre- or post-synaptically. This is in contrast to the preferential presynaptic action of clonidine in reducing peripheral parasympathetic nerve-evoked salivation.


Effect of age on noradrenaline sensitivity of mesenteric resistance vessels in spontaneously hypertensive and Wistar-Kyoto rats.

1. We have compared the noradrenaline sensitivity of 150 micron arterial resistance vessels taken from a specific place in the mesenteric bed of spontaneously hypertensive (SH) rats and of control Wistar-Kyoto (WK) rats at three ages: 6 weeks, 12 weeks and 24 weeks. 2. The noradrenaline sensitivity of the vessels under normal conditions was the same at all ages in both SH and WK rats (ED50 about 3 mu mol/l). 3. After addition of cocaine (which inhibits the uptake of noradrenaline in the nerve terminals) all vessels became more sensitive to noradrenaline, but at all ages the increase in sensitivity was greater in the vessels of SH rats, suggesting that the smooth muscle cells in these vessels had a greater intrinsic noradrenaline sensitivity than the vessels of WK rats. 4. Since elevation of the blood pressure in the SH rats occurs mainly between the ages of 6 and 12 weeks, the results suggest that the greater intrinsic smooth muscle cell sensitivity of the SH rat vessels is a factor which is amongst the primary factors responsible for the development of hypertension in the SH rat.


Intraluminal dilatation of renal artery stenosis.

1. In 13 patients with hypertension and renal artery stenosis the stenosis was dilated by an intra-arterial balloon catheter under local anaesthesia. 2. In all but one instance arteriography after the dilatation showed considerable widening of the stenosed area. 3. Six patients had a temporary increase of serum creatinine that lasted only a few days. 4. In seven patients, who had a prolonged transit time at renography, this marker of renal blood flow improved after the dilatation. 5. The effect of the dilatation on the blood pressure in this group of patients, selected on arteriographic criteria only, was variable, but comparable with results of renovascular surgery. 6. Dilatation of renal artery stenosis by an intra-arterial balloon catheter is a promising treatment for patients with hypertension and renal artery stenosis. It is a rapid procedure needing only local anaesthesia. Complications in our experience so far are minor.


Renovascular hypertension: comparison of medical and surgical therapy.

1. Results of medical and surgical therapy were compared in 28 patients with hypertension and unilateral renovascular ischaemia. 2. Renal function remained normal in both groups throughout the study period. After 6 months of follow-up systolic and diastolic blood pressures were significantly lower in the surgically treated patients. After 12 months of follow-up there was no significant difference between the two groups in diastolic blood pressure and after 24 months of follow-up there was no significant difference between the two groups in either systolic or diastolic blood pressure. 3. Sixty per cent of surgically treated patients were cured 6 months after operation, but only 40% remained cured after 24 months of follow-up. 4. All patients cured at 6 months who subsequently required antihypertensive medication had arteriosclerotic renovascular disease.


Vascular reactivity in the pathogenesis of spontaneous hypertension.

1. Alterations in vascular reactivity were assessed in isolated artificially perfused kidneys from stroke-prone spontaneously hypertensive (spSH) rats at different stages of hypertension and after neonatal sympathectomy with 6-hydroxydopamine (6-OHDA). 2. During the pre-hypertensive stage, and the early and chronic stages of hypertension, the responses to noradrenaline, vasopressin, serotonin and angiotensin II were enhanced in renal vascular beds from spSH animals compared with age- and sex-matched Wistar-Kyoto (WK) rats; dose-response curves were shifted to the left, had steeper slopes, greater maximal responses and decreased thresholds. 3. With increasing severity and duration of hypertension, renal vascular resistance at maximal vasodilatation increased, the slopes of the dose-response curves were steeper and maximal responses were greater. 4. Neonatal sympathectomy with 6-OHDA greatly attenuated but did not prevent the eventual development of hypertension; furthermore, this treatment had no effect on the enhanced resistance or reactivity in renal vascular beds from spSH rats. 5. The appearance of enhanced resistance and reactivity in the early stages of hypertension and the inability to prevent these vascular changes by neonatal sympathectomy suggest that these alterations are a primary pathogenic mechanism in spSH rats.


An 8 month longitudinal study of changes in elastic and muscular arteries and veins of the rabbit with sustained hypertension after abdominal aorta constriction.

1. Long-term changes in the function and structure of arteries and veins in response to an elevation in arterial pressure have been studied in the rabbit after partial abdominal aorta constriction. 2. Transient changes occur in the vasculature in association with the rise in arterial pressure. 3. The dominant change seen after arterial pressure elevation has been maintained for 8 months is an increase in arterial wall mass, including an increase in vascular smooth muscle cell number, and in some arteries an increase in internal diameter. 4. It may be inferred from this limited study of elastic and muscular arteries that structural alteration represents the over-riding response of the vasculature to an elevation in intramural pressure.


Utilization of the poison center for the teaching of clinical toxicology to medical and pharmacy students, housestaff, and health care professionals.

The Massachusetts Poison Information Center has proved to be a good location for the teaching of clinical toxicology to physicians, pharmacists, and nurses at all periods of their training and professional development. With a continuous source of clinical problems, the availability of sophisticated information resources, and a wide array of clinical consultants, a center can become the setting for formal courses in toxicology, for fellowship training, and for continuing education. Review of clinical cases, discussion of management issues, literature reviews, bedside toxicology teaching, and formal weekly toxicology seminars are used to accomplish the educational goals of the program.


3,4-methylenedioxyamphetamine overdose.

MDA was indicated in the death of a 35-year-old male. Blood, tissue, and urine concentrations of MDA were measured by ultraviolet spectrophotometry after identification by gas chromatography/mass spectrometry. The concentrations found were within the range of previously reported fatal MDA levels.


Acute tetrachloroethylene fatality.

Tetrachloroethylene was indicated in the accidental death of a man clearing a line in a dry-cleaning establishment. Blood and tissue concentrations were measured by gas chromatography-mass fragmentography. Distribution of tetrachloroethylene was consistent with its lipophilic properties, being highest in the brain and lowest in the lung tissue.


Congenital defects in calves from maternal ingestion of Nicotiana glauca of high anabasine content.

Administration of Nicotiana glauca to four cows from the 50th to the 75th days of gestation induced congenital deformities in their calves. All four calves had arthrogryposis of forelimbs and one also had spinal curvature and rib cage deformity. The plant material contained 0.113% of the piperidine alkaloid anabasine as authenticated by gas chromatography and by infrared spectroscopy. Because of the presence of anabasine at a high concentration and because of its structural relationship to known teratogens, anabasine may be responsible teratogen.


Acetaminophen assay: the clinical consequences of a colorimetric vs a high-pressure liquid chromatography determination in the assessment of two potentially poisoned patients.

Following acetaminophen (APAP) overdosage, plasma half-life of APAP elimination appears to be a good prognostic indicator of potential hepatic toxicity. A half-life of greater than 4 hr is often associated with liver injury. In two patients who each allegedly ingested greater than 13 gm of APAP, serial assay procedures were performed using both a colorimetric (nitrous acid chromophore) method and HPLC for all samples. The data obtained were used to determine the plasma half life. A comparison of the results obtained from both methods revealed a significant variation. It appears that the colorimetric method, at lower plasma concentrations of APAP (less than 50 microgram/ml), overestimates the actual drug concentration, resulting in the calculation of a falsely prolonged plasma half-life. This may result in the unnecessary implementation of antidotal therapy. The HPLC method is considered to be more specific than the colorimetric analysis and to better reflect actual plasma APAP concentrations, especially at lower concentrations of APAP.


Digoxin acute intoxication: evaluation of the efficiency of charcoal hemoperfusion.

Since there is no widely used method of reducing the severity of massive digoxin intoxication, the capacity of hemoperfusion with coated, activated charcoal to remove digoxin was evaluated in a case of suicidal digoxin ingestion (25 mg). Seven hours after ingestion the digoxin plasma level was equal to 8.9 ng/ml. This was decreased to 4.5 ng/ml after 6 hr hemoperfusion. The amount of digoxin adsorbed by the column represents 4.8% of the absorbed dose. At a blood flow rate of 170 ml/min, the mean digoxin clearance by hemoperfusion was 44.5 +/- 26.9 ml/min. From these results we conclude that charcoal hemoperfusion in acute digoxin intoxication is of little value.


Temporal lobe epilepsy--a syndrome of sensory-limbic hyperconnection.

Psychological changes in patients with temporal lobe epilepsy are considered. Prior observations of correlated psychiatric diagnoses and objections to these are reviewed. Specific features of behavior and thought, derived from the literature and clinical experience, are suggested as a more effective way of characterizing the interictal syndrome; their accuracy is supported by quantitative results of an ongoing study, Enhanced affective association is proposed as a mechanism underlying these diverse features. This is interpreted in the light of theoretical and experimental accounts that anatomical connection between sensory and limbic structures are established within the temporal lobe. In contrast to sensory limbic disconnection which results in dissociation of stimuli from affective values, it is suggested that the epileptic process effects sensory limbic hyperconnection, leading to a suffusion of experience with emotional coloration.


Normal and abnormal forgetting in organic amnesia: effect of locus of lesion.

Speed of forgetting by the patient H.M. was examined in two experiments using picture recognition tests. In both experiments stimulus duration was manipulated to equalize initial performance by H.M. and others, and speed of forgetting was investigated over a period of one week. In the first experiment, where initial performance was high, H,M. appeared to forget faster than normal controls. In the second experiment, where initial performance was somewhat lower, H.M. was shown to forget faster than both controls and Korsakoff patients (who forget at a normal rate). These results suggest a functional difference between the amnesia with hippocampal lesions and the amnesia of Korsakoff's disease.


Lateralized psychological impairment associated with CT lesions in head injured patients.

Twenty-six adult patients with CT scans were given the Wechsler Adult Intelligence Scale (WAIS) during recovery from an acute head injury. Focal lesions were observed on the initial CT scans of 24 patients. These included 13 in the right hemisphere, 8 in the left hemisphere and 3 in both hemispheres. Diffuse cerebral swelling was observed in the remaining 2 patients. Both the standard WAIS examination (11 subtests) and a shorter version described by McFie (7 subtests) were used to assess psychological impairment associated with CT documented lesions. The McFie method involved a special scoring procedure that utilized reference subtests as an index of premorbid functioning. When mean algebraic differences between Verbal and Performance subtests were used, both methods differentiated left and right-sided lesions to a highly significant degree (p less than .001). Lateralized lesions yielded significant differences on 3 individual subtests (1 Verbal and 2 Performance) with the McFie method and on 6 individual subtests (all Verbal) with the standard WAIS procedure. Wechsler's Deterioration Quotient did not discriminate between groups. It was concluded that the traditional distinction between Verbal and Performance subtests on the WAIS was valid for CT documented lesions, and the shorter McFie version was as effective as the standard WAIS in lateralizing psychological dysfunction. Acknowledgements. This research was supported by Contract NS 5-2316 and Grant NS 08803 from the National Institutes of Health. We are grateful to Drs. Thomas A. Gennarelli and Howard I. Hurtig for patient referrals and neurological evaluations.


Visual agnosia: the dual deficit of perception and recognition.

This case of visual agnosia is of special interest because of its causation by trauma, of the unusually long follow-up (10 1/2 years), and the evidence for dual deficits of recognition and perception. Although most of the findings were characteristic of associative visual agnosia with preserved perceptual function, the poor copying, contrasted to better spontaneous drawing, suggested apperceptive agnosia as well. Prosopagnosia, alexia without agraphia, Balint's syndrome, visual static agnosia and simultanagnosia were also observed. The patient had persisting amnestic syndrome, but no dementia or aphasia. The responses to visual stimulation were perseverations, form confusions and confabulations. Visual evoked potentials were severely, bilaterally abnormal and computerized tomographic localization showed bilateral lesions also. The stages of recognition are analysed through this case of visual verbal disconnection and the importance of memory in perception is highlighted.


Capacity for holding sustained attention following commissurotomy.

To assess the relative capacities of the two cerebral hemispheres to sustain prolonged mental concentration, the performance of commissurotomized patients and normal controls was tested on monotonous sorting and signal detection tasks. The two series of tasks all required the maintenance of focused attention but differed in the amount of motor activity involved. Results showed that attentional capacity was different for active than for passive tasks in the patient group. During the active sorting tasks, commissurotomy patients were able to sustain continuous attention for periods of up to an hour while in the passive signal detection tasks, a decline in general levels of arousal was evident within ten to twenty minutes. The maintenance of generalized attention with minimal proprioceptive and external stimulation was thus found to be markedly weakened following commissurotomy. Neither hemisphere was consistently inferior to the other in sustaining mental concentration. The unique ability of commissurotomy patients to efficiently carry out mutually conflicting volitional decisions while sorting with the hands simultaneously points up the role of the intact commissures in unifying attentional components of cognitive processing.


Influence of sex and handedness on hemispheric functioning.

Forty normal adult volunteers comprising an equal number of right- and left-handed males  and females solved simple multiplication problems presented visually to one cerebral hemisphere while various competing stimuli were simultaneously presented to the other hemisphere. The contribution of sex of subject, handedness, hemisphere of presentation and the nature of the competing stimulus in relation to task performance was examined. Each of these variables was significantly associated with correct responses and errors, with few statistically significant interactions. Females and dextrals made more correct responses than males or sinistrals. Type of error depended upon which hemisphere received the problem, with the right hemisphere yielding more errors of commission and the left more errors of omission. Simultaneously presented identical or different arithmetic problems resulted in the most errors compared to the other competing stimuli.


Articulatory and phonological aspects of consonant substitutions in apraxia of speech.

The articulatory and distinctive features in 825 consonant substitutions produced by nine subjects with apraxia of speech were analyzed. The articulatory and distinctive features of the target consonants were retained beyond chance levels. The substitution patterns observed were very systematic in that more substitutions were made in the initial word position and stops, alveolars, and voiced consonants were used most often as substitutes for target consonants. The retention and usage of the features in the substitutions were closely related to the phonological markedness of the features, Most of the markedness changes were from marked-to-unmarked. The relationships between distinctive features and their markedness suggest that apraxia of speech is primarily a phonological disorder that is manifested in articulatoriy changes. It appears therefore that speakers with apraxia of speech systematically reduce linguistic complexity and simplify the production of consonants. In addition, the substitutions made in apraxia of speech are similar to those made by children.


On the relationship of hemispheric specialization and developmental dyslexia.

Hemispheric specialization for linguistic material was compared for normal and dyslexic subjects under dichotic listening (Experiment 1) and hemi-retinal presentation (Experiment 2) conditions. In both experiments, group data indicated that dyslexic subjects were, overall, less accurate in their performance than normals but that both groups showed similar right ear/visual field superiority. However, examination of individual subjects scores in both experiments indicated that the distribution of lateralization scores for dyslexic subjects was bimodal, whereas that for normal subjects was unimodal. These results suggest that the dyslexic 'population' is heterogeneous with regard to cerebral lateralization and that previous work treating it as homogeneous is most likely misleading. It appears important to both carefully examine individual subject data in such studies and to consider the consequences of there being different types of cerebral lateralization etiologies for what has been typically considered to be a homogeneous dyslexic population.


Further suggestions for cerebral CT-localization.

A method of obtaining lateral diagrams of brain lesions or structures from CT-scan pictures has been described and tested for accuracy with satisfactory results. Possible sources of error are discussed.


Recognition of random shapes in unilateral brain damaged patients: a reappraisal.

The performance of unilateral brain-damaged patients on recognition of random shapes was investigated by means of two different experiments. In experiment I interitem similarity and number of response-choice alternatives were varied to evaluate their possible influence on the subjects' performance. In experiment II stimulus exposure time was varied, In both experiments left brain-damaged patients with visual field defect obtained lower scores than control subjects. Right brain-damaged patients with visual field defect obtained scores significantly lower than controls only in the brief exposure condition.


Differential impairment of memory in Korsakoff's syndrome.

Groups of Korsakoff, alcoholic and non-alcoholic subjects were given picture-recognition memory (patterns and objects) and verbal learning tasks. Korsakoff subjects were impaired relative to the two control groups on verbal learning and object-picture memory; on pattern memory Korsakoff and alcoholic subjects were comparable but both were inferior to non-alcoholics. These findings gave some support to the idea (Butters and Cermak, 1976) that visuo-spatial functions (represented here by pattern memory) are impaired through chronic alcoholism whilst the development of Korsakoff's syndrome induces an additional impairment in semantic processing of information (represented here by verbal learning and object-picture memory).


Theory and practice in the measurement of laterality.

Using data from a divided visual field task, it is shown that correlations between laterality measures and overall accuracy are not a consequence of the level of accuracy constraining the achievable range of laterality, but depend on the design of current laterality measures and on the differential correlation of each hemisphere's scores with total accuracy. Comparing four laterality measures on 125 subjects shows that, although the laterality distributions differ in dispersion, the four measures are significantly intercorrelated and give nearly identical indications of average lateralisation. It is concluded that laterality measures may be of some limited use in comparing experimental results from different sources rather than in evaluating theories of cerebral asymmetry.


Xanthinol nicotinate in the management of leg ulcers associated with haemoglobinopathies.

The therapeutic role of xanthinol nicotinate, with its potent action on the peripheral circulation, in promoting healing of leg ulcers when added to conservative measures of ulcer treatment in adult beta-thalassaemia major and sickle cell thalassaemia, was evaluated in a double-blind crossover trial in 16 patients suffering from multiple leg ulcers. Conservative measures of ulcer treatment were leg raising in horizontal position for 14 hours, bed-rest, local antiseptic dressings and antibiotics. Xanthinol nicotinate or placebo was administered in a daily dose of 8 tablets (2400 mg) for 10 weeks. Comparison of the treatment results of conservative measures plus xanthinol nicotinate and those of conservative measures plus placebo revealed a statistically significant higher rate of complete ulcer healing during xanthinol nicotinate therapy (p less than 0.01). Apart from a low incidence of generalized itching and flushing at the start of the trial, xanthinol nicotinate was well tolerated in the prescribed dose.


Clobetasone butyrate compared with betamethasone valerate in the treatment of atopic and contact dermatitis.

In a double-blind, randomized study, 0.05% clobetasone butyrate cream was found to be as effective as 0.1% betamethasone valerate in the treatment of 48 patients with atopic or contact dermatitis, after 2 weeks as well as after 4 weeks of treatment. Side-effects with both drugs were rare and mild.


Pimozide as a replacement for maintenance therapy in chronic schizophrenia.

An open 12-week study was carried out to investigate the use of pimozide (12 mg once daily) as a replacement for antipsychotic maintenance therapy in 30 chronic schizophrenics who had responded poorly to previous neuroleptic monotherapy or polytherapy. After 8 weeks of treatment with pimozide, all 18 symptoms of the Brief Psychiatric Rating Scale were improved from previous treatment values. These differences were statistically significant for conceptual disorganization, depressive mood, hostility and motor retardation. Eleven patients who clearly responded well during the trial and consequently continued pimozide monotherapy were judged, 1 year later, to be functioning as well, or better, than with pre-trial drug treatment.


Amoxapine in depressive illness.

A double-blind trial was carried out in 29 patients recently admitted to hospital with depressive illness to compare the effectiveness and side-effect liability of treatment with amoxapine and imipramine. Both drugs were given in a dosage of 25 mg 3-times daily over a period of 4 weeks, and patients' progress was assessed using psychiatric and psychological rating scales for depression. Although amoxapine and imipramine proved equally effective, response to amoxapine was quicker and appeared to have the same effect after 1 week as did imipramine after 2 weeks. In addition, dryness of the mouth was complained of most frequently by patients taking imipramine.


Piracetam in chronic brain failure.

A double-blind, placebo-controlled trial was carried out on 109 aged patients with minimal or with moderate chronic brain failure to assess the effectiveness of piracetam (2.4 g per day) in preventing the progression of dementia. Patients received piracetam or placebo each for 6 weeks, the order of treatment being at random. The results of 19 psychological tests, repeated at 6-weekly intervals, showed that piracetam produced statistically significant improvement in only one of them and then only during the first 6 weeks of treatment. These findings, therefore, do not support the usefulness of piracetam in the treatment of such patients.


Inhibition of artifically-induced asthma by reproterol ('Bronchospasmin').

A study was carried out in 25 patients with asthma caused by exposure to occupational antigens to investigate the effectiveness of reproterol in protecting and terminating the bronchoconstrictor response to inhaled antigens. The results of lung function tests showed that the immediate reactions to the provocation test could be reversed by reproterol given either at the time of the reaction or shortly before challenge.


A fixed combination of metoprolol and hydrochlorothiazide for hypertension: a multi-centre study.

A multi-centre, open study was carried out in 140 hypertensive patients to investigate the hypotensive effect of 2 tablets of a fixed combination of 100 mg metoprolol plus 12.5 mg hydrochlorothiazide when taken either once-daily or twice-daily, each for 4 weeks. Blood pressure and pulse rate measurements were taken at rest, during and after exercise, on entry and at the end of each treatment period. The mean resting blood pressures were 168/108 mmHg, 151/98 mmHg and 150/96 mmHg at pre-trial, after the twice-daily dosage period and after the once-daily dosage period, respectively. The corresponding figures for exercise blood pressure were 191/115 mmHg, 176/105 mmHg, and 174/102 mmHg. Few side-effects were reported. It is concluded that once-daily dosing with this combination product is an effective and well-tolerated treatment for mild to moderate hypertension throughout the full 24-hour period.


Ultrastructural transitions associated with the development of the bladder cells of the trichomes of Atriplex.

Early in development, bladder cells are characterized by the absence of a vacuole or vacuoles, the presence of autophagic vesicles, and numerous, unaggregated ribosomes. With the formation and expansion of the central vacuole, the ribosomes become aggregated and elements of rough endoplasmic reticulum become apparent. This developmental transition is probably related to the production of proteins involved in ion accumulation in the vacuole. Throughout expansion, invaginations of the tonoplast and membraneous structures are associated with the vacuole. These may be indicative of a continued lytic function for this compartment. Also, dictyosomes are continuously present and dictyosome vesicles are associated with both the plasmalemma and tonoplast, which suggest that they contribute to both membrane systems during expansion of the cell and vacuole.


Unstable nuclear DNA in hypoglossal neurons of adult mice.

To demonstrate the existence of unstable or metabolic DNA in normal mammalian neurons and to study the effect of peripheral nerve injury on this metabolic DNA, adult mice were given repeated injections of high doses of 3H-thymidine (3H-T) on the day before injury to the left hypoglossal nerve. The animals were killed at intervals up to 33 days after the injections of 3H-T. Analyses of grain counts showed a low but significant elevation in the number of radioautographic grains per unit area of hypoglossal neuronal nuclei above background levels for up to 5 days after 3H-T injection. Digestion of the tissue with DNase lowered the nuclear grain counts to background levels, confirming that the DNA was indeed labelled. Although there was a loss of labelled material from the neuronal nuclei with time, there was no difference between injured and uninjured neurons at any of the intervals tested after injection of 3H-T.


Diagnostic evaluation of the pelvic and abdominal lymphatic system.

Evaluation of the pelvic and abdominal lymphatic systems is the subject of renewed interest by radiologists, radiotherapists, surgeons and medical oncologists. The primary reason for this interest has been the rapid advance of diagnostic imaging technology, particulary in ultrasonography and computerized tomography (CT). Another reason is the realization that with some neoplasms, particularly gynecologic neoplasms, there has been little progress in long-term survival in spite of aggressive local management. A possible explanation for this is "understaging" of neoplasms by previous radiologic procedures. Although lymphangiography has a proved and well-defined place in the diagnostic regimen, it remains tedious, time-consuming and invasive. Gray-scale ultrasound and CT have been widely used for several years and their role, limitations and relationship to lymphangiography have become established. The purpose of this monograph is to provide a short review of the lymphatic system and lymphangiogram, with particular attention to the recent radiologic literature. The role and limitations of the various diagnostic modalities are discussed and the lymphatic drainage and common pelvic neoplasms (as approached in the recent literature) are reviewed. No attempt has been made to define the lymphatic drainage of abdominal visceral organs.


90-day sub-chronic inhalation toxicity of a mercapto-functional silicone oil in rats.

A mercapto-functional poly(dimethylsiloxane) silicone oil vapor (0.15 and 0.45 mg/l) was generated by passage of air through the heated oil and rats were subjected to these vapors over a 90-day period. An extensive pathological, clinical and hematological workup failed to demonstrate any significant effects of this exposure. In addition, weight gains over the experimental period were comparable to controls.


The influence of hyperoxia on the acute toxicity of paraquat and diquat.

Hyperoxia has been shown to enhance the toxicity of the herbicide paraquat. Experiments were conducted to learn more about the effects of oxygen following acute poisoning with paraquat as well as the structurally related herbicide, diquat. Rats were injected intravenously with various doses of diquat or paraquat and placed into an atmosphere of either 100% oxygen or room air. The time required for 50% lethality (LT50) of both diquat and paraquat was greatly diminished by hyperoxia and was dependent upon the herbicide dosage. Rats treated with 40 or 80 mg/kg diquat and exposed to 100% oxygen had a shorter LT50 than those treated similarly with paraquat. A dose of 20 mg/kg was equitoxic in 100% oxygen while rats treated with 5 or 10 mg/kg diquat had a longer LT50 than rats treated with the same dose of paraquat. All animals exhibited severe respiratory distress terminally. The plasma concentrations and tissue distribution of either herbicide at 20 mg/kg were the same in oxygen and air exposed animals. When oxygen concentrations were varied between 100% and 60% rats treated with 20 mg/kg diquat or paraquat exhibited increasing but equal LT50's. In 40% oxygen diquat treated rats died more rapidly than paraquat treated rats. These data demonstrate a toxic interaction between hyperoxia and diquat as well as paraquat.


Absorption and distribution of C.I. Solvent Red 24 in rats; intra-tracheal administration of 14C labeled dye.

1-((2-methyl-4-[(2-methyl phenyl)azo] phenyl)azo)-2-naphthalenol (C.I. Solvent Red 24) was prepared having a 14C label on the methyl group of the central ring and was administered in suspension intra-tracheally to a male and a female rat. After 96 hours in metabolism cages, the animals were sacrificed and 14C counted in various organs and in urine/feces samples taken periodically up to 96 hours. Absorbed colorant was defined as that percentage of the total dose of radioactivity not present in the lung parenchyma after 96 hours relative to the total amount recovered and amounted to about 60%. Of this, about 98% was excreted in the urine and feces, the latter being the major excretory pathway. No free colorant was found in either feces or urine. Fractional percentages of the absorbed radioactivity were found in various tissues including the liver, and 4-amino-2',3(14C) dimethylazobenzene was identified in the urine after acid hydrolysis.


Toxicity of 1,4-dihexylpiperazine.

Attempts to synthesize the insect repellent, N,N'-dihexyl-N-carbomethoxyethylenediamine, led to an impurity which exhibited strong toxicity in the rabbit eye irritation test. Isolation of the impurity led to its identification at 1,4-dihexylpiperazine.


[Cholestasis diagnostics. Experiences with the percutaneous transhepatic cholangiography (PTC) using the Chiba needle (author's transl)].

We were successfull in doing a percutaneous transhepatic cholangiography (PTC) using the Chiba needle in 29 out of our 32 first cases including 19 out of 20 icteric and 10 out of 12 unicteric patients. Already when getting familiarized with the procedure the PTC seems to be superior as compared to the endoscopic retrograde cholangiography (ERC) in regard to results, risks, inconvenience to the patient, costs and technical skill. In this way the cholestasis diagnostics could be improved also in smaller hospitals missing the personnel and instrumental requirements to do the ERC procedure.


[Pancreatic neoplasms and risk of thrombosis].

Among all cancers of the pancreas, the liver and the bile ducts with icterus terminal lung embolism ist seldomer then among the same cancers without icterus. The risk of terminal lung embolism is among all tumours of the abdominal region higher than among all tumours of the thorax region, because the compression of the vena cava inferior increases the risk of thrombosis with lung embolism. The prevalence of adenocarcinoma among all cases with lung embolism is caused by the fact, that cancers of the abdomen are more frequent adenocarcinomas then all other tumours.


[Multilobular biliary liver cirrhosis as a purely hepatic form of mucoviscidosis].

Report about a patient with intraoperative and histological secured multilobular biliary cirrhosis of the liver and local formed purulent bile-duct and gall inflammation as an isolated hepatical form of the cystic fibrosis of the pancreas.--The character was complicated by the development of a portal vein high pressure and esophagus varicose vein haemorrhage, who at once needed a Shunt operation. Fromout the point of our view Sulprim is a good way to the therapie of purulent bile-duct inflammation in the case of cystic fibrosis of the pancreas.


[Diabetic angiopathy. Proteinuria as an initial symptom].

Follow up studies in 19 diabetic patients with manifestation in the youth. Proteinurie within few years; later on nephropathy: 7 cases with glomerulosclerosis, 8 with arteriolosclerosis, 3 with pyelonephritis and 1 with chronic glomerulonephritis. In all cases retinopathy, very often coronarsclerosis, seldom peripheral and cerebral sclerosis. 14 patients died, mostly in young age in consequence of nephropathy. Proteinurie is a malignant symptom of diabetic angiopathy; in contrast to the retinopathy.


[The influence of infusions and amino-acids on the determination of ammonia by means of indophenol-reaction (author's transl)].

It will analyse and discuss the influence of fructose-, glucose-, sorbitol- and argininmalat-infusions, of ascorbit acid and vitamin-B-complex as well as of 13 different amino-acids on the determination of ammonia by means of indophenol-reaction. With this the frequent of liver-cirrhosis i.v. administer substances trouble the determination of ammonia just as little (exception: arginin-malat), how amino-acids in physiological and little pathological range.


Time course of distribution to tissues of 125I-somatomedin A injected into the rat.

125I-somatomedin A (SMA) was injected iv into rats. Distribution studies in rats showed concentrations of radioactivity to be high in kidney and plasma, low in brain, and intermediate in other tissues. The concentration of total and trichloracetic acid (TCA) precipitable radioactivity in rat blood and tissues fell at rapid rate. Ninety per cent of the radioactivity was in the urine in 24 hr, and only 15% of urine radioactivity was TCA precipitable. The half-life of the radioactivity in TCA-precipitable fraction from blood and that from tissues were nearly identical (about 6 hr). In both liver and kidney, TCA-precipitable radioactivity was detected in membrane and/or organellar fraction and cytosol fraction. Sephadex G-200 chromatography at neutral PHY AT NEUTRAL PH of plasma after injection of 125I-SMA revealed 3 peaks of radioactivity in higher molecular weight region than purified SMA.


Studies on the nuclear binding of steroid hormone-receptor complex; characteristics of binding of nuclei from fetal rat liver to 3H-dexamethasone-liver cytoplasmic receptor complex.

Binding of 3H-dexamethasone (Dex)-rat liver cytoplasmic receptor complex to nuclei from fetal rat livers in vitro exhibited a high-affinity and saturable nature (Kd=1.5 X 10- M, maximal binding sites=470 fmole/mg DNA), and the binding was inhibited competitively by prior injection of Dex in vivo. While binding of 3H-Dex-receptor complex to nuclei from adult rat liver was in low affinity and unsaturable, and injection of Dex prior to the sacrifice of animals did not influence the nuclear binding to 3H-Dex-receptor complex in vitro. Differential salt-extraction with KCl solution of the nuclear bound 3H-Dex receptor complex revealed the presence of salt-extractable and residual forms of bound receptors. The amount of the fraction extracted with 0.3 M KCl reached its maximum at 10 min after the start of incubation, while the 1.0 M KCl-extractable and residual fractions reached their maximum plateaus after 30 min of the incubation. Scatchard analysis revealed that the binding of the receptor complex to the 0.3M and 1.0M KCl fractions was saturable, while the residual fraction did not show any tendency of saturation under the experimental conditions employed in the present study. The results obtained in this work were compared to those which have been reported by other investigators.


A case of multiple extra-adrenal pheochromocytomas.

A 22 year old man with two extra-adrenal pheochromocytomas located in the mediastinum and in the pelvis is presented. We believe this is the first report in Japan of extra-adrenal multiple pheochromocytomas in adult located in the two distant places.


Binding protein of somatomedin A in serum from men and rats.

After gel chromatography of human and rat serum at pH 7.4, all endogenous somatomedin A was recovered in the high molecular weight range. The largest peak was found in the gamma-globulin (II) region and the next largest peak found in the albumin region (III). The amounts of somatomedin A in the peak II region increased in serum from acromegalies and decreased in serum from growth hormone deficient patients. Four radioactive peaks were observed after gel chromatography of serum incubated with 125I-somatomedin A. Only the two peaks corresponding to peaks II and III out of the four peaks were displaced by adding 50 microgram of partially purified cold somatomedin A. The radioactivity of peak II decreased in sera from growth hormone deficient patients and increased after growth hormone administration. These observations support the hypothesis that the growth hormone regulates not only somatomedin A but also its carrier protein.


Central hypertensive actions of angiotensin I, II and III in conscious rats.

The effects of intracerebroventricular administrations of three natural angiotensins, angiotensin I (ANG I 3.8 X 10-11-9.4 X10-10 mol/kg body weight), II (9.6 X 10-12-2.4 X 10-10 mol/kg body weight) and III (2.7 X 10-10 2.5 X 10-9 mol/kg body weight) on systemic blood pressure were investigated in conscious rats. Angiotensin II (ANG II), ANG I and angiotensin III (ANG III), increased blood pressure in a dose-related manner. The order of potency of angiotensins was ANG II greater than ANG I greater than ANG III. The intraventricular administration of a converting enzyme inhibitor (SQ 14225, 6.9 X10-8 mol/kg) abolished the central effect of ANG I, while an angiotensin II analogue ([Sar1-Ala8]ANG II, 1.1 X 10-8 mol/kg) administered intraventricularly inhibited the central pressor effects of these three angiotensins. These results suggest that ANG II is a main mediator of the renin-angiotensin system in the central nervous system.


Differential effects of prostaglandin F2 alpha on oxytocinergic and non-oxytocinergic neurones in the paraventricular nucleus of the lactating rat.

The effects of the prostaglandin F2 alpha (PGF2 alpha) given into the third cerebral ventricle on the unit activity of neurosecretory neurones in the paraventricular nucleus (PVN) were studied in urethane-anesthetized rats. The firing activity of PVN neurones was recorded extracellularly and 50 neurones were antidromically identified as neurosecretory neurones. Thirty of them were classified oxytocinergic neurones because they gave a burst of action potential 12-15 sec before reflex milk ejection and the remaining twenty PVN neurones which showed no response prior to reflex milk ejections were regarded as non-oxytocinergic ones. Twenty-five (83%) of the30 oxytocinergic neurones increased in the firing rate following the intraventricular (IVT) injection of PGF2 alpha (500ng in 1 microliter of isotonic saline) and the responses lasted for about 20-30 min. The remaining 5 (17%) oxytocinergic neurones showed no response in the firing rate to IVT PGF2 alpha. Fifteen (75%) of the 20 nonoxytocinergic neurones decreased in the firing activity in response to IVT PGF2 alpha, and the remaining 5 (25%) of them showed no response. IVT injection of isotonic saline (1 microliter) did not affect the firing activity of both the oxytocinergic and nonoxytocinergic cells. The intramammary pressure was slightly increased by the IVT administration of PGF2 alpha. These findings indicate that IVT PGF2 alpha has a differential action on oxytocinergic and non-oxytocinergic neurones in rats.


Changes in circulating L-thyroxine and L-triiodothyronine of the masu salmon, Oncorhynchus masou accompaning the smoltification, measured by radioimmunoassay.

Serum levels of L-thyroxine (T4) and L-triiodothyronine (T3) of the masu salmon, Oncorhynchus masou, were measured by radioimmunoassay during the months from March to September. Serum levels of T4 and T3 varied from 0.06 to 1.44 microgram and from 0.06 to 0.35 microgram per 100 ml serum respectively, although T4 content could not be detected in some specimens. T4 levels showed a seasonal fluctuation in which a higher value was observed in April when parr-smolt transformation was proceeding. T4 level in spring, particularly in April and June, was significantly higher in smolt than in parr. T3 content showed a small variation during the observed months and did not increase at smoltification, although the content tended to decrease to a minimum level in September when T4 level showed also the lowest level.


Circannual variation of mortality rate following a single injection of hydrocortisone in newborn rats.

Under constant experimental conditions of room temperature and illumination, a highly significant seasonal difference was observed in the mortality rate of rats which received hydrocortisone on the first day of life. The rate was high in winter and low in summer. Inborn circannual variation of the susceptibility to exogenous corticosteroid was shown to exist in newborn rats.


Statistical evaluation of factors influencing prognosis of gastric cancer patients: Predication of prognosis on patient clusters.

We found ten clusters of gastric cancer patients in Imanaga's group under a cancer research project organized by the Ministry of Health and Welfare, and evaluated the prediction of prognosis of those patients in each cluster by using the censored regression of postsurgical survival time on a "prognosic" factor which has been extracted from nine explanatory variables observed mainly at the time of surgery. Consequently, the ten clusters were interpreted and confirmed to be useful for prediction of the patient prognosis by comparison of the failure rates among those clusters and between treated (administration of chemotherapy) group and control group.


Cancer epidemiology in Japan.

Patterns, change in occurrence, causative risk factors, and control strategy for cancer of each site in Japanese populations were studied by applying standard methods and techniques of biostatistics and epidemiology. As the results, cancers in Japan were classified into two groups: one on the decrease (stomach, cervix) and the other on the increase (lung, colon, pancreas, breast, prostate, urinary organs, leukemia). Analysis of vital statistics, national nutrition survey data, and on-going prospective study data revealed change in selective dietary intake and increase in cigarette consumption are the major factors responsible for such trend. Epidemiological characteristics and major risk factors of cancers of stomach, colon, pancreas, lung, breast, uterine cervix, ovary, endometrium, prostate, urinary bladder, and leukemia in Japan were summarized. A limited effect of mass screening was observed in the case of stomach cancer in addition to the strong effect of diet and nutrition. Cigarette smoking was confirmed to be the major causative factor of lung cancer in Japan. A close association of increased intake of animal fat and breast cancer risk in Japanese women was also observed.


Review of the methods of quantification.

In order to analyze qualitative observations, methods of quantification or optimal scaling have been proposed by Fisher, Guttman, and Hayashi. According to these methods, scores are assigned optimally in some objective and operational sense to the qualitative categories. The present paper mainly reviews Hayashi's four methods of quantification from the mathematical point of view. They are widely used, especially in Japan, in various fields such as social and marketing surveys, psychological research, medical research, etc., where information is obtained mainly in the form of qualitative categories. The first and second methods are applied to the case where an external criterion is present, and are used to predict the external criterion or to analyze the effects of factors. On the other hand, the third and fourth methods are applied to the case where no external criterion is present, and are used to construct a spatial configuration so as to grasp the mutual relationship of the data. After reviewing Hayashi's four methods, we discuss two topics which have been pointed out as the problems to be solved in applying the methods of quantification. One is quantification for ordered categories and the other is statistical consideration. With respect to these topics we review some recently developed methods including the studies due to the present author. Finally we mention briefly several computer programs available in Japan.


Discussion of Tanaka's paper.

The theory of quantification is a method of statistical data analysis of categorical data. In other words, this is a kind of data theory and is closely related to optimum scaling method. This method has been mainly developed by Guttman in Israel and Hayashi in Japan. The multidimensional scaling method, which has been recently developed, is considered to be a continuation of the theory of quantification. Tanaka discussed mathematically some of Hayashi's methods of quantification. The present paper, gives an overview of the methods developed by him and other closely related methods and gives the orientation of those methods introduced by Tanaka. Then, as an illustration of exploratory categorical data analysis, the experimental data of Grizzle are analyzed by using the second method of quantification. The data structure is shown heuristically as a spatial configuration of factors in two-dimensional Euclidean space.


Recent application of quantification II in Japanese medical research.

Hayashi's Quantification II is a method of multivariate discrimination analysis to manipulate attribute data as predictor variables. It is very useful in the medical research field for estimation, diagnosis, prognosis, evaluation of epidemiological factors, and other problems based on multiplicity of attribute data. In Japan, this method is so well known that most of the computer program packages include the Hayashi Quantification, but it seems to be yet unfamiliar with the method for researchers outside Japan. In view of this situation, we introduced 19 selected articles of recent applications of the Quantification II in Japanese medical research. In reviewing these papers, special mention is made to clarify how the researchers were satisfied with findings provided by the method. At the same time, some recommendations are made about terminology and program packages. Also a brief discussion of the background of the quantification methods is given with special reference to the Behaviormetric Society of Japan.


Designing case-control studies.

Identification of confounding factors, evaluation of their influence on cause-effect associations, and the introduction of appropriate ways to account for these factors are important considerations in designing case-control studies. This paper presents designs useful for these purposes, after first providing a statistical definition of a confounding factor. Differences in the ability to identify and evaluate confounding factors and estimate disease risk between designs employing stratification (matching) and designs randomly sampling cases and controls are noted. Linear logistic models for the analysis of data from such designs are described and are shown to liberalize design requirements and to increase relative risk estimation efficiency. The methods are applied to data from a multiple factor investigation of lung cancer patients and controls.


Statistical analyses of the relative risk.

Let P1 be the probability of a disease in one population and P2 be the probability of a disease in a second population. The ratio of these quantities, R = P1/P2, is termed the relative risk. We consider first the analyses of the relative risk from retrospective studies. The relation between the relative risk and the odds ratio (or cross-product ratio) is developed. The odds ratio can be considered a parameter of an exponential model possessing sufficient statistics. This permits the development of exact significance tests and confidence intervals in the conditional space. Unconditional tests and intervals are also considered briefly. The consequences of misclassification errors and ignoring matching or stratifying are also considered. The various methods are extended to combination of results over the strata. Examples of case-control studies testing the association between HL-A frequencies and cancer illustrate the techniques. The parallel analyses of prospective studies are given. If P1 and P2 are small with large samples sizes the appropriate model is a Poisson distribution. This yields a exponential model with sufficient statistics. Exact conditional tests and confidence intervals can then be developed. Here we consider the case where two populations are compared adjusting for sex differences as well as for the strata (or covariate) differences such as age. The methods are applied to two examples: (1) testing in the two sexes the ratio of relative risks of skin cancer in people living in different latitudes, and (2) testing over time the ratio of the relative risks of cancer in two cities, one of which fluoridated its drinking water and one which did not.


Some applications of categorical data analysis to epidemiological studies.

Several examples of categorized data from epidemiological studies are analyzed to illustrate that more informative analysis than tests of independence can be performed by fitting models. All of the analyses fit into a unified conceptual framework that can be performed by weighted least squares. The methods presented show how to calculate point estimate of parameters, asymptotic variances, and asymptotically valid chi 2 tests. The examples presented are analysis of relative risks estimated from several 2 x 2 tables, analysis of selected features of life tables, construction of synthetic life tables from cross-sectional studies, and analysis of dose-response curves.


Statistics and biomedical research.

Medical observations of leukemia or Hodgkin's disease clusters in time and space have led statisticians to invent techniques to evaluate the probability that these occurrences were due to chance. A difficult computation in human genetics was simplified by a matrix devised by a non-genetical statistician, and readily adapted to newly emerging computer-processing. The experiences exemplify the special opportunity in Japan to enhance research by merging mathematical talent with biomedical observations.


Role of mathematical concepts in cancer research.

The role of mathematics in cancer research is not confined to epidemiology (population level). The expected contribution of it in various levels is exemplified stepwise. At the individual level, prediction of life expectancy of a cancer case or psychological analysis of life-threatened patient; at the tissue level, stochastic estimation of future metastases; at the cellular level, model contruction for abnormal metabolic processes in malignant cell; at the molecular level, elucidation of carcinogenetic mechanism from a thermodynamic standpoint of view.


Estimation of safe doses: critical review of the hockey stick regression method.

The hockey stick regression method is a convenient method to estimate safe doses, which is a kind of regression method using segmented lines. The method seems intuitively to be useful, but needs the assumption of the existence of the positive threshold value. The validity of the assumption is considered to be difficult to be shown. The alternative methods which are not based on the assumption, are given under suitable dose-response curves by introducing a risk level. Here the method using the probit model is compared with the hockey stick regression method. Computational results suggest that the alternative method is preferable. Furthermore similar problems in the case that response is measured as a continuous value are also extended. Data exemplified are concerned with relations of SO2 to simple chronic bronchitis, relations of photochemical oxidants to eye discomfort and residual antibiotics in the lever of the chicks. These data was analyzed by the original authors under the assumption of the existence of the positive threshold values.


Statistical principle and methodology in the NISAN system.

The NISAN system is a new interactive statistical analysis program package constructed by an organization of Japanese statisticans. The package is widely available for both statistical situations, confirmatory analysis and exploratory analysis, and is planned to obtain statistical wisdom and to choose optimal process of statistical analysis for senior statisticians.


A method of record linkage.

In cancer epidemiology, prospective approaches are very important both in testing etiological hypotheses and in evaluating preventive procedures. Prospective studies, however, are very difficult and expensive, because a large number of people and a long period of observation are necessary for a satisfactory study. As a data source for follow-up studies, population-based cancer registry is very useful. The Osaka Cancer Registry has been in operation since December, 1962. Since 1968 the data processing, including the work of collation, has been semicomputerized. In order to identify cancer patients, we use the following six indices: date of birth, first Chinese character of a person's family name, address a: city, ward, town or village, address b: further details. i.e., street, avenue, section, hamlet etc., site, and sex. When we have data on the collation indices for the subjects to be followed up, we can conduct follow-up studies easily and accurately, using a semicomputerized collation method similar to that in the cancer registration system. Because the master file of the Osaka Cancer Registry contains the data of cancer cases reported and all cancer deaths among the residents of Osaka Prefecture, we can follow up the subjects living in Osaka Prefecture and obtain data about vitually all cancer incidences and deaths among them. In this follow-up method by means of record linkage to the cancer registry, some considerations should be taken into account for the following factors; coverage of cancer data in the Osaka Cancer Registry, reliability of the collation method, and address of the subjects to be followed up. As an example of a study with this method, we present the follow-up study of the screenees of a mass screening program for stomach cancer.


Hazardous substances, the environment and public health: a statistical overview.

The purpose of this paper is to provide an overview of the statistical problems that exist and procedures that are available when attempts are made to assess the possible harm which has been or might be caused by substances in the environment. These issues bear directly on important decisions of public policy such as those related to the establishment and enforcement of regulations.


Animal experimentation and its relevance to man.

The problem of quantitatively estimating human cancer risk based upon animal carcinogenesis studies is reviewed. Mathematical functions for dose-response relationships are discussed with particular emphasis on multistage models. These models are based upon a single cell somatic mutation theory for the carcinogenesis process. It is shown that the multistage model and others which incorporate background additively are well approximated in low dose region by a linear function. The relationship between time-to-tumor and the multistage model is indicated. This relationship is important when dealing with less than life time exposure such as with data from many occupational studies. Design of bioassay experiments and its impact on risk estimation is noted. Finally, the problem of species-to-species extrapolation is considered.


Statistical approaches to toxicological data.

Statistical techniques as applied to toxicological data are discussed. Issues concerning statistical hypothesis testing and combining studies are considered as well as design of experiments. The problems surrounding risk assessment are also mentioned.


Implications for human health.

To analyze the implications for human health, the toxicologist requires four sets of data: the results of toxicity and other studies in animals; quantitative data on actual or potential human exposure; whatever information is available on effects of exposure in man; and the statistical extrapolations from the dose-response relationships in animals to the (usually) much lower levels of human exposure. Professional expertise in toxicology is essential to assess the nature and severity of the toxic effects observed in animals, including such characteristics as potential for progression, irreversibility and production of incapacity. Given sufficient data, an estimate can be arrived at of the likelihood that such effects will be elicited in human populations of differing susceptibilities. The criteria by which the overall implications for human health can be judged comprise both the direct effects on man, as well as the indirect consequences stemming from environmental impacts.


The law of toxic substances.

The law of toxic substances dates back to Medieval England, but the present comprehensive federal regulatory scheme was developed over the past two decades. This article presents a brief overview of the federal law of air and water pollution, solid waste control, and the regulation of chemicals.


Toxic substances from coal energy: an overview.

Environmental concerns over increased coal consumption are fully justified by the past history of coal use. Although improved technology has provided some safeguards, increased utilization will require mining practices, emission control technologies, and waste disposal procedures that are not yet fully integrated into the routine use of the coal energy system. The Committee on Health and Evnironmental Effects of Increased Coal Utilization identified six critical environmental issues which are of concern: coal mine worker health and safety, reclamation of arid lands from surface mining, the health effects of coal combustion products, toxic trace elements in coal combustion wastes, acid fallout, and global effects of carbon dioxide in the atmosphere. This presentation addresses the first four of these issues.


Methodological problems arising from the choice of an independent variable in linear regression, with application to an air pollution epidemiological study.

In epidemiological studies using linear regression, it is often necessary for reasons of economy or unavailability of data to use as the independent variable not the variable ideally demanded by the hypothesis under study but some convenient practical approximation to it. We show that if the correlation coefficient between the "practical" and "ideal" variables can be obtained, then a range of uncertainty can be obtained within which the desired regression coefficient of dependent on "ideal" variable may lie. This range can be quite wide, even if the practical and ideal variables are fairly well correlated. These points are illustrated with data on observed regression coefficients from an air pollution epidemiological study, in which pollution measured at one station in a large metropolitan area (containing 40 aerometric stations) was used as the practical approximation to the city-wide average pollution. The uncertainties in the regression coefficients were found to exceed the regression coefficients themselves by large factors. The problem is one that may afflict application of linear regression in general, and suggests caution when selecting independent variables for regression analysis on the basis of convenience, rather than relevance to the hypotheses tested.


Population registries and other record resources for epidemiologic cancer research in the United States and Japan.

On the basis of the author's experience in epidemiologic studies on cancer in both the United States and Japan for the last 15 years, advantages and disadvantages of various record systems that can be utilized for epidemiologic cancer studies in these two countries are compared. Both countries are equally well provided with vital statistics and census records. Descriptive studies can be conducted without difficulties in both countries. For analytic studies, the Koseki record or family registration system in Japan provides an excellent tool in tracing subjects. However, Japanese record systems have problems as to management of hospital records, preservation of death certificates, etc. On the whole, restrospective cohort studies, particularly studies on patients, are more difficult in Japan than in the United States. There appear to be no material differences between these two countires as to case-control studies.


Role of mathematics in cancer research: attitudes and training of Japanese mathematicians.

An extensive survey of attitude towards scientific information of scientists in Japan was conducted in Japan. It was published in a technical report, and this survey is reviewed in this paper, with the hope that this will furnish findings important in working out the plan for promoting exploitation of mathematical talent in biomedical research. Findings are concordant with the impression of foreign visitors: (1) pure mathematicians tend to concentrate on mathematics only; (2) applied mathematics and statistics are heavily oriented toward industry; (3) mathematicians and pharmacologists are very different in their attitudes to scientific information. Based on the personal experience of the author, difficulties to be circumvented in utilizing aptitudes for mathematics and/or statistics in biomedical research are discussed.


Developing clues to environmental cancer: a stepwise approach with the use of cancer mortality data.

Clues to environmental determinants can often be derived from the patterns of mortality from cancer. This review focuses on the stepwise approach of using cancer mortality maps, supplemented by correlation studies linking mortality rates with demographic and industrial data at the county level, to generate hypotheses to cancer etiology which can then be pursued by analytical epidemiological studies. Advantages and limitations of this approach and its application in the study of lung cancer in the United States are described.


National cancer mortality and incidence in Japan.

In Japan cancer mortality statistics have been prepared by site, sex, and age group since 1937. The trends in age-adjusted death rates for selected sites from 1937 to 1975 in intervals of two or three years, and the age-adjusted death rates for some sites by prefecture in 1968-1972 were summarized. Concerning the accuracy of cancer mortality statistics, special consideration should be given to senility in Japan. In 1975 deaths due to senility accounted for 4.3% of all deaths for all ages. Though the regional cancer registration was being operated in 16 prefectures in Japan as of 1976, the incidence rates were published for only six prefectures. The percentage of cases registered from death certificate only in six registries in Japan was compared with that in the registries in the United States, indicating that the completeness of registration was yet unsatisfactory in Japan. As an index of accuracy of diagnosis, the percentage of cases confirmed histologically was also compared.


Study of cancer mortality by grid square method.

The grid square method as used in Japan has been standardized by the government, by use of the lines of the earth's latitude and longitude. The basic unit covers an area of approximately one square kilometer. An evaluation of this method is focused on the geographical distribution of cancer mortality in the city of Tokyo over a period of six years. The results indicated that for stomach and lung cancers, there was a very clear geographical distribution. High stomach cancer areas were similar for both males and females, and by comparing data with census data, it was evident that the blue-collar areas showed high mortality. High lung cancer areas were also similar for both males and females, but the distribution was opposite to that of stomach cancer, i.e., the higher mortality was observed in white-collar areas. Because the basic area unit of one square kilometer was too small for statistical analysis of geographical distribution, the moving average of nine grid squares as well as a "combined grid square method" based on population density was used. By this study a number of advantages of the grid square method as opposed to methods employing existing government boundaries became evident. The boundary lines do not move with political expediencies. X-Y coordinates can be easily defined for statistical analyses by computer, facilitating computer mapping, calculating the center of distribution, determination of the contour lines, and the estimation of values in places which lie between sampling stations.


Multivariate analysis of cancer mortalities for selected sites in 24 countries.

In order to analyze the pattern in the geographical distribution of cancer death in 24 countries of the world, correlation coefficients were calculated between pairs of mortality rates of different cancer sites, using the data for 13 sites in males and 14 sites in females over 18 years from 1950 to 1967. Then factor analysis by means of varimax method was performed on 13 x 13 correlation matrix for males, 14 x 14 correlation matrix for females and 27 x 27 correlation matrix for males and females combined. As a result of factor analysis, three factors are extracted, which are commonly recognized in both males and females. The first factor has high positive factor loadings on pancreas, prostate (for males), skin, and intestine cancers, and negative loadings on stomach and liver cancers. The second factor has high positive factor loading on rectum, intestine, and lung cancers, and the third factor on larynx, oral, and esophagus cancers. Factor analysis based on 27 x 27 correlation matrix revealed that the third factor of both sexes are heterogeneous with regards to the distributions of the factor score. In order that we may find some clues to develop an etiological hypothesis for each site of cancer, we obtained the correlation coefficient between the scores of the extracted factors and the variables on food and environmental agent, and performed stepwise regression methods as well. One of the most striking results we obtained was that excessive drinking of alcohol and the lack of appropriate intake of fruit are suspected as etiological promoters in the pathogenesis of oral, esophagus, and larynx cancers in males.


Normal and abnormal intestinal absorption by humans.

Adults eating a Western diet digest and absorb ingested food containing approximately 100 g fat, 350 g carbohydrate, and 75 g protein daily. Normal fat absorption requires adequate gastric, pancreatic, liver-biliary, mucosal, and lymphatic function. Carbohydrate and protein absorption is much less dependent on liver-biliary and lymphatic function. The intestine has a large reserve capacity for digestion and absorption of nutrients which is due to both excess function and to adaptive changes which increase function in one segment of the digestive-absorptive system when it is decreased or lost in another segment. The large reserve capacity explains why most of the prevalent intestinal diseases seldom cause clinically detectable changes in absorption. However, there are more than 30 less-common human diseases which cause malabsorption of one or more nutrients. Those that cause the malabsorption syndrome, i.e., steatorrhea and weight loss, can be conveniently categorized according to the major deficiency leading to the absorptive defect as follows: insufficient pancreatic enzyme activity, insufficient bile acid, disease of the small intestinal wall, multiple defects, mechanism unknown, and drug-induced malabsorption. A few diseases, most of which are congenital, cause malabsorption of only one or a few related nutrients such as lactose malabsorption in lactase deficiency. Most of the tests currently in use for detecting and diagnosing the cause of malabsorption are relatively insensitive and nonspecific. Chemical analysis of the fat in a three-day stool collection remains the single best test for diagnosing the malabsorption syndrome. However, a breath test using Triolein labeled with either the radioactive or stable isotope of carbon may be an important recent advance. Other breath tests are also currently being investigated for quantitating absorption or malabsorption of various substances including bile acids and various sugars. Studies of the function of the intestinal epithelial cells are usually best accomplished using tissue obtained by per oral biopsy. Biopsy specimens are used for many types of study including light and electron microscopic examination, chemical and enzymatic assays, tissue culture, and uptake of various radiolabeled compounds.


Environmental contaminants and intestinal function.

THE ENVIRONMENTAL CONTAMINANTS WHICH HAVE THEIR MAJOR EFFECTS ON THE SMALL INTESTINE MAY BE CLASSIFIED INTO FIVE MAJOR CATEGORIES: (1) bacterial, viral, and parasitic agents, (2) food and plant substances, (3) environmental and industrial products, (4) pharmaceutical agents, and (5) toxic agents whose metabolic effects are dependent on interreaction with intestinal bacterial flora, other physical agents (detergents), human intestinal enzyme deficiency states, and the nutritional state of the host.Bacterial, viral, and parasitic agents are the most important of all such agents, being responsible for significant mortality and morbidity in association with diarrheal diseases of adults and children. Several plant substances ingested as foods have unique effects on the small bowel as well as from contaminants such as fungi on poorly preserved grains and cereals. Environmental and industrial products, in spite of their widespread prevalence in industrial societies as contaminants, are less important unless unexpectedly intense exposure occurs to the intestinal tract. Pharmaceutical agents of several types interreact with the small bowel mucosa causing impairment of transport processes for fluid and electrolytes, amino acid, lipid and sugars as well as vitamins. These interreactions may be dependent on bacterial metabolic activity, association with detergents, mucosal enzyme deficiency state (disaccharidases), and the state of nutrition of the subject.