Heart disease screening of school children using abbreviated electrocardiogram and phonocardiogram. By recording the electrocardiogram and phonocardiogram simultaneously using three abbreviated leads, 23,216 (6 and 7 years of age) elementary school children were screened for heart diseases. One hundred and one cases (0.44%) with congenital heart diseases, ten cases (0.04%) with acquired heart diseases and 100 cases (0.43%) with electrocardiographic abnormalities were discovered. From these observations, we conclude that this screening method applied on school children is useful in discovering the previously unrecognized heart diseases, especially atrial septal defect, primary myocardial disease and arrhythmia.


Studies on medically important flies in Thailand. V. On 32 species belonging to the subfamilies Muscinae and Stomoxyinae including the taxonomic keys (Diptera: Muscidae). Flies from different geographical parts of Thailand were collected to study their medical importance as well as making a zoogeographical study. After examination, 32 species of 10 genera, Orthellia, Mitroplatia, Morellia, Pyrellia, Rypellia, Haematobia, Haematobosca, Stygeromyia, Haematostoma and Stomoxys, belonging to Muscidae were identified and these are reported in this paper. Some of these are newly recorded ones from this country. This study is based on the specimens available in the authors' collection.


Action of parathyroid hormone, with special reference to its anabolic effect on different kinds of tissues in rats (I). The effect of parathyroid hormone (PTH) on the spongiosa of the proximal tibia and the alveolar bone in immature rats was studied using a time marker by the injection of lead acetate. 1) When intact rats were fed on a low calcium diet, the promotion of the apposition of the alveolar bone and the longitudinal formation as well as the resorption of the spongiosa were observed, but no change was detected in the serum calcium level. The resorption was more remarkable than the formation. 2) By parathyroidectomy (PTX) or thyroparathyroidectomy (TPTX) the effect described in 1) disappeared completely, but there subsequently occurred a fall of the serum calcium level and a marked inhibition of the formation and resorption. The decrease in the appositional formation was stronger than in the longitudinal formation. 3) When PTH was injected into the rats having undergone PTX or TPTX, all of the effects in 2) were reversed with the recovery of the apposition being at an extremely high rate. All the foregoing results indicate that PTH has an evident anabolic action in addition to the action of increasing the bone resorption and that the sensitivity to PTH is stronger in the periosteal bone than in the spongiosa.


Action of parathyroid hormone, with special reference to its anabolic effect on different kinds of tissues in rats (II). The effect of parathyroid hormone (PTH) on the formation of the incisor in the rats was investigated using a time marker by the injection of lead acetate. 1) When intact immature rats were fed on a low calcium diet, the rate of the longitudinal and appositional formation of the incisal dentin was increased. 2) Both formations were inhibited by parathyroidectomy (PTX) or thyro-parathyroidectomy (TPTX), the inhibition being stronger in the appositional than in the longitudinal formation. The mechanism generating the characteristic responses (thin dentin and irregularity of dentin formation) which appeared after the operations was made clear. 3) All of the effects in 2) were reversed by the injection of PTH. However, the restoration in the appositional formation was faster in appearance and higher in rate than in the longitudinal formation. The results of 1) to 3) indicate that PTH has an anabolic effect on the hard tissues. 4) The sensitivity of the tissues to PTH varies according to their embryological origin.


Action of parathyroid hormone, with special reference to its anabolic effect on different kinds of tissues in rats (III). The effect of parathyroid hormone (PTH) on mineralization and matrix formation was studied on the incisal dentin of immature rats by using a time marker as well as the histochemical method. 1. When the hypersecretion of PTH was caused by a low calcium diet, mineralization and matrix formation were both accelerated. 2. Both mineralization and matrix formation were clearly inhibited by parathyroidectomy or thyro-parathyroidectomy which brought about a widening of the predentin (dentinoid) as a result of the conspicuous inhibition of mineralized matrix formation. The maturation of the matrix seemed to be inhibited also. 3. Demineralization was lower and slower in the labial than in the lingual dentin. 4. The inhibitory effect disappeared totally by the PTH injection, but the restoration of matrix formation was faster compared with that of mineralization. 5. The increase or decrease in mineralization did not necessarily occur in parallel with that in matrix formation. 6. Acid mucopolysaccharide formation in the dentin depended clearly on the quantity of PTH.


A biomathematical study on implant design and stress distribution. Three types of implant were simulated by the two-dimensional finite element method using the mechanical properties of human mandible and implant material as input data. Type 1 was a blade implant, type 2 was blade implant with subperiosteal wings in buccolingual direction, and type 3 was subperiosteal implant with no blade. The effect of bucco-lingual subperiosteal wings in decreasing the stress concentration around the neck portion of the blade implant was investigated under three kinds of occlusal force. In conclusion, the greatest stress concentration was observed at the cortical bone around the neck portion of T-1 blade implant. It was effective in decreasing the stress concentration at this neck portion to change the implant design from T-1 to T-2 or T-3.


Effects of colchicine on osteoblast in rat: an ultrastructural study. The present study was an attempt to investigate the effects of colchicine on the ultrastructure of rat osteoblasts with special reference to the microtubular function in vivo. Rats were killed at intervals of 2, 4, 8, 12 and 24 hours after the colchicine injection (0.1 mg per 100 g of body weight, subcutaneously). At 2 and 4 hours after the injection, the secretory granules and small vesicles accumulated in the Golgi area of the osteoblasts. The dilated spherical cisterna of the rough endoplasmic reticulum and the large vacuoles appeared, being located in the periphery of the cell. Microtubules were rarely found in the cytoplasm. Small masses of microfilaments of 80 to 110 A in diameter were found also in the cytoplasm. According to the special staining for collagen, it was indicated that the contents of the secretory granules might be collagen-like materials. At 8 hours after the injection, the shape of the osteoblasts transformed to a round profile and the autophagic vacuoles increased in the cytoplasm. At 12 and 24 hours after the injection, the osteoblasts seemed to be destroyed by the breakdown of the plasma membrane and by the increase of the autophagic vacuoles. It is suggested that colchicine affects the secretory process of the bone matrix and the cytoskeletal system of the osteoblasts by interfering with the structure and the function of the microtubules and colchicine also interferes with the function of the plasma membrane followed by the destruction of the osteoblasts.


Facial clefts in Danish twins.

Facial clefts in Danish twins. A total of 74 Danish twin pairs with cleft lip +/- palate (CL(P)) and isolated cleft palate (CP) born in Denmark from 1941 to 1969 were studied. Eight pairs were of indeterminate zygosity status' and 26 pairs of unlike sex were dizygous (DZ). Of the remaining 42 like-sexed pairs, zygosity assignments were made from genotyping and physical resemblance data. Twelve pairs were given MZ status and thirty pairs DZ status. The following data was calculated: 1) in contrast to other reports, the incidence of either CL(P) or CP was not increased for either MZ or DZ twins; 2) using the pairwise method for concordance rate calculation, concordance rates for CL(P) twins were: MZ = 36 per cent; DZ = 1.5 per cent. For CP, MZ = 33 per cent; DZ = 0 per cent. The results support the concept that heredity is a prime factor in the etiology of clefting, but the low MZ concordance rates also suggest genetic heterogeneity in this cleft population.


Airway management in the repair of craniofacial defects. The operative repair of craniofacial defects presents the surgeon with critical problems regarding airway management. Thirty-seven per cent of our series of 100 children operated upon for a variety of cranofacial deformities had some difficulty in airway management. Those patients with mandibular dysostoses and those requiring midface advancement (Le Fort III) had the highest incidence of airway problems. Our suggested management of the airway is described with emphasis upon the importance of close cooperation between the plastic surgeon, otolaryngologist and anesthesiologist.


The dynamics of Passavant's ridge in subjects with and without velopharyngeal insufficiency--a multi-view videofluoroscopic study. Passavant's ridge was studied in 43 patients via multiview videofluoroscopy incorporating the simultaneous recording of speech. Ratings of the videotapes were made at full speed, in slowmotion, and by stop-framing. The following results were found: (1) Just as there are variable patterns of velopharyngeal closure, there were also variations in the way in which Passavant's ridge is positioned relative to the velum, and in the ridge's subsequent role in velopharyngeal narrowing or closure. (2) The ridge was the primary pharyngeal structure at the level of the velum that closed or locally narrowed the velopharyngeal portal in 37% of patients. (3) Passavant's ridge usually appeared as a structure encompassing both the lateral and posterior pharyngeal walls, and its presence was usually associated with active lateral pharyngeal wall motion. (4) Passavant's ridge was more prominent when the head was in the hyper-extended rather than the neutral position. (5) Passavant's ridge moved in a highly consistent manner, synchronous with velar movement.


A comparison of three technics of palatorrhaphy: in-hospital morbidity. We report the first randomized prospective comparison of different techniques of palatorrhaphy. The in-hospital morbidity of the Wardill-Kilner repair (Group I), von Langenbeck repair (Group II), and von Langenbeck repair with superiorly based pharyngeal flap (Group III) was evaluated in 47 patients. There were no deaths. Transfusion was needed only in Group I patients (p less than 0.01). Postoperative airway obstruction was significantly more common in Group III patients than in Group I (0 per cent or II (6 per cent) (p less than 0.05). Thus the in-hospital morbidity was least following the von Langenbeck repair.


A comprehensive study of pharyngeal flap surgery: tailor made flaps. Three methods of pharyngeal flap surgery were analyzed with multiview videofluoroscopy and nasopharyngoscopy at least six months post-operatively. It was found that, by varying the type of insertion of the flap into the palate, post-operative flap width could be "tailored" to the size of the gap in the velopharyngeal sphincter. The value of varying flap width according to gap size was assessed by analyzing speech results in 60 patients specifically assigned for narrow, moderate, or wide flaps. Results show a marked improvement in the effectiveness of pharyngeal flap surgery when operations are prescribed according to the degree of lateral pharyngeal wall motion seen pre-operatively.


A retrospective study of hearing impairment in three groups of cleft palate patients. Three groups of cleft palate patients were evaluated for hearing impairment and secretory otitis at age five to determine the effect of myringotomy and tube placement. Each group consisted of 23 patients (46 ears). Hearing levels and otoscopic evaluations were obtained retrospectively from medical records. Group I had had no myringotomies. Group II had myringotomies after the initial palate closure and only when deemed necessary. Group III had had myringotomies at the initial palate closure and subsequently as needed. Optimal timing for myringotomy in cleft palate patients to maximize hearing at school age could not be determined. The need for myringotomy must be determined by clinical judgement on an individual basis.


A longitudinal cephalometric study on unilateral cleft lip and palate subjects. The facial growth of nine male and 9 female subjects with surgically repaired unilateral cleft lips and palates was compared to that of 20 male and 15 female non-cleft individuals. Different cephalometric landmarks were identified on the cranial base and maxillary complex, and eleven different parameters were measured. Univariate longitudinal growth profile and mean vector analyses as well as multivariate and cross-sectional comparisons were performed between male, female, and combined normal and cleft groups. Linear data comparisons indicated statistically significant differences in the growth profile and mean vector analyses of several of the parameters describing the relationship (SNA and SNAns) and dimensions (Ans-Ptm and A-Ptm) of the maxillary complex. Incremental data comparisons on the same parameters (SNA, SNAns, Ans-Ptm and A-Ptm) indicated statistically significant differences in the mean vector longitudinal analysis and the univariate cross-sectional analysis. Most of these significant differences were concentrated in the older age comparisons (7 to 8, 8 to 9, and 9 to 10 years). Where significant differences existed, the normal sample increments were usually greater than the cleft sample increments.


The social effects of craniofacial deformity and its correction. A survey of our first 50 patients having craniofacial surgery was done. An attempt was made to determine the impact of facial deformity on social function for both the patient and his family and how function was altered by surgical correction. This was accomplished by a uniform series of questions. All patients were at least one year postoperative. The results emphasize that facial deformity played a dominant role in patients' lives prior to surgery and that surgical intervention led to improved social functioning in a number of areas. Meaningful data was collected on three groups of patients: 11 adults, 18 adolescents, and 17 children. Changes perceived were strikingly different in the three groups. Eight-seven percent of all patients would make the decision to have surgery again, and at least 50 percent had objective evidence of improved function. However, the survey also suggests that the extreme stress produced by the treatment may create family problems for which support is necessary.


Hearing sensitivity of adults with cleft lip and/or palate. This study is designed to investigate the hearing sensitivity of adults with repaired clefts of the lip and/or palate or congenital velopharyngeal inadequacy (VPI). Hearing sensitivity was analyzed with respect to pure tone air conduction thresholds and the extent of air bone gap. In addition to age, type of cleft and type of physical management of the palate were taken into account. The results of the study indicated that the thresholds of individuals with clefts of the palate or VPI exceeded normal limits. There were no significant differences in thresholds among the four types of palatal clefts or among the types of physical management of the palates.


Written language skills of children with cleft palate. The written language abilities of children with cleft palates aged eight to 13 were studied to compare performance with norms for the Picture Story Language Test. Although intelligence of this sample, as measured by the performance portion of the WISC, was skewed toward the superior and very superior ranges, the group ranked below the 50th percentile in total words used, words per sentence, and syntax quotients. Also, percentile scores on the PSLT declined as the age of the subjects increased. These results differ from the Ebert, McWilliams, and Woolf (1974) study where younger children with cleft palates (ages six to eight) were found to exhibit age-appropriate written language. The influence of factors affecting language development among the cleft palate population, such as methods and success of management, hearing, articulation, intelligence, sex, and psychosocial adjustment needs to be further investigated.


Hypertension and brain catecholamine distribution in the Hebrew University Sabra, H and N rats. 1. The concentration of catecholamines was measured in several brain areas of the Hewbrew University Sabra rat (SB rat), and in two substrains selected for their respective sensitivity (H) or immunity (N) to hypertension. 2. Hypertension was induced in SB rats by DOCA-salt, renal artery constriction and NaCl 1.7% drinking. The noradrenaline content was consistently elevated in the medulla oblongata of hypertension animals. In other brain areas the rise in noradrenaline varied in the different types of hypertension. 3. Administration of DOCA-salt to H and N rats, while causing marked hypertension in the former, had no effect on noradrenaline in either strain. 4. Untreated, normotensive N rats had in the medulla oblongata, significantly higher concentrations of noradrenaline than did H rats. 5. Differences in brain noradrenaline may explain the inherited susceptibility or resistance to hypertension in H and N rats.


Purification of human renal renin.

Purification of human renal renin. 1. Human renal renin has been purified 200 000-fold from cadaver kidney cortex by a method which employs affinity chromatography on aminohexyl peptstatin. 2. The product of this purification has a specific activity of 400 Goldblatt units/mg when compared with Haas human renin standard. 3. This product appears as a single band on sodium dodecyl sulphate gel and polyacrylamide-disc gel electrophoresis. Renin enzymatic activity was recovered after elution from a polyacrylamide-disc gel run at pH 7.8. 4. Yield with this method was 1%.


Is high-molecular-weight-renin binding of renin to the protease inhibitors and lipoproteins? 1. Two high-molecular-weight forms of renin (molecular weights 800 000 and 70 000) are present in mouse plasma. 2. The 800 000 form could be activated and converted into the fully active 40 000 form, by acid or limited proteolysis. The 70 000 form was activated without change in molecular weight. 3. In addition to its enzymic activity, renin was measured by a direct radioimmunoassay, which revealed that the current acid treatment of plasma did not activate all the renin present. 4. Renin is stored as fully active 40 000 renin, with a specific enzymic reactivity of 0.4 times 10(-3) GU ng(-1), in the submaxillary gland of mice. 5. Pure 125I-labelled 40 000 submaxillary renin did not bind to plasma proteins. However, by changing the tertiary structure of renin, it was bound to some of the plasma protease inhibitors; alpha2-macroglobulin, inter-alpha-trypsin inhibitor and alpha2-antithrombin. It was also bound to alpha1- and beta1-lipoprotein, albumin and an unidentified plasma protein. No binding was seen to more than 50 other studied plasma proteins.


Cryoactivation of plasma renin.

Cryoactivation of plasma renin. 1. The mechanism of increased renin activity after human plasma had been kept at -5 degrees C for 4 days (cryoactivation) was investigated. 2. The increase in renin activity of human plasma by cryoactivation was closely correlated to the increase obtained by incubation with trypsin (r = 0.88, P less than 0.001, n = 10). 3. An inhibitor of thiol enzyme, N-ethylmaleimide did not inhibit cryoactivation. 4. Soyabean trypsin inhibitor and di-isopropylflurophosphate (DFP) inhibited cryoactivation, suggesting that the cryoactivation may be due to the action of a trypsin-like serine enzyme. 5. In an experiment in the rat haemorrhagic shock caused parallel and cryoactivated plasma, the renin activity being about two times higher in the latter. No significant differences were found in the concentrations of renin and renin substrate between the non-cryoactivated and cryoactivated plasma samples. 6. The results may indicate that a destruction of an inhibitor of the renin-renin substrate reaction is responsible for the increase of renin activity after exposure of rat plasma to low temperature. A trypsin-like enzyme in plasma might have destroyed the inhibitor during this procedure.


Different secretion patterns of active and inactive renin in man. 1. In plasma samples from normal subjects and patients with untreated essential hypertension, the concentration of inactive renin (as measured after acidification) was on average 4-5 times higher than the concentration of active renin (as measured without acidification).2. Plasma angiotensin II concentration was correlated to active renin but not to inactive renin. 3. A hyperacute stimulation induced by infusion of saralasin resulted in a marked rise of active renin, whereas inactive renin remained unchanged. 4. An acute stimulation induced by frusemide and ambulation led to a considerable rise in active renin and a slight, but significant, rise of inactive renin. 5. Stimulation with oral thiazide over 5 days induced a seven-fold rise of active renin, with a doubling of inactive renin. Thiazide treatment for 3 months led to a four-fold rise of active renin and a three-fold rise of inactive renin. 6. There was no difference between the concentrations of inactive renin in systemic plasma, ipsilateral and contralateral renal venous plasma in 12 patients with renovascular hypertension, neither before nor after infusion of saralasin with the associated fall in blood pressure. 7. We conclude that the time constants pertinent to secretion or release of active and inactive renin in man are of different orders of magnitude.


Renin secretion by the human kidney.

Renin secretion by the human kidney. 1. 20 subjects with uncomplicated essential hypertension were studied, 10 of whom were on propranolol treatment. Several blood samples for determination of total and active renin were drawn simultaneously from the renal artery and vein after angiographic studies. 2. In all patients renal blood flow was measured by Hippuran-clearance at the time of blood sampling. Intrarenal blood flow was assessed by xenon-washout. 3. The results indicate that under basal conditions renin is secreted mainly in the active form, although secretion of inactive renin does occur. During propranolol treatment there is a tendency for secretion of active renin to be reduced.


Acid-activated renin responses to hydrochlorothiazide, propranol and indomethacin. 1. Six essential hypertensive patients (five with low renin) were treated in successive weeks with placebo; hydrochlorothiazide 100 mg (382 micromol)/day; hydrochlorothiazide and 50 mmol of sodium/day diet; hydrochlorothiazide, 50 mmol of sodium diet and propranolol 160 mg (544 micromol)/day; and hydrochlorothiazide, 50 mmol of sodium and indomethacin 100 mg (287 micromol)/day. 2. Although blood pressure remained unchanged and serum potassium fell on diuretic with or without low salt, there was a marked increase of active renin and a lesser increase of inactive renin, resulting in an increased proportion of active to total renin. 3. Propranolol decreased both active and inactive renin, but not significantly. 4. Indomethacin produced a marked suppression of active renin, a smaller reduction in inactive renin, and a reduction of the ratio of active to total renin almost to placebo values. 5. Blood pressure rose to control values on indomethacin despite the fall in renin whereas it fell with propranolol with little change in renin. 6. Serum aldosterone rose with stimulation but remained elevated despite effective renin suppression with indomethacin and continuing reduced serum potassium concentration.


Different responses of active and inactive plasma renin to various stimuli. 1. The response of active and inactive plasma renin to orthostasis and frusemide and to inhibition of prostaglandin synthesis by indomethacin was tested in normal human volunteers. 2. Active renin increased by orthostasis and frusemide and decreased by indomethacin. The latter also blunted the increase of active renin after stimuli. 3. Inactive renin was slightly increased by orthostasis, but was not significantly influenced by acute administration of frusemide or inhibition of prostaglandin synthesis by indomethacin. 4. The results show differences in the response of active and inactive renin to stimuli and suppression. Opposite changes of active and inactive renin were not observed in the experimental conditions studied.


A renal carcinoma secreting inactive renin. 1. A patient presented with mild hypertension, a raised plasma total renin concentration but a normal plasma angiotensin II concentration. The discrepancy was due to a high concentration of inactive renin in the plasma. 2. A renal carcinoma was detected and removed. The tumour contained a higher proportion of inactive renin than was found in uninvolved areas of the kidney. After unilateral nephrectomy, the plasma concentration of inactive renin fell to normal. 3. Six months later, plasma inactive renin concentration again increased and a metastasis was detected in a rib. Excision of the rib together with radiotherapy resulted in a fall in plasma inactive renin to normal. 4. The inactive renin in plasma and tumour extracts was activated to the same extent by acid treatment and by trypsin.


Soluble pepstatins: a new approach to blockade in vivo of the renin-angiotensin system. 1. Synthesis of several pepstatin A derivatives was performed with the aim of increasing water solubility without altering the capacity to inhibit the renin-angiotensinogen reaction. 2. Pepstatinyl-arginine-O-methyl ester was studied in vitro and in vivo and compared with pepstatin A and with the arginine salt of pepstatin A. 3. This compound inhibited in vitro the reaction between purified hog renin and the synthetic renin N-acetyl-tetradecapeptide or the natural rat renin substrate. The inhibitory constant was of the same order of magnitude as that of pepstatin A. 4. In renal hypertensive rats, the bolus injection of pepstatinyl-arginine-O-methyl-ester or of the arginine salt of pepstatin decreased blood pressure to the same extent as a bolus injection of Sar1, Ala8-angiotensin II.


Steroidogenic and pressor activity of angiotensin analogues in the rat. 1. A classical 6 point assay in vitro for measuring aldosterone stimulating activity has been developed. 2. The steroidogenic potency of Ile5-angiotensin II was 62% of that given by Val5-angiotensin II. Ile5-angiotensin III (Des-Asp1-Ile5-angiotensin II) was likewise 50% as active as Val5-angiotensin III (Des-Asp1-Val5-angiotensin II). Similar results were obtained in the pressor and myotropic assays. 3. Ile5-angiotensin III and Val5-angiotensin III had only 7% and 16% respectively of the steroidogenic activity of Val5-angiotensin II. 4. Sar1-Ile5-angiotensin II was 2.3 times as potent as Val5-angiotensin II in aldosterone-stimulating activity. The corresponding activities of Me2-Gly1-angiotensin II, Pro1-angiotensin II and Pro31-angiotensin II were 71%, 15% and 3% of Val5-angiotensin II respectively.


Differences in reflex control of arterial pressure and renin release during head-up tilting in the cat. 1. Anaesthetized cats were subjected to two 10 min trials of head-up tilting spaced 30 min. Arterial pressure, heart rate, blood flow to an innervated kidney and to the contralateral denervated one, and renin release from both kidneys were measured. 2. The same haemodynamic changes and comparable increases in renin release from innervated kidneys occurred during both episodes of tilting when cats were subjected to sham cervical vagotomy between the two tilting trials. 3. Bilateral cervical vagotomy, performed after the first episode of head-up tilting, did not affect the haemodynamic response to the change in posture, but significantly and markedly reduced the increase in renin release from the innervated kidney. 4. After sino-aortic denervation a marked and sustained arterial hypotension occurred during tilting, and the postural increase in renin release from the innervated kidney was even greater. 5. In no condition, even during the marked fall in blood pressure in sino-aortic denervated cats, did head-up tilting increase renin release from the denervated kidney. 6. It is concluded that maintenance of arterial pressure during tilting is mainly due to sino-aortic reflexes, whereas vagal reflexes are mostly responsible for the postural increase in renin release.


Effects of prostaglandin E2 and prostaglandin F2alpha upon urinary kallikrein excretion in rats. 1. In normally hydrated rats prostaglandin F2alpha (PGF2alpha) in doses of 5 microgram/100 g body weight given subcutaneously every 2 h (three times) induced a significant increase in urinary kallikrein activity, and in sodium, potassium and water excretion for 8 h after the first injection. In moderately hyperhydrated rats loaded 2.5% of body wt. with 0.5% NaCl solution, PGF2alpha produced similar changes in kallikrein activity and electrolyte excretion. 2. In normally hydrated rats prostaglandin E2 (PGE2) in the same conditions and doses as in 1 had no effect on kallikrein activity, showing a tendency to decrease potassium and water excretion. 3. PGE2 in doses of 5, 12.5 and 25 microgram/100 g body wt. in overhydrated rats given 2.5% and 0.5% NaCl and 5% of tap water/100 g body wt. 1 h later, significantly increased kallikrein activity in the urine collected for 120 min after the injections. A significant decrease in potassium and water excretion was observed with the highest dose. 4. PGF2alpha, had no effect on kallikrein activity in overhydrated rats, but an increase in sodium and a decrease in potassium excretion was seen at the highest dose. 5. The different actions of PGE2 and PGF2alpha may be part of a regulatory mechanism associated with the kallikrein-kinin system which contributes maintainance of extracellular fluid homeostasis.


Renal prostaglandin production in the Japanese (Kyoto) spontaneously hypertensive rat. 1. Renal venous and urinary prostaglandin E2 (PGE2) and prostaglandin F2alpha (PGF2alpha) were measured in spontaneously hypertensive (SH) rats and Wistar-Kyoto normotensive rats (WKy) of 4 different ages, ranging from 4 to 54 weeks. 2. Renal venous (plasma) PGE2 and PGF2alpha were similar in WKy and SH rats at all ages, except for greater PGF2alpha in 40-54 week old SH rats. 3. Urinary (24 h) PGE2 and PGF2alpha were similar in WKy and SH rats at all ages, except for greater PGE2 in 7-12 week old SH rats. 4. There was a significant trend for renal venous and urinary PGE2 and PGF2alpha to decrease with advancing age. 5. These experiments did not show evidence that the SH rat kidney, in vivo, has an abnormality of PGE2 or PGF2alpha production or degradation, which alters secretion or excretion of either prostaglandin.


Effects of indomethacin alone and during diuretic or beta-adrenoreceptor-blockade therapy on blood pressure and the renin system in essential hypertension. 1. Indomethacin was administered alone or in addition to either diuretic or propranolol therapy to three groups of patients with essential hypertension on a free sodium diet. 2. Indomethacin administration reduced renin secretion by about 30% in untreated uncomplicated hypertensive patients and by about 75% in those whose renin secretion had either been stimulated or suppressed by maintained diuretic or beta-adrenoreceptor-blockade therapy. 3. Indomethacin administration produced no net effect on blood pressure in untreated patients with uncomplicated hypertension but it blunted or reversed the antihypertensive effect of either diuretic or propranolol therapy. 4. Salt and water retention may be an important factor in the blood pressure-raising effect of indomethacin during diuretic or propranolol therapy: In addition, prostaglandin synthesis may be important in counteracting increased alpha-adrenergic tone, which may limit the blood pressure-lowering effect of beta-adrenoreceptor-blockade. 5. Because of these interactions and their pressor potential indomethacin should be used with caution when combined with either diuretics or beta-adrenoreceptor blockers.


The natural history of hypertension in turkeys. 1. Variables involved in the genesis of hypertension in male broad-breasted white turkeys include social environment, obesity and high salt intake. 2. The hypertension is characterized by low plasma renin activity and, with increasing age, normal to high plasma aldosterone. 3. Medionecrosis of the abdominal aorta is a common pathological finding. 4. The absence of atherosclerotic plaques is probably related to the high concentrations of alpha-lipoproteins.


An altered relation between arterial pressure and plasma angiotensin II concentration resulting from prolonged infusion of angiotensin II. 1. Infusion of angiotensin II into dogs at constant dose over 2 weeks caused a progressive rise in arterial pressure. 2. When the infusion was stopped the pressure dropped slowly from hypertensive levels over 48 h. 3. Dose-response studies at weekly intervals showed progressive elevation, without steepening, of the plasma angiotensin II-blood pressure curve. 4. Thus, during prolonged administration of angiotensin II, a given plasma concentration of the peptide can sustain a higher arterial pressure than it can during acute infusions.


Changes in cardiac output during the development of renal hypertension in sodium-depleted dogs. 1. Chronic renovascular hypertension developed in uninephrectomized, sodium-depleted dogs in association with a decrease in cardiac output. 2. With sodium and volume repletion of these animals, cardiac output returned to normal but the high level of arterial pressure was unchanged; consequently, the peripheral arterioles dilated. 3. These observations provide evidence against the theory of whole-body autoregulation.


Central nervous system pressor responses in rats susceptible and resistant to sodium chloride hypertension. 1. The pressor responses to hypertonic saline and angiotensin II introduced into the left lateral ventricle were both significantly greater in salt-sensitive (S) rats compared with salt-resistant (R) rats, with all rats on a low Na diet. 2. When S rats were given thiazide to nullify the pressor effect of dietary NaCl, their blood pressure averaged only 5 mmHg higher than that of the R rats; nevertheless, these S rats had significantly higher central nervous system pressor responses to angiotensin II and hypertonic saline. 3. Thus, if excessive dietary Na increases blood pressure by way of action on the central nervous system, these heightened pressor responses could partially account for the NaCl hypertension in S rats. Alternatively, depressed central nervous system pressor responses in R rats could partially explain the resistance of R rats to NaCl hypertension.


Intrarenal control of urine concentration by angiotensin II. 1. The intrarenal role of angiotensin II in the recovery of urinary concentration after frusemide was examined in anaesthetized dogs by the intrarenal infusion of angiotensin II antagonists. 2. Renin secretion and renal inner medullary blood flow (tissue clearance of intraparenchymatously injected 133Xenon) were simultaneously measured before and 3 h after frusemide injection. 3. Intrarenal angiotensin II blockade delayed the recovery of urinary osmolality after frusemide. 4. An inverse relationship was found between renin secretion and renal inner medullary blood flow.


Role of persistent vascular renin after bilateral nephrectomy in Goldblatt-two kidney hypertension. 1. Aorta homogenate contains renin-like activity which on incubation generates angiotensin I over a wide pH range. 2. Rat aortic renin measured at an incubation pH of 6.5 rose and fell in parallel to plasma renin with salt depletion and salt-loading respectively. Renin little relationship with plasma renin. 3. Aortic renin (pH 6.5) was elevated in Goldblatt-two kidney hypertension and slowly fell for 24h after bilateral nephrectomy whereas the fall in plasma renin was complete by the first hour. Aortic renin (pH 5.3) was also high, but did not fall after bilateral nephrectomy. 4. Aortic renin (pH 6.5) is probably derived from plasma renin whereas renin measured at pH 5.3 is probably a tissue renin. 5. The prolonged half-life of aortic renin (pH 6.5) explains the observation that the renin-angiotensin system appears to be active in maintaining blood pressure for several hours after bilateral nephrectomy whereas the decline in plasma renin is rapid and does not continue significantly beyond 1 h.


Neuronal and vascular reactivity in isolated perfused kidneys during the development of spontaneous hypertension. 1. Vascular reactivity was studied in Tyrode solution perfused kidneys from young (7 weeks) and mature (4-6 months) spontaneously hypertensive rats (SH rats). 2. The response to nerve stimulation was greater in the kidneys from young SH rats than in those from young control rats, both in control solution and after inhibition of the disposition of noradrenaline; both groups exhibited the same sensitivity to noradrenaline, angiotensin II and barium chloride. 3. The response to nerve stimulation was normal in kidneys from mature SH rats, but responses to noradrenaline, angiotensin II and barium chloride were greater than the control. 4. Cocaine potentiated the response to nerve stimulation more in the kidneys from mature SH rats than in those from the control rats. 5. The results suggest that renal sympathetic nerves release more noradrenaline than normal in the young SH rats, which could be an important factor in causing hypertension. 6. In the established phase of spontaneous hypertension the vascular reactivity to exogenous agonists is increased, probably as a consequence of high blood pressure; the more efficient neuronal uptake causes normalization of the response to sympathetic nerve stimulation.


Effects of enkephalins on arterial blood pressure are reduced by propranolol. 1. The cardiovascular effects of enkephalins have been tested in normotensive Wistar-Kyoto rats. Methionine-enkephalin and leucine-enkephalin increased blood pressure and heart rate after infusion into the brain ventricles. 2. After intravenous injection, blood pressure was increased by methionine-enkephalin and leucine-enkephalin, but heart rate was increased by methionine-enkephalin only. 3. Propranolol treatment reduced the increases in blood pressure following intraventricular methionine-enkephalin and leucine-enkephalin, while only the methionine-enkephalin-induced increases in heart rate were reduced by propranolol. 4. Heart rate and blood pressure responses after intravenous administration of methionine-enkephalins and leucine-enkephalin were not affected by propranolol. 5. Since opioid peptides occur in the blood and in regions of the brain involved in blood pressure regulation, the demonstrated cardiovascular effects to intraventricular and intravenous enkephalins support a role of these peptides in central and peripheral mechanisms of blood pressure control.


Redistribution of regional blood flow after administration of saralasin in salt-depleted dogs. 1. Salt depletion was produced in five dogs by a low salt diet and daily administration of frusemide for 5 days; a control group of five dogs was placed on the same diet, to which 2.5 g of sodium chloride was added. 2. Saralasin infusion (0.5 microgram min-1 kg-1) reduced mean aortic blood pressure and total peripheral vascular resistance and increased cardiac output in salt-depleted dogs, but did not affect the heart rate and left ventricular dP/dt. 3. Saralasin infusion increased mean aortic blood pressure slightly in normal dogs; other systemic haemodynamic parameters did not change significantly. 4. Saralasin decreased hepatic arterial flow in both normal and salt-depleted dogs, but increased blood flow to left ventricle and kidneys only in salt-depleted dogs. 5. These results suggest that saralasin exerts a partial agonist effect in normal dogs to increase arterial blood pressure, but causes a depressor response during salt depletion because it reverses the vasoconstrictor effect of angiotensin II, particularly on the renal and coronary circulations.


The role of vasopressin in blood pressure control and in experimental hypertension. 1. The role of vasopressin in blood pressure control and in the pathogenesis of one-kidney Goldblatt hypertension in the conscious dog was investigated. 2. Infusion of synthetic arginine vasopressin to elevate plasma levels approximately five-fold caused bradycardia in normal dogs and increase in mean arterial blood pressure in dogs with pharmacological autonomic blockade. 3. A similar degree of elevation of plasma vasopressin concentration was observed after mild non-hypotensive haemorrhage. 4. Renal artery constriction in unilaterally-nephrectomized dogs caused a rise in plasma renin activity and only a doubling of plasma vasopressin concentration, but a marked rise in mean arterial blood pressure. 5. Vasopressin may play a role in normal cardiovascular homeostatic responses, but its role in the pathogenesis of this form of hypertension is unlikely to be significant.


The relationship between blood pressure and aortic collagen metabolism in renal hypertensive rats. 1. Biosynthesis and deposition of collagen, as well as DNA and total proteins, are increased in aortae of rats after 1, 3 and 6 weeks of hypertension. 2. The maximal increase in the rate of synthesis of collagen is observed within one week of hypertension when the stress to the arterial wall is maximal. 3. Reserpine administration prevents hypertension and inhibits the increase of collagen metabolism. 4. At any time of evolution of the hypertension, a linear positive correlation is found between the collagen content in the aorta and the level of blood pressure. 5. These data suggest that synthesis of matrix components by the arterial smooth-muscle cells is controlled by variation in the blood pressure level and is not a direct consequence of circulating humoral factors liberated by the ischaemic kidney.


Evidence for an unidentified, adrenocorticotrophic hormone-dependent mineralocorticoid maintaining hypertension in young women with hypoaldosteronism. 1. Pronounced hypoaldosteronism was found in five young women with low-renin hypertension and characteristic features of the mineralocorticoid hypertensive syndrome. 2. There was no overproduction of the mineralocorticoids 11-deoxycorticosterone and 18-OH-11-deoxycorticosterone. 3. Dexamethasone restored blood pressure to normal, decreased body weight, increased plasma potassium, and increased plasma renin activity and aldosterone excretion in all patients. 4. The data suggest overproduction of an unknown adrenocorticotrophic hormone-dependent mineralocorticoid maintaining hypertension in these patients.


Pharmacokinetics of intravenous and oral pindolol in hypertensive patients with chronic renal failure. 1. The pharmacokinetics of intravenous and oral pindolol were determined in 24 hypertensive patients with normal or impaired renal function. 2. In patients with normal renal function, the total clearance of the drug was the sum of both the renal and non-renal clearances in equal parts. The non-renal clearance was found to equal the hepatic clearance directly measured from the hepatic extraction ratio and hepatic blood flow. 3. Compared with patients with normal renal function, patients with chronic renal failure exhibited (i) unchanged transfer rate constants and distribution volumes, (ii) decreased total body clearance with decreased renal clearance and unchanged non-renal clearance. 4. Analysis of data obtained after oral administration of the drug by the Loo-Riegelman method showed that the pindolol absorption kinetic was non-linear. Compared with patients with normal renal function, patients with chronic renal failure exhibited (i) a significantly decreased fraction of dose effectively absorbed, (ii) an increased initial rate of absorption. The initial rate of absorption was inversely correlated with creatinine clearance. 5. The study provided evidence that in patients with renal insufficiency, (i) no increase in the metabolism of the drug accompanied the decrease in renal function, and (ii) decreased bio-availability was associated with a reduced fraction of the dose effectively absorbed and an increased rate of absorption.


Effects of labetalol on systemic and pulmonary haemodynamics at rest and during exercise in hypertensive patients. 1. Labetalol was administered to 18 hypertensive patients for an average duration of 2.44 weeks, with an average final daily dose of 1.65 g. 2. Labetalol decreased resting heart rate by 16% and maximal exercise heart rate by 21%; the phenylephrine-induced rise of systolic brachial artery pressure was reduced by 36%. 3. During labetalol brachial artery pressure was lowered by 29/15 mmHg in the recumbent position, by 41/23 mmHg at rest sitting, and by 53/23 mmHg at maximal exercise; total peripheral resistance was not significantly affected at rest recumbent, but was reduced at sitting and at exercise; cardiac output decreased in all conditions. 4. Labetalol reduced mean pulmonary artery and capillary wedge pressures only in the sitting position. Pulmonary vascular resistance remained unchanged. 5. The drug produced significant decreases of plasma renin activity and of plasma aldosterone concentration.


Effect of selective and non-selective beta-adrenoreceptor blockade on calf blood flow in hypertensive patients. 1. Dose-response curves of isoprenaline were constructed in nine hypertensive patients before and after either propranolol or metoprolol. 2. The decrease of diastolic blood pressure and increase of heart rate with isoprenaline were significantly more inhibited by propranolol than by metoprolol. 3. The increase in calf blood flow with isoprenaline was significantly more depressed after propranolol than after metoprolol. 4. The results suggest that the response of the vessels in the limbs to sympathetic stimulation is much less affected after metoprolol than after propranolol.


Haemodynamic effects of a calcium antagonistic agent (nifedipine) in hypertension: therapeutic implications. 1. In 27 severe primary hypertensive patients nifedipine (10 mg), administered orally, induced prompt (-21% of control at 30 min) and persistent (-17% at 120 min) fall of mean arterial pressure mediated through reduction of peripheral vascular resistance with rise of cardiac output. 2. The sublingual route (nine cases) showed more rapid onset of action and equal antihypertensive effectiveness. 3. In five patients with hypertensive crisis and acute left ventricular failure, the drug strikingly reduced systemic and pulmonary arterial pressures and relieved pulmonary oedema. 4. Prompt efficacy, ease of administration, absence of important side effects indicate that nifedipine may be a useful therapeutic agent in severe hypertension and in critical conditions that require rapid lowering of blood pressure.


Sodium and renin in the hypertension of early renal disease. 1. Plasma renin activity, response to saralasin and exchangeable sodium have been measured in 43 patients with early renal disease. 2. Blood pressure was directly proportional to plasma renin activity. However, mean plasma renin activity was lower in patients with renal disease than in normal controls. 3. Blood pressure fell in response to saralasin infusion in proportion to the pre-infusion plasma renin activity. 4. Exchangeable sodium in hypertensive patients with renal disease did not exceed that in normotensive patients in contrast to earlier reports. Discrepancies may arise from the difficulty in interpreting measured exchangeable sodium in relation to body build.


Treatment of mild hypertension.

Treatment of mild hypertension. 1. A total of 206 patients, elderly males with hypertension (diastolic blood pressure 95--110 mmHg) were followed for periods varying from 1 to 5 years, 107 patients with diastolic blood pressure less than 95 mmHg were followed over the same period, and 101 patients with diastolic blood pressure greater than or equal to 110 mmHg were also followed. 2. The mortality of each group and the effect of therapy for hypertension on mortality has been compared. 3. The incidence of myocardial infarct in the group treated with thiazide diuretics is greater than in the other groups. 4. It would appear unlikely that therapy will improve the prognosis in elderly people with mild hypertension.


Relationship between the hypotensive and renin-stimulating actions of diuretic therapy in hypertensive patients. 1. The pressor role of renin stimulated by chronic diuretic therapy has been assessed in 31 patients with essential hypertension by infusing the angiotensin II antagonist, saralasin, immediately before and at the end of 2 weeks' treatment with the diuretic, chlorthalidone. 2. Under diuretic therapy the change in blood pressure caused by saralasin was found to be correlated to plasma renin activity values, in such a way that small pressor responses were again observed in patients whose renin was mildly stimulated by the diuretic, whereas a marked depressor response occurred in patients whose renin was markedly increased. 3. On the other hand, the hypotensive effect of chlorthalidone was correlated to values of plasma renin activity under diuretic therapy in an opposite direction: indeed little or no decrease and sometimes an increase in blood pressure were observed in patients with marked renin activation by diuretic therapy. 4. It is concluded that stimulation of renin release by chronic diuretic therapy can be considered a factor limiting the hypotensive activity of diuretic drugs.


Raised serum lipid concentrations during diuretic treatment of hypertension: a study of predictive indexes. 1. The serum concentrations of cholesterol and triglycerides were measured before and during the treatment of hypertension. Thirty-six patients were treated with hydrochlorothiazide and 29 with spironolactone. 2. Serum cholesterol increased from 214 to 227 mg/100 ml (P less than 0.005) and triglyceride did not change during treatment with hydrochlorothiazide. Serum triglyceride increased from 112 to 133 mg/100 ml (P less than 0.05) and cholesterol did not change during treatment with spironolactone. 3. Serum lipid responses to diuretics varied among patients. To identify patients susceptible to larger increases, subgroup analysis was carried out. Patients who were younger and had lower pretreatment serum cholesterol and systolic blood pressure had larger increments in cholesterol during treatment. In these subgroups coronary risk status did not improve during therapy. 4. The incidence of myocardial infarction may not be reduced so long as diuretics serve as first-line drugs in the treatment of mild hypertension.


Benzothiadazine diuretics and death from myocardial infarction in hypertension. 1. Case records were examined of 66 patients who died while being treated for high blood pressure. 2. The possibility that benzothiadazine diuretics may have some deleterious as well as beneficial effects was investigated. 3. It is possible that the thiazides may have some adverse clinical effects, at least in females, with regard to the incidence of myocardial infarction in hypertensive patients.


Increased ratio between serum beta- and alpha-lipoproteins during diuretic therapy: an adverse effect? 1. The effect of diuretic therapy on serum lipids and lipoprotein fractions was evaluated in 16 normal or labile hypertensive subjects who received in cross-over fashion chlorthalidone, frusemide or mefruside, each for 4 weeks (group A); and in 13 patients with essential hypertension treated with chlorthalidone for 6 weeks (group B). 2. All three diuretics significantly increased the ratio between serum beta- and alpha-lipoprotein fractions. This was due to an increase of the serum beta-lipoprotein fraction while the alpha-lipoprotein fraction was not changed significantly (group A) or decreased (group B). Serum cholesterol or triglycerides tended to be increased, but mean changes were often not significant. 3. The observed alterations in serum lipoproteins are consistent with the possibility of an increased risk for coronary heart disease which could offset partly the beneficial effects of a lowered blood pressure in diuretic-treated patients with hypertension.


Effect of prazosin on blood pressure and plasma renin activity in man. 1. The effects of oral administration of 4.5 mg of prazosin/day on blood pressure and on plasma renin activity were assessed in patients with essential hypertension and in healthy normotensive volunteer subjects. 2. Mean blood pressure in the hypertensive group fell significantly within 2 weeks of treatment, whereas heart rate was little affected. None of the parameters measured in the normotensive subjects during treatment with prazosin revealed significant changes. 3. Sub-classification of the hypertensive patients into low-, normal- and high-renin categories revealed significant decreases of renin in all six patients with high renin- and in four out of 12 patients with normal renin- but not in the two patients with low renin-essential hypertension. 4. The results indicate the prazosin exerts its hypotensive action and suppresses plasma renin activity particularly in patients with high renin-essential hypertension. These may be considered to have increased sympathetic drive. 5. Conceivably, the blood pressure-lowering effect of prazosin is affected by peripheral vasodilatation and also by a decreased venous return to the heart.


Side-effects of antihypertensive treatment: a placebo-controlled study. 1. A questionnaire, modified from Bulpitt & Dollery (1973), inquired about 20 symptoms commonly associated with hypertension or its drug therapy in 1017 subjects (age 30--69 years). Groups consisted of (a) active therapy, (b) placebo, (c) no tablets, and (d) a non-study control group. The response rate was 96% in the first three groups and 92% in group (d). 2. The subjects in groups (a), (b) and (c) constituted part of a placebo-controlled, patient-blind intervention study in the treatment of mild hypertension (The Australian National Blood Pressure Study). 3. After age/sex adjustment of the data, only sleepiness and self-assessed depression were found to be more common in the actively treated group. Impotence, failure of ejaculation and nocturia were age-related symptoms. Generally, complaint rate was higher in females. 4. The knowledge of a mild hypertensive condition or its modern drug therapy lead to very few symptoms in a non-hospital population who already have a fairly high 'complaint level'.


The role of nurse practitioners in hypertension care. 1. Two groups of hypertensive patients, randomly assigned to either physician or nurse practitioner care, were compared, after two years of follow up, with respect to diastolic blood pressure reduction and utilization and costs of medical services. In addition, satisfaction with hypertension are was evaluated. 2. There was no statistical difference in mean diastolic blood pressure reduction between the physician and nurse practitioner groups. 3. Patients in the nurse practitioner group made more visits for hypertension care than those in the physician group; thus, even though the cost per nurse practitioner visit was lower than the cost per physician visit, the total annual cost of care per patient was higher in the nurse practitioner group. 4. Patients followed by nurse practitioners were very satisfied with their care. 5. Nurse practitioners provide excellent hypertension care and thereby save valuable physician time.


Blood pressure control: the effect of facilitated access to treatment. 1. Effectiveness of hypertension care has been compared in patients treated at a Union health centre and at their place of work. 2. Patient adherence and blood pressure control is not affected by the place of treatment. 3. A systematic approach to treatment can be successful in a large population group.


Results of a national therapeutic trial conducted in 10,000 hypertensive patients by 2000 general practitioners. 1. 10,294 hypertensive patients were treated and followed by 2200 general practitioners under the supervision of 130 cardiologists and nephrologists. 2. The treatment groups, randomly allocated, were designated to use three distinct antihypertensive drugs, administered alone, and combined two-by-two. 3. Some 75% of patients had a supine diastolic blood pressure of less than 95 mmHg after 4 months treatment. 4. A total of 12% of patients had dropped out by 4 months from entry; no clear relationship was established between side effects and drop out.


The hypertension register of the North Karelia project. 1. One major subprogramme of the North Karelia Project was the hypertension programme which aimed at lowering of the high blood pressure among the whole population, and expecially among middle-aged men. The hypertension programme consisted of intervention integrated with the existing health care structure of the county of North Karelia. 2. The hypertension register, which was the major tool of the programme, aimed to maintain patients in treatment and to get information about the development of the programme. Registration of hypertensive subjects was continuous between 1972 and 1977 and registered patients had annual follow-up examinations. 3. After 5 years of the programme, there were approximately 17 000 registered patients which is 9.7% of the total population. 4. Proportion of drop-outs at the annual follow-up examinations was less than 10%. 83% of the registered hypertensive subjects were under drug treatment after 3 years intervention. The percentage of normotensive subjects increased significantly year by year. 5. Preliminary results from the stroke register of the North Karelia Project indicate that the incidence of stroke decreased as hypertension control was improved.


Improvement in foetal growth with treatment of maternal hypertension in pregnancy. 1. A highly significant inverse relationship was found between blood pressure in untreated hypertensive subjects in late pregnancy and birth weight. 2. Reversal of this intrauterine growth retardation was achieved in 19 patients by treatment of hypertension with oxprenolol. 3. No adverse effects from oxprenolol were found in the patients or in their babies.


Relationship of blood pressure to sodium excretion in a population survey. 1. Blood pressure, height, weight and 24 h urinary output of sodium, potassium and creatinine were measured in over 500 adults of each sex during a health survey of the population of a small town. 2. Both systolic and diastolic pressure were significantly related to Quetelet's index (weight/height2) and heart rate. 3. There was no significant relationship between blood pressure and output of sodium or potassium, sodium/potassium ratio or sodium/creatinine ratio.


Biochemical correlates of the increase in blood pressure with age. 1. Blood pressure, plasma renin activity, plasma aldosterone, urinary noradrenaline during sleep (UNA-S) and several estimates of sodium intake were determined in 379 normotensive subjects (age 13--70) to investigate the relationship of these variables to blood pressure. 2. Blood pressure was correlated with age, weight, plasma renin activity UNA-S, and estimates of sodium intake. There variables were frequently intercorrelated. 3. Multiple-correlation analysis revealed that after removal of the effects of age, blood pressure was related to weight, plasma renin activity, UNA-S and estimates of sodium intake. 4. However, multiple-regression analysis failed to demonstrate an effect of plasma renin activity, UNA-S, or estimates of sodium intake on blood pressure when the effects of age, weight, race and sex were removed. 5. Careful matching of subjects by age, weight, race and sex in studies of blood pressure and biochemical factors in normal subjects is crucial to proper interpretation of such data.


The effect of mental arithmetic on blood pressure variability and baroreflex sensitivity in man. 1. Baroreflex sensitivity was tested in three normal, three borderline and one hypertensive subject before and during mental arithmetic, the prolongation of pulse interval caused by a provoked rise in blood pressure being used as a measure of baroreflex sensitivity. 2. Baroreflex sensitivity was significantly decreased during mental arithmetic. 3. During mental arithmetic the arterial pressure fluctuated markedly. 4. These findings suggest that in man, as well as animals, the defence of alerting reaction depresses baroreflex control and thus contributes to the rise in blood pressure seen at this time.


Are racial differences in essential hypertension due to different pathogenetic mechanisms? 1. Plasma noradrenaline concentration and plasma renin activity were measured in a control, British, urban population (n = 115) in which blacks were matched for age and sex with whites. 2. Similar measurements were made in subjects with essential hypertension (77 white and 23 black), and 48 healthy normotensive white civil servants. 3. In controls blood pressure was significantly higher in blacks; it correlated with age in both races and with pulse rate in blacks. There were no significant racial differences in plasma noradrenaline which was positively correlated with age in both blacks and whites. Mean plasma renin activity was 55% lower in blacks, and this difference was not related to urinary sodium excretion. 4. In hypertensive subjects plasma noradrenaline positively correlated with age in blacks. This relationship was not found in whites in whom 20% of young hypertensive subjects (less than 45 years) had significantly raised plasma noradrenaline. Plasma renin activity was again significantly lower in blacks. In white hypertensives plasma noradrenaline and renin activity were significantly correlated. 5. There may be racial differences in the pathogenesis of essential hypertension.


Blood pressure circadian rhythm in essential hypertension. 1. Both systolic and diastolic blood pressure show a well defined circadian variation in ambulatory hypertensive subjects. 2. Blood pressure is highest in the mid-morning (10.00 hours) and lowest during sleep at 03.00 hours. 3. Treatment with oxprenolol (taken during the day) reduces daytime blood pressure but is less effective during the night and early morning.


Arousal and the circadian rhythm of blood pressure. 1. We have recorded ambulant intra-arterial blood pressure in five normo- and 14 hyper-tensive subjects over 24 h, particular attention being paid to the time of arousal. 2. The data were edited beat-by-beat before storing systolic, diastolic, and mean blood pressure +/- SD for every 2 min period on a computer file. 3. When pooled hourly mean data are plotted there is a rise of 52.9 mmHg systolic and 22.3 mmHg diastolic pressure from 03.00 hours to 11.00 hours in the 14 hypertensive subjects. 4. When the data are plotted in 20 min periods for the hours before and after arousal it is clear that the major rise in pressure occurs abruptly at that time. The 2 h period before arousal shows only a small rise in pressure, i.e. 6.9 mmHg systolic and 2.9 mmHg diastolic. 5. It is suggested that the apparent rapid early morning rise of blood pressure is an artifact of the method of analysis.


Pseudohypertension in the elderly.

Pseudohypertension in the elderly. 1. Direct intra-arterial blood pressure (radial artery) has been compared with indirect blood pressures using a regular sized adult cuff and a thigh cuff, with a mercury sphygmomanometer, in 24 hypertensive patients aged 62--84 years, and in 16 hypertensive patients aged 29--59 years. 2. The patients were studied because they were suspected of having a false elevation of their indirect blood pressure, since they had diastolic pressures over 100 mmHg, without hypertensive retinopathy, cardiac hypertrophy, or nephropathy. 3. Indirect diastolic pressure was falsely elevated by 30 mmHg or more in 12 out of 24 of the subjects over age 60, and in four of the 16 of those under age 60. Pseudohypertension (indirect diastolic greater than 100 mmHg, direct diastolic greater than 90 mmHg) was present in 12 subjects over age 60 and 5 under age 60. 4. Errors in indirect measurement of blood pressure are a serious problem, particularly in the elderly. Direct intra-arterial measurement may be useful in the management of hypertension.


Plasma noradrenaline and the pressor action of exogenous noradrenaline in normotensive subjects and patients with essential hypertension. 1. An inverse relationship was found between plasma noradrenaline and reactivity to exogenous noradrenaline in normotensive subjects. 2. The relationship between plasma noradrenaline and reactivity was distrubed in age-matched patients with essential hypertension. 3. A multiple-regression analysis showed a highly significant correlation between adrenergic activity and reactivity to noradrenaline and the mean arterial blood pressure level (r = 0.91). The results suggest that adrenergic activity and pressor response to noradrenaline combined are important determinants of arterial blood pressure. 4. An inverse relationship could also be demonstrated between plasma renin activity and reactivity to exogenous angiotensin II. No difference was observed between normotensive and hypertensive subjects.


Circulating catecholamines and systolic time intervals in labile and sustained hypertension. 1. Average supine circulating total catecholamine concentrations were found to be higher than the normal range in about 50% of patients with labile hypertension and in about 30% of patients with sustained essential hypertension. 2. These higher resting concentrations were mainly due to an increase in adrenaline in labile hypertension and to an increase in noradrenaline in sustained hypertension. 3. Patients with elevated catecholamine concentrations were also characterized by a higher heart rate, by an increased myocardial contractility and by greater hypotensive response after treatment with beta-adrenoreceptor blocking agents. 4. These studies suggest the existence of sub-groups of hypertensive patients with increased sympathetic tone.


Plasma noradrenaline concentrations and haemodynamics in the early stage of essential hypertension. 1. Plasma noradrenaline concentrations and haemodynamic status were simultaneously studied in young patients with uncomplicated essential hypertension and in age-matched normal controls. 2. Resting plasma noradrenaline in the controls tended to increase slightly, but progressively, with age. The hypertensive subjects had significantly higher plasma noradrenaline concentrations than those in the controls, but these values did not show any age-related variation. The response of plasma noradrenaline to the standing position tended to increase with age in the controls, whereas plasma noradrenaline in the hypertensive subjects showed a wide range of responses without any fixed relationship with age. 3. The cardiac index was significantly greater in the labile hypertensive subjects than in the controls, whereas total peripheral resistance was significantly greater in the sustained hypertensive subjects than in the labile patients and in the controls. Mean arterial pressure in these patients was closely related with the value of total peripheral resistance rather than with the cardiac index. 4. Of the patients with raised plasma noradrenaline 80% showed significantly increased values of either total peripheral resistance or cardiac index. Plasma noradrenaline was correlated significantly to total peripheral resistance, and marginally to mean arterial pressure. 5. These findings support the view that sympathetic nervous overactivity is an important factor underlying the haemodynamic findings in these patients.


Plasma noradrenaline, age and blood pressure: a population study. 1. Mean supine plasma noradrenaline was lower in 12 male laboratory staff (0.24 +/- 0.02 microgram/l) than similarly normotensive out-patients (0.44 +/- 0.07 microgram/l). 2. In 164 non-medical hospital staff, plasma noradrenaline increased with age in white males only. 3. Plasma noradrenaline was significantly higher in women than men. 4. There was no relationship between supine blood pressure and plasma noradrenaline in normotensive or hypertensive subjects.


Free and conjugated catecholamines in human hypertension. 1. Noradrenaline and adrenaline in the adrenal vein of essential hypertensive patients are almost exclusively (99%) unconjugated or free. However only 17% of dopamine is free, the rest is conjugated. The further the site of sampling from the adrenal vein the closer come the free catecholamines to their normal peripheral venous proportion (noradrenaline + adrenaline 20%, dopamine less than 1% of total catecholamines). Deviations from these patterns help to detect the site and type of secretion of phaeochromocytoma. 2. Essential hypertensive patients have, compared with control subjects, higher conjugated plasma dopamine, less urinary free and conjugated dopamine with blunted urinary free dopamine and sodium responsiveness to frusemide. Conjugated noradrenaline + adrenaline, mean arterial pressure and age are positively interrelated. 3. Patients with primary aldosteronism have elevated plasma and urinary total dopamine. After removal of the adenoma urinary dopamine excretion decreases to normal. 4. Elevated conjugated dopamine appears to reflect a compensatory activation of the dopaminergic vasodilator pathway in hypertension, the total urinary dopamine excretion an intrinsic deficiency or compensatory increase of a dopamine-modulated natriuretic mechanism.


Relation of plasma noradrenaline to blood pressure, age, sex and sodium balance in patients with stable essential hypertension and in normotensive subjects. 1. Plasma noradrenaline was measured in 125 patients with stable essential hypertension (WHO I-II) and in 107 normotensive control subjects lying and standing. 2. In normotensive subjects and in patients with essential hypertension no sex-related differences of plasma noradrenaline were found between age-matched groups. 3. Plasma noradrenaline was not related to sodium balance indexed by urinary sodium/creatinine ratio. 4. In patients with essential hypertension plasma noradrenaline increases with age. 5. Mean plasma noradrenaline concentrations are significantly higher in patients with essential hypertension compared with age-matched normotensive subjects both lying and standing. 6. In patients with essential hypertension diastolic blood pressure and heart rate correlated significantly with supine plasma noradrenaline concentrations.


Noradrenaline secretion by the human kidney. 1. In 20 subjects with uncomplicated essential hypertension, 10 of whom were on propranolol treatment, several blood samples were drawn simultaneously from the renal artery and vein after angiographic studies. In these samples we determined concentrations of noradrenaline, active renin, aldosterone and cortisol. 2. Renal blood flow was measured in all patients by Hippuran-clearance and xenon-washout. 3. Despite marked variations in the arteriovenous difference of noradrenaline, it was apparent in both groups that the kidney is able to release noradrenaline. 4. In the propranolol-treated group noradrenaline secretion with untreated hypertensive patients.


The kinetics of plasma noradrenaline in normal and hypertensive subjects. 1. The kinetics of plasma noradrenaline have been determined in normal and essential hypertensive patients by intravenous injection of tritiated noradrenaline and serial mixed venous sampling. 2. The metabolic clearance rate of plasma noradrenaline in normal subjects was approximately 1 1 min-1 m-2, whereas in essential hypertensive patients it was significantly reduced to approximately 0.6 1 min-1 m-2. 3. Metabolic clearance rate was negatively correlated to mean arterial blood pressure and total peripheral resistances. 4. Particularly low values of metabolic  clearance rate were found in two patients with congestive heart failure and one with phaeochromocytoma. 5. We propose that the access of plasma noradrenaline to the main removal mechanisms takes place in competition with the flow of unlabelled endogenous noradrenaline directly released by nerve endings. The slower removal of plasma noradrenaline in essential hypertension could then express a larger release of endogenous noradrenaline in this condition.


Relationship of basal plasma noradrenaline to blood pressure, age, sex, plasma renin activity and plasma volume in essential hypertension. 1. The relationship of basal plasma noradrenaline to blood pressure, age, sex, urinary sodium excretion, and plasma volume has been examined in 117 untreated ambulatory patients with essential hypertension. 2. No significant correlations between basal plasma noradrenaline and either age or sex were apparent in the total group of essential hypertensive patients. In addition, no significant correlations were observed between plasma noradrenaline and 24 h urinary sodium excretion. 3. Basal plasma noradrenaline concentration was significantly higher in high renin essential hypertensive subjects compared with those with normal or low plasma renin activity. 4. Plasma noradrenaline was reduced significantly in relatively young patients with low renin essential hypertension, but appeared to be normal in other low renin subjects. 5. Basal plasma noradrenaline correlated significantly with blood pressure in patients with normal or low renin essential hypertension but the relationships were only significant in male patients. 6. No significant relationship between basal plasma noradrenaline and either blood pressure or plasma volume could be demonstrated in this population of essential hypertensive patients.


Dental hygienists in Poland.

Dental hygienists in Poland. The activities of dental hygienists in Poland since 1974 are described. About 600 dental hygienists graduated in Poland up to 1977 but only 32% of them are still working in the profession. Their main activities are: dental health education, fluoride prophylaxis and assisting in dental clinics. Although the work of about 50% of the hygienists is poorly organized, they are regarded as useful in dental care by 23 Heads of district dental clinics who employ dental hygienists.


Prevalence of dental caries among workers in the sweets industry in Israel. The purpose of the present study was to assemble data on the prevalence of dental caries among workers in the sweets industry. Four industrial establishments were selected for the study. All production-line workers were included. Altogether 722 participants. The control group consisted of a group of production-line workers in five textile industrial establishments, altogether 812 examinees. The results indicate that the mean DMFT values recorded for the sweets industry workers were significantly higher than those recorded for the control group of workers. The mean DMFT scores recorded for workers in the sweets industry employed for over 10 years were significantly higher than those recorded for workers in the same industry employed for 3-10 years and for up to 3 years.


Saliva-based colorimetric test as an index of gingival inflammation in epidemiologic studies. There is a pressing need for a reliable, low-cost method of assessing the gingival and periodontal status of large population groups. Existing indexes, despite their value in dental public health, are still too subject to examiner variability for use by uncalibrated examiners. This study describes an evaluation of a quick, inexpensive, extraoral colorimetric test for gingival inflammation, based on a reaction between saliva and the test material. It could probably be applied by non-professional personnel. In this study, the test was applied to a population of elementary schoolchildren, dental hygiene students and faculty, and adult inmates of two correctional institutions. These populations were chosen on the assumption that they would exhibit varying intensities of gingival inflammation. Values obtained from the colorimetric test carried out by one researcher were compared with Gingival Index (GI) scores observed by a different examiner. Results suggest that the colorimetric test may be a valid, reliable means of detecting major differences in the prevalence of gingival inflammation in most adult populations, although having little, if any, useful application among children at the mixed dentition stage.


Age-standardized incidence rates of primordial cyst (keratocyst) on the Witwatersrand. Cases of primordial cysts derived from the records of all the hospital pathology departments and private pathology practices on the Witwatersrand, were recorded for the 10-year period 1965-74. The population at risk (1970 census) was 974,390 Whites and 1,567,280 Blacks. Age-specific morbidity rates for each sex and race were calculated, as well as age-standardized incidence rates standardized against African, World and European standard populations. The age-standardized incidence rates for primordial cysts, standardized against a World standard population, per million per year are 0.61, 0, 4.86 and 3.50 for Black males and females and White males and females, respectively. In the population at risk, primordial cysts are much more common in Whites than in Blacks, the incidence being eight times higher in White males than in Black males. The present study confirms that there is a bimodal age distribution but with a higher incidence of the cyst in the age group 50-64 years than previously suspected. This may be either because a substantial number of cases remain undiagnosed for many years or because there are two groups of primordial cyst: one which is triggered in young patients and the other in older patients.


Oral cancer and precancer as diseases of the aged. Some cancers, especially sarcomas, favor younger age groups, whereas others, particularly carcinomas, are most likely to develop in older age groups. The relative frequency, mortality and morbidity rates are defined using lip and tongue cancer as examples. The paper demonstrates how oral cancer rates increase with age. For tongue cancer there is a worsening of the prognosis with advancing age. The synergistic effect of tobacco and alcohol and its relation to age is also dealt with. For leukoplakia there is also a higher rate with increasing age, although there is a shift towards younger ages when compared with oral cancer. Tobacco, age and leukoplakia are also discussed. The increased cancer and precancer rate in older people may be due to age changes in the oral mucosa making it more vulnerable to the action of carcinogens.


Prevalence and awareness of malocclusion in Swedish men. Previous orthodontic treatment, the awareness of malocclusion, the demand for orthodontic treatment and the prevalence of malocclusion were studied in 389 Swedish men, aged 21-54 years (mean age 32 years). Nine percent had been treated with an orthodontic appliance and 15% reported that permanent teeth had been extracted on orthodontic indications. Malposition of teeth was found in 75%, with rotation as the most common type of malposition. Crowding was recorded in 43% and spacing in 18%. Fifty-seven percent had some occlusal anomaly. The need for orthodontic treatment was rated on a four-point scale. It was found that 76% were in need of treatment. The need for treatment was only slight in half of the men but moderate to urgent in 25% of the sample. About a quarter of the men were aware of malposition of front teeth, equally often for maxillary and mandibular teeth, but only about 1% were aware of malposition of posterior teeth. Only a few percent thought they were in need of orthodontic treatment. The presence of malocclusion was correlated to age, place of birth and educational level. This might perhaps be a consequence of tooth loss.


Clinical appearance of dental fluorosis in permanent teeth in relation to histologic changes. Based on studies in Northern Tanzania a new classification system of dental fluorosis is proposed. The classification system includes 10 scores designed to characterize the degree of dental fluorosis affecting buccal/lingual and occlusal surfaces. With aid of polarized and ordinary light microscopy the histologic features behind the individual scores are described. The macroscopic appearance of increasing degrees of dental fluorosis were well correlated to the degree of subsurface porosity. Above a certain level of subsurface hypomineralization various degrees of loss of surface enamel occurred, presumably as a result of posteruptively acquired injuries. Application of the new classification system to samples of children born in areas with 3.5, 6.0 and 21.0 parts/10(6) F- in the water supplies revealed that the distribution of dental fluorosis within the individual followed the same pattern irrespective of fluoride concentration in the water. While the classical Dean index was unable to distinguish between dental fluorosis in the 6.0 and the 21.0 parts/10(6) area it was possible with the new system to disclose that particularly the posterior teeth were significantly more affected in the latter area. Comparisons of degree of dental fluorosis with available measurements of enamel thickness proved that the within-tooth as well as within-dentition variations are determined by enamel thickness rather than length of exposure to body fluids. The limitations of the Dean index are discussed with special attention to its validity as a biological index in relation to current efforts to determine the minimal toxic effect of fluoride on the dental hard tissues.


Distribution of dental fluorosis in the primary dentition. By the use of a new classification system of dental fluorosis, primary and permanent teeth were examined in samples of children born in areas with 3.5, 6.0 and 21.0 parts/10(6) F- in the water supplies. The severity of dental fluorosis was lower than in the corresponding permanent teeth, but a significant increase in severity was noted with increasing concentration of fluoride in the drinking water. The distribution of dental fluorosis within the dentition followed the same pattern irrespective of fluoride content of the water. Thus, a progressive increase in severity was noted from the anterior to the posterior teeth. This pattern is presumably determined by variations in enamel thickness. The much thinner enamel layer of primary teeth may also explain the lower degree of dental fluorosis in these teeth rather than a maternal barrier to fluoride. The degree of dental fluorosis observed in medium and high fluoride areas did not support the hypothesis that the rapidly growing skeleton of infants prevents fluoride-derived enamel changes.


Dental caries and fluorosis in Arussi province, Ethiopia. A dental health survey was carried out in the Arussi province in Ethiopia. The survey comprised 1,700 persons between 6 and 54 years of age in five age groups from four areas of the province. The present paper deals with findings on dental fluorosis and dental caries. Dental fluorosis was found in 18% of the subjects, mainly in a very mild form. The fluoride content of the water (0.2-0.3 part/10(6) F-) in combination with a high tea consumption was assumed to give a fluoride intake optimal for caries prevention. The prevalence of dental caries was low. Thirty-eight percent of the 6-7-year-old group had decayed primary teeth and 51% of the total sample had decayed permanent teeth. Comparisons with a study from 1958 revealed that the prevalence of dental caries had increased in the last few decades, probably due to the recently adopted habit of using sugar in the diet.


[Experimental gingivitis--a photogrammetric comparative study]. Inflammation of the gingiva was induced in 29 subjects ranging in age from 20 to 29 by discontinuing all forms of oral hygiene for three weeks. The course of the inflammation was followed during the developmental period and the following therapy phase with the PMA index, the plaque index, and monophotogrammetry. The results tend to indicate that gingival swelling develops more gradually and recedes more rapidly after treatment has been instituted than could be assumed from the current standard periodontal indexes.


[The effect of plaque on gingival swelling in experimental gingivitis]. The results of investigations with 15 subjects tend to indicate that a direct relationship exists between dental plaque and gingival swelling. The results were discussed.


[The Gottron syndrome from the dentist's viewpoint, case report]. Facultative changes in the teeth, mouth, and jaw in addition to acrogeria, acromicria, and facial erythema are found with Gottron's syndrome. Hypoplasia of the jaw, changes in the position of the teeth, or disproportional relations in the vertical dimensions of the face have been observed. These findings were also recorded in the case described here. The possibility of Gottron's syndrome should be considered if several of the above-mentioned symptoms are present.


[Organic foreign bodies in the maxillary sinus]. A case was reported in which a foreign body was identified in the maxillary sinus during the course of a radiologic dental examination. The foreign body proved to be a calculus. Analysis of the calculus revealed no foreign body responsible for the crystallization. The possibility of local formation of a calculus of the maxillary antrum was discussed.


[Experiences with active oral hygiene as a preventive treatment in patients with deciduous and mixed dentition]. The results of a study of active oral hygiene treatment in children between the ages of 4 and 12 was reported. It is absolutely imperative that both the children and the parents be highly motivated to carry out consistant oral hygiene. The basic level of oral hygiene for children can be considerably improved if the children are instructed in the appropiate technique for tooth brushing and allowed to practice; the children should be regularly checked by the dentist.


Methotrexate encephalopathy. A neuropathologic study. The present report is a neuropathologic study of three patients who died from a severe form of necrotizing encephalopathy following intrathecal methotrexate therapy and craniospinal irradiation for acute lymphoblastic leukemia. During the early phase the lesion presented as multifocal coalescing areas of coagulation necrosis in the deep white matter. In the diseased areas the myelin was lost and the axons were severely swollen and fragmented. During the late stage the white matter was reduced to a thin gliotic calcified layer. The pathogenesis of this lesion is unclear, but the preferential involvement of the white matter with sparing of the cortical gray matter and basal ganglia makes it unlikely that direct chemical injury is the cause. The distribution of the lesion suggests a vascular disturbance due to endothelial injury caused by interaction of the methotrexate with tissue infiltrated by leukemic cells and altered by irradiation.


HLA frequencies in cancer: a third study. Frequencies of 25 HLA antigens in 526 Caucasian patients were compared to those in 629 healthy controls who were HLA-typed between September 1975 and February 1977. Haplotypes were compared for 711 patients and 549 controls typed between September 1974 and December 1976. Frequency deviations were found in those with ALL, AML, breast cancer, lymphoma and ovarian cancer, but only the increase in A29 in AML patients was statistically significant when corrected for the number of specificities. Interesting associations, when compared with earlier studies, include elevation of AW24 in both ALL and AML patients and increased B27 in ALL patients. Significant haplotype differences were increased A3-B8 and absence of A1-BW17 in ALL patients and increased A11-B5 and A2-BW40 as well as absence of A2-B5 in AML patients.


Specialization in dentistry.

Specialization in dentistry. Specialization in dentistry is appropriate for any country, in order to serve its primary functions--to provide a sound dental educational base, to meet the needs of special patients, to react to the complex needs of society on behalf of the dental profession, and to meet the growth needs of individual dentists. Each country must determine for itself the types and numbers of dental specialties it needs to meet the demands of its people. However, as specialties develop, attention should be directed toward preventing an unnecessary over commitment of resources to the education and training of more specialists than are needed. Such an excess of specialists would dilute or compromise the concept of the general practitioner, which must be maintained to insure for the public ready access into the dental health care system.


Effect of fluoride concentration on rehardening of enamel by a saliva substitute. An evaluation was made of the effect of different concentrations of F on the ability of OraLube, a saliva substitute developed by the Veterans Administration designed for use by xerostomic patients, to reharden enamel surfaces. Test preparations contained either 0, 1.0, 2.0, 3.0, 4.0 or 5.0 ppm and groups of softened enamel surfaces were treated with these solutions for 30 minutes. Treatment with saliva substitute containing no F did not significantly alter the hardness of enamel surfaces. Including 1.0 ppm F in the formula induced a rehardening of about 5 per cent; 2.0 ppm F solution rehardened at a 12.5 per cent rate. Additional F up to 5.0 ppm did not increase rehardening significantly. The inclusion of 2.0 ppm F in OraLube assures that, in addition to its ability to relieve intraoral soft tissue problems associated with xerostomia, an optimal rehardening potential is provided.


Induction of erythroid differentiation in murine erythroleukemia cells by N-substituted polymethylene diamides. Various N-substituted polymethylene diamides were synthesized and tested for their potency to induce erythroid differentiation in murine erythroleukemia cells. N,N,N',N'-tetramethyl-1.6-hexane-dicarboxamide (IIc) was the most potent inducer among 15 compounds tested. The effectiveness of this compound was similar to that of hexamethylene bisacetamide (HMBA). HMBA has a different amide linkage order from that of IIc. HMBA and IIc at a concentration of 5 mM had similar effects on the cell growth rate and induced a similar frequency of benzidine-positive cells. However, hemoglobin production was 1.5 times more effective with IIc. Polymethylene diester, diamide, dihydrazide and dianilide had no effect on the induction of hemoglobin synthesis. The N-alkylated amide group appears to be required for induction of differentiation in murine erythroleukemia cells.


Cytolytic activity of circulating human monocytes on transformed and untransformed human fibroblasts. Monocytes from the peripheral blood of 10 normal adult human donors were tested for their cytolytic activity on untransformed or SV40-transformed, early passage, human fibroblasts. Two pairs of human fibroblast lines (2303 and SV40-2303, 2931 and SV40-2931) were used and lysis was assessed in terms of release of [3H]thymidine from prelabelled target cells over a 72-h incubation period. High levels of cytolytic activity were consistently observed on transformed fibroblasts at attacker to target cell (A:T) ratios ranging from 5:1 to 40:1. Low, but significant, lysis of untransformed cells was observed only with two donors at the highest (40:1) A:T ratio tested. With all donors, the cytolytic activity on transformed lines was significantly greater than on untransformed fibroblasts. Thus natural human monocyte-mediated cytotoxicity is preferentially expressed on transformed, as compared to untransformed, cells although sparing of the latter is not absolute.


Sister chromatid exchanges and chromosomes in chronic myelogenous leukemia and cancer families. Spontaneous sister chromatid exchanges and banded karyotypes were studied in blood lymphocytes from 96 individuals: seven patients with chronic myelogenous leukemia, 15 normal controls, and five "cancer families" comprising 12 cancer patients, 40 tumor-free blood relatives and 22 spouses. The families had: malignant melanoma; Epstein-Barr virus-associated malignancies and a birth defect syndrome; non-Hodgkin lymphoma and diverse carcinomas; Hodgkin's lymphoma and adenocarcinomas; and acute myelogenous leukemia. In addition to the Philadelphia chromosome in chronic myelogenous leukemia patients, karyotypic abnormalities, especially breaks and fragments, were found in 29% of cancer family members, but were inconsistent and usually attributable to radiotherapy. Mean sister chromatid exchange values were normal in chronic myelogenous leukemia, but low (by t-test) in tumor patients and their blood relatives in cancer-prone families. In tumor patients, mean sister chromatid exchange levels fell as age increased. After adjusting for this age effect, no significant differences remained among groups. In patients at high risk of cancer (because they have chronic myelogenous leukemia or a strong family history of cancer), spontaneous sister chromatid exchange rates were not a marker of cancer risk.


On the evolutionary stability of the female-biased sex ratio in the wood lemming (Myopus schisticolor): the effect of inbreeding. The evolutionary stability of the female-biased sex ratio observed in the wood lemming (Myopus schisticolor) is discussed. The hypothesis analysed is that the skewed sex ratio is maintained as a result of partial and/or recurrent inbreeding. Fredga et al. (1976, 1977) have suggested that an X-linked mutant gene, X, affects the male-determining action of the Y chromosome, thus converting some XY individuals into females. By a mechanism of selective non-disjunction in the foetal ovary only X-carrying eggs are produced. In particular the stability of that genetic mechanism (or the X chromosome) is analysed by considering the introduction of a "suppressing" sex-linked mutant gene Y. Several deterministic simulation models assuming father-daughter and/or brother-sister matings have been developed and analysed. It is concluded that in the case of extremely strong inbreeding, the hypothesised genetic mechanism may, as a result, be evolutionarily stable. Interpreting field observations on microtine rodents in general it is concluded that only a few species are likely to experience such extreme cases of inbreeding. The wood lemming and the related collared lemming (Dicrostonyx troquatus), another case which seems to have XY-females, are likely to exhibit sufficiently strong inbreeding.


Synaptonemal complex and crossing-over: structural support or interference? Positive cross-over interference is attributed to the prevention of crossing-over by the growing synaptonemal complex. This conjecture is based on a report in the literature that the selection of prospective cross-over sites may actually precede a proper synapsis of homologous chromosomes during meiotic prophase. A genetic test of this notion is suggested using a properly marked trisomic configuration, applicable to a variety of organisms.


Crystallites dimensions of enamel.

Crystallites dimensions of enamel. In this paper the average diameter of enamel crystallites in mature, deciduous and fluorosed human enamel as well as in bovine enamel (in vivo and in vitro remineralized) is discussed. The investigation was carried out on broken surfaces of the various kinds of enamel with a scanning electron microscope. Corrections have been applied for the thickness of the gold-layer deposited. The average crystallite diameters for sound, deciduous and fluorosed human enamel were : 36 nm; 46 nm and 81 nm, respectively. The values for sound, remineralized in vitro and remineralized in vivo bovine enamel were 57 nm; 97 nm and 63 nm, respectively. The results indicate furthermore that if a correction for the sputtered goldlayer is applied, the results for SEM and TEM microscopy are in good agreement with each other. The difference between in vivo and in vitro remineralized bovine enamel is most likely due to differences in speed of remineralization and/or the presence of saliva.


[Electromyographic silent period in the masseter and temporal muscles]. For some years, many authors have studied the silent periods (S.P.) in masticatory human muscles, during voluntary clenching, biting or mastication as well as during electrical or mechanical stimulation of various parts of the mouth. This S.P. appears as a flattening in the electromyograph tracing taken from masseter and temporalis anterior muscles simultaneously. After an analysis of the methods and results of previous authors, we give and discuss our result, obtained from records on masseter and temporalis anterior muscles, on right and left sides, on healthy subjects. They tapped first their teeth, then masticated pea-nuts, pieces of apple and soft bread. We obtained 571 S.P. after recording 1 745 cycles, and in contrary to the opinion of most of the authors, we were not able to obtain simultaneous S.P. in all four muscles at every cycle, except on 26 occasions. To conclude, we discuss our observations and suggest pathways for the inhibiting reflex of masticatory muscles during functions.


The nature and nurture of epithelial-mesenchymal interactions during tooth morphogenesis. Epithelial-mesenchymal interactions during tooth morphogenesis are inductive and instructive developmental processes as well as permissive and regulatory processes. Data is available to support the early influences of enamel organ epithelium upon a responding mesenchyme in the determination of dental morphogenetic fields (Dryburg, 1967; Miller, 1969). Mesenchymal specificity appears to be operant during tooth shape and form and during the induction of secretary amelogenesis (Kollar, 1972). These heterotypic tissue interactions can be observed in vivo and in vitro. The cellular responses to these interactions appear to be transcriptional, translational and post-translational; as a direct consequence of the interactions, new gene products are synthesized and secreted and/or pre-existing gene products are amplified (Hata and Slavkin, 1978). The mechanism(s) by which epithelial-mesenchymal interactions function may best be learned through critical investigations of differentiation alloantigens, receptors, coupling components within the plasma membrane, translating components by which epigenetic external cues become internal chemical information, and the associations between peripheral and integral proteins within the plasma membrane and intracytoplasmic microfilaments and microtubules.