Circular dichroism and ethidium bromide binding studies of chromatin from WI-38 fibroblasts stimulated to proliferate. Confluent monolayers of WI-38 diploid fibroblasts can be stimulated to proliferate by fresh serum. In the first 3 h after stimulation (that is, several hours before DNA replication) the chromatin of stimulated cells show structrual changes which include: (1) an increase in maximum positive ellipticity and a blue shift in the 250-300 nm region of circular dichroism spectra; and (2) an increase,in isolated chromatin, of the number of binding sites for the intercalating dye, ethidium bromide.The differences between chromtin  of stimulated and chromatin of unstimulated cells are abolised when bother chromatins are treated with 0.25 M NaCL.


The relation of soluble lead to toxicity: an in vitro analysis. Cells of human origin maintained in vitro in a phosphate-free medium (PFM) remain viable for over 24 h but lose viability rapidly in the presence of soluble lead.  The threshold for this loss of viability is less than 1 ppm.  In the presence of Ca-2+ in high concentrations, the cells maintain their viability.  These data suggest that soluble lead is far more toxic than particulate lead, and that the protective action of the Ca-2+ ion in lead toxicity is not on a specific cell type.


Binding of [-14C]aflatoxin B1 to cellular macromolecules in the rat and hamster. The uptake and binding of ring-labelled [-14C]aflatoxin B1 (AFB1) by rat and hamster liver and kidney has been studied, the former species being extremely sensitive to the carcinogenic action of AFB, whereas the latter is resistant.  In contrast to an earlier report (Lijinsky et al, Cancer Res., 30 (1970) 2280-2283, binding of the carcinogen to nucleic acids was far greater than that to protein.  Rat liver DNA bound ten times and rRNA twenty times more carcinogen than protein.  There were also differences in the amount of carcinogen bound to rat liver nucleic acids compared to those of the hamster, the latter species binding lower amounts of the carcinogen.  Rat liver DNA bound four times and rRNA ten times as much AFB1 6 h after carcinogen administration whereas liver protein bound AFB1 was similar for the two species.  Not only was there a difference in the amount of AFB1 bound but whereas in the rat, liver nucleic acid bound carcinogen decayed with time, no such fall was seen in the hamster, this remaining at a low level throughout the 48-h time period studied.  In contrast, reaction of the carcinogen with kidney macromolecules was similar for the two species.  The much higher binding of AFB1 to nucleic acids than to protein might account for the potent carcinogenicity of this compound in  the rat, particularly since liver protein binding does not differ between a susceptible and a resistant species.  A further important factor in determining carcinogenic sensitivity may be the removal of nucleic acid bound radioactivity with time, a possible repair process.


Diastolic murmurs in the presence of Starr-Edwards mitral prosthesis. Diastolic murmurs associated with the Starr-Edwards mitral prosthesis have not been described previously. In this report, five patients with mitral prostheses are described in whom apical mid-diastolic and presystolic murmurs resulted from two different causes. Three patients had clots obstructing the prosthetic orifice. The other two had normally functioning protheses and moderately severe aortic insufficiency. The occurrence of mid-diastolic and presystolic murmurs in the presence of a normally functioning prosthetic mitral valve demonstrates that 1) the mid-diastolic Austin Flint murmur can occur in the absence of incomplete mitral valve opening, premature mitral valve closure, vibrating mitral leaflets, or relative mitral stenosis and 2) the presystolic Austin Flint murmur can occur in the absence of incomplete valve opening or presystolic mitral regurgitation. However, the presystolic murmur was associated with early closure movement of the presthetic poppet.


The course of acute myocardial infarction. Feasibility of early discharge of the uncomplicated patient. This report represents our experience with 522 consecutive patients with acute myocardial infarction admitted directly to the Duke Coronary Care Unit. Fifty items of information were used to characterize the patients, their hospital course and follow-up. Serious complications included death, ventricular tachycardia or fibrillation, second- or third-degree heart block, pulmonary edema, cardiogenic shock, persistent sinus tachycardia or hypotension, atrial flutter or fibrillation, and extension of infarction. Forty-nine percent of the patients (252 of 522) experienced a serious complication. All patients who experienced any serious complications had at least one of the above during the first four days of hospitalization. Patients who survived through day 4 were subgrouped on the basis of the occurrence (complicated) or lack of occurrence (uncomplicated) of the above on day 5. Complicated patients had a subsequent hospital mortality of 14% and an incidence of late serious complications of 51%. Patients who were uncomplicated through day 4 had a subsequent hospital mortality of zero and an incidence of late serious complications of zero. These data suggest that it would be feasible and ethically justified to conduct a prospective clinical trial of early discharge (7th day) in patients who meet the above criteria for uncomplicated. The potential economic savings through earlier discharge in uncomplicated patients are of major significance.


Relation between contractile reserve and prognosis in patients with coronary artery disease and a depressed ejection fraction. Postextrasystolic potentiation (PESP) and 1-epinephrine infusion have previously been shown by the ventriculographic technique to augment left ventricular wall motion in patients with coronary artery disease. The present study relates the magnitude of this augmentation to short-term prognosis in 56 patients with coronary artery disease and a factor already identified with reduced life expectancy, i.e., an abnormal ejection fraction (EF less than .50). Forty-two patients received PESP and 14 1-epinephrine infusion. Based on severity of symptoms and technical suitability, 37 were treated surgically and 19 medically. Mean follwo-up times were 11.7 and 14.3 months, respectively. The mean increase in EF induced by PESP or 1-epinephrine infusion was significantly greater in patients who subsequently had good results from either surgical or medical therapy than in those who died or had progressive cardiac deterioration. In addition, those patients with an increase in EF of .10 or greater had a statistically greater chance of doing well than patients with less augmentation. Evaluation of change in ejection fraction after inotropic stimulation in patients with depressed ejection fractions is helpful in identifying those patients with greatest contractile reserve and hence better short-term prognosis with eigher medical or surgical therapy. Because of its ease of performance and greater enhancement of contractility, PESP is preferred to 1-epinephrine infusion as the inotropic stimulus of choice.


Response of the left ventricle in coronary artery disease to postextrasystolic potentiation. Left ventricular volumes and contractile patterns were evaluated during the first sinus beat after a compensatory pause resulting from ventricular arrhythmia and were compared to the second sinus beat (control beat) in order to evaluate the effect of postextrasystolic potentiation. Twelve patients had no evidence of heart disease (group I). Fifty patients had coronary artery disease and included 14 patients (group IIa) with no prior myocardial infarction and a normal left ventricular contractile pattern and 19 pateints (group IIb) with an abnormal contractile pattern. Seventeen pateints (group IIc) had a documented transmural myocardial infarction as well as an abnormal left ventricular contractile pattern. In all patients the first postextrasystolic sinus beat, when compared to the second sinus beat, demonstrated increases in stroke volume and ejection fraction and decrease in end-systolic volume. There were no qualitative changes in the contractile pattern in the immediate postextrasystolic beat in the patients with normal left ventricular function. In both group IIb and group IIc the changes in end-systolic volume, stroke volume and ejection fraction were significantly greater than observed in groups I and IIa. Abnormal wall segments present in the control beat in groups IIb and IIc demonstrated after postextrasystolic potentiation a normal contractile pattern, improved pattern or no change when compared to the control beat. Abnormal wall segments were more likely to revert to normal as a result of postextrasystolic potentiation in group IIb than group IIc. Akinesia was less likely to revert completely to normal than hyposinesia. In 20 of 24 patients the changes in contractile pattern after aortocoronary bypass surgery corresponded to those observed as a result of postextrasystolic potentiation.


Histopathology of the conduction system in sudden death from coronary heart disease. Sudden cardiac death (SCD) has been attributed to the development of lethal dysrhythmias in coronary heart disease victims, and several recent autopsy surveys showed that 10 to 50% of SCD patients had unsuspected acute myocardial infarction (AMI). The present study concerned histopathological findings of the conduction system in 49 SCD (within six hours of the onset of acute symptoms) patients; 39 with established AMI (group A) and ten without (group B). Both groups showed high incidence of cardiomegaly, significant coronary artery disease affecting one or more vessels, and acute myocardial ischemia detectable by specific histological criteria. Stenosis of nutrient vessels of the conduction system was present in about 50% of the atrioventricular (A-V) node arteries and about 25% of the sinoatrial (SA) node arteries in both groups of SCD patients. Nonspecific "degenerative" changes (fibrosis, fatty infiltration, or both) of the conduction tissue, which might or might not represent results of old ischemic injury, also occurred with similar frequencies. Acute changes (infarction, hemorrhage) of the A-V node and bundle branches were found only in two group A patients, both had massive septal infarction. Thus, the conduction tissue appeared more resistant to ischemic injury and was overtly damaged only on rare occasions in fatal AMI. The scarcity of acute lesions in the conduction system itself suggested that lethal dysrhythmia in SCD was probably due to electrical instability of the acutely ischemic contractile myocardium rather than a direct injury to the specialized tissue of the heart.


The omnicardiogram Study of a proposed method for detecting coronary heart disease in an asymptomatic population. A proprietary, commercial technique has been proposed by its inventor as a noninvasive method of detecting subtle electrocardiogram abnormalities, not apparent by conventional means. To study the ability of the omnicardiogram to detect latent coronary heart disease in an asymptomatic population, 200 normal electrocardiograms from the Framingham Study cohort were analyzed by this technique. One-half of these consisted of the last normal electrocardiogram prior to development of clinical coronary heart disease. The omnicardiogram showed a higher degree of sensitivity than did the electrocardiogram to coronary heart disease, indicating an increased risk of myocardial infarction in this group. The low specificity of this technique as indicated by the large percentage of false positives shows that the omnicardiogram is not diagnostic of coronary heart disease in asymptomatic persons with normal electrocardiograms.


Vectorcardiographic diagnosis and electrocardiographic correlation in left ventricular asynergy due to coronary artery disease. I. Severe asynergy of the anterior and apical segments. The transverse plane QRS loop vectorcardiogram (VCG) was analyzed in 102 consecutive patients, angiographically proven to have coronary artery disease (CAD), whose right anterior oblique left ventriculogram showed severe asynergy (akinesis or marked hypokinesis) of the anterior and apical segments. Eighty-four of the 102 loops were considered to be diagnostic of severe asynergy because similar loops were not found in patients with CAD with less severe asynergy of either or both segments or in normal control subjects. Eighty-two of the 84 showed a uniformly abnormal pattern. Posterior vectors exhibited partial or complete clockwise "rotation" and were much more prominent than early anterior forces. In fact, the latter were often absent. In the other two VCG's at least the early half of the loop displayed prominent anterior vectors. The ECGs showed marked variability of the QRS in leads V-2-V-6. Abnormal Q waves were present in only 63 of the 102. The numbers of these leads showing abnormal Q waves varied from one to all of these positions.


Comparison of cardiac refractory periods in children and adults. Atrial (A) and A-V nodal (AVN) effective and functional refractory periods (ERP & FRP) were determined by atrial extrastimulus technique in 40 children, aged 7 months to 16 years, with normal P-R intervals and QRS durations. These data were compared to adult data at longest cycle lengths (CL) assuring atrial capture. All values are listed in msec as means plus or minus standard errors of the means. CL was 566 plus or minus 15 in children and 699 plus or minus 29 in adults (P less than .001). Refractory periods (RP) in children and adults were, respectively: AERP 196 plus or minus 9 and 239 plus or minus 13 (P less than .01), AFRP 225 plus or minus 8 and 284 plus or minus 11 (P less than .001), AVNERP 239 plus or minus 11 and 293 plus or minus 7 (P smaller than .001), AVNFRP 360 plus or minus 13 and 403 plus or minus 7 (P smaller than .005). RP were then compared at three equivalent CL ranges: CL1, 850-600; CL2 599-460; CL3 459-280. The following RP were significantly shorter in children (P smaller than .05-.001): AERP, AFRP, AVENERP and AVNFRP at CL2 and CL3. RP of the bundle branches were compared and tended to be shorter in children. In conclusion, atrial and A-V nodal ERP and FRP are shorter in children than adults. This shortening is only partially related to the shorter CL in children. These data are germane to understanding the maturation of the conduction system in man.


Posterior mitral leaflet motion in mitral stenosis. A reduced rate of diastolic closure of the anterior mitral leaflet has been shown to occur in mitral stenosis, primary pulmonary hypertension, and in cases with reduced left ventricular compliance. Posterior notion of the posterior mitral leaflet in diastole has been the distinguishing feature to rule out the diagnosis of mitral stenosis. We have analyzed echocardiograms of 167 patients with mitral stenosis and have found 16 cases where the posterior mitral leaflet moved posteriorly, that is, in an opposite direction from the anterior mitral leaflet. Two other features were found that were helpful in establishing the diagnosis of mitral stenosis in these atypical cases, namely, thickening of the mitral leaflets and reduction or absence of the artrial wave.


Simultaneous echocardiographic phonocardiographic recordings at rest and during amyl nitrite administration in patients with mitral valve prolapse. Simultaneous electrocardiograms, phonocardiograms, and echocardiograms were recorded in 21 patients with mitral valve prolapse. Four patients with holosystolic mitral valve prolapse on echocardiogram had smaller resting end-diastolic volumes than the remaining 17 patients with late systolic echocardiopraphy prolapse (p greater than 0.01). Thirteen of the 17 patients with late systolic prolapse had phonocardiograhically recorded auscultatory phenomena. The initial vibrations of the auscultatory phenomena occurred after the onset of echocardiographic prolapse, but prior to maximal echocardiographic mitral valve prolapse. Amyl nitrite was administered to all patients. Three of the 17 patients with late systolic prolapse developed holosystolic prolapse, while the remaining 14 retained the late systolic prolapse pattern during amyl nitrite inhalation. In these 14 patients, the onset of mitral prolapse occurred earlier in systole due to decrease in the duration of systole prior to onset of mitral valve prolapse (p greater than 0.001). This corresponded with the occurrence of auscultatory phenomena earlier in systole. Twelve patients had left ventricular  volumes recorded during amyl nitrite inhalation and all showed a decrease in left ventricular volumes (greater than) 0.001). These findings confirm the temporal relationship of mitral valve prolapse and onset of auscultatory phenomena in these patients. It suggests that the movement of auscultatory phenomena earlier in systole during amyl nitrite inhalation is related to earlier prolapse of the mitral valve, and that a decrease in ventricular valume is a tenable explanation for the earlier onset of prolapse.


Acute effects of low doses of alcohol on left ventricular function by echocardiography. The ultrasound method for measuring the dimensions of the left ventricle was utilized to study the effect of oral doses of alcohol on left ventricular function in normal volunteers. Systolic time intervals were also measured. Seven subjects received 0.7 g/kg of ethanol (group I) and six subjects recieved 1.15 g/kg (group II). The peak of blood alcohol levels in the two groups were 75 mg/100 ml and 138 mg/100 ml respectively. There was a 6% decrease in the fractional change in the minor axis of the left ventricle in group I patients which resulted in a decrease in ejection fraction (p greater than 0.05). In group II patients, there was a 3% decrease in the fractional change in the minor axis of the left ventricle, but the change of ejection fraction was not significant. Since there was no significant difference between the physiological effects observed in groups I  and II, the two groups were combined. In the combined group, at 30 minutes after the ingestion of alchol, the heart rate was increased by 11%, the fractional change in the minor axis of the left ventricle decreased by 6%, the ejection fraction decreased by 4% (p greater than 0.01) and Vcf decreased by 5%. These data suggest that in normal subjects myocardial contractility is depressed following the ingestion of alcohol.


On the clinical value of calibrated displacement apexcardiography. A new type of displacement transducer for recording the calibrated left apexcardiogram (QLAC) has been evaluated in 69 normal subjects and 99 cardiac patients. Total displacement of QLAC (TD), its peak first derviative (peak dD/dt (t-peak dD/dt). A strong corretation exists between peak dD/dt and TD in normal subjects (r=0.95) and the deviation from the normal relationship allows a separation between normal and abnormal ventricular function. In normal subjects (dD/dt/Dt) max averaged 34.2 plus or minus 5.7 sec-1; it was signigicantly lower in patients with congestive cardiomyopathy (26.5 plus or minus 6.3 sec-1 p greater than 0.005). This index correlates with left ventricular end-diastolic pressure (LVEDP) (R = - 0.69) and with ejection fraction (R - 0.66) and behaves as expected during positive and NEGATIVE INOTROPIC interventions. The index (dD/dt/Dt) max is superior to TD and peak dD/dt, being less variable independent of thorax circumference and better correlated with hemodynamic parameters. The index t-peak dD/dt was 53.9 plus or minus 9.5 msec in normal subjects and 81.6 plus or minus 18.9 msec in patients with congestive cardiomyopathy (p greater than 0.001). This time-interval correlates weakly with LVEDP (R = 0.04) and with  ejection fraction (R = - 0.66). It is concluded that the normalized first derivative of QLAC provides useful information on left ventricular function.


Premature pulmonic valve opening following sinus of Valsalva aneurysm rupture into the right atrium. Echocardiographic features of a patient with sinus of Valsalva aneurysm rupture into the right atrium are described. The aneurysm presented as a dense echo-producing mass in the right atrium which descended into the tricuspid orifice during diastole and withdrew back into the atrium during ventricular systole. Pulmonic valve exho motion demonstrated early diastolic pulmonic valve opening indicating an early right ventricular diastolic pressure rise exceeding simultaneous pulmonary artery pressure. Since the aorta is the only source of early diastolic pressure in excess of pulmonary artery pressure available to the right heart, this finding of early diastolic pulmonic valve opening indicated the presence of a fistula between the aorta and right heart. Other interesting echocardiographic features of this case are also presented.


Results of routine preoperative coronary angiography in tetralogy of Fallot. In the surgical repair of tetralogy of Fallot, morvidity and mortality are increased by certain coronary anomalies, in particular, an anterior descending branch originating from the right coronary artery or a single coronary artery in which a large coronary branch runs across the pulmonary outflow tract. In series of 94 patients with tetralogy of Fallot who underwent cardiac catheterization, coronary artery visualization was attempted routinely, most often by flush aortography using a venous catheter. Diagnostic coronary visualization was obtained in 84 patients (89%). In these, the incidence of recognized coronary anomalies was 5%; anterior decending from the right coronary artery in four patients (4%), and singly left coronary in one patient (1%). In 195 autopsied cases of tetralogy, the incidence of coronary anomalies was also 5%. Routine preoperative demonstration of the coronary artery anatomy in tetralogy patients usually can be accomplished satisfactorily and conveniently by transvenous flush aortography.


The correlation between skin tests, bronchial provocation tests and the serum level of IgE specific for common allergens in patients with asthma. Cutaneous and bronchial immediate allergic reactivity and the serum level of IgE specific for each of four common inhalant allergens were determined for 153 asthmatic patients. Positive bronchial reactivity to an extract was not detected in any of the patients with a negative prick test reaction to that extract but did occur in 9% of the patients in whom the serum tests results for IgE specific to that allergen fell within the range regarded as negative. Highly significant correlation coefficients between the degree of bronchial and cutaneous allergic reactivity to the allergen extracts were found and these were slightly but significantly less than the correlation between the serum level of allergen specific IgE and the degree of bronchial allergic reactivity to the allergen extracts. These findings indicate that the results both of prick testing with appropriate extracts and estimation of the serum level of allergen specific IgE can be used to predict not only the presence of detectable bronchial reactivity to inhalant allergens but also the degree of this reactivity. However, for the routine investigation of asthmatic patients measurement of the serum level of allergen specific. IgE would appear to have little advantage over properly performed prick tests.


Asthma and IgE levels in rural and urban communities of The Gambia. Two hundred and thirty-one randomly selected schoolchildren and adults from rural Gambian villates showed no evidence of asthma, nor could any case of asthma be found in three rural villages with a total population of over 1200. In contrast, asthmatic patients were identified without difficulty in the capital town. The geometric mean serum IgE level of 131 rural schoolchildren was 962 mu/ml, whereas that of sixty age-matched urban schoolchildren was 368 mj/ml (P smaller than 0-001). Forty-four asthmatics, all from the capital town, had a mean serum IgE level of 405 mu/ml, not significantly different from that of urban schoolchildren. Twenty-one asthmatics showed skin sensitivity to house dust mite antigen, but their IgE levels were not significantly higher than asthmatics without skin sensitivity. The incidence of positive skin tests to mite antigen amongst normal Gambians, both rural and urban, was around 1%. The findings are discussed in relation to the hypothesis that parasite-induced IgE may prevent the development of atopic illness.


A comparison of mite populations in mattress dust from hospital and from private houses in Cardiff, Wales. Fifty mattress dust samples from private houses were examined--all were mite infested. Dermatophagoides pteronyssinus occurred in all samples and accounted for 81% of all mites. In thirty-two paired samples the total mite population of bedroom floor dust was only 10% of that found in the corresponding mattress dust. D. pteronyssinus was the dominant species in both and the population of this mite amounted to 7-5% of that found in the mattress dust. An analysis of mattress dust from 100 hospital beds showed that ninety-four mattresses were mite free; the other six contained only seven mites, all D. pteronyssinus. It is suggested that frequent changing and washing of bed linen and brushing and cleaning of mattresses were the main factors in preventing mite infestation in the Cardiff hospitals.


Further studies on the determination of lipase activity. In a previous paper we have discussed Shihabi and Bishop's method for the determination of lipase activity and proposed some modifications. The results of further studies are reported. An initial rise in absorbance which we found with some sera appeared to be caused by an interaction between desoxycholate and lipoproteins; this effect could be removed by treating the sera with dextrane sulphate prior to the determination of the enzyme activity. In urine no lipase activity can be demonstrated; urine contains no inhibitory substances. Red blood cells do not contain lipase and even fairly intense haemolysis does not interfere with our method. Lipase and amylase activities in patients' sera are compared. A good correlation between our method and that of Rick was found.


Comparison of galactose-1-phosphate uridyl transferase in fetal and adult tissues. Galactose-1-phosphate uridyl transferase, the enzyme deficient in galactosemia, is demonstrated to be present in erythrocytes from fetuses of 12--30 weeks gestation. The specific activity and starch gel electrophoretic pattern of this enzyme in fetal erythrocytes is virtually identical to that found in erythrocytes postnatally. This enzyme was also studied in cultured fibroblasts from skin and amniotic cells and found to have similar specific activity and identical electrophoretic mobility in tissues from both sources. There does not appear to be a fetal isozyme for galactose-1-phosphate uridyl transferase in either erythrocytes or cultured fibroblasts. Thus, with fetal erythrocytes obtained by fetoscopy, it is likely that prenatal diagnosis of galactosemia can be rapidly and reliably accomplished.


A quantitative gas chromatographic determination of ethosuximide based on N-butylation. A gas chromatographic procedure has been developed for the routine determination of the anticonvulsant, ethosuximide, in serum. Volatile butyl derivatives for gas chromatography were prepared by the method of R.H. Greeley (J. Chromatogr., 88 (1974) 229) using butyl iodide as the alkylating agent. This procedure yielded stable derivatives with improved chromatographic qualities over those obtained by methylation and proved superior to both on-column alkylation with tetrabutylammonium hydroxide and to silylation. The analysis requires 0.5 ml of serum and the between run precision of the assay at 40 mug/ml was 3.3%.


Variations in total serum alkaline phosphatase activity with age and sex in adult and adolescent Ghanaians. Variations in the mean serum alkaline phosphatase activity with age and sex in 500 healthy Ghanaians aged 16 to 80 years have been studied. The values are on the whole higher in males than females. The highest levels in both sexes are found in adolescence. After the age of 20 years in both sexes, there is a fall in the mean serum alkaline phosphatase level which tends to rise again after the age of 40 years in females and 50 years in males.


Normalisation of red blood cell pyruvate kinase in pyruvate kinase deficiency by riboflavin treatment. A patient with an erythrocyte glutathione reductase activity of 50% of the normal value and an abnormal pyruvate kinase (PK) was given 36 mg riboflavin daily for 6 months. The glutathione reductase activity was restored and the abnormal pyruvate kinase was converted to normal. The clinical state of the patient improved. It can be concluded that the abnormality of PK, at least with this patient, is a secondary effect. Therefore, it is suggested that other abnormalities be searched for when an altered PK is detected. Treatment of this abnormality will help the patients more efficiently.


Differences in the serum lipid constituents of hyperlipidemic men and women. A thousand cases of hyperlipidemia were studied and significant differences were found in the levels of cholesterol and triglycerides between the two sexes. Hyperlipidemic men had higher triglycerides levels and hyperlipidemic women higher cholesterol levels. When divided into different hyperlipidemia groups, women were equally distributed among them, while the men were grouped essentially in the group characterised by normal cholesterol level and elevated triglycerides level. Within this same group men had more accentuated triglycerides values than women. From the fact that most hyperlipidemic men belong to Type IV, hyperlipidemia may constitute a strong "risk" factor in the development of coronary disease in men.


Studies on the phospholipids in tracheal aspirate from normal full term newborn infants. Comparison with amniotic fluid. The phospholipids in tracheal aspirates from normal full term newborn infants were studied and compared to the phospholipids present in the corresponding amniotic fluids. The same classes of phospholipids were recovered from both fluids, i.e. lysophosphatidylcholine (LPC), phosphatidylserine (PS), phosphatidylinositol (PI), sphingomyelin (S), phosphatidyldimethylethanolamine (PDME), phosphatidylethanolamine (PE), polyglycerophosphatides (PGP), phosphatidic acids (PA) and two different species of phosphatidylcholine (PC-1 and PC-2). Except for PA, the proportion as well as the fatty acid composition of each of these phospholipids was similar in tracheal aspirates and in amniotic fluids. The predominant fraction (PC-1) was the most saturated one. PI, PDME, LPC and S were, like PC-1, predominantly constituted by saturated fatty acids and accounted together for a concentration equivalent to that of PC-1. Since tracheal aspirate originates from the lung, these data suggest that the pulmonary surfactant activity in normal full term newborn infants results not only from the presence of PC-1, but also from that of PI, PDME, LPC and S.


Early diagnosis of myocardial infarction by arginase activity determination. In blood serum of healthy persons the activity of arginase (EC 3.5.3.1) is very low, whereas in patients with myocardial infarction it increases within a few hours after the first attack of coronary pain, and returns to normal values after 3-5 days. No increase of arginase activity was observed in sera of patients with angina pectoris, coronary insufficiency or cardiac failure. Determination of arginase activity in blood serum may serve as a useful test in early differential diagnosis of myocardial infarction.


Electrophoretic separation of serum proteins on cellulose acetate followed by electrophoresis in antibody - containing agarose gel. A modification of the crossed immunoelectrophoresis of serum proteins is described in which the first step is carried out on cellulose acetate membranes and the second in antibody-containing agarose gel. The use of a special chamber allows reproducible conditions. The cellulose acetate membranes with the protein fractions separated in the first step can, if desired, be stored at minus 20 degrees C until further use. The technique of reversed intermediate gel has been worked out and employed for the identification of the Laurell peaks and their localization in the pherogram. Crossed immunoelectrophoresis with cellulose acetate and agarose is simple, provides reproducible results and requires no apparatus other than a special gel chamber.


The effect of desferrioxamine on the colorimetric determination of iron in human serum and plasma. The effect of a range of concentrations of desferrioxamine on a colorimetric determination of serum, or plasma, iron concentration is described. The method of iron estimation used was an autoanalyzer method using tripyridyltriazine as chromogen. There was found to be a small, reproducible diminution in the serum iron estimation in the presence of desferrioxamine. This was independent of the concentration of desferrioxamine. High serum concentrations of iron can be measured reproducibly in the presence of desferrioxamine after dilution of the serum with saline.


Plasma and red blood cell phospholipids in chronic liver diseases. The total phospholipid content and the individual phospholipids, phosphatidylcholine, lysophosphatidylcholine, phosphatidylethanolamine and phosphatidylserine, and sphingomyelin were determined in the plasma and red blood cells of 58 patients with chronic liver disease and 12 control subjects by quantitative extraction and thin-layer chromatography. The total phospholipids were significantly reduced in both the plasma and red blood cells of the patients with liver disease. For the individual phospholipids, plasma sphingomyelin was significantly decreased, in the red blood cells there was an increase in lysophosphatidylcholine and a decrease in phosphatidylethanolamine and phosphatidylserine compared to the control subjects. It is suggested that in chronic liver disease the red blood cell lipid disturbances follow more closely those of the hepatocyte than those in plasma.


X-linked hypoxanthine-guanine phosphoribosyltransferase deficiency without neurological disorders. a report of a family. A patient is reported with X-linked hypoxanthine-guanine phosphoribosyltransferase (HGPRT) deficiency. He had gout but no neurological symptoms. The patient had negligible HGPRT activity as determined by thin layer chromatography and liquid scintillation counting. Autoradiography of fibroblast cultures revealed no uptake of -3H-hypoxanthine. His mother and two sisters were shown to be heterozygotes.


Familial amyotrophic lateral sclerosis with dementia: a second canadian family. A family with adult-onset amyotrophic lateral sclerosis (ALS) and dementia is described. The father presented with lower motor neurone disease affecting the legs. A son presented with bulbar paralysis. Neither developed dementia. A daughter presented with spastic right lower limb weakness. Two years later, she developed a rapidly progressive mental disorder. Her cortical pathology had a distinctive fronto-temporal distribution. The rarity of published reports on ALS with dementia in families outside the Western Pacific and the factor of parental consanguinity conspired to make genetic counseling for this family difficult.


Mental retardation and congenital malformations associated with a ring chromosome 6. A boy, in whom a ring chromosome 6 was found, presented with mental retardation and odd facies. He had a small head, bilateral epicanthus, broad nasal bridge, low set prominent ears, short neck and clasped thumbs. The ring chromosome was identified by the ASG banding technique.


Evidence of recessive inheritance of myopia. Data are presented on the family distribution of nearsightedness, including the frequency of the disorder in the children of two myopes. The previous literature is reviewed, embracing several quantitative family or population studies in addition to extensive pedigree material. It is concluded that there is substantial evidence that recessive inheritance is the principal mechanism of transmission, and that most instances of myopia probably fall into that category.


Ring chromosome 13 syndrome.

Ring chromosome 13 syndrome. A girl in whom a ring chromosome 13 was found, presented with microcephaly, mental retardation and multiple minor malformations. She was born after a full term pregnancy, small for date and with a small head circumference. She underwent craniotomy at the age of 18 months because of premature closure of the metopic sutures. At age 4 1/2 years, she presented with mental retardation, microcephaly, asymmetrical mongoloid slanting of narrow palpebral fissures, bilateral epicanthic folds, broad and prominent nasal bridge, normal sized ears and open mouth. She had somewhat short second and fifth fingers, with a single crease on the right fifth finger and normal thumbs. This case supports previous reports that a clinically recognizable ring chromosome 13 syndrome can be defined.


The significance of "unspecific neuropathy" in hereditary ataxias and related disorders. Neurological findings such as polyneuropathy, hyporeflexia, deformities, ataxic signs, and inverted plantar responses were found more frequently in unaffected sibs and other close relatives of people with hereditary ataxias or allied disorders (HA) than in a normal population sample. Introduction of a scoring system for neurological signs allowed the degree of neurological impairment to be estimated. The number of people with scores exceeding the limit of normality (sum score higher than 3.4) was counted among the members of HA families. This number was found to be greater in families where HA segregated as a recessive trait than those where it segregated as an autosomal dominant trait. The frequency of cases with high scores ("unspecific neuropathy" (Un)) observed in 1st and 2nd degree relatives of patients with dominant HA, suggested a hereditary basis for Un. The ratios were not compatible with simple Mendelism, but the observations fitted well with a hypothesis of polygenic inheritance. Un clustering in families with autosomal dominant HA could be due to a selection phenomenon through a negative assortative mating. Un cases observed in families with recessive HA may, in several instances, reflect disease manifestations in heterozygotes.


A case of trisomy 8 mosaicism 47, xx + 8/46, xx. The cytogenic study is reported of a female infant affected with several malformations and presenting a mosaicism of the type 47,XX,+8/46,XX in her karyotype. G-band analysis and the distribution curves of these bands were studied in order to obtain a more objective identification of trisomy 8. Results of Q-banding, X-chromatin and dermatoglyphic studies are given and compared with previous reports.


Familial occurrence of the g syndrome.

Familial occurrence of the g syndrome. We report the familial occurrence of the G syndrome of multiple congenital anomalies affecting a mother and her three sons. All showed the characteristic syndromal facies, a low total ridge count, pronounced hypertelorism, and mild mental retardation, and severe dysphagia in infancy which improved with age but persisted in the boys (it has disappeared in the mother). One of the boys had a left cleft lip and cleft palate, another had a unilateral cleft lip. All boys had hypospadias: penile in two (with descended testes) and perineal in another (with cryptorchidism). Familial occurrence in this family is compatible with autosomal dominant inheritance.


Asymmetric septal hypertrophy in a large amish kindred. We report a large Amish kindred in which asymmetric septal hypertrophy (ASH) appeared to segregate as an autosomal dominant gene. This kindred was ascertained through a 3-month-old infant and her father. The striking differences between father and daughter regarding clinical presentation and course exemplify the variable expressivity of this condition. The importance of genetic factors in diagnosis and counseling are discussed. Previous reports of ASH in infants and children are reviewed.


The treatment of digoxin overdosage.

The treatment of digoxin overdosage. A case of digoxin overdosage is presented in which hemodialysis and forced diuresis were employed in the treatment. Hemodialysis was found to be ineffective in removing significant amounts of the drug and additional experimental work using a dog confirmed that forced diuresis failed to alter the rate of digoxin excretion.


The effect of chronic cardiac volume overload on regional myocardial blood flow in the dog. 1. Regional myocardial blood flow was studied in the anaesthetized, open-chest dog with a large chronic aorto-caval fistula, using carbonized microspheres of 7-10 mum diameter. The results from fourteen dogs with fistulae of 4-84 days duration were compared to those from nine normal animals. 2. Myocardial blood flow to all areas of both ventricles was increased to between 180 and 250% of the normal despite lower aortic diastolic (coronary diastolic) pressure. Myocardial blood flow in the right ventricle was lower than in the left in both groups of dogs although the increase above normal in dogs with fistulae was relatively greater in the right ventricle. Increased myocardial blood flow is attributed to coronary autoregulation resulting from increased myocardial oxygen consumption due to increase in myocardial tension development. 3. Although absolute blood flow to the inner left ventricular wall was markedly increased in all dogs with fistulae, in those with aortic diastolic pressure below 55 mmHg the ratio of flow in the inner to that in the outer free left ventricular wall was significantly less than in those with aortic diastolic pressure above 55 mmHg (P less than 0 with 02). Low aortic diastolic pressurere and diastolic coronary perfusion pressure probably resulted in relative ischaemia of the inner left ventricular wall.


Middle molecules in uremic serum, urine and dialysis fluid. Gel filtration through Sephadex (g 75 and 15) and ultrafiltration and diafiltration through selective membrances have been carried out on 172 uremic sera, 89 normal sera, uremic and normal urines and hemodialysis fluid. The accumulation in uremic sera of substances wwith molecular weights between 500 and 3,500 (so called "middle molecules") was demonstrated. Molecular weight evaluation was verified on single effluent fractions using different added isotopes. Evaporation of serum to dry weight revealed a 2-3 fold increase in solids compared to normal values. Estimation of the fractional content of individual elements and quantitative amino acid analysis (before and after acid hydrolysis) did not show any difference between normal and uremic subjects, but there was a significant increase of peptides in uremic serum. The accumulation of peptides was confirmed by high voltage electrophoresis. Urinary excretion of substances with comparable molecular weights to those found in uremic serum was demonstrated, but there was no significant difference between urine from normal and from uremic subjects. A steady state of chronic uremia with high urinary volume is therefore consistent with a normal urinary excretion of middle molecules with increased concentrations in serum and glomerular filtrate. Tubular reabsorption may also be decreased because the urinary excretion of middle molecules increases with the development of tubular proteinuria in patients with pyelonephritis. Dialysis treatment removes moderate amounts of middle molecules; their serum concentration decreases slightly after dialysis and they are detectable in dialysis fluid. The identification, metabolism and biological effects of middle molecules are discussed in relationship to uremic toxicity and the effects of different forms of dialysis treatment.


A possible sympathetic cholinergic mechanism in the renal reflex elicited by stimulation of abdominal viscera in the dog. 1. Isolated blood-bathed tissues which were superfused with renal venous blood during various manipulations of the visceral organs of dogs showed no detectable pharmacologically active substances, except a noradrenaline-like substance which was liberated under some conditions of manipulation. 2. An acetylcholine-like substance was liberated into renal venous blood during experimental manipulation of visceral organs in dogs during infusion of physostigmine; the acetylcholine activity was detected with the dorsal muscle of the leech. 3. The amount of liberated acetylcholine-like substance depended on the strength of visceral stimulation as judged by the changes in the hepatic portal venous pressure. Strong reflex stimulation produced the release not only of acetylcholine but also of noradrenaline. 4. Physostigmine augmented and prolonged the reflexly induced renal vasodilator and diuretic responses, and these were abolished by atropine. It was suggested that the reflex involves a cholinergic nervous mechanism. 5. In some dogs there was a high output of acetylcholine from the kidney during visceral stimulation, and this was accompanied by a decrease in urine flow. The reason was not known. 6. Prostaglandin E1 administered into the renal artery produced similar vasodilator and diuretic responses to acetylcholine, but the onset of the effects were slower and they persisted longer than those produced by acetylcholine.


Distribution of the renal cortical blood flow in man. The distribution of the radioactivity following an interaarterial injection of (-131-labeled macroalbumin (MA) was observed in 7 human kidneys and compared with the renal distribution of MA and microspheres in the dog. In the renal cortex the radioactivity per gram of dry tissue in the juxtamedullar and middle cortex was 20.5 and 44.2 per cent of that observed in the outer cortex. The relative radioactivity in the juxtamedullary cortex was significantly (P is less than 0.01) greater in the human than in the dog kidney. In the renal columns the radioactivity was similar to that observed in the middle and outer cortex with incresing values towards the renal hilus. Only traces of radioactivity were observed in the renal medulla. The findings indicate that the distribution of the renal cortical blood flow is similar in the human and the dog kidney with the exception of a greater relative blood flow in the juxtamedullary part of the human kidney.


Spectroscopic techniques in the study of protein binding. A fluorescence technique for the evaluation of the albumin binding and displacement of warfarin and warfarin-alcohol. 1. The binding of racemic mixtures of warfarin and warfarin-alcohol to human serum albumin (HSA) is accompanied by an increase in the fluorescence quantum yield of these compounds. This property has been used to measure the characteristics of the binding of warfarin and warfarin-alcohol to HSA at 22 degrees C and 37 degrees C. Within the limits of the technique, no significant differences between the number of binding sites and strength of binding at the tight site at either temperature were observed. 2. The fluorescence of warfarin and warfarin-alcohol was used to label their binding site on HSA and to study the effects of other drugs on their binding. The results indicate that these two molecules are bound to the same site on HSA. 3. The validity of using changes in the fluorescence of warfarin as a measure of its displacement from HSA was investigated. Good correlations were observed between drug-induced decreases in the fluorescence of bound warfarin and displacement as measured by equilibrium dialysis. The displacement of warfarfin, as detected by fluorescence, correlates well with the increase in free warfarin resulting from addition of therapeutic drug concentrations to undiluted human serum. 4. The most potent displacing agents, by all the methods used, were iophenoxic acid, phenylbutazone and oxyphenylbutazone. The first of these is no longer used clinically, but the latter two are and have been reported to cause hypoprothrominaemia by displacing warfarin from HSA. The present study indicates that changes in the fluorescence of warfarin bound to HSA can be used to measure displacement of bound warfarin and to screen drugs that may cause clinically significant interactions by this mechanism.


Alterations in renal tubular sodium and water transport in polycystic kidney disease. Thirty patients with chronic renal diease -10 with polycystic kidney disease (PKD) and normal GFR; 10 with PKD and GFR is less than 30 ml+min; 10 with chronic glomerulonephritis (CGN) and GFR is less than 30 ml+min -and 10 normal subjects were investigated. The ability to concentrate urine maximally (T-CH2O) after water deprivation and the renal handling of water and electrolytes following hypertonic volume expansion were studied. A defect in T-CH2O was common in PKD patients even with normal GFR. In PKD patients with normal GFR, volume expansion was not followed by a natriuretic effect of the same magnitude as in controls. This ""inadequate natriuresis after volume expansion"" may be explained partly by chronic hyponatremia and partly by a functional defect, i.e. the incomplete arterial vasodilation in the kidney. At comparable degrees of renal insufficiency, T-CH2O was lower in PKD than in CGN patients. It seems likely that in PKD patients the increased endogenous osmotic load has exaggerated the tubular defect in urine concentration already present at normal GFR. Furthermore, volume expansion was followed by a significant increase in fractional sodium excretion only in PKD patients with renal insufficiency.


Occurrence of 5-hydroxy-3-indoleacetic acid in urine from several animal species. 1. The normal levels of 5-hydroxy-3-indoleacetic acid (5HIAA) were determined in the urine of four species of laboratory animals (dog, rabbit, rat and guinea-pig). 2. When 5HIAA excretion was calculated as mg/24 h, the output in the four species was in the order of rabbit greater than dog greater than guinea-pig greater than rat; but when it was calculated as mu/mg of creatinine, the order was guinea-pig greater than rabbit greater than rat greater than dog. 3. There were significant differences in the excretion of urinary 5HIAA between males and females within two species: rats and dogs.


Are non-absorbable indicators of comparable value in the human stomach made abnormal by taurocholic acid? 1. The substances chromium-51 (51CrCl3) and phenolsulphonphthalein (phenol red; PR) were compared as non-absorbable indicators in the human stomach after alteration of ionic permeability by taurocholic acid. 2. Control and test solutions containing 10 mM taurocholic acid and indicators at pH 1 were instilled into the stomach and sampled immediately and after 15 min. The ratios of the initial and final concentrations of the indicators (Ci/Cf) were compared. 3. Correlation coefficients of the Ci/Cf ratios for the two indicators were 0 with 91 in control studies and 0 with 75 after taurocholic acid instillation; there was no significant difference between either indicator. During taurocholic acid instillation, Ci/Cf values tended to fall compared to controls. 4. In a smaller number of subjects in whom polyethylene glycol (PEG) was also measured as a non-absorbable indicator, results were similar to those obtained with 51Cr and PR. 5. 51Cr, PR and PEG are comparable indicators in the normal human stomach and when it is made abnormal by a lipid-soluble agent such as unionized taurocholic acid, though the correlation between indicators is reduced in the abnormal stomach. 6. No evidence of increased absorption of any indicator was found in spite of the increased ionic permeability produced by taurocholic acid.


Lithium induced nephrogenic diabetes insipidus: changes in plasma vasopressin and angiotensin II. Nephrogenic diabetes insipidus associated with high basal levels of plasma arginine vasopressin developed in a patient during lithium therapy. Fluid deprivation was accompanied by an increase in the concentration in peripheral venous plasma of vasopressin and angiotensin II, a rise in plasma osmolality and a modest rise in urine osmolality. Infusion of arginine vasopressin produced comparable levels of plasma vasopressin to those found during fluid deprivation, with no overall change in plasma angiotensin II and little change in urine volume or osmolality. It is suggested that angiotensin II may be responsible for the difference in ability to concentrate urine under these two conditions. Following death by self-poisoning, renal histology revealed distinct structural changes in the distal tubules: such lesions have not previously been described in man and it is suggested that the occurrence of nephrogenic diabetes insipidus while on lithium therapy may be related to tubular damage.


Pressure-flow relationships in the peripheral circulation of the dog with isoprenaline. 1. The effects of isoprenaline on the pressure-flow relationships in the peripheral circulation were studied in five anaesthetized dogs during right heart bypass procedures. 2. Isoprenaline (1 mug/kg per min) produced a significant drop in arterial pressure and arterial resistance. 3. There was a significant decrease in the resistance to venous return which resulted in a significant increase in venous return. 4. The findings suggest that the increase in cardiac output produced by isoprenaline results in large part from dilatation of venous resistance vessels.


Mammography, xeroradiography, and thermography. The concept of early breast cancer as a palpable mass with limited secondary manifestations is rapidly changing. Thanks largely to mammography, a malignant breast neoplasm can be detected long before it forms a mass. Because cure rates in this stage are high, reliable means of early detection and diagnosis are of deep concern. Early detection has certainly been the major influence in reducing mortality from cancer of the cervix, and results of recent studies indicate that this will also be true for cancer of the breast.


Diagnosis of occult fractures and dislocations. The principles to be followed in the identification of occult injuries include: a good history and physical examination to arouse a high index of suspicion; high quality radiographs; radiographs of the whole bone and associated joints above and below, particularly in the lower cervical spine and hip; special views to delineate fractures, particularly oblique films, tangenital and axial views and stress films. Tomograms may also be helpful; follow-up and re-check films, especially with fractures and epiphyseal injuries. With early identification of fractures that are commonly missed, these injuries eventually cease to be occult and appropriate management can be instituted.


Un-united fracture of the scaphoid.

Un-united fracture of the scaphoid. The anterior approach as described by Matte and Russe for treatment of ununited fractures of the scaphoid was employed in 48 patients using autologous cortical cancellous pegs and chips. Operative intervention occurred in an average period of 14 months after fracture. The average time to radiological union was 3.5 months; the average follow-up was 2 years. Union occurred in 43 patients. The anterior approach is recommended because of its simplicity. Neither avascular necrosis nor a small proximal pole fragment are contraindications to the procedure.


The holding power of orthopedic screws in vivo. Great difficulty is encountered in choosing screws for internal fixation, for screws differ in material, geometry, dimension, and in insertion technique. Recently claims have been made that self-tapping screws cause necrosis of bone and result in fibrous tissue formation, with loss of holding power. This investigation was undertaken to study the healing of bone about screws inserted for a period of 3 months. Self tapping and non-self tapping screws were employed. The Vitallium screws not only differed in dimension, but also in configuration of the thread, with the smaller of the self-tapping screws exhibiting a "V" thread in distinction to the buttress thread of the larger screw. The histologic data were correlated with the holding power of the screws as obtained by means of a push out test, performed with the aid of an Instrom testing machine. The largest screw tested, the 4.5 mm non-self tapping stainless steel AO screw (Type 1), provided the greatest safety factor to push out loading over the period tested in the unloaded system. The self tapping and non-self tapping screws of similar material and size were found to maintain comparable holding power at all intervals tested in vivo in the unloaded system. No histological differentiation could be made with regard to both death or tissue reaction around the implant, between the stainless steel or cobalt chromium alloy materials, nor between the self tapping and non-self tapping insertion methods.


Non-union of the odontoid process. An experimental investigation. A clinical study of fractures of the odontoid process showed a 62 per cent failure on union. Of many features studied, only displacement and its direction had a definite bearing on non-union of the fracture. Blood supply was considered as a possible etiological factor. The blood supply of the human odontoid was elucidated by means of studying 19 human autopsies by means of microangiography. The dog was found to have a similar blood supply and hence, was used as the experimental model. Two osteotomies were performed; one below the accessory ligaments and one above the accessory ligaments. All osteotomies carried out below the accessory ligament united and all carried out above failed to unite. Microangiographic studies revealed however, that avascular necrosis was not the cause of non-union. Further anatomic studies revealed that different size gaps occurred depending on the level of the osteotomy, with a large gap occurring in the osteotomy of the odontoid which was performed above the accessory ligament. First the result of immobilization and the healing of the odontoid osteotomy was derived, by carrying out an instant occipito-cervical fusion by means of wire loops and methylmethacrylate. In distinction to the free floating apical segment of non-immobolized spines, with a high odontoid osteotomy, the occipito-cervical fusion resulted in a dense fibrous tissue stabilizing the apical fragment but at no time was bony union observed. A final attempt was to secure immobilization and reduce the gap, by carrying out only a partial osteotomy. The osteotomy was performed in such a way that the posterior cortex was left intact. Union occurred in all instances. The fracture gap and movement play a definite role in the pathogenesis of pseudarthrosis of the odontoid process. Where gap and movement were eliminated, union occurred. It is difficult to transpose this experimental situation to the clinical one, for the assessment of gap clinically, is only radiographic. This method is much too imprecise to be of value in this assessment. The fact however, that a high rate of non-union is associated with a high degree of displacement, supports the experimental thesis.


Antibiotics in human hematoma and wound fluid. Using the total hip replacement patient, we measured the level of antibiotic in the wound at the time of surgery, the wound drainage for 36 to 48 hours after surgery and over a 10 day period in incubated surgical debris obtained at the time of total hip replacement. The antibiotics sodium oxacillin, lincomycin hydrochloride and sodium cephalothin were administered in standard doses at 6 hour intervals. In one group of patients the antibiotic was begun at the time of surgery, in a second group the antibiotic was begun 24 hours after the completion of surgery. Sodium oxacillin, lincomycin hydrochloride and sodium cephalothin produce antibiotic levels in the venous serum consistently above the level obtained in the simultaneous would drainage specimens. Sodium oxacillin and lincomycin hydrochloride used as described in this study are capable of bathing the area of the surgical wound with concentrations of antibiotics above the minimal inhibitory concentrations. This is evidenced by the antibiotic levels above minimal inhibitory concentrations found in the wound drainage. Sodium cephalothin levels in the wound drainage were below measurable levels in 3 of 4 patients. Sodium oxacillin and lincomycin hydrochloride antibiotic levels in the surgical wound debris and simultaneous venous clotted specimens diminished progressively in a similiar manner indicating no additional effects of the surgical wound debris on the antibiotic's biologic effectiveness. Sodium cephalothin dropped below measurable levels in three days. Measurable levels of antibiotics appeared in the wound aspirate well above the minimal inhibitory concentration in patients receiving their initial dose of sodium oxacillin 24 hours after surgery.


Some physical and mechanical factors affecting the simple shear strength of methylmethacrylate. An investigation of the effect of kneading time on the simple shear strength of cold-cured plain methylmethacrylate bone cement and on the effect of anchor-hole configuration on the load-carrying capabilities of the cement anchor-hole configuration demonstrates that at a strain-rate of 10-3 rad/second, the mean simple shear strength of the cement was 251.65 (plus or minus 3%) for both 30-second and 2-minute kneading times. Increasing the loading rate to 10-1 rad/second increased the simple shear strength of 326.20 kg/cm-2 (plus or minus 2%). The geometric configuration did not significantly affect the maximum shear load-carrying capabilities of the methylmethacrylate.


Kinematics of the knee after prosthetic replacements. A method was developed for describing the flexion-extension motion of the knee joint in a sagittal plane, by employing ciné radiography and then plotting the loci of three points on the femur relative to the tibia. Normal knees displayed similar patterns, the curves were smooth, and flexion-extension curves superimposed. A standard knee outline with standard curves was defined, with which to compare the abnormal and prosthetic knees. Arthritic knee patterns differed significantly from the normals. The curves were irregular and the flexion-extension curves were different. Instability, joint surface irregularity and muscle spasm were thought to be the main causes. The curves for the MacIntosh tibial plateaus were abnormal in a similar way to the arthritics. This may have been due to residual instability and to the replacement of only one bearing surface. The condylar replacement prostheses (the uni-condylar, duo-condylar and Geometric) tended to produce close-to-normal knee patterns, probably due to restoration of a relatively normal geometry, and to replacement of both bearing surfaces. The knees with fixed hinge prostheses (Walldius, Shiers and Guépar) showed abnormalities of motion and of the relative postion of the femur on the tibia. These features would be undesirable for the correct functioning of soft tissues around the knee. The stabilo-condylar hinge, which did not require much bone resection, gave a motion comparable to the condylar replacements.


Accessory spinal nerve injury.

Accessory spinal nerve injury. In 7 cases of peripheral lesion of the spinal accessory nerve 4 were produced by malignancy, two by iatrogenical resection of lymph nodes, one by an en bloc dissection of the neck for arteriovenous malformation. Incapacity following the injury is quite marked and includes weakness of the sternomastoid and trapezius muscles, as well as pain presumably from traction on the brachial plexus. The importance of avoiding the nerve in surgical intervention in the neck must be strongly emphasized. A review of the literature suggests that in fresh injuries the spinal accessory nerve should be explored and resutured. Our own experience, however, with nerve repair has been disappointing.


Bacterial contamination of the surgical knife. Two hundred and eight skin knives and 374 deep knives were evaluated in 153 clean orthopedic cases with and without a horizontal wall-less laminar air-flow system. There was no statistical difference in contamination frequency between the skin and the deep knives with and without the laminar air-flow. However, the knife blades were found to be contaminated less than laminar air-flow was used than when it was not (P less than 0.005). No correlation could be made between the cultures of the wound edges and the depth of the wound with the contaminated knife blades.


Treatment of coccidioidomycosis infection of bone with local amphotericin B suction-irrigation. Report of a case. A 29-year-old man with coccidioidomycosis of the tarsal bones and toxic reactions to intravenous Amphotericin B was treated by surgical curettage and local suction-irrigation system of Amphotericin B. The patient responded to treatment and was free of disease 2 years later. Local suction-irrigation with Amphotericin B may be a valuable adjunct in the treatment of coccidioidomycosis infection of bone.


Coracoid fracture associated with acromioclavicular dislocation. A case report. When a fracture of the coracoid process is identified by clinical examination and X-rays, one should always be aware of a possible acromioclavicular dislocation. Clinical exam and X-rays of the shoulder with weights in the patient's hand will help substantiate the diagnosis. Reduction of the acromioclavicular dislocation (by whatever means desirable) seems to reduce the coracoid fracture well. Obviously, this combination of injuries precludes the use of coracoclavicular methods of fixation as a method of treatment. Acromioclavicular joint reduction and secure internal fixation generally provides adequate coracoid fracture reduction and allows subsequent healing.


Recurrent ulnar-nerve dislocation at the  elbow. Recurring luxation of the ulnar nerve at the elbow is not uncommon (16.2%), occurring about equally in young and old, male and female, athletes and non-athletes but the greater mobility is usually at the dominant arm. The probable cause of such dislocation is congenital laxity of supporting ligaments. Being more vulnerable to injury than normally-positioned nerves, however, complicating neuritis can does occur. Subluxating nerves which stop on the tip of the medial humeral epicondyle upon 90 degrees or more of flexion at the elbow are more subject to direct trauma than completely displaced neural structures which cross the epicondyle upon elbow flexion. The latter may develop friction neuritis which occurs most frequently in industrial workers and occasionally requires surgical transfer. Deep intramuscular implantation, with or without neurolysis, is definetely superior to subcutaneous placement of the affected nerve. In this report are described chemically-induced ulnar neuritis from cortisone injections about the medial humeral epicondyle; pressure ulnar neuritis in patients with enforced bed rest and from improper positioning on operating table with permanent neural deficit and the relationship of such hypermobile ulnar nerves to extension-flexion (whiplash) trauma to the neck. It is emphasized that most of these complications could have been avoided had the patient and his physician known that such anomalies were present. Of particular importance is the avoidance of pressure to the medial aspect of a flexed elbow in surgical patients under general anesthesia. The unrelated co-existence of intermittently-symptomatic hypermobile ulnar nerves and extension-flexion neck trauma may occur. Recognition of isolated unlar neuritis in these patients is definitely important from the diagnostic, treatment and medical-legal aspects of such cervical spine injuries.


Stabilization of comminuted fractures of the distal inch of the radius: percutaneous pinning. Comminuted fractures of the distal inch of the radius have always been difficult to stabilize. Closed reduction and plaster cast fixation frequently result in recurring deformity and some loss of wrist function. A method of closed pinning with proper placement of multiple small Kirschner wires to supplement plaster cast fixation in selected comminuted fractures helps retain anatomical position of the major fragments of the distal end of the radius. This method is sound in principle and we recommend its use in the treatment of severly comminuted fractures of the distal end of the radius.


Synovial chondromatosis and instability of the proximal tibiofibular joint. A patient with synovial chondromatosis involving both posterior compartments of the right knee and proximal tibiofibular joint had continued pain and weakness after partial synovectomy. The "Helfet Test" for proximal tibiofibular joint instability was positive; the fibular head was prominent and tender. Following excision of the proximal fibula, the patient was symptom free. This case demonstrates that it is essential to evaluate all joints involved with a disease process prior to surgical intervention.


Ligamentous injuries of the knee in skiing. A scoring system for the long-term comparative evaluation of patients with knee ligament injuries was presented. Twenty-four patients hospitalized for injuries to knee ligaments from skiing accidents were examined at a mean of more than 4 years after hospitalization. Eighteen had required surgery, and most were found not to have high scores at the long-term follow-up evaluation. Mechanisms of injury to explain why certain types of falls result in particular injuries were presented.


Instrcapsular epiphyseal osteoid osteoma of ankle joint. A case report. A 12-year-old boy with ankle pain following minor trauma was found after a month of conservative treatment to have a small sclerotic lesion in the anterolateral distal tibial epiphysis. At operation, a vascular, raised, intracapsular epiphyseal lesion was removed. Microscopic examination revealed an osteoid osteoma. To the authors' knowledge no previous example of intracapsular epiphyseal osteoid-osteoma has been reported.


Osteogenesis imperfecta tarda. The morphology of rib biopsies. Undecalcified bone biopsy specimens from 10 normal individuals and 8 osteogenesis imperfecta patients, 2 to 30 years of age, were analyzed using microradiography as well as ultraviolet, tungsten and polarized light microscope techniques. Biopsies of ribs most reliably reflected the disease process of osteogenesis imperfecta when compared to those biopsies of long bones in the lower extremities deformed enough to require corrective surgery. The rib biopsies consistently revealed that there is a rapid surface turnover of histologically well-organized but osteopenic bone. The high rate of bone turnover is similar to that seen in very young normals but in osteogenesis imperfecta turnover rate does not appear to decline with age. The percentage of surface involved in active new bone formation and in osteoclastic resorption is notably elevated. Excessive osteocyte osteolysis is also characteristic.


Resection of the forefoot in rheumatoid arthritis. A long-term review of 272 resections of the metatarsal heads and bases of the phalanges in 128 patients with severe rheumatoid feet is presented. The longest follow-up is 11 years and the average follow-up was 4.7 years. Recurrent deformity and callus formation was usually due to a long metatarsal shaft. The operation, when properly performed, can correct severe deformities of the forefoot with a high percentage of satisfactory results.


Subcoracoid neurovascular entrapment.

Subcoracoid neurovascular entrapment. A review of 19 patients with upper limb symptoms is presented; 3 patients had bilateral symptoms. The patients were young (22-44 years) and only 4 were women. The symptoms were usually precipitated by injury. Aching pain the the neck and shoulder area, upper arm and forearm, with some intermittent numbness were the main complaints. These symptoms may be aggravated or relieved by altering posture. The most constant and diagnostic physical finding was tenderness and reproduction of symptoms with pressure over the neurovascular bundle underneath the coracoid process and pectoralis minor. There are no constant positive findings on regular radiographs. Electromyography and venography were of doubtful diagnostic significance. Conservative measures were rarely curative but often alleviated some of the symptoms. These measures included local heat, and postural exercises with elevation and rotation of the shoulder forward. The neurovascular bundle was decompressed by dividing the pectoralis minor surgically in 10 limbs. This relieved the radiating symptoms in each case although mild aching pain in the shoulder had remained in 4 instances. This syndrome can be recognized clinically and may be controlled in half of the cases by conservative means. If the diagnosis is well localized, surgical release offers good relief.


The microhardness of articular cartilage. The standard metallurgical technique of microhardness testing was useful for investigations on the physical properties of articular cartilage. The problem of visco-elasticity of the cartilage was overcome by using a brittle lacquer coating as a memory device. The surface layer was the hardest plane when the superficial layer was intact. Removal of the superficial layer however, made this plane the softest. There was no variation in hardness with depth. The plane at right angles to the vector of movement of the joint was harder than the plane parallel to the vector of movement. This indicates the presence of a secondary fiber system in the middle layer of articular cartilage. The fibers in this system run predominantly at right angles to the direction of motion of the joint.


Observations on osteoarthritis of the hip joint. A correlation of the X-ray changes with the pathological changes seen in arthritic hips obtained at surgery or from cadavers, reveals 6 different patterns of osteoarthritis of the hip. The study suggests that the pathogenesis of the degenerative changes is different in each type and as such, would influence the results obtained by surgical intervention.


The management of spinal deformities in Duchenne muscular dystrophy. A new concept of spinal bracing. A clinical study of 62 patients with Duchenne Muscular Dystrophy has suggested 2 pathways in the pathogenesis of the spinal deformities. In the first pathway, the patients develop an initial kyphosis due to the loss of paravertebral muscle thus placing the intrinsic ligamentous spine in an unstable position. The spine then develops a lateral curve accentuated by pelvic obliquity. In the final form, axial rotation of the spine and pelvis occurs to produce a severe deformity. In the second pathway the intrinsic spine assumes the more stable position of hyperextension with a level pelvis. This position remains relatively unchanged during the period of wheelchair confinement even though muscle deterioration progresses. A significant increase in the severity of the deformity occurs with age in those patients with unstable spines. None of the other factors examined affected the severity of the lateral curvature. A spinal brace has been designed to keep the spine extended and the pelvis level while the patients sits in his wheelchair. The purpose is to encourage the inexorable progression of muscular deficiencies to follow the second pathway. Various modifications of wheelchairs also may help to maintain spinal stability.


An evaluation of discography in the localization of symptomatic levels in discogenic disease of the spine. On the basis of a review of 507 patients, discography was a reliable diagnostic procedure in determining the symptomatic level in discogenic disease of the cervical and lumbar spine. The value of discography of the spine is as both a functional and anatomical assessment. Its value in the cervical spine is largely as a functional assessment, with reproduction of the patient's specific pain pattern on a consistent basis at a particular level. It is a reasonably simple procedure, provided that adequate radiographic facilities are available, and strict adherence to aseptic technique is carriet out. The performance and interpretation requires a considerable amount of skill and experience. However, it is a useful adjunct to solving the perplexing problem of the surgical management of pain in discogenic disease of the spine.


The allotransplantation of partial joints in the treatment of osteoarthritis of the knee. Nine allografts replacing part of the knee have been carried out in 8 patients. In all patients the graft was incorporated without clinical evidence of rejection. In one case a low grade infection was brought under control without surgery and thus far has not impaired the results. All patients have a good functional range of movement and the alignment of the knee has been maintained by the grafts which display little or no collapse at all. Histological evidence in one case revealed cartilage viability at 14 months. Two years interim observations are encouraging enough to continue on with this technique in the knee with disease severe enough not to be helped by osteotomy but not so diffusely damaged as to require total knee arthroplasty.


A transverse loading system applied to a modified Harrington instrumentation. Observations using standard Harrington Instrumentation revealed that while maximal distractive forces are applied it is possible to produce further correction of spinal deformity by applying a lateral force. Modifications to the standard Harrington Instrumentation by applying a transverse loading system have been made in order to produce this added correction. The transverse load is applied as nearly as possible in the same plane as the bearing points of hooks, i.e., below the axis of the rods. Transverse loading helps to reduce the distance from the apex of the curve to the midline, thereby producing a more stable spine as well as providing additional support on the convex side. The system is ideal for flexible curves with little kyphosis. Photogrammetry reveals that there was no significant rotation occurring after the application of the transverse load. To date, Instrumentation has been used in 10 patients with success.


Protrusio acetabuli in rheumatoid arthritis. Protrusio acetabuli is common is rheumatoid arthritis. Progression of this deformity can be measured by serial roentgenograms. The inward progression of the femoral head is the result of upward migration of the acetabular roof and collapse of the femoral head which appears to occur in a ratio of approximately two to one. Adrenal cortical steroids may play a significant role in the etiology of this condition in rheumatoid arthritis. This complication of intrapelvic protrusion of the prosthetic acetabulum following total hip replacement has been presented and suggestions made to overcome this problem. Early operation on those patients showing rapid development of protrusio may prevent complications.


Treatment of infected un-united femoral shaft fractures. Twenty patients treated for osteomyelitis following intramedullary fixation of fractures of the femoral shaft were assessed from the standpoint of antibiotics, internal fixation, drainage, sequestrectomy and external support. Analysis of intramedullary fixation in the form of Küntscher nailing with respect to the rate of union, duration of treatment and number of operative procedures, suggests that rigid intramedullary fixation is superior to plates and screws and plays an important role in development of union in the presence of infection.


A study of weight transmission through the knee joint with applied varus and valgus loads. An electromechanical device is described which permits measurement of the amount of weight borne on each compartment of the knee during varying amounts of lateral angulation. A lateral angulation of only 3 degrees in either direction completely unloaded the opposite condyle. The correction to be obtained by tibial osteotomy of varus or valgus knee deformity should permit the mechanical axis of the extremity to pass the tibial spines on the side opposite the deformity. An angular deviation of 3 degrees more than that required to restore the mechanical axis to normal position is sufficient.


Sagittal mobility of the normal ankle.

Sagittal mobility of the normal ankle. In children and adults, there is a physiological anterior sagittal displacement of the talus which decreases when the examination is repeated in equinus. The displacement occurs when the examination is performed with or without apparatus, with manual stress or with weights. The diminution of the normal sagittal mobility of the talus when the examination is performed with the ankle in the position of equinus, it attributable to the intact anterior talofibular ligament which becomes taut when the ankle is in a position of flexion. A pathological drawer sign will be noted following an isolated tear of the anterior talofibular; under those circumstances sagittal instability is increased and is not appreciably affected by repeating the examination in a position of ankle equinus.


The diposi tion of morphine in surgical patients. The disposition of serum morphine following administration of 10 mg/70 kg was determined by a sensitive and specific radioimmunoassay in 31 anethetized surgical patients ranging in age from 23 to 75 yr. Following iv injection, 93 per cent of the morphine disappeared from the serum within 5 min. The early serum levels of the drug (2 min) correlated directly with the patients' ages (r equal to 0.63, p smaller than 0.01). Patient 23 to 50 yr of age averaged 0.29 mug/ml, whereas patients 51 to 75 ur of age averaged 70 percent higher, 0.49 mug/ml. The serum half-life between 10 and 240 min was independent  of age and averaged about 2 hr after either iv or im administration. Following im admininstration, morphine was rapidly absorbed, with peak levels occurring within 10 to 20 min. The decline in morphine serum levels paralleled the decline in morphine analgesia and was coincident with the apperance of morphine glucuronide in the serum. These studies demonstrate the applicability and specificity of the radioimmunoassay for morphine and suggest that serum levels of morphine may be a useful and objective indicator of its pharmacologic activity.


Plasma levels and symptom complaints in patients maintained on daily dosage of methadone hydrochloride. Plasma methadone levels, symptom complaints, and urine tests for illicit opiate use were followed weekly in 17 patients on a methadone maintenance program. There were very large differences between patients in the plasma level established at a given dosage, implying large differences in the rate of methadone metabolism. Despite virtually constant daily dosage, the plasma methadone levels fluctuated greatly from week to week and from day to day in individual patients. With rate exceptions there was no relationship between plasma methadone level and symptom complaints or between weekly chamges in plasma methadone level and changes in symptom complaints. Except possible to identify the ocassional patient with unusually low plasam methadone levels, the determination of methadone levels is not likely to be or practical value in methadone programs.


Unaltered metabolism of antipyrine and tolbutamide in fasting man. Effects of fasting on the metabolsim and distribution of antipyrine and tolbutamide were studied in 13 obese, but otherwise healthy, volunteers. Only 6 of the 13 subjects decreased their metabolic clearance rate (MCR) during fasting; no significant change occurred during fasting in the mean MCR of either drug. These results are in contrast with reported changed rates of drug metabolism in fasting experimental animals. The apparent volume of distribution (aVd) of antipyrine decreased during fasting in each of 7 subjects receiving oral test doses of antipyrine; the mean control value plus or minus standard deviation was 61 plus or minus 16 1, whereas  during fasting the mean became 52 plus or minus 17 1. The aVd plus or minus SD of tolbutamide decreased in 4 of the 6 volunteers receiving intravenous test doses of tolbutamide; the mean control value in these6 volunteers was 8.3 plus or minus 1.7 1; during fasting it was 7.4 plus or minus 1.91.


Pharmacokinetics of carbamazepine in normal man. The bioavailability of commercial carbamazepine talbets with and without meals was compared to a propylene  glycol solution respect to extent of absorption in 6 normal humans after a dose of 6 MG/KG. The presence of dose-dependent kinetics within a clinically sigificant range was also investigated. Serum and urine samples were assayed by gal-liquid chromatography (GLC). Carbamazepine is rapidly absorbed from the propylene glycol solution. Eight per cent of the dose was absorbed from the commercial tablet, resulting in therapeutic serum concentrations(30 to 6 mcg/ni). The data were consitent with disolution rate-limited absorption. Mean half-lives ranged from 31 to 35 hr. No dose-dependent kinetics were observed following administration of does of 3. 6. or 9 mg/kg. The fraction of dose abosrbed, the fraction excredted unchanged in urine, the time of maxium serum concentration, and absorption and elimination half-lives appear to be independent of dose. The time course of side effects could not be correlated with serum carbamazepine levels, suggesting that metabolities contributed to side effects.


Influence of congestive heart failure on blood vessels of lidocaine and its active monodeethylated metabolite. The blood concentrations of lidocfaine and its active monodeethylated metabolite, monethylglycinexylidide (MEGX), were measured in 31 patients who were receiving infusiions of lidocaine intravenously. In 3 patients who were studied intensively, the elimination half-life of MEGX was 120 min, which was similar to the elimination half-life of lidocaine  (139 min). An addition 3 patients demonstrated a higher ratio of the concentration in blood of MEGX to lidocaine, and the MEGX may have contributed, in 1 patient, to the central nervous system toxicity that occurred during the infusion. Elevated concentrations of MEGX in blood were associated with congestive heart failure (r equalto 0.5, p equal to 0.004). Our data suggest that the elimination of MEGX may be decreased in patients with depressed cardiac output and sympathomimetic compensation.


Influence of acute viral hepatitis on phenytoin kinetics and protein binding. Patients with liver disease are thought to have abnormal responses to drugs metabolized by the liver, although supportive evidence is sparse. The influence of acute viral hepatitis on the pharmacokinetics and protein binding of phenytoin (DPH) was examined in 5 patients. A longitudinal study design was used so that each patient acted as his own control. DPH clearance was unaffected by acute viral hepatitits over theconcentration range studie, but the percentage of unboudn DPH increased by an average of nearly one-third during acute viral hepatitis. A small decline in serum albumin concentration and elevated serum bilirubin levels may be responsible for the alterations in protein bindig. These results indicate that acute inflammatory liver disease has complex and perhaps paradoxical effects on durg disposition. Clinical and laboratory observations including plasma durg concentrations, still provide the best means for adjusting dosage regimens in patients with fluctuating hepatic function.


Carbenicillin therapy in patients with normal and impaired renal function. Optimun therapy with carbenicillin entails the use of high serum concentrations and the risk of significant dose-related toxicity. We report a study of serum clearance method of dose adjustment of carbenicillin patients with normal and imparied renal function. This method was found to provide serum concentrations considered to be satisfactory in every instance, by either constant-rate or intermittent infusion, and should enable greater precision in the use of the antibiotic. Implications of these findings aimed at providing dosage schedules for patients with renal failure are discussed.


Pharmacokinetics of actinoymcin D in patients with malignant melanoma. The distribution and  excretion of tritiated actinomycin D have been determined in 3 adult patients with disseminated malignant melanoma. In the blood, the drug  was preferentially taken up into nucleated cells. The urinary and fecal excretion was prolonged and only about 30 per cent of the dose of actinomycin was recovered in 9 days. There was evidence that the drug was concentrated in bone marrow and tumor cells, but did not readily cross the blood-brain barrier. The long tissue half-lige of actinomycin D suggeststhat an intermittenr schedule of administration would be the most effective.


Effects of oral propranolol in normal subjects. The effects of oral propranolol were evaluated in 10 normal volunteers. The resting heart rate decreased from the mean control value of 68 plus or minus 3.3 (SE) to 56 plus or minus 2.8 beats per minute (bpm) on propranolol (p smaller than 0.001, paired test). Mean systolic blood pressur also decreased from 125 plus or minus 5.0 to 114 plus or minus 4.2 mm Hg (p smaller than 0.03). Resting systolic time intervals were unaffected by propranolol. Mean maximal treadmill exercise tolerance time was not significantly altered by propranolol although the mean heart rate systolic blood pressure product a maximal exertion was markedly decreased (1.91 plus or minus 0.17 vs 2.62 plus or minus 0.17 times 10-4, p smaller than 0.004) . The nonsignificant effect of oral propranolol on resting systolic time intervals and maximum exercise tolerance despite significant changes in  heart rate and blood pressure at rest and duringexercise stand in contrast to the reported effects of intravenous propranolol. Explantations for this difference between the effects of oral and intravenous propranolol in normal subjects are examined.


Sulfamethizole-induced inhibition of diphenlhydantoin, tolbutamide, and warfarin metabolism. The influence of sulfamethizole on the metabolism of diphenylhydatoin (DPH) tolbutamide, and warefarian is examined. In 8 patients DPH means half-life (T/2) increased from 11.8 plus or minus 3.6 hr to 19.6 plus or minus 5.2 hr and mean metabolic clearance rate (MCR) decreased from 43.7 plus or minus 16,8 to 28.1 plus or minus 9.1 ml/min durus or minus 1.2 to 9.2 plus or minus 1.2 hr MCR decrease from 17.0 plus or minus 5.4 to 10.5 plus or minus 1.2 ml/min. In 2 patients warfarin T/2 increased fron an average of 64.7 to 92.7 hr and MCR decreased from 1.65 ml/min to 1.05 ml/min. In 4 patients on long-term DPH treatment after 1 wk on sulfamethizole inhibits hepatic metabolism of DPH, tolbutamide, and warfarin.


Automatic localization of curved wires used in brachytherapy. The COUREP program. The localization of sources used for brachytherapy has become more difficult since radium sources are replaced by flexible wires such as Iridium 192 wires. We describe the COUREP program which automatically reconstructs the real 3-D arrangement of curved wires from two orthogonal radiographs of the implant. The data used by the program consist mainly of the projections of the wires on the radiographs expressed as the co-ordinates of points selected on these projections individually on each radiograph. The output consists of the 3-D co-ordinates of points located on the wires with optionally a graphic output including the plotting of a perspective view of the implant.


Interactive simulator for pharmacokinetics of repetitive drug dosing. DRUGSIM is a highly interactive program allowing simulation of the effects of repeated drug administration by a variety of routes on plasma concentrations of drugs over a period of time. Drug parameters are read from a data file; prescriptions are obtained from the user at various points during run time. The results for one or two compartment pharmacokinetics are plotted on a storage display tube, and the user is queried for further prescriptions. Simulation involves a point-slope method with a variable time step. The program is written in Fortran IV and run on a DEC PDP-10 computer using a Computek 611 display terminal.


A computer program for automatic recording and processing of renograms. A program is described, which performs automatic uptake, plotting and processing of radio-hippuran renograms obtained from a gamma camera, using an on-line minicomputer system. The program is written in machine language for a ND 50/50 system equipped with a PDP8-L processor, but translation for other nuclear medicine EDP system is easy. Minimum configuration requirements are: (i) 4K processor with TTY; (ii) external clock; (iii) magnetic tape transport; and (iv) 4K + 4K buffered camera interface or additional 8K of storage plus camera interface. Camera interface is computer-controlled and includes two AD-converters, a display unit for buffer storage and interest-areas selection facility. Operation starts recording 40 scintiphotographs of 30 sec each. Then, kidney uptake curves are obtained by subtraction of blood and tissue background, and diagnostic parameters, such as the initial slope, the maximum uptake point and 50% activity time, are computed. The only manual intervention required is the computer-assisted selection of interest-areas of kidneys, and blood and tissue background. Time required is 20 min for uptake of renograms and 5 min for processing and output, thus allowing routine execution of good quality renography, including hardcopy printout of both kidney uptake curves and diagnostic paramerers.


On the separation of semiperiodic superimposed point processes: application to electromyographic signals. A method for the separation of semiperiodic (Gaussian probability distribution of intervals with moderate coefficient of variation) superimposed point processes, to be implemented on a digital computer is described. The efficiency of the filter used for the extraction of the underlying event sequences from the pooled array has been investigated by simulation. Approximately 80 percent of the events belonging to the underlying sequence to be extracted were recovered (with the addition of "impurity events"), still preserving the mean rate and coefficient of variation of the original indicidual sequence concerned. The program was used on an example of an actual electromyographic recording (comprised of a number of motor units discharging simultaneously), resolving the number of motor units involved, their mean rates, and the coefficient of variation of the individual action potential sequences.


The BACTLAB system - a data system for bacteriological routine. An implemented version of a data system for routine bacteriology is described which uses punch cards to capture all administrative data and OMR (optical mark recognition) documents for the bacteriological findings: diagnosis, antibiotic sensitivity patterns, phage type etc. The output includes reports for the customers and report lists for the laboratory, as well as surveys over findings of pertinent bacteria produced twice each month. In addition bills are produced at regular intervals, both for hospitals and for private patients. All results are stored on magnetic tape in order to make later analysis possible. The system has also been adapted for use in a research project for the study of postoperative infections.


An off-line system for in-time analysis of cardiac catheterization data and for establishment of a cardiological database for retrospective studies. The system described may be divided in two major parts: (i) automatic analysis of cardiac catheterization data running off-line on a Siemens 305 computer; (ii) storage and retrieval of the results from these analyses and additional data from related departments (thoracic surgery, internal medicine and clinical physiology) in a cardiological database on an IBM 370/155 computer. The first part is described with special regard to (i) operation and control during the phases of data collection, pre-processing, processing and storage of results; (ii) the presentation of the results in a complete and readable form and (iii) the modular design of the software. The results of an evaluation of the computer methods versus manual methods are also presented. The second part has been described with regard to the type of data entered in the cardiological database. The structure of the database and the programs used for storage and retrieval have not been described in detail in the present publication.


A model for sieving of macromolecules by the glomerular membrane of the kidney. The transport of water and of macromolecules across the glomerular membrane of the kidney depends on the membrane parameters (radius, length and number of pores) as well as on the hydrostatic and oncotic pressures on either side of the membrane. The filtration pressure decreases along the capillary loops from afferent to efferent end. Water and solute flows are thus given by a system of two differential equations. The sieving coefficient of the macromolecules is the ratio of solute to water flow. In the program described the differential equations are solved by the Runge-Kutta method (fourth order). Rosenbrock's method of minimization is used to adjust the theoretical to the experimental sieving coefficients. The pore radius, total pore area per unit of path length and conductance of the membrane, as well as the intracapillary hydrostatic pressure and its gradient can thus be determined.


Pathology of Mycoplasma agalactiae induced granular vulvovaginitis (GVV) in goats. Granular vulvovaginitis (GVV) was experimentally produced in female kids by topical application of M. agalactiae on the scarified vulvar mucosa. Grossly visible GVV lesions were seen in 25 out of 30 infected kids, yet all were positive for microscopic lesions. Microscope lesions that appeared by 7 days post infection (DPI) were comprised of stromal oedema, lymphocytic infiltration into the lamina propria and perivascular accumulation of a few lymphocytes. The lesions observed between 28 and 49 DPI were comparable to those of spontaneous cases (severe). The changes seen in kids euthanized between 56 to 70 DPI were suggestive of the chronic stage of the disease. M. agalactiae was reisolated from all the infected kids from 7 to 70 days after inoculation. The pathology and pathogenesis of this condition have been described and discussed.