Quantitative observations of the effect of sex-steroids on the postnatal development of LH-cells. An immunohistochemical study.

The effects of sex-steroids on the LH-cell development in neonatal rats were studied. The cells were stained immunohistochemically by applying anti-HCG serum. On the second day after birth some of the animals of both sexes were gonadectomized and simultaneously injected with testosterone or estradiol (50 or 200 microgram). The remaining animals were either gonadectomized or injected with either one of the sex-steroids. The LH-cell numbers in each group were determined on the 12th day of age from serially cut histological sections of the pituitary. In castrated males the number of LH-cells was about twice that of the intact animals. In the so-called sex-zone, LH-cells tended to be hypertrophied in castrates. These alterations in the appearance of LH-cells did not occur after ovariectomy. In gonadectomized animals injected with sex-steroids (200 microgram), the cells were markedly reduced in number and size, both in males and females. Testosterone injection (50 microgram) into intact newborn animals also suppressed the numerical development of LH-cells, especially in females. These alterations were particularly evident in the sex-zone in both sexes. Thus the present findings show that sex-steroids may be involved in sexual differences in morphological development of LH-cells in newborn rats.


The passage of spermatozoa through the vitelline membrane in the domestic fowl, Gallus gallus.

The developing outer layer of the vitelline membrane of the ovum in the posterior part of the infundibulum of the domestic fowl contains many spermatozoa in nearly parallel orientation with its inner layer. When the acrosomal region of a spermatozoon approaches or contacts the inner layer, promptly undergoes the acrosome reaction. The outer acrosomal membrane and overlying plasma membrane fuse together and the apical region of the acrosome opens, so that the acrosomal contents are released. Meanwhile the spermatozoon remains a time in contact with the surface of the inner layer, and the network of the inner layer just under the tip of the sperm head begins to be dissolved. This dissolution extends downward forming a tunnel, approximately 9 micrometer in diameter. The spermatozoon then passes through the inner layer obliquely via the central region of the tunnel and arrives at the perivitelline space.


The myelination of the cerebellar cortex in the cat.

The myelination of the cerebellar cortex of the cat was investigated in 61 cats aged from 3 hrs post partum to two and a half years. The first myelinated fibers appear at the time of birth in the central medullary ray. Before the onset of myelination, all fibers reach a critical diameter of about 1 micrometer. About the 14th day of life the number of oligodendrocytes in the prospective while matter increases markedly. Thereafter, the oligodendrocytes invade the inner granular layer. It therefore seems that the myelination of the cerebellar cortex proceeds from the central medullary ray towards the granular layer. At the 60th day of postnatal life, most of the afferent and efferent fiber systems are myelinated. These findings are discussed in relation to the development of function and the maturation of the electrical activity of the cerebellar circuit.


Effect of ovarian steroids on DNA synthesis in explanted human adult resting mammary tissues.

A study has been made on the selective influence of the ovarian steroids, estradiol and progesterone, on three distinct parts of cultured, explanted human adult resting mammary tissue: lobules, interlobular and large ducts. The addition of estradiol elicited the highest stimulation of 3H-thymidine incorporation in large ducts. When progesterone was added DNA synthesis occurred mainly in interlobular ducts. The isolated action of both steroids on lobules was quantitatively comparable, but the time sequence of DNA synthesis was different. The possible significance of these findings is discussed.


The nonsurgical retrieval of intracardiac foreign bodies--an international survey.

An international survey of nonsurgical retrieval of intracardiac foreign bodies provided data on 180 published and unpublished cases. The data was analyzed to evaluate the respective merits and drawbacks of the 3 basic retrieval techniques, the snare, the wire basket, and the endoscopy forceps, the routes and methods of insertion, the success rate, and the complications. Eighty percent of foreign bodies were polyethylene central venous pressure catheters, cut in two by the needle introducer. The site of lodgement of these fragments was predictable and determined by the site of entry and length of the fragment. The basic retrieval instruments and their modifications are described. Operating instructions are detailed together with adjunct methods of repositioning fragments for easier retrieval. Factors associated with the small percentage of unsuccessful retrieval attempts include fragments totally in the distal pulmonary artery, extravascular lodging sites, chronically-implanted fragments, and pacemaker-catheter fragments. For the vast majority of cases, however, these simple and uncomplicated techniques have been highly successful and widely utilized in the nonsurgical retrieval of intracardiac foreign bodies.


Loss of indicator in the thermodilution technique.

The use of a second thermistor for detecting the injectate temperature in the extravascular segment of a standard right heart thermodilution catheter is described. Experiments with chilled (0 degrees C) indicator show that the temperature of the injectate as it enters the catheter is always greater than zero and that it depends on time and the gradient between indicator and surroundings; that serial injections made 30 to 60 seconds apart are successively cooler and do not plateau until the third injection. These variables amount to an overestimation in the cardiac output of 3 to 12%.


Aortic root motion determined by ultrasound: relation to cardiac performance in man.

The purpose of this study was to determine if aortic root systolic anteroposterior excursion measured ultrasonically is related to cardiac performance. Aortic motion was 9 +/- 1.5 mm (mean +/- SD) in 30 normal subjects (range 7-12 mm). Ten patients with coronary artery disease and congestive failure and 10 with congestive cardiomyopathy had significantly smaller values of 4 +/- 1.2 and 5 +/- 1.7 mm, respectively (P less than 0.001). In 28 subjects undergoing cardiac catheterization, aortic root motion correlated positively with stroke volume (r = 0.59), but did not correlate significantly with ejection fraction. By increasing heart rate in 14 subjects from 75 to 174 beats/min with atrial pacing, stroke volume decreased from 81 +/- 22 to 34 +/- 14 ml/beat and aortic excursion from 10 +/- 1.6 to 5 +/- 1.5 mm (P less than 0.001). This study has shown: 1) Aortic root motion less than or equal to 6 mm indicates left ventricular dysfunction; 2) stroke volume correlates positively with, but cannot be accurately predicted from, root motion.


Proof by catheterization of mitral valvular origin of a systolic click.

A patient with a loud intermittent midsystolic click presented a problem in differential diagnosis between mitral valve prolapse (intracardiac origin of the click) and left pneumothorax (extracardiac origin). External phonocardiography performed at the time of cardiac catheterization revealed that this loud midsystolic click disappeared whenever a catheter was positioned across the mitral valve. It reappeared whenever the catheter was removed from the transmitral position. Selective left ventriculography confirmed the diagnosis of mitral valve prolapse.


Significance of momentary pressure changes during isovolumic relaxation.

Sudden momentary fluctuations of left ventricular, aortic, right ventricular, and pulmonary arterial pressure were noted during isovolumic relaxation of the respective ventricles. The presence of such transients raised questions related to their meaning and significance. The purpose of this report is to emphasize the nonartifactural nature of these pressure transients and to describe their origin and significance in the cardiac cycle. Pressure transients were observed in 31 of 32 patients with normal aortic valves, and in 17 patients with normal pulmonary valves in whom right-sided measurements were made. Such transients, however, were absent on the left ventricular and aortic pressure recordings of three patients with calcific aortic stenosis. These sudden changes in pressure are indicative of momentary compressions and rarefactions of the blood that occur within the ventricles and their respective arterial chambers. Whenever present, pressure transients were noted to occur coincident with the major aortic or pulmonary components of the second sound. Since intraaterial sound pressure is derived from the pressure signal by litering the low frequencies and amplifying the high frequencies, one can deduce that intraarterial sound pressure is in fact a representation of these pressure changes. The recognition of these pressure transients on an otherwise smooth ventricular, aortic, or pulmonary arterial pressure places in proper perspective their role in the production of the second heart sound.


Mechanism of electrical alternans in patients with pericardial effusion.

Electrical alternans concomitant with pericardial effusion has been considered a pathognomonic sign suggestive of a large effusion with cardiac tamponade, particularly if there is P wave alternans as well as QRS alternans. However, the mechanism of this phenomonon remains controversial. A patient with pericardial effusion secondary to adenocarcinoma of the lung with metastases, pericardial effusion, electrical alternans, and cardiac tamponade was studied by echocardiography, right and left heart catheterization, and pericardiocentesis. Hemodynamic data were consistent with cadiac tamponade. The echocardiogram demonstrated a large anterior and posterior pericardial effusion. Noncongruous motion of the septum and posterior wall was pericardial effusion. Noncongruous motion of the septum and posterior wall was recorded at a rate equal to the heart rate. In addition, congruous motion of the septum and posterior wall was recorded at a rate that was half the heart rate and corresponded to the electrical alternans. The congruous movement disappeared after pericardiocentesis, as did the electrical alternans. The electrical alternans is synchronous with and due to the pendulous movement of the heart within the pericardial sac, as demonstrated by echocardiogram and cineangiograms.


Case report of congenital tricuspid insufficiency.

Congenital tricuspid insufficiency is a rare disease secondary to malformations of the tricuspid valve and their chordae tendinae. Diagnosis is difficult but worthwhile, since surgery can be performed. We report one case repaired by surgery.


Extrinsic compression of the heart by tumor masquerading as cardiac tamponade.

A patient with known intrathoracic tumor presented with findings suggestive of cardiac tamponade. At cardiac catheterization, the entire heart was displaced superiorly and anteriorly by the tumor mass, and this accounted for the observed cardiac hemodynamics, in the absence of discernible pericardial effusion.


Snare retrieval of a catheter fragment with inaccessible ends from the pulmonary artery.

Frequent use of central venous lines has led to an increasing problem with embolized catheter fragments which have become lodged in the right heart and pulmonary vasculature. Removal of catheter fragments is justified because of a high complication rate when they are left in situ. Using a snare retrieval apparatus catheter fragments may be quickly and easily removed. In the past year we have seen 3 patients with embolized catheter fragments. One case was unusual in that its transverse position in the pulmonary vasculature required initial dislodgement with a pigtail catheter before it could be successfully snared. The literature and our experience suggest that most, if not all, catheter fragments in the right heart and pulmonary circulation can be successfully retrieved without resorting to thoracotomy.


Calcification in an intramyocardial mass lesion: isolated calcification of an accessory papillary muscle in a patient with mitral prolapse.

Cardiac catheterization in a 50-year-old male with mitral leaflet prolapsed revealed a filling defect with calcification in the high posterolateral wall. At surgery, the lesion was found to be a calcified accessory papillary muscle with thickened, calcified chordae to the posterior leaflet. The calcification and fibrosis were felt to be due to friction lesions between elongated chordae and the endocardium. Intracardiac calcification in mitral leaflet prolapsed may suggest calcified mitral apparatus.


Activity of partially purified protein chain initiation factors from the livers of dimethylnitrosamine-treated rats.

Partially purified polypeptide chain initiation factors were prepared from the 0.5 M KCl wash of rat liver microsomes. Their activities in connection with dimethylnitrosamine (DMNA)-induced inhibition of protein synthesis were studied by use of the following reactions: (1) poly(U)-directed binding of Phe-tRNA to ribosomes, (2) formation of a GTP-dependent ternary initiation complex with Met-tRNAf, (3) binding of Met-tRNAf to 40-S ribosomal subunits, (4) assembly of a Met-tRNAf containing 80-S ribosomal initiation complex and (5) ribosome-dependent GTPase activity. The inhibition of protein synthesis with DMNA was not associated with a loss of factor activity in any of these reactions. In the binding of Met-tRNAf to 40-S subunits there was a noticeable increase, probably related to the stability of the resulting complex. The Met-tRNA deacylase activity was also increased.


Induction of sister chromatid exchanges by styrene and its presumed metabolite styrene oxide in the presence of rat liver homogenate.

Styrene and its metabolite styrene oxide were tested for their ability to induce sister chromatid exchanges (SCE) in CHO cells. Styrene oxide appeared to be a potent inducer of SCE. Styrene itself did not increase the number of SCE per metaphase, even in the presence of a metabolic activation system. The metabolic activation system decreased the SCE induction caused by styrene oxide. Induction of SCE by styrene in the presence of metabolic activation occurred when cyclohexene oxide was used as an inhibitor of the enzyme epoxide hydrase.


The affinity of cytochrome P-450 for ethyl isocyanide: an explanation of double soret spectra.

The 2 pH dependent peaks formed in the Soret region by the treatment of reduced hepatic microsomes or purified cytochrome P-448 with ethyl isocyanide do not exhibit identical dependence on ethyl isocyanide concentration. This behavior and other facts regarding double Soret spectra can be explained by a simple expostulation involving lipophilic and corrdinate binding of pi-acceptor ligands.


Influence of protein or cystein deficiency on hepatic subcellular distribution of methyl mercury in two rat strains.

The influence of protein deprivation and cystein deficiency on the distribution of methyl mercury between 4 subcellular fractions of liver was studied in 2 rat strains (Wistar, strain R and Sprague-Dawley). Kept on a standard diet, the 2 strains showed a similar distribution pattern, with the highest mercury level found in the cytosol, followed by the mitochondrial, microsomal and nuclei fractions. The protein free diet caused on increase in the total amount of bound mercury in both strains, the greatest increase, being found in livers from strain R rats. The cystein deficient diet, on the other hand, gave rise to diverging results. Whereas the level of mercury bound to the subcellular fractions was increased in livers from strain R rats, it was markedly reduced in livers from Sprague-Dawley rats.


Influence of protein deficiency on the inhibition of hepatic microsomal detoxication by methyl mercury in two rat strains.

N- and C-oxygenation of N,N-dimethylaniline was studied in liver microsomes from 2 rat strains (Wistar, Strain R and Sprague-Dawley) subjected to protein deprivation and methyl mercury pretreatment, separately and in combination. A striking interstrain difference was observed. Strain R microsomes from 2 rat strains (Wistar, Strain R and Sprague-Dawley) subjected to tion, but little effect after methyl mercury pretreatment. With Sprague-Dawley microsomes, C-oxygenation was slightly reduced after both treatments. N-oxygenation was little affected in either strain. Methyl mercury treatment of protein deprived rats strongly inhibited C-oxygenation in microsomes from both strains, with N-oxygenation being unaffected in strain R microsomes whereas markedly reduced in microsomes from Sprague-Dawley.


Stereoselectivity and affinity in molecular pharmacology. III. Structural aspects in the mode of action of natural and synthetic auxins.

Analysis of available potency estimates for 35 pairs of enantiomeric arylcarboxylic acids with auxin activity (flax-root-growth inhibition test) revealed extensive correlations between the activity of the more potent and less potent isomers, as well as between the log of the ratio of potencies and the log potency of the more active isomer when structurally similar analogs are compared. 5 structural subgroups were discernible (n, eudismic-affinity quotient (EAQ), r2); (1) arylpropionic acids (6, -0.36, 0.66); (2) 2-naphthoxy-carboxylic acids (6, +1.07, 0.99); (3) 1-naphthoxycarboxylic acids (3, +1.56, 0.96); (4) ortho-substituted phenoxycarboxylic acids (10, +0.97, 0.96) and (5) ortho-unsubstituted phenoxycarboxylic acids (10, +0.56, 0.70). For achiral lower homologs such as auxin itself 3-indolyl-acetic acid (IAA), phenoxyacetic acid and 1-naphthoxyacetic acid, extrapolated potencies were found to agree well with experimental values. On the basis of these observations an auxin receptor is postulated and binding arrangements are described which explain most of the experimental data available. A 3-point attachment when allowed is the only binding mode compatible with the reported data.


Stereoselectivity and affinity in molecular pharmacology. IV. A search for eudismic-affinity correlations among angiotension II analogues.

In order to establish the applicability of eudismic analysis (correlation between potency and the ratio of isomer potencies), the extensive data reported on the biological activities of angiotensin II analogues were examined. For a series of 13 heptapeptides epimeric at the N-terminal residue, apparent correlations were found for pressor activity in vivo, but not for 10 of them on the basis of their myotropic activity under in vitro conditions. The analogues belongning to sub-groups displaying correlations have side chains of sufficiently different nature so that their grouping is questionable. 3 octapeptides epimeric at the second residue displayed an excellent correlation for their pressor activity. The demonstrated differential metabolic susceptibility of these epimers, however, casts further doubt on the usefulness of the data as a measure of their potency. The lack of a correlation under in vitro conditions would indicate that eudismic-affinity correlations (EAC) may be limited to epimers which differ less in their properties than these angiotensin analogues. Nevertheless, until better receptor affinity estimates become available, the observed correlations may be useful in advancing our knowledge of the angiotensin II receptor in particular, and of stereoselective molecular recognition in general.


[The problems of surgical tactics in the treatment of pancreatic pseudocysts and related complications].

On the basis of 45 cases of operated pseudocyst, the Authors tackle the problem of surgical tactis in treatment of these lesions and any complications. The paper outline the contribution that recent diagnostic methods--such as endoscopic retrograde cholangiopancreatography, computed tomography and ultrasonography--have made to solution of the problem and establishes the criteria for emergency or elective operation. In the first condition, consisting in cases of complications (haemorrhagic, suppurative, perforative etc.), abnormal development of pseudocysts and serious impairment of the patient's general conditions, the treatment of the pseudocyst generally takes the form of external drainage. The second condition, obtainable after a sufficient period of "ripening", usually consists in a cysto-digestive shunt or cysto-parenchymal demolition in view of the high morbidity arising from external drainage. Surgical treatment of the pseudocyst is completed by therapy of any basic chronic pancreatitis and by correction of probable associated lesions affecting the bile and digestive tracts and the splanchnic venous circulation. In the reported cases, 28 patients were treated by cysto-digestive shunt, 8 by cysto-parenchymal demolition and 9 by external drainage. There were 37 combined operations.


[Treatment of early and late complications of surgery of pancreatic pseudocysts].

Among 45 operations for pseudocysts the authors report 9 cases of complications, three of them early (haemorrhage and acute pancreatic necrosis) and six delayed (persistence of fistulae and relapse); in six of these surgery was performed and two of them died. Among the different types of surgery performed, external drainage proved to be the one most burdened by complications (2/3 of cases), while their incidence was far lower in internal shunt (2 cases out of 28) and cysto-parenchmal demolitions (one case out of eight). Attention is drawn to the danger of post-operative haemorrhage and the need to combat this complication with decision. For recurring pseudocysts and for fistulae which do not benefit from conservative treatment, the surgical operation, when it does not result in demolition, must be capable of correcting the canalicular alterations of the base pancreatitis.


[Traumatic rupture of the diaphragm caused by closed injury].

Our experience with 26 Patients who sustained traumatic laceration of the diaphragm caused by blunt forces is described. Automobile accidents were the most frequent cause of rupture and young adult males the most vulnerable. The left hemidiaphragm is most frequently injured, but with sufficient force significant tears in the right hemidiaphragm will occur. Most of these patients sustained injury to multiple organ systems. The preoperative diagnosis of traumatic diaphragmatic hernia is based on a high index suspicion, close and continued observation of the patient, and correct interpretation of roentgenograms of the chest. The mortality rate is high owing to the magnitude of the injuries.


Absence of particle and fiber release from commercial transfusion blood microfilters.

The objective of this study was to evaluate the level of particle or fiber shedding by the five types of commercially available transfusion microfilters (Bentley, Fenwal, Johnson & Johnson, Pall and Pioneer Filters). The study was performed in a class 100 laminar flow clean bench in order to minimize particulate contamination from extraneous sources. Particle-free phosphate buffered saline was flushed through each of 12 filters of each type. The effluent particles or fibers were collected on clean Millipore filters, and their number and size determined by light microscopy and by examination of photographs of the whole Millipore filters. In addition in the case of selected representative particles identification was sought by means of scanning electron microscopy. Small particles in the effluent media were electronically counted. The microfilters did not release significant quantities of particles of fibers greater than 10 micrometer at filtration rates of 300--600 cc/min. No release of any characteristic particles or fibers was observed for any of the filter types. The present study indicates that insignificant levels of particulate matter would be introduced into blood by any of the five types of blood microfilter.


Early detection of hypovolemia from directional arterial flow velocity.

The effect of hypovolemia on femoral artery vascular resistance and directional arterial flow velocity was determined in six mongrel dogs. Progressive withdrawal of blood was associated with an increase in femoral arterial resistance and reverse flow velocity and a decrease in forward flow velocity. The percentage increase in the ratio of peak reverse to peak forward flow velocity (Vr/Vf) varied in a positive linear fashion with the percent increase in femoral artery vascular resistance, (r = 0.69, P less than 0.001). The femoral arterial peripheral vascular resistance and peak Vr/Vf increased significantly before arterial pressure declined. These alterations in peak Vr/Vf occur early in the course of hypovolemia and are a sensitive index of extremity hemodynamics associated with hemorrhagic induced hypovolemia.


Effect of endotoxin on glucose uptake by the isolated forelimb of the dog.

Recent research has demonstrated that an increase in glucose utilization by skeletal muscle occurs in hemorrhagic shock. It is conceivable that the hypoglycemia of gram-negative septic shock is, in part, due to increased glucose utilization by peripheral tissues. The hypothesis tested in this study was that there is an increase in glucose uptake by the isolated innervated and/or denervated forelimb of the dog subjected to endotoxin shock. Results indicate that endotoxin does not affect a net increase of glucose uptake by the isolated forelimb. No increase in uptake occurred when blood glucose concentration was normal. However, when endotoxin hypotension induced a significant hyperglycemia or when arterial glucose concentration was elevated by glucose administration an apparent increase in forelimb glucose uptake occurred. It is concluded that endotoxin does not increase the uptake of glucose by skin and muscle except that it causes hyperglycemia secondary to increased sympathoadrenal discharge in the shock state. Thus, if the dog becomes sufficiently hyperglycemic, an apparent increase in glucose uptake occurs, probably because of accumulation of glucose in the interstititial space of skin and muscle.


Plasma cathepsin activity and reticuloendothelial phagocytic function during hemorrhagic shock.

The present study evaluated two forms of hemorrhagic shock in terms of changes in plasma lysosomal enzyme activity, reticuloendothelial system (RES) phagocytic function, and plasma opsonic activity. Hemorrhagic shock was induced in rats by withdrawal of a fixed volume of blood equivalent to 3% body weight or by maintaining the arterial blood pressure at 40--45 mm Hg. Plasma cathepsin activity did not increase until after one hour of hypotension, and was increased 2.7-fold two hours after a 3% body weight hemorrhage and 11-fold after two hours at a blood pressure of 40--45 mm Hg. Phagocytic index and plasma opsonic activity were decreased in animals reinfused at 0, 30, or 120 minutes following a 3% body weight hemorrhage and in animals reinfused 0, 30, and 90 minutes following hemorrhage to a blood pressure of 40 mm Hg. There was a strong temporal relationship between the changes in phagocytic index and plasma opsonic activity; however, the decrease in RES function occurred earlier than the increase in plasma lysosomal enzyme activity. These results suggest that the depression of RES function during shock may be mediated, in part, by a deficit in circulating opsonic activity and that RES depression occurs prior to shock-induced cellular injury during hemorrhagic shock.


Use of play materials in treating a severely handicapped child.

A 4-year-old boy with a physical handicap severe enough to preclude his manipulating materials, participated in a play intervention designed to help him to deal with some of his limitations. His skill in communicating to the therapist and in utilizing vicarious experiences allowed him to participate fully and successfully in therapy, although several modifications had to be made in the usual play procedures. The basic techniques of play therapy may therefore be of use to other motorically handicapped children who are capable of verbalizing and fantasizing. During the course of the therapy, this child also evidenced some unusual perceptions of the world. The lack of opportunity to have the customary sensorimotor experiences had apparently delayed his development of object permanence. This finding is consistent with Piaget's theory, which emphasized early motoric behaviours as prerequisites to later intellectual operations.


Cardiac output and regional blood flow following trauma.

The changes in cardiac output (Q), regional blood blow (Qr) and regional vascular resistance, and arterial pressure were studied in rats subjected to moderate (LD0) or severe (LD50) traumatic shock. Q and Qr were determined using microspheres at 15, 60 and 180 min posttrauma. Arterial pressure decreased in both groups at 15 min and recovered by 3 hr after sublethal (LD0) trauma, while arterial pressure did not return to control levels after LD50 trauma. Q decreased in both groups at 15 min and returned to control only in the LD0 trauma group by 3 hr. Cerebral, coronary, and hepatic arterial flows and resistances were maintained in both groups. Renal, intestinal, and splenic flows decreased and resistances increased in both groups by 15 min and returned to control levels by 3 hr only in the LD0 trauma group. Total hepatic and hepatic portal flows decreased at 60 min and returned to control levels at 3 hr after LD0 trauma, while there was significant depression in these parameters 3 hr after LD50 trauma. Therefore, sublethal and severe trauma resulted in early redistribution of flow favoring the coronary, cerebral, and hepatic arterial beds. However, renal, intestinal, splenic, and portal flows remained depressed only in severely traumatized rats, suggesting that continued hypoperfusion is a factor in the multiple organ failure and death following severe traumatic injury.


Sharing the caring: a Swedish approach to short-term care of mentally handicapped children.

The setting up of a short-stay home, which offers temporary care for mentally handicapped children living with their parents in the Swedish county of Ostergötland, is described. It illustrates an approach which parents, care staff and the supervising psychologist have all found satisfactory in contrast to the provision available in hospital units.


Inhibited response to isoproterenol and altered action potential of beating rat heart cells by human serum in septic shock.

Human serum, obtained within 24 hours after the onset of septic shock, was evaluated for its effects on the chronotropic response of cultured rat myocardial cells to isoproterenol. Transmembrane action potential (AP) was measured in some experiments. Sera obtained after the first four to five hours, when central venous pressure (CVP) was normal or high, inhibited increased cell beats, while this property was not evidenced for samples taken soon after septic shock when CVP was low. Sera were also found to alter AP in much the same way as Sotalol, an adrenergic beta-blocking drug. These two effects were never observed with control sera obtained from healthy male adults at rest. These findings demonstrate that sera from patients in septic shock depress the beta-adrenergic response of rat myocardial cells, after the early phase of septic shock characterized by sympathoadrenergic activity. They strongly suggest the mediation of unidentified humoral factors, which might interfere in the pathogenesis of myocardial dysfunction during the intermediate phase of septic shock.


Reentrant ventricular arrhythmias in the late myocardial infarction period. 6. Effect of the autonomic system.

The effect of the autonomic system on conduction disorders in the infarction zone (IZ) and related reentrant ventricular arrhythmias (RVA) in the late myocardial infarction period in the dog was studied utilizing averaged recordings of the reentrant pathways from the epicardial surface of the IZ. Vagal (V) stimulation was found to have no significant direct electrophysiologic effect while sympathetic (S) stimulation resulted in a direct slight improvement of conduction in the IZ. However, because of the marked rate-dependency of conduction in the IZ, the effects of both V and S stimulation were modified through changes in the heart rate. The bradycardia produced by V stimulation resulted in improvement of conduction in the IZ and disappearance of RVA, while the tachycardia induced by S stimulation resulted in worsening of conduction in the IZ and the occurrence of RVA. Thus, in spite of its slight enhancing effect on conduction in the IZ, the propensity of S stimulation to induce RVA was primarily due to its tachycardiac effect.


Stroke volume calculated from the mitral valve echogram in patients with and without ventricular dyssynergy.

A formula was derived for calculating mitral valve stroke volume (MVSV) using the rate of mitral valve (MV) opening (DE slope on the MV echogram), the vertical disease between the mitral leaflet echoes early in diastole (EE), the electrocardiographic PR interval and heart rate. The formula was tested prospectively on 80 consecutive patients from whom 95 simultaneous MV echograms and either thermodilution (45) or Fick (50) cardiac outputs were obtained. Sixteen patients were normal; 54 had coronary artery disease; three had cardiomyopathy; and seven had nonrheumatic mitral regurgitation (MR). Linear regression for stroke volume was r = 0.90, SEE +/- 6, and for cardiac output r = 0.83, SEE +/- 0.5 liter for the 73 patients without MR. The presence or absence of ventricular dyssynergy did not alter statistical findings. MVSV consistently overestimated forward stroke volume for the seven patients with MR. This study shows that the MV echogram provides an accurate, widely applicable method for calculating MVSV.


Physician and patient exposure during cardiac catheterization.

A survey of the literature was conducted to establish the anticipated ranges of exposure to both physicians and patients during cardiac catheterization. A brief explanation of a technic for using time-lapse photography and a computer model for exposure calculation is presented. The thermoluminescent dosimeter (TLD) results used as controls for exposure values calculated by the developed technique are presented in detail. Physician eye exposures of approximately 20 mR per cardiac catheterization procedure were measured, which would suggest a limit of five procedures per week for physicians. The average patient skin entrance exposure of 28 R is high, as is the 12 mR gonadal exposure; however, they are accepted because of the possible benefits of the procedure.


Use of time interval histographic output from echo-Doppler to detect left-to-right atrial shunts.

The primary purpose of this study was to attempt to select, by examination of the time interval histogram (TIH) output of a range gated pulsed Doppler (RGPD), all children with left-to-right shunt at the atrial level from a pool of 57 children. Fifty-four of the children had various forms of acyanostic cardiac disease. A secondary purpose was to identify any associated lesions in those children with atrial defects. Examiners were unfamiliar with the children and their diagnoses. Results were interpreted independently by two examiners. Detection of diastolic TIH dispersion was used when studying the right atrial outflow tract to separate children with atrial left-to-right shunts from control children. All controls were judged negative by this technique, and 13 of 14 children with atrial shunts were detected by both examiners; the 14th was detected by one examiner. Of a total of 308 TIH decisions on the atrial shunt group, 298 were made identically by both examiners for a 97.7% agreement, demonstrating the objectivity of the method. This study demonstrated the usefulness of the TIH evaluation, indicating that continued investigation and equipment improvements are warranted.


Hemodynamic effects of intravenous phentolamine in low output cardiac failu;e. Dose-response relationships.

Nineteen patients with chronic low output cardiac failure were studied before, during and after infusion of phentolamine in doses of 10, 20, 30 and 40 microgram/kg/min. Significant reduction of left- and right-sided pressures and increases in cardiac index and heart rate (HR) were present within 15 minutes of starting phentolamine at the 10 microgram/kg/min dose. Minimal additional effect was observed at 30 minutes. Increased dose from 10 to 20 mu/kg/min resulted in small but significant (P less than 0.05) additional reduction in pressures and increases in HR. No additional significant changes occurred at doses of 30 or 40 microgram/kg/min. Significant hemodynamic changes persisted for at least an hour (53 +/- 3 min) after the phentolamine infusion was discontinued. Near maximal ;emodynamic effects occur within 15 minutes of starting phentolamine infusion and can be achieved at doses of 10 to 20 microgram/kg/min. Increased HR during phentolamine infusion may limit its usefulness in patients with ischemic heart disease.


Multiple coronary arterioventricular fistulae.

A 62-year-old man who died suddenly was found at autopsy to have multiple coronary arteriosystemic fistulae involving all three major coronary arteries and both ventricles. This is the second such case reported and the first with biventricular involvement and autopsy findings. A congenital bicuspid valve was also present. Numerous small blood vessels opened onto the endocardial surface of both ventricles and there were microscopic foci of persistent embryonic spongy myocardium.


The development of pulmonary vascular obstructive disease after successful Mustard operation in early infancy.

Pulmonary vascular obstructive disease developed postoperatively in an infant with aortopulmonary transposition and intact ventricular septum who underwent a Mustard operation in 3 months of age. Preoperative catheterization had shown normal pulmonary artery pressures. Four months after surgery, catheterization showed pulmonary artery systolic pressure above the systemic level and a tortuous, attenuated pulmonary vascular tree visualized angiographically. Early corrective surgery may not preclude the development of pulmonary vascular obstructive disease in patients with aortopulmonary transposition.


A case-control study of regular aspirin use and coronary deaths.

Information was collected for a large number of coronary risk factors on a series of 568 married, white men, aged 30--70 years, who died from coronary heart disease. Information on the same risk factors was collected on an equal number of living controls matched on age, sex, marital status and neighborhood. For regular aspirin users (i.e. greater than or equal to 4 days per week) compared with non-users, the crude matched pair risk ratio estimate was 1.0 (95% confidence limits 0.9--1.1). Even after controlling for possible confounding effects of other variables using a paired multiple logistic regression analysis, there was no evidence of association. These data provide no evidence for a preventive role of regular aspirin intake in coronary deaths.


The Björk-Shiley aortic prosthesis: flow characteristics, thrombus formation and tissue overgrowth.

Thrombus formation and tissue overgrowth were observed in nine Björk-Shiley aortic prostheses recovered six months or longer after implantation. These pathologic findings may be attributed to the flow characteristics of the prosthesis. The open disc of the valve separates the flow into two unequal regions. Varying degrees of thrombus formation were observed in the minor outflow region, including the depression in the aortic face of the disc and the metal strut bridging this area. Tissue overgrowth was noted along the perimeter of the prosthesis adjacent to the minor outflow region. That overgrowth further reduced the available cross section for flow in this already constrained area. In vitro velocity measurements with a laser-Doppler anemometer identified a zone of stagnation about 20 mm wide near the aortic face of the disc. The average velocities in the major and minor outflow regions were around 100 and 25 cm/sec, respectively, and the corresponding peak-shear stresses were approximately 700 and 150 dynes/cm2. There is reason, then, to attribute the thrombus formation and tissue overgrowth to the stagnation zone and the low shear in the minor outflow region.


A chronically implanted system for automatic defibrillation in active conscious dogs. Experimental model for treatment of sudden death from ventricular fibrillation.

Ventricular defibrillation was acheived in active conscious dogs with a chronically implanted automatic system composed of a defibrillator and an alternating current fibrillator. The hermetically sealed defibrillator is encased in titanium, weighs 250 g and has a volume of 145 ml. The sensor continuously monitors ventricular electircal activity and recognizes fibrillation by the absence of isoelectric potential segments. Fibrillation is induced by placing a magnet over the implanted fibrillator. The resulting syncope closely resembles the clinical entity of sudden death, while the defibrillator automatically restores normal rhythm with a truncated exponential pulse of 30 J, 15 seconds after the onset of the arrhythmia. The operational status of the defibrillator can be tested in vitro and noninvasively in vivo with an external analyzer. This experimental model allows for the first time a long-term study of the automatic implantable defibrillator approach to prevent sudden death from ventricular fibrillation under a variety of physiopathologic conditions.


Noninvasive recording of His-Purkinje activity in man by ORS-triggered signal averaging.

Mobile instrumentation and a clinically applicable method have been developed for external His bundle recording. High gain signal amplification (10)(5) filtering (30--300 HZ) and averaging (128 or 256 consecutive cycles) are used. Acquisition of signals arising in the P-R interval is triggered by the patient's QRS signal at the end of that interval. The precordial bipolar electrodiogram is digitized at 5k HZ with 8 bit resolution and transferred to a 1,024 word, 18 bit signal averager. The averaged signal is then displayed on an oscilloscope and photographed. Good correlations were obtained between direct intracardiac and precordial recordings in experimental animals and in humans. Noise level after averaging was below 0.3 microV, and there was good elimination of asynchronous atrial and ectopic ventricular activity. With averaging of 128 or 256 consecutive cycles, the signal attenuation after propagation to the chest wall was in the range 1:2000 to 1:4000 in comparison with the directly recorded His bundle activity deflections. The noninvasive method may be of value in follow-up of acute and chronic disturbances of atrioventricular conduction, as well as in studies of effects of pharmacologic interventions.


IgE antibodies to wheat flour components. Studies with sera from subjects with baker's asthma or coeliac condition.

Sera from two subjects with baker's asthma and six patients with coeliac condition were examined for the presence of IgE antibodies with specificities for wheat flour components. Sera were studied using the radioallergosorbent test (RAST) together with whole flour and thirteen purified and partially purified flour fractions. IgE antibodies to a number of flour components were demonstrated in the allergic bakers' sera, but the strongest reactivities were observed with wheat albumins and globulins. A more detailed examination of the flour water-soluble proteins using RAST inhibition methods demonstrated that albumins were more reactive with the allergic sera than the globulins. Apart from the results with the water-soluble proteins, the two sera showed a different pattern of reactivity with the other flour preparations. No IgE antibodies to whole flour or any of the flour components, including A gliadin, were found in the coeliac sera. Failure to detect wheat gluten- or gliadin-specific IgE antibodies indicates that IgE-mediated reactions are not important in the pathogenesis of coeliac condition. Levels of total IgE in the sera from the coeliac subjects were elevated and, with two of the sera, some success was achieved in identifying the allergens responsible for the elevation. We propose that elevation of serum IgE may frequently occur in coeliac condition and may arise due to an increased uptake of antigens via the damaged intestinal mucosa.


Activation of the alternative pathway of complement by grain. I. C3PA conversion and quantification of complement consumption by rye.

Ground whole rye and airborne rye dust of comparable size distribution were tested for their ability to activate the complement cascade via the alternative pathway. Precipitin-negative pooled normal human serum was incubated with increasing amounts of the two rye dusts. Electrophoresis of the resultant supernatant fluids demonstrated the conversion of the proactivator of the third component of complement to the gamma-migrating activator of the third component. This activation was completely prevented by pre-treating the serum with the chelator EDTA, while pre-treatment with EGTA allowed suboptimal arc conversion, strongly implying that complement was activated via the alternative pathway. Quantification of the supernanant fluids showed dose-dependent complement consumption as defined by both CH100 immunodiffusion and CH50 tube haemolytic techniques. Airborne rye dust showed a greater quantitative potential than ground whole rye for activating the alternative pathway. These results indicate the possibility of the direct action of airborne organic dusts on the induction of inflammatory sequelae in the lungs of both sensitized and unsensitized individuals.


Tyrophagus putrescentiae: an allergenically important mite.

The incidence of positive skin tests to the mite Tyrophagus putrescentiae was measured and compared with skin reactions to Dermatophagoides pteronyssinus and other allergens in Australian and New Guinean populations, and mite counts were determined in Sydney and New Guinea houses. Positive reactions to T. putrescentiae were as frequent as those for D. pteronyssinus in asthmatics in Sydney and were the commonest positive reactions in the normal New Guinea population. T. putrescentiae-specific serum IgE levels were determined and some IgG cross-reactions of D. pteronyssinus and T. putrescentiae antigens were demonstrated. It is suggested that T. putrescentiae is an important source of allergen and should be considered whenever D. pteronyssinus is thought to be a problem. A convenient method for culturing and isolating T. putrescentiae is described.


Atopy and bronchial reactivity in Australian and Melanesian populations.

In order to compare the prevalence of atopy and bronchial hyperreactivity among Papua New Guinian (P.N.G.) and Australian populations, skin prick tests and methacholine bronchial challenge tests were performed. A civilian and an army population from each country were examined and those with past or present asthma, recent respiratory tract infection and chronic lung disease were excluded. No statistical difference in the prevalence of atopy was found between the four populations. In the P.N.G. population 40 and 49%, and in the Australian population 27 and 39%, were found to be atopic, without symptoms of past or present allergic disease. The house dust mites were the commonest allergens in all populations. In response to methacholine (0.3 mg), only 6% of subjects had falls in 1 sec forced expiratory volume (FEV1) of more than 12% (upper limit of normal range) and only two were in the asthmatic range. There was no correlation between the degree of bronchial hyperreactivity and atopic status; however, the degree of bronchial hyperreactivity was slightly greater in the New Guinea civilian than in the Australian civilian population. In the absence of asthma, atopic status does not appear to cause increased bronchial reactivity, suggesting that some factor other than atopy must be present for the development of bronchial hyperreactivity characteristic of asthma.


Estimation of theophylline in plasma by thin-layer chromatography.

1. A quantitative thin-layer chromatographic procedure for theophylline has been evaluated. An internal standard, 3-isobutyl-1-methylxanthine, a compound similar in properties to those of theophylline is added to the specimen prior to extraction to eliminate the need for accurate measurements of volume during extraction or analysis. 2. This method does not show interference from other xanthines and from a number of drugs commonly prescribed with thephylline. It has an acceptable correlation with a reference gas-liquid chromatographic procedure. 3. This procedure is capable of handling batches of six or more samples faster than the serial processing of either high performance liquid chromatography or gas-liquid chromatography.


The production of creatine kinase isozyme BB in sera of a patient with prostatic carcinoma and in tumor homogenates.

1. A CK(BB) fraction was observed in sera of a patient with prostatic carcinoma. The fraction accounted for 59% of the total enzyme activity. A metastatic tumor of a prostatic carcinoma was observed to contain solely the CK(BB) isozyme. An embryonal testicular carcinoma was observed to have a higher percentage of the CK(BB) fraction when compared to the adjacent tumor free testicular tissue in a third patient. These studies suggested that in certain carcinomas there are tissue isozyme modifications at the molecular level. The isozymic modification was suggested as a reversion towards an embroyonic pattern as the adult molecular form tended to disappear while the fetal form increased. This too suggests that the isozymes of CK may be a useful model in elucidating the mechanism through which this transition occurs. 2. The high percentage of CK(BB) in the sera of the patient with metastasis was discussed. The origin could not be determined, but either a primary tumor or a metastatic tumor by their enzyme modifications could account for this increased fraction in sera.


An automated method for the analysis of nicotinic acid in serum.

Rational antihyperlipemic therapy based on the use of nicotinic acid and its derivatives and/or combinations demands a rapid and reliable method for monitoring nicotinic acid blood levels. To this end, an automated colorimetric method for the analysis of nicotinic acid in serum has been elaborated. For serum from rats, dogs and man given p.o. nicotinic acid or 3-pyridine methanol, the method is greater than 90% specific for nicotinic acid. The limit detection for nicotinic acid is 2 microgram/ml based on 0.15 ml of serum or 0.3 microgram/ml based on 1.5 ml of serum.


Automation of diphenylhydantoin and phenobarbital measurements using the ABA-100 with emit reagents.

1. The EMIT-AED procedures for phenobarbital and diphenylhydantoin have been adapted for use on the ABA-100. 2. A basic language computer program has been developed for data reduction and quality control. 3. Within-run and run-to-run coefficients of variations were, in general, less than 8% across the concentration range tested. 4. Performance data on agreement of duplicates and recovery from "spiked" samples were aceptable. 5. The automated procedure provides a two-thirds savings in reagents.


Sensitivity of in vitro diagnostic dipstick tests to urinary protein.

Two commonly used brands of reagent strip (dipsticks) were evlauated for their sensitivity to Bence-Jones and seven other urinary proteins. Both brands showed significant differences in sensitivity to albumin, glycoprotein, ribonuclease and lysozyme; both were most sensitive to albumin and least sensitive to globulin. Furthermore, their comparative sensitivities to these proteins also differed markedly. These differences in sensitivity could lead to underestimation of protein content in urine specimens. Tests on urines from patients with multiple myeloma showed that a negative urinary dipstick test result did not rule out the presence of the disease.


Reaction rate studies of two enzymatic cholesterol reagent kits.

Reaction rate studies were carried out on various specimens using two commercial enzymatic cholesterol determination reagent kits (BMC and Worthington). The time required for complete colour formation differed between the two reagent systems and each kit required different incubation times for the standards and specimens to come to color completion. The choice of standards was found to be very important when using these enzymatic kits.


A semi automated procedure for the measurement of 3-methoxy-4 hydroxy mandelic acid.

A semi automated procedure for the determination of 3-methoxy-4-hydroxy-mandelic acid (HMMA) in urine has been evaluated. This procedure offers advantages in simplicity, speed and precision over existing manual techniques which utilize spectrophotometric fluorimetric and gas liquid chromatographic methods. The urine is extracted with ethyl acetate from a highly acidic sample, purified by extraction into acetate buffer and the diazo colour reaction developed. All stages of the procedure are carried out using the Brown and semi-automatic extractor equipped with partition tube. The within and between assay coefficient of variation obtained on pooled freeze-dried urine samples was 6.7% and 7.7% respectively.


Bis(2-ethylhexyl)phthalate concentrations in the serum of hemodialysis patients.

Bis(2-ethylhexyl) phthalate is extracted from artificial kidneys, both in vivo and in vitro. Perfusion of whole blood through arterial-,venous tubing (that supplied with the dialyzer) for 1 h in vitro yielded 3.23 mg of the compound, while similar perfusion of the tubing plus the artificial kidney yielded 6.10 mg. Its mean concentration after dialysis in patients undergoing hemodialysis was 751 microgram/liter of serum. Patients who had undergone more than 50 hemodialysis treatments showed significantly higher postdialysis concentrations than patients who had undergone fewer. Uptake of bis(2-ethylhexyl) phthalate by the blood during a dialysis session followed two patterns. One set of patients showed a maximum concentration at 3 h, the second set showed a steady increase until the end of dialysis. Bis(2-ethylhexyl) phthalate appeared to be rapidly cleared from blood, most being removed within 5 to 7 h of completion of dialysis.


Micromethod for determination of creatinine in biological fluids by high-performance liquid chromatography.

We describe a procedure for the rapid and specific measurement of creatinine, in which it is separated from other compounds in serum or urine by paired-ion chromatography and is quantified by measuring its absorbance at 200 nm. The procedure can be done on as little as 10 microliter of serum. Between-day precision studies for concentrations of 13 and 62 mg/liter yielded coefficients of variation of 6.9 and 2.2%, respectively. Analytical recovery of various amounts of creatinine added to plasma exceeded 95% in all cases. The proposed procedure was compared with the continuous-flow procedure by analyzing a series of serum and urine specimens by both methods. There was excellent agreement for urine specimens, but with serum the results by the present method were significantly (P less than 0.001) lower.


Urinary polyamine excretion during the menstrual cycle.

Urinary polyamines were measured by a fluorometric thin-layer chromatographic technique in samples collected daily throughout a single menstrual cycle by each of 13 healthy women. Polyamine excretion fluctuated considerably, but excretion of putrescine, spermidine, and spermine combined was consistently greatest during menstruation, sometimes extending into the early follicular phase of the cycle. Enhanced excretion of polyamines was also noticed in many individuals at the approximate time of ovulation.


High-performance liquid-chromatographic assay for chloramphenicol in biological fluids.

We describe a method for measuring chloramphenicol by high-performance liquid chromatography. The assay involves a single extraction of the biological sample with ether, evaporation of the extract, and chromatography of the residue, redissolved in methanol. A reversed-phase column with an eluting solvent of methanol/water (30/70 by vol) is used. Chloramphenicol is eluted from the column in about 4 min and is well separated from the internal standard (mephenesin), which is eluted at 5.5 min. Absorption of the effluent at 278 nm is monitored and measured. As little as 0.1 microgram of the antibiotic can be analyzed after its extraction from a 0.1-ml sample. The method is suitable for rapid and specific analysis for the drug in plasma, urine, cerebrospinal fluid, and other biological fluids.


Improved iodination of peptides for radioimmunoassay and membrane radioreceptor assay.

Generally applicable methods for iodinating and purifying small peptide radiolabels for radioimmunoassay and membrane radioreceptor are described in detail. Resulting improvements in radioreceptor assay and radioimmunoassay, as well as results of analyses of specific activity, separation from unlabeled peptide, and storage characteristics, are presented for luliberin, corticotropin, melanotropin, and calcitonin.


Simple, rapid method for determination of propionic acid and other short-chain fatty acids in serum.

A semimicro method for measuring propionic and other short-chain fatty acids in serum is presented. The procedure requires as little as 200 microliter of serum. Data are provided for premature infants, children, adults, and patients with propionicacidemia.


(Washington University case conference): acute pancreatitis, hyperlipemia, and normal amylase.

This case focuses on the biochemical findings in acute pancreatitis and the role of the laboratory in the diagnosis and management of such patients. It also illustrates a major unappreciated problem in the use of amylase determinations in patients with acute pancreatitis: normal serum amylase activity in the presence of hyperlipemia.


Evaluation of the JET technique for extracting drugs from urine.

A rapid extraction method preliminary to analysis for drugs in urine is described. Extraction columns containing purified cotton fiber (JETUBE, Manhattan Instrument Co., Santa Monica, Calif.) are shown to give high (approximately 90-97%) extraction efficiencies for some commonly prescribed or abused drugs, notably phenobarbital, amphetamine, morphine, and methadone. Analysis time, extraction efficiency, convenience, and eluate purity with a modified JET procedure are shown to be superior to results obtained with XAD-2 resin columns.


Posture and the composition of plasma.

For a group of normal medical students, we examined the effect of posture on the concentration of a number of constituents in plasma. On standing, there is a significant increase in plasma total protein, albumin, calcium, alkaline phosphatase, bilirubin, and cholesterol--all proteins or substances bound to protein. Although it is possible to make an allowance for postural variations in plasma calcium, no correction is possible for changes in protein concentrations and care is needed whenever the precise values are important, as in the follow-up of patients with the nephrotic syndrome.


Creatine kinase isoenzyme variants in human serum.

In serum from about 800 patients, total creatine kinase and its subunit B activities were determined by the recommended Scandinavian creatine kinase method in the absence and presence of a creatine kinase M subunit inhibitory antibody. Eight patients had supranormal subunit B activities, but normal or near-normal values for total creatine kinase activity. Electrophoresis of sera from these eight patients showed, in addition to the normally migrating isoenzyme MM, one or two abnormally migrating creatine kinase isoenzyme bands, located between normally migrating isoenzymes MM and MB. Experimental data suggest that these abnormal bands may be isoenzyme BB with changed electrophoretic mobility. The eight patients had no particular disorder in common.


Myoglobinemia in children with progressive muscular dystrophy.

Out of 13 patients with congenital muscular dystrophy myoglobinemia was proven in four, and nine of 13 cases of Duchenne dystrophy showed myoglobinemia by counterimmunoelectrophoretic technique. Serum myoglobin was positive in 14 out of 15 patients whose serum creatinine phosphokinase (CPK) levels rose above 2500 units, whereas positive myoglobinemia was obtained in only one patient in eleven with lower CPK levels. All the myoglobinemic patients were less than 5 years of age in the case of congenital muscular dystrophy and less than 9 years of age in the case of Duchenne dystrophy. Thus, the leakage of myoglobin into the serum from the damaged muscle seemed closely correlated to the age of the patients and level of serum CPK, but not to the type of disease.


Tryptophan metabolism in Japanese and British women and its relationship to endogenous steroid levels.

The excretion of the tryptophan metabolites L-kynurenine, 3-hydroxykynurenine, 3-hydroxyanthranilic acid and xanthurenic acid, by normal Japanese and British pre-menopausal, menopausal and post-menopausal women was measured after a loading dose of L-tryptophan. No significant difference was found between the mean excretion levels of the two races. A correlation with the level of plasma oestradiol and the excretion of L-kynurenine and also with the total of the four metabolites was found in pre-menopausal British women but not in Japanese women.


Similar behaviour of lecithin:cholesterol acyltransferase and pseudocholinesterase in liver disease and hyperlipoproteinemia.

Using exogenous substrate for its assay, lecithin:cholesterol acyltransferase (LCAT) was found to be decreased in liver disease and higher than normal in endogenous hypertriglyceridemia. LCAT activity was positively correlated with serum cholesterol and triglyceride. However in the six patients with excessive hypertriglyceridemia (type V), LCAT activity was lower than in type IV hyperlipoproteinemia. LCAT activity was not changed significantly in type II-a hyperlipoproteinemia. A striking parallel was noted between plasma LCAT and serum pseudocholinesterase activity. It suggested that both these liver secretion enzymes might be induced by an accelerated turnover of serum lipids and lipoproteins. Pathogenical implications of these findings are briefly discussed.


An immunoradiometric assay for the acidic ferritin of human heart: application to human tissues, cells and serum.

Human tissues contain ferritin molecules with a range of isoelectric points but immunoassays for detecting serum ferritin have generally employed antibodies to the more basic liver or spleen proteins. To study the distribution of more acidic ferritins in tissues and serum acidic ferritin has been isolated from normal human heart and a two-site immunoradiometric assay for this protein developed. This assay gives little cross-reaction with spleen ferritin. Tissue ferritins have been fractionated by anion exchange chromatography and assayed with both spleen and heart antibodies. The spleen ferritin assay detects the more basic ferritin and the heart ferritin assay the more acidic ferritin. Acidic ferritins were found in heart, kidney, reticulocytes and HeLa cells. In sera from normal subjects and patients with iron overload, myocardial infarction, leukaemia and carcinoma only low concentrations of heart ferritin were found, although in the pathological sera spleen ferritin concentrations were generally raised. Circulating ferritin contains only a small proportion of molecules with the immunological characteristics of acidic heart ferritin.


Lead, copper, and cadmium in teeth of normal and mentally retarded children.

Whole teeth obtained from handicapped children and from controls have been analysed for lead by anodic stripping voltammetry. No significant differences were found between the two groups. Teeth originating from the same patient showed systematic variations in lead content that are dependant on anatomical tooth type. The nature of this association is discussed. Analyses of sectioned teeth revealed, for cadmium and copper, unexpectedly large variations. High concentrations of cadmium found in the tips of deciduous incisor teeth indicate a probable contribution from maternal blood.


Urinary excretion of macromolecular acidic glycosaminoglycans in Werner's syndrome.

The urinary acidic glycosaminoglycans (AGAG) of Werner's syndrome were isolated, purified and characterized by gel-chromatography, cellulose acetate electrophoresis, chemical analysis, streptomyces hyaluronidase susceptibility and viscometry. The AGAG appeared at the first peaks of the 0.6 M and 0.8 M fractions obtained through Sephadex G-100 were mainly a a hyaluronic acid (HA). HA was composed of 16% of the urinary AGAG. The AGAG at the first peak had the maximum molecular weight of 360 000 in the 0.8 M fraction followed by lesser molecular weights in the other fractions.


Human serum Zn-alpha2-glycoprotein in amniotic fluid.

Human serum Zn-alpha2-glycoprotein (Zn-alpha2-GP) was found to be present in the amniotic fluid in the mean concentration of 0.98 +/- 0.40 mg/100 ml, which represents about one-tenth of its concentration in the maternal serum (9.65 +/- 1.18 mg/100 ml). Its concentration in the amniotic fluid was proportional to the amniotic fluid total protein and very approximately to the maternal serum Zn-alpha2-GP. The relationship between the maternal serum Zn-alpha2GP and the maternal serum total protein as well as between the amniotic fluid total protein and the maternal serum total protein was found to be not significant. The amniotic fluid Zn-alpha2-GP as well as the amniotic fluid total protein showed some increase during gestation to reach the highest values at the end of the second trimester. At present both the origin and significance of the amniotic fluid Zn-alpha2-GP are not known.


Comparison of alkaline phosphatase isoenzymes determined by an inhibition method and by electrophoresis.

A chemical inhibition procedure suitable for the routine determination of alkaline phosphatase (AP) isoenzymes in serum has been adapted for use with a fast kinetic analyzer, System Olli 3000. The results of this procedure are compared with the electrophoretic separation of alkaline phosphatase isoenzymes. The comparison of the results obtained indicates that the AP-urea/AP ratio can be used to differentiate between patients with bone and liver disease and that it is possible to estimate the relative bone and liver isoenzyme activities from this ratio quickly using two simple equations.


Human fetal organ alkaline phosphatases.

The properties of human fetal alkaline phosphatase (ALP) have been compared with those of purified human adult hepatic and intestinal ALPs. The ALPs from different human fetal organs were divided into two groups. One terminated universal type was presented in fetal liver, spleen, adrenal, kidney, lung, heart, pancreas, thymus and bone, and was similar to adult hepatic-type ALP. The other terminated intestinal type was presented in fetal intestine and meconium and was similar to adult intestinal ALP. The activity of human fetal intestinal ALP increased markedly with the advance of intra-uterine life during fetal development, and that of human fetal thymus ALP increased slightly.


[Postprandial variations in serum bile acid levels in humans free of hepatic or intestinal diseases (author's transl)].

The levels of unsulfated, free or conjugated cholic, deoxycholic and chenodeoxycholic acids were measured using gas chromatography in 39 humans free of hepatic or intestinal diseases before and 10, 60, 120 and 180 min after ingestion of a standard meal. The probable maximal levels were determined with an error risk lower than 0.05. In fasting subjects, the observed values are comparable with those obtained by other authors working with gas chromatography or radioimmunoassay. Meal ingestion does not influence in the same way the serum levels of the various bile acids: the chemodeoxycholic serum level rose significantly in all cases whereas cholic and deoxycholic serum levels rose only in two-thirds of observed subjects; 60 and 120 min after the meal for chenodeoxycholic acid, and only 60 min after the meal for cholic acid, the mean values are significantly higher than the fasting ones; 120 min after the meal, the chenodeoxycholic and total bile acid probable maximal levels (respectively 7.4 and 10.3 micrometer) are twice the fasting ones. The cholic to chenodeoxycholic serum level ratio is nearly always lower than 1 but may reach 3. On the basis of these results, the validity and efficacy of the exploration tests based on serum bile acid level determinations are discussed.


Biliary bile acids in uncomplicated pregnancy and in cholestasis of pregnancy.

Conjugated and sulfated bile acids were determined by gas-liquid chromatography and by high-pressure liquid chromatography in gallbladder bile samples of four pregnant women at term and of two patients with cholestasis of pregnancy. In healthy pregnant women the mean ratio of cholyl/chenodeoxycholyl/deoxycholyl glycine was 3.7 : 1 : 0.23 and that of taurine conjugates 3.0 : 1 : 0.25, respectively. In gallbladder bile pool of non-pregnant females these ratios were 1.0 : 1 : 0.00 and 1.0 1 : 0.70, respectively. Thus cholic acid predominated in pregnancy bile. In patients with cholestasis of pregnancy, cholid acid comprised 90% of total biliary bile acids, the proportion of chenodeoxycholic acid was greatly decreased and nonsulfated deoxycholic acid was not detected. The proportion of sulfated bile acids of total biliary bile acids was between 0.4 and 1.2% in uncomplicated pregnancy and 0.3 and 0.5% in cholestasis patients.


Exocytosis plays an important role in catecholamine secretion from human pheochromocytoma.

Plasma dopamine beta-hydroxylase (DBY) activity, urinary catecholamine (CA) and vanillylmandelic acid (VMA) were studied pre- and postoperatively in 20 patients with pheochromocytoma. Preoperative plasma DBH activities were distributed widely, ranging from normal to very high; the mean value of DBH as well as urinary CA and VMA was significantly greater than that of normal subjects. Postoperative falls of plasma DBH activity, of urinary CA and of VMA were by 76%, 96% and 83% of the preoperative level, respectively. Significant correlations were observed between postoperative falls of individual DBH activities, urinary VMA and weight of the tumors, whereas there was correlation neither between preoperative DBH activity and urinary CA, nor between the rate of postoperative falls of these respective values. These findings suggest that pheochromocytoma is capable of secreting DBH, and wide variations in the rate of DBH output from these tumors may account for varying capacity of CA biosynthesis in the tumor. Further, it may be concluded that the process of exocytosis plays an important role in the mode of CA secretion by these tumors, although secretion through diffusion may be operating as well.


Glutathione and gamma-glutamylcysteine in whole blood, plasma and erythrocytes.

A method for the simultaneous determination of glutathione and gamma-glutamylcysteine in capillary blood samples is described. The whole blood levels of glutathione and gamma-glutamylcysteine are t.09 +/- 0.20 mmol/l and 25 +/- 8 mumol/l (M +/- S.D.), respectively. The plasma concentration is approximately 4 mumol/l for both compounds. It is important to treat the blood samples with a reducing agent before protein precipitation to release glutathione and gamma-glutamylcysteine from disulfide linkages since, otherwise, 30--40% of the glutathione and 80% of the gamma-glutamylcysteine is lost with the protein precipitate. Whole blood is preferable to washed erythrocytes for the analysis since the washing procedure involves losses of, especially, gamma-glutamylcysteine.


A radioassay for pyrimidine-5'-nucleotidase activity.

A simple method for the determination of pyrimidine-5'-nucleotidase activity in red cells is described. The radioactive uridine released after incubation with [5-3H]] uridine 5-monophosphate (UMP) is separated on DEAE-cellulose paper and counted. This method does not require preliminary dialysis of the hemolysate and is 50-fold more sensitive than that based on the measurement of the inorganic phosphate released. One patient with pyrimidine-5'-nucleotidase deficiency was detected with this method.


Quantitative determination of 3-ethyl-5-hydroxy-4,5-dimethyl-delta3-pyrrolin-2-one in urine using gas-liquid chromatography.

A method is presented for the quantitation in urine of 3-ethyl-5-hydroxy-4,5-dimethyl-delta3-pyrrolin-2-one, a substance associated with hepatic porphyria and psychiatric disorders. The method involves gas-liquid chromatography following solvent extraction using one of two other heterocyclic compounds as internal standards. Quantitation of this substance in the urine of a group of normal subjects is also reported.


Multiple steroid receptors in male breast carcinomas.

Specific cytosol receptors for estradiol, progesterone and dihydrotestosterone were detected in human male breast carcinomas. Competition studies with excess unlabelled steroids showed that the receptors were distinct binding proteins. The properties and binding specificity of the estradiol receptor in a male breast carcinoma were very similar to those found in female breast tumors. The possible clinical significance of the presence of steroid receptors in male breast tumors is discussed.


Hyperprolactinaemia and impotence.

Clinical, laboratory and radiological findings were evaluated in twenty-nine men who had raised serum prolactin concentrations and pituitary tumours. Twenty-one had functionless pituitary tumours ('prolactinomas') and eight had acromegaly. Supraseller extension was detected in twenty of the twenty-six men who had lumbar airencephalography. Three patients were studied before, sixteen before and after and ten only after pituitary ablative therapy. Seventeen of these men complained of complete lack of libido and impotence and six had impaired libido and sexual potency; only six patients in this series denied reproductive symptoms. Thirteen of the impotent subjects had small soft testes, ten reduced facial and body hair and three had marked gynaecomastia. No features of hypogonadism were noted in the six patients without reproductive symptoms and none of the patients had galactorrhoea. Serum prolactin concentrations were higher and serum testosterone concentrations lower in the impotent men compared with those with normal sexual potency. Serum LH and FSH (both basal and in response to LHRH) oestradiol and oestrone concentrations were not different between the two groups and, except in those with post-operative hypopituitarism, were within the normal range. Following successful lowering of prolactin concentrations by surgery or bromocripitine or both, serum testosterone rose and potency returned; by contrast failure to lower prolactin concentrations was associated with persistent impotence and hypogonadism. The endocrine profile of low serum testosterone concentrations with gonadotrophins which had not risen into the range usually seen in primary hypogonadism (together with the parallel increase of LH and testosterone in one patient studied sequentially during treatment which suppressed prolactin levels to normal), suggested that the impaired gonadal function was caused by a prolactin-mediated disturbance of hypothalamic-pituitary function.


Somatostatin inhibits the pentagastrin-induced release of serum calcitonin in medullary carcinoma of the thyroid.

The effect of somatostatin on the secretion of calcitonin was studied in four patients with medullary carcinoma of the thyroid (MCT). The basal serum calcitonin level was markedly elevated in all cases. A bolus injection (100 microgram) of somatostatin followed by an intravenous infusion (5 microgram/min) for 60 min suppressed the basal calcitonin level in three of the four patients by 24-42%, while it had no inhibitory effect in one case. In another experiment, the pentagastrin-stimulated (6 microgram/kg s.c.) calcitonin release was partially blocked by a simultaneous i.v. injection of somatostatin (200 microgram) in all four patients studied. These experiments add human calcitonin to the list of hormones whose release in inhibited by somatostatin.


The effect of short-and long-term corticosteroid treatment on sleep-associated growth hormone secretion.

Eight healthy medical studients and four renal transplant patients had blood sampled two or three times hourly throughout EEG monitored nocturnal sleep. This was carried out on the healthy subjects for a total of 12 nights without medication (control nights asleep), a total of 12 nights following 40 mg of flucortolone the previous morning, and a total of 6 nights with similar blood sampling when sleep was prevented (control nights awake). Four renal transplant patients who were receiving long-term therapy with prednisolone were similarly studied (total of 7 nights asleep). Circulating corticosteroid and growth hormone (GH) levels were determined. A peak of GH was seen during the first 2 h of sleep on the control nights when slow-wave sleep predominated. The GH peak was absent on the control nights awake. The pattern of plasma corticosteroid levels was identical during control nights asleep and awake. Both single-dose and chronic corticosteroid administration inhibited the GH peak associated with slow-wave sleep. Chronic corticosteroid therapy, but no single-dose administration in the morning, suppressed the circadian rise of plasma corticosteroids which normally occurs late in sleep.


Technetium uptake in the management of thyrotoxicosis.

The thyroid uptake of 99m-technetium after 7 days of triiodothyronine was measured at the end of a course of antithyroid drugs in ninety-seven patients with thyrotoxicosis who were then followed up for at least 1 year. The relapse rate in sixty-six patients in whom the uptake was suppressed to less than 4% was 21% whereas it was 90% in those patients in whom the uptake was more than 4%. A prediction of the outcome on the basis of whether the uptake was more or less than 4% would have been correct in 82% of patients. Serial tests during treatment show that a correct prediction could have been made one year after starting treatment in 86% of cases depending on whether the uptake at that time suppressed to more or less than 6%. The initial unsuppressed 99m-technetium successfully predicted the likelihood of relapse after a course of antithyroid drugs in 75% of patients. We recommend that alternative therapy should be advised in those patients whose uptakes fail to suppress below 6% after 1 year of drug therapy.


Insulin infusion into the portal and peripheral circulations of unanaesthetized dogs.

Changes in glucose, phosphate, potassium, non-esterified fatty acids (NEFA) and insulin in peripheral venous blood were compared in five unrestrained fasted dogs during different rates of insulin infusion by the portal and peripheral circulation. The 'low' rate of insulin infusion was that required to produce a fall in plasma glucose of 0.56-0.83 mmol/l (0.024 u/kg/h female, 0.012 u/kg/h male). Two-fold and four-fold higher rates are referred to as 'medium' and 'high' rates, respectively. In all dogs, dose-related reductions in the glucose concentration of peripheral blood resulted from increasing the rate of insulin by either route. At 'low' and 'high' rates of infusion the net response was independent of the route of administration, but the 'medium' rate of insulin infusion led to a greater degree of hypoglycaemia when given peripherally than intraportally. As expected, insulin infused peripherally resulted in graded increases in peripheral insulin levels as the rate of infusion was increased from low to high while, paradoxically, intraportal administration at low and medium infusion rates resulted in a mean decrease of peripheral insulin levels from control, the low-dose producing the most consistent fall. The fact that hypoglycaemia accompanied this fall during portal infusion suggests that these low doses of insulin had a direct effect on plasma phosphate resulting from the change in route of administration of insulin (i.e. increase during portal and decrease during peripheral infusion) also suggests a direct hepatic effect of insulin given intraportally.


Discriminant analysis in the differential diagnosis of hypercalcaemia.

Linear discriminant analysis, a multivariate statistical procedure, applied to serum calcium, phosphate, alkaline phosphatase, bicarbonate, chloride, creatinine and tubular reabsorption of phosphate, proved to be effective in distinguishing patients with Primary Hyperparathyroidism from other hypercalcaemic patients in eithy-four retrospective cases. The application of the model to thirty-four prospective cases enabled us to separate correctly, hyperparathyroid patients from non-parathyroid hypercalcaemic patients.


The secretion of thyrotrophin with impaired biological activity in patients with hypothalamic-pituitary disease.

We describe here two patients with hypothyroidism due to pituitary-hypothalamic disease in whom basal thyrotrophin (TSH) levels measured by radioimmunoassay (RIA) were elevated yet when measured by a cytochemical bioassay (CBA) were found to be normal. This finding and the absence of the normal rise of thyroid hormones in response to thyrotrophin-releasing hormone (TRH) mediated release of TSH confirms for the first time the secretion of TSH with impaired biological activity. Primary thyroid disease as a cause for the elevated immunoreactive TSH was excluded by the absence of circulating thyroid antibodies and by a normal thyroidal radioiodine uptake response to exogenous TSH.


Hyperthyroidism induced by secondary carcinoma in the thyroid.

A young women presenting with hyperthyroidism proved to have diffuse infiltration of the thyroid with carcinoma probably from a primary breast adenocarcinoma. The gland was diffusely infiltrated with tumour although the thyroid follicles were intact. Blood thyroid hormone levels were raised but thyroid uptake of iodine was undetectable. It is suggested that the tumour released a locally active agent which stimulated hormone release but not iodine uptake, the latter being very low due to suppression of TSH.


Influence of hyperprolactinaemia due to metoclopramide on gonadal function in men.

Five clinically normal male volunteers were given metoclopramide, 10 mg t.d.s. for 6 weeks. During treatment prolactin concentrations were elevated (over 50 ng/ml) in all. LH, FSH, testosterone and cortisol concentrations were not altered. No change was observed in LH or FSH responses to LHRH testing 4 weeks after the beginning of therapy, compared with pre-treatment values. A reduction in seminal volume and total sperm count were observed in each subject. Four noticed a decrease in libido and three lost spontaneous erections. While the metoclopramide-induced hyperprolactinaemia could be the cause of the observed changes in semen and erectile activity, it is possible that this dopamine receptor blocking drug might directly affect central or peripheral mechanism of erection, the testes or accessory organs.


Fibre-optic transillumination of the sinuses: a comparison of the value of radiography and transillumination in antral disease.

The development of transillumination of the paranasal sinuses is reviewed. A technique of transillumination with a fibre-optic source is described. In acute sinusitis there was a very significant correlation between radiography and transilluminometry.


Branchiogenic carcinoma.

An unusual case of upper cervical carcinoma probably of true branchial origin is presented and the literature relevant to this condition reviewed. Branchiogenic carcinoma is a rare condition and should not be diagnosed in the absence of the 4 criteria laid down by Dr Hayes Martin, viz. that the carcinoma should arise in the wall of a branchial cyst, that it should occur along a line from the tragus to the clavicle along the anterior border of sternomastoid, that the histology should be compatible with the branchial apparatus and that no other primary tumour should come to light in a 5-year follow-up. A fifth criterion, ie. the demonstration of premalignant changes in the epithelium of the cyst, is suggested to aid a conclusive diagnosis.


Involvement of the carotid artery in tumours of the head and neck.

Carotid artery involvement in neck tumours causes great concern to surgeons because of the unpredictable effects of carotid artery clamping or excision. Various methods of pre- and peroperative assessment of crossover cerebral circulation are reviewed. The management of 3 cases with extensive tumour involving the carotid artery is described. This comprises a combined operation involving a head and neck surgeon and vascular surgeon using a temporary carotid shunt followed by permanent autogenous vein graft to the internal carotid artery. It is suggested that thorough preoperative investigation combined with a more radical surgical approach can give a more satisfactory outcome in cases of head and neck tumours involving the carotid artery.


The assessment of adenoidal size by radiological means.

The purpose of this study was to evaluate the accuracy of radiology in the assessment of both adenoidal size and the size of the nasopharyngeal airway. There was a good correlation between the preoperative assessment of the size of the adenoid by radiology and the actual size of the adenoid removed at surgery. A method of estimating the size of the nasopharyngeal airway is described. There was a good inverse correlation between the size of the airway and the weight of the adenoid.


Partial laryngectomy for recurrent cancer after irradiation.

Attention is drawn to the problems of surgical resection by partial laryngectomy after full therapeutic dosage of Telecobalt irradiation. Material is presented from 2 main treatment centres to indicate trends in surgical treatment and the complications experienced. End results are given which confirm a reasonable expectation of cure and functional conservation by vertical partial laryngectomy for recurrence of glottic cancer after irradiation. However, the results of treatment of recurrent supraglottic cancer by horizontal partial laryngectomy gave much cause for concern in terms of complications and survival. In conclusion an attempt is made, based on the quoted experience, to define the position of conservation surgery after full dosage irradiation of the larynx.


Iontophoretic anaesthesia of the tympanic membrane.

Anaesthesia of the tympanic membrane by iontophoresis of lidocaine is a painless and safe method for myringotomy and grommet insertion. Thirty-nine patients with serous otitis media and 11 patients with Ménière's disease had their tympanic membranes anaesthetized by iontophoresis of lidocaine; analgesia was perfect for all of them. In the patients with serous otitis media, the insertion of grommets was carried out easily and without pain. Major problems or complications have not been encountered during this study.


Surgical approach to the diagnosis of tumours occurring in the superior mediastinum.

The nature of tumours lying in the superior mediastinum can frequently be decided by the radiologist using a range of techniques varying in sophistication from the plain chest radiograph to transvenous biopsy. Histolocical proof of such lesions usually requires surgical exploration and of the methods available it is believed that mediastinotomy is the safest and most rewarding in terms of positive results. Radical excision of tumours and management of tracheal lesions require the greater surgical access afforded by thoracotomy, median sternotomy and the sternal resection of Grillo.


Middle ear implantation: its place in the immunohistophysiology of lymphoid tissue.

The concept of immunotolerance in otological tissue grafting is presented against the background of some fundamental aspects of immunohistophysiology. Available experimental and clinical data on tympanoplasty with allografts are evaluated in relation to this phenomenon of abolished immune reactivity.


The significance of stimulation in the leucocyte migration test as an indicator of cellular hypersensitivity--studies using Tamm-Horsfall glycoprotein as antigen.

To determine whether stimulation of leucocyte migration in the presence of an antigen is a reliable indicator of sensitization, the results of leucocyte migration using a kidney antigen (Tamm-Horsfall glycoprotein) were compared with those of lymphocyte transformation using the same antigen and with the lymphocyte cytotoxicity for cells known to synthesize this antigen. There was a close correlation between the results of all three tests and these findings strongly suggest that the stimulation of leucocyte migration as an immunological phenomenon was as valid as inhibition in demonstrating sensitization.


Lymphocyte responses to phytohaemagglutinin in patients with asbestosis and pleural mesothelioma.

Quantitative impairment of lymphocyte responses to phytohaemagglutinin (PHA) has been demonstrated in six (21%) out of twenty-eight patients with asbestos-associated pulmonary fibrosis, in comparison with a group of unexposed normal controls. The impairment tended to occur in patients with fairly severe fibrosis, comparatively short duration of exposure to asbestos dust and with increases in serum immunoglobulin levels. One patient with asbestosis and an associated bronchial carcinoma also had depressed lymphocyte responses to PHA. These findings suggest a relationship between defective T-lymphocyte function and the fibrotic response in asbestosis. Whether it is also linked with the development of lung cancer, occurring either before or at a pre-clinical stage of tumour growth, and is of value in identifying patients especially at risk should now be explored in longitudinal studies. However, eight out of ten patients with asbestos-associated pleural mesothelioma and without lung fibrosis showed no evidence of impaired cellular immunity, either by in vitro testing with PHA or by vivo delayed hypersensitivity skin testing, indicating that impaired T-lymphocyte function is unlikely to be a common finding in all types of asbestos-associated malignancy.


Complex arming in antibody-dependent cell-mediated cytotoxicity: ultrastructural studies of the interaction between human effector cells armed with aggregated anti-DNP antibody and DNP-coated erythrocytes.

We have examined, by transmission electron microscopy, mixtures of DNP-coated chicken red blood cells and normal human peripheral blood leucocytes 'armed' with alkali-aggregated anti-dinitrophenyl (DNP) antibody. The combination of these observations with chromium release assays enabled us to identify four types of effector cell interacting with the target erythrocytes, viz. phagocytic and non-phagocytic monocytes, neutrophils and lymphocytes. Comparison of these findings with previous work, using antibody-coated targets, allowed us to conclude that the mechanisms and cell types involved are similar. We also demonstrated the short-lived cytotoxic potential of cells armed in this manner.


Warfarin sodium: steady-state plasma levels and patient age.

1. Steady-state plasma levels of warfarin were measured in thirty-nine ambulatory patients attending a haematology clinic. 2. Plasma concentrations, plasma clearance, and prothrombin ratio showed no significant differences when patients below 65 years of age were compared with those above 65 years. The mean daily maintenance dose of warfarin required was marginally greater for the younger patients but the difference was not statistically significant (P = 0.10). 3. A significant relationship was found between the daily maintenance dose of warfarin required by all patients and their mean steady-state plasma level (r = 0.5667, P less than 0.001). 4. For one elderly hospitalized patient it was apparent that there was a marked depression of the vitamin K-dependent clotting factor synthesis by warfarin which was associated with a hypoprothrombinaemic response.


Assessment of the coronary vasodilator action of SK&F 24260 in the dog.

1. The effects of SK&F 24260 administered intravenously or intraduodenally on the coronary outflow, coronary arteriovenous oxygen difference (A-V O2), myocardial oxygen consumption (MVO2), systemic blood pressure, heart rate and atrioventricular (AV) conduction time were examined in open-chest dogs. 2. SK&F 24260 in doses of 0.3-10 microgram/kg, i.v., caused a dose-dependent increase in coronary sinus outflow, but the increase was smaller with 30 microgram/kg, i.v., than with 10 microgram/kg, i.v. 3. SK&F 24260 (0.3-30 microgram/kg, i.v.) decreased A-V O2 and MVO2 in a dose-dependent manner. 4. SK&F 24260 (0.3-30 microgram/kg, i.v.) decreased systemic blood pressure and heart rate, and increased AV conduction time. 5. Intraduodenal administration of SK&F 24260 (1 mg/kg) produced almost the same effects on coronary sinus outflow, A-V O2, MVO2, systemic blood pressure, heart rate and AV conduction time as did the intravenous administration of the compound (10 microgram/kg). 6. The property of SK&F 24260 to increase the coronary blood flow and to moderately decrease MVO2, systemic blood pressure and heart rate indicates that this agent is a potential antianginal drug.


Pressor action of pyridine-2-aldoxime in malathion poisoning.

1. Intravenous injections of pyridine-2-aldoxime (PAM) produced a marked, prolonged and dose-related rise in blood pressure in anaesthetized cats treated with malathion (MT) and without malathion (NMT). 2. The pressor effect of PAM was significantly reduced by phentolamine and phenoxygenzamine, but unaffected by hexamethonium. 3. Pretreatment with guanethidine and reserpine almost completely abolished the pressor response to PAM. 4. The results indicate that PAM has a potent sympathomimetic action which appears to be mediated through release of catecholamines from storage sites.


Blood access.

Blood access is the most important determinant for the continued well-being of an end-stage renal failure patient, maintained on hemodialysis. From the variety of angioaccess techniques available today, the choice of one most suitable for a patient, applied at the appropriate time with an exacting technique may liberate the patient from incessant fear of loss of his "life line". Quinton-Schribner shunt as a prototype of external prosthetic angioaccess devices made life on the artificial kidney possible, but repeated thrombosis, inevitable infection, limitations of activity and threat of accidental dislodgement have severly restricted its usefulness. The internal arteriovenous fistula and its several modifications have almost completely supplanted the use of external prosthetic devices. When the procedure of choice, a direct arterio-venous fistula, is not applicable, an interposed graft of biologic prosthetic origin may be employed. Percutaneous femoral vein catheterization and veno-venous dialysis is an acceptable, indeed a valuable "stop gap" measure.


The influence of subacute dyflos administration on the sensitivity to agonists of longitudinal and circular muscle preparations of the guinea-pig ileum.

1. Changes in the EC50 values to various agonists in longitudinal and circular muscle preparations of guinea-pig ileum were investigated following daily pretreatment of the animals for 10 days with dyflos (1.2 mg/kg, s.c.). 2. In the longitudinal muscle no significant change in sensitivity to acetylcholine and potassium chloride was noted following dyflos treatment. Marked subsensitivity to carbachol and histamine was observed. 3. In circular muscle a marked supersensitivity to acetylcholine occurred and there was no change in sensitivity to carbachol. 4. Dyflos treatment induced an increase in the slope of the log concentration-response curve and the maximal contractile response obtained to agonists in both longitudinal and circular muscle preparations. An increase in tissue mass was also associated with dyflos pretreatment. 5. Subsensitivity development was not attributable to changes in affinity for agonists at the receptor site but rather to changes at the post-receptor level leading to a nonspecific subsensitivity.


Some biochemical responses of rat skeletal muscle to a single subcutaneous injection of a toxin (notexin) isolated from the venom of the Australian tiger snake Notechis scutatus scutatus.

1. Some biochemical responses of mammalian skeletal muscle to a single subcutaneous injection of a purified toxin from the venom of the Australian tiger snake, Notechis scutatus scutatus, have been investigated to determine the role of changes in peptide hydrolase enzymes in the muscle wasting caused by notexin administration. 2. Within 6 h of injection, serum creatine kinase activity was increased by five- to ten-fold, and remained elevated for at least 24 h. 3. There was an initial inflammatory response in the muscle adjacent to the site of injection; by 12 h after injection, muscle wet weight increased by 60%. 4. After the initial increase, wet weight fell to about 50% of normal at 7 days. Normal wet weight was achieved by 20 days after the injection. Over the period 1-20 days after the injection of the toxin, the changes in wet weight were mirrored by changes in non-collagen protein content. 5. The activities of cathepsin B and acid proteinase were increased following the injection of the toxin. By 2 days after injection, there was a ten-fold increase in the activity of cathepsin B, and a seven-fold increase in the activity of acid proteinase. The activity of both enzymes become normal by 20 days. 6. Experiments utilizing a variety of cytotoxic drugs suggested that the acid proteinase and cathespin B are primarily located within invading phagocytic cells. 7. The results are discussed with reference to the previously described pathology of toxin-damaged skeletal muscle.