A method for measurement of liver iron fractions in needle biopsy specimens and some results in acute liver disease.

Methods are described for measurement of total tissue iron, ferritin iron, haem iron and ferritin protein in approx. 15 mg of tissue obtained by liver biopsy. The validity of these methods is examined by comparison with the values observed in larger samples of the same post-mortem derived liver tissue. Correlation coefficients vary between 0.80 and 0.99 (n = 11--16). It appears that in post-mortem liver tissue the haem iron concentration is higher than in biopsy specimens from patients. Analysis of liver biopsy specimens from patients with hepatitis showed a large variation in the mean iron content of the liver ferritin molecules. Also, the non-ferritin depot iron concentration and ferritin protein concentration is quite variable. It is suggested that in cases of advanced ferritin catabolism during hepatitis the mean percentage of iron in ferritin molecules often increases while at the same time the non-ferritin depot iron fraction decreases, probably because of iron release from the liver.


Post-synthetic changes in creatine kinase isozymes (EC 2.7.3.2).

1. An in vivo change from creatine kinase MM3 into MM2 and finally into MM1 was described earlier in sera of patients during a post-myocardial infarction period. The same change takes place in vitro. 2. Parallel to this change, a turn-over from the MB2 isozyme into the MB1 form can be detected in vitro. 3. Immediately after the mixing of various extracts from heart tissue and other muscles with a serum with low creatine kinase activity, only MM3 and MB2 can be detected. MM1, MM2 and MB1 are not present in muscle cells. From these three observations it can be concluded that the phenomenon of the three MM and two MB isozymes is postsynthetic (i.e. epigenetic). Furthermore evidence is presented that the change from MM3 into MM1 is brought about by a thermolabile substance. This factor transforms one of the two M2 chains, present in the MM3 form, into a M1 chain. This results in the MM2 isozyme. Later on the second M2 chain is also transformed, resulting in the MM1 isozyme. The same mechanism is proposed for the observed change in MB pattern.


Beta-hexosaminidase activities in tears and plasma, diphosphoglycerate in blood of diabetic patients.

In a study on 10 normal controls, 7 pregnant women and 16 diabetic patients, beta-hexosaminidase in tears and 2,3-diphosphoglycerate in blood were investigated for possible use as index for diabetic retinopathy during pregnancy. Tears were used as source for beta-hexosaminidase because the concentration in plasma and the isoenzyme pattern are affected by the occurrence of a placentar isoenzyme in pregnancy. It has been found that in diabetes the concentration of beta-hexosaminidase in plasma may be elevated, but that it remains unchanged in tears and that there is no correlation between the plasma and tear values in all individuals. Neither beta-hexosaminidase in tears nor 2,3-diphosphoglycerate in blood appears as indicator for the onset or development of diabetic retinopathy.


A new reference method for the determination of the total CO2 concentration in biological fluids.

It appeared that a part of a measuring system recently developed for the determination of the oxygen content of blood (Dijkhuizen, P., Kwant, G. and Zijlstra, W.G. (1976) Clin. Chim. Acta 68, 79), was perfectly suitable for measuring the total CO2 content of blood, plasma or other fluids. CO2-free room air is pumped through an extraction vessel in which all the CO2 of the sample is set free by an acid reagent, and swept by the carrier gas to a titration vessel containing a BaCl2 solution. CO2 is bound as BaCO3 and the ensuing H+ titrated with an NaOH solution. The method was tested by measuring a series of Na2CO3 reference solutions. The values measured by titration amounted to 99.4 +/- 0.8% of the concentration of the reference solutions (range 10--50 mmol 1(-1). The coefficient of variation was 1.8% for 5 mmol 1(-1) solutions and 0.2% for 50 mmol 1(-1) solutions. In measuring a series of 60 blood samples the coefficient of variation as calculated from duplicate determinations was 1%.


Methylmalonate excretion in a pregnancy at risk for methylmalonic acidaemia.

In a pregnant woman, who had given birth to a child with methylmalonic acidaemia previously, urinary methylmalonate was measured at various intervals in the second half of the pregnancy. A significant increase was observed towards term. The child proved to be affected. This procedure enabled the detection of an affected fetus in the third trimester of pregnancy. If a case of methylmalonic acidaemia is detected in this way, treatment can be started immediately after birth.


Radioimmunoassay of digoxin employing charcoal entrapped in magnetic polyacrylamide particles.

Charcoal and magnetisable ferric oxide were entrapped in a polyacrylamide gel and, after lyophilisation and micronisation, empolyed for the uptake of free antigen in a radioimmunoassay for digoxin. The results obtained were similar to those using a conventional charcoal separation method.


Comparison of total urinary oestrogens and total serum oestriol in pregnancy.

The total oestrogens detected by fluorescence in 24-h urine and the concentration of total oestriol detected in serum by radioimmunoassay were estimated in 51 women during the second half of pregnancy. The statistical analysis showed a linear regression between urinary excretion and serum concentration according to the equation y = -2.89 + 2.82x (y = serum oestriol). The correlation coefficient over all pairs of estimations (N =567) was r = 0.69, which is very highly significant (P less than 0.0001). The analysis of the individual pregnancies showed that the linear correlation coefficient was significant (P less than 0.05) in 35 cases, poorly significant (0.05 less than P less than 0.1) in 3 cases and not significant (P less than 0.1) in 5 cases. The correlation could not be calculated in 8 cases because the number of estimations was too small. These values were compared empirically (normal/pathological). There was agreement in 6 cases and no agreement in 2 cases. The results show on the one hand that the radioimmunological estimation of total oestriol in serum can be used in the same way as urinary excretion of oestrogens for monitoring the feto-placental unit. On the other hand, the study confirms that a "simple" fluorimetric Kober-Ittrich method can give at least the same clinical information as a radioimmunoassay of relatively high cost. It may be concluded indirectly from the results that a considerable diurnal rhythm or substantial day-to-day fluctuation in the production of oestriol are unlikely.


Quantitation of human serum antithyroglobulin antibodies by a two-site radioimmunoassay.

A two-site solid-phase radioimmunoassay for measuring serum antithyroglobulin antibodies applicable to human serum is described. The sequential steps of the procedure include the adsorption of thyroglobulin (Tg) on polystyrene tubes and the binding of the antithyroglobulin antibody to solid phase followed by the fixation of labelled thyroglobulin. The optimal experimental conditions for the adsorption of unlabelled Tg, the uptake of the antibodies and the fixation of labelled Tg have been defined. The test is specific for antithyroglobulin antibody and its reproducibility and precision are satisfactory. The radioassay showed a good correlation with the hemagglutination method and, also, was found to be more sensitive. Levels of antithyroglobulin IgG in positive sera ranged from 0.3 microgram/ml to several mg/ml. In contrast to the double antibody radioimmunoassay for antithyroglobulin antibodies, this solid-phase radioassay is easier to perform; moreover, it is relatively independent of the quality, the purity and the specific activity of the tracer.


Performance of various mathematical methods for computer-aided processing of radioimmunoassay results.

Interpolation and regression methods are available for computer aided determination of radioimmunological end results. We compared the performance of 6 algorithms (weighted and unweighted linear logit log regression; quadratic logit log regression, smoothing spline interpolation with a large and small smoothing factor, respectively, and polygonal interpolation and the manual curve fitting on the basis of three radioimmunoassays with different reference curve characteristics (digoxin, estriol, human chorionic somatomammotrophin (HCS)). Great store was set by the accuracy of the approximation at the intermediate points on the curve, i.e. those points that lie midway between two standard concentrations. These concentrations were obtained by weighing and inserted as unknown samples. In the case of digoxin and estriol the polygonal interpolation provided the best results, while the weighted logit log regression proved superior in the case of HCS.


Human beta-mercaptopyruvate sulfurtransferase: distribution in cellular compartments of blood and activity in erythrocytes from patients with hematological disorders.

The distribution of mercaptopyruvate sulfurtransferase (EC 2.8.1.2) in human blood cell compartments has been studied. Almost all of the enzyme activity in whole blood was confined to erythrocytes, but the activity per litre cell volume was higher in platelets than in erythrocytes. Leukocytes contained very low concentrations of the sulfurtransferase and plasma was devoid of activity. The enzyme activity of blood hemolysates from normal subjects and patients with various erythrocyte disorders was also determined. Significantly higher sulfur transferase activity was found in male subjects in comparison with females. The enzyme activity per litre erythrocytes was increased in blood from patients with iron deficiency anemia, whereas less clear-cut differences with respect to normals were found in other diseases studied.


Studies on kallikrein-kinin system in plasma of patients with acute pancreatitis.

The fact that esterolytic activity is significantly elevated in plasma of patients with acute pancreatitis and that it correlates with the serum amylase level was confirmed. No kinin activity, however, was detected in plasma. To characterize the esterolytic activity, patient and normal plasmas were chromatographed on Sephadex G-200 and the esterolytic and the kinin-forming activities of each fraction were examined. In the present study, it was speculated that during attacks of acute pancreatitis, kallikrein with amylase might be liberated into blood from the pancreas. It was confirmed that almost all of the kallikrein liberated was combined with alpha1-macroglobulin, and alpha2-macroglobulin-bound kallikrein itself possessed kinin-forming activity.


Variations in erythrocyte uroporphyrinogen I synthetase activity in non porphyrias.

The activity of erythrocyte uroporphyrinogen I synthetase has been measured in various cases of non-porphyric affections. The results indicate a diminution of this activity in some of the studied cases of chronic renal insufficiency and chronic polyarthritis. This modulation in activity mitigates against its use as a diagnostic criterion of acute intermittent porphyria. On the other hand, an increase in urosynthetase activity has been noted in acute and especially chronic hepatic affections. This increase seems to be connected with the severity of the hepatic affection. The relationship is illustrated particularly in the case of viral hepatitis associated to an AIP, where the increasing activity of the urosynthetase masks for many weeks the congenital deficiency peculiar to this AIP. Our study thus indicates that the diagnosis of AIP based on the activity of the urosynthetase must take into account the pathological context in which the investigation is realised.


Serum total lipids, lipoproteins cholesterol, apoproteins A and B in cardiovascular disease.

Serum total lipids and lipoproteins cholesterol were determined in 33 survivors of myocardial infarction (MI) and in 75 subjects with peripheral vascular disease (PVD). Measurements were also made by a quantitative immunological assay of Apoprotein A (Apo A) and B (Apo B). Apo A levels were significantly lower in cases than in controls. In those cases with low levels of Apo A, high density lipoprotein has a higher cholesterol content as compared with controls. A negative correlation between high density lipoprotein cholesterol and low density lipoprotein cholesterol was found in controls and PVD subjects. The findings suggest that Apo A is associated to MI and PVD and its quantitative determination is predictive of cardiovascular disease.


Determination of molybdenum in human serum by neutron activation analysis.

Several investigators have reported serum molybdenum determinations in healthy humans. However, their results diverge quite widely. We determined the element by neutron activation analysis in 30 individuals. We found a mean value of 0.58 ng/ml, a standard deviation of 0.21 ng/ml and a range of 0.28--1.17 ng/ml.


A new method for simultaneous determination of bile acids in human bile without hydrolysis.

A method for simultaneous determination of major bile acids in human bile without prior hydrolysis is described. The unconjugated, glycine- and taurine-conjugated bile acids are separated into groups by ion-exchange chromatography on a newly developed lipophilic gel, piperidinohydroxypropyl Sephadex LH-20 (PHP-LH-20). Subsequently, resolution of each group into cholate, ursodeoxycholate, chenodeoxycholate, deoxycholate and lithocholate is attained into two stages by high-performance liquid chromatography on a micron-Bondapak C18 column. First, 0.3% ammonium carbonate/acetonitrile (9 : 4, v/v) is used for separation of the latter three as a mobile phase. Cholate and ursodeoxycholate are separated in 0.3% ammonium carbonate/acetonitrile (11 : 4, v/v). The present method is applicable to quantitation of free and conjugated bile acids in human bile with satisfactory accuracy and precision.


Platelet 5-hydroxytryptamine accumulation in depressive illness.

The uptake of 5-hydroxytryptamine (5-HT) by blood platelets from controls, depressed patients and recovered depressed patients has been determined using short incubation times and low substrate concentrations. The affinity of serotonin for the platelet membrane appears to be normal in acutely depressed and recovered depressed patients. The capacity of transport of 5-HT through the platelet membrane is impaired in these depressive patients and this impairment is independent of the psychiatric status of the patients and is discussed in the light of the electrolyte and enzyme disturbances that are associated with depressive illness.


A rapid method for assay of branched-chain keto acid decarboxylation in cultured cells and its application to prenatal diagnosis of maple syrup urine disease.

A sensitive assay for measurement of branched-chain keto acid decarboxylation in small numbers of fibroblasts or amniotic cells grown in the wells of a microtitre plate using [1-14C]leucine as substrate is described. The method was applied to the amniotic cells from a pregnancy at risk for maple syrup urine disease and a heterozygous fetus predicted.


Modification of human pancreatic amylase isozymes by peptidoglutaminase I and II.

The effects of peptidoglutaminase (PGln-ase) I and II on human pancreatic juice amylase purified as an isozyme were investigated. Several amylase isozymes were formed which corresponded to minor components of pancreatic amylase isozymes, indicating that appearance of amylase isozymes are due to enzymic deamidation. A similar result was observed when the purified amylase isozyme was incubated with the supernatant of human pancreatic juice whose amylase was previously removed by adsorption onto raw corn starch. These findings are discussed in connection with amylase isozymes in the sera of the patients suffering from pancreatic inflammation.


A simple quantitative index of the P3 amylase isoenzyme in the diagnosis of acute pancreatitis.

Following a report (Legaz, M.E. and Kenny, M.A. (1976) Clin. Chem. 22, 57--62) that the amylase isoenzyme, P3, is elevated in acute pancreatitis but not in other conditions a new "P3 Index" is proposed. This reflects the ratio of the P3 isoenzyme to the major salivary isoenzyme, S1. The P3 Index eliminates the problems of peak overlap which prevent accurate detection or direct quantitation of P3. In acute pancreatitis a large increase in 3 produces a serum P3 Index of below 80%. Normal serum exhibits a P3 Index of above 80%. Most causes of hyperamylasaemia observed without acute pancreatitis also exhibited a P3 Index of above 80%. The P3  Index seems to be a useful aid to the diagnosis or exclusion of acute pancreatitis in patients exhibiting equivocal hyperamylasaemia.


Lipoamide dehydrogenase in cultured human skin fibroblasts.

Lipoamide dehydrogenase was identified in cultured skin fibroblasts of normal individuals and patients with Friedreich's ataxia. The optimum conditions for its assay were defined. Data disclosed a normal range of 36--122 mumol/min/mg protein in control fibroblasts and 61--112 mumol/min/mg protein in patients fibroblasts. Numerous precautions should be taken in handling fibroblast cultures for lipoamide dehydrogenase determination.


Serum magnesium circadian rhythm in human adults with respect to age, sex and mental status.

25 subjects volunteered to document circadian changes in serum magnesium. 4 groups were formed: 7 healthy young males (24.0 years +/- 3.9), 6 elderly males (82.5 years +/- 7.5), 6 elderly females 81.2 years +/- 10.7) and 6 elderly insame subjects of both sexes (80.5 years +/- 8.6). They were socially synchronized with a diurnal activity (07.00 to 21.00 for the old subjects; 07.00 to 23.00 for the young ones) and nocturnal rest. The subjects followed a spontaneous diet. Venous blood was sampled at 4-h intervals and fixed clock hours (07.45, 11.45, 15.45, 19.45, 23.45, 03.45) during 24 h. The single cosinor method was used for the statistical analysis of the time series. A statistically significant circadian rhythm is detected in three of the groups: young males, elderly males and elderly females (no rhythm detection in elderly insane subjects). The 24-h mean is higher in elderly subjects than in the young one. The rhythm amplitude is larger in elderly males than in young ones. The acrophase (peak time) location in the 24-h scale is 10.12 h for elderly females, 11.35 h for elderly males and 16.36 h for young males.


Plasma protein concentrations in hypertriglyceridaemic subjects. Effect of clofibrate and comparison with normal subjects.

Clofibrate, a widely used hypolipidaemic agent was given for twelve weeks to ten subjects with hypertriglyceridaemia. Its effect on lipoprotein-lipids and caeruloplasmin, IgA, IgM, alpha2-microglobulin and transferrin was assessed by comparing analyses at 4, 8 and 12 weeks on therapy with the means of values at two weeks before and at the start of treatment. The normal variation in plasma proteins was assessed in six healthy volunteers during the same period of time. On clofibrate, very low density lipoprotein (VLDL) cholesterol and triglyceride concentrations fell, but the concentrations of cholesterol in low density (LDL) and high density (HDL) lipoproteins showed no consistent change. Caeruloplasmin and IgM concentrations decreased significantly, IgA showed a limited falls (significant only at 8 weeks) and alpha2-macroglobulin did not change. The concentration of transferrin increased on therapy. No relationships were found between the falls in VLDL-lipid concentrations and the alterations in other plasma proteins. No significant variation occurred in the concentrations of lipids or proteins in the normal subjects during the period of study. The results indicate that clofibrate exerts general effects on protein metabolism.


Red-cell pyrimidine 5'-nucleotidase and lead poisoning.

In an effort to determine its value as a biological index of lead poisoning, we investigated the red-cell pyrimidine 5'-nucleotidase (Py5N) activity, along with the classical parameters, in 22 subjects with varying degrees of lead intoxication. In all cases, the red-cell Py5N activity was found to be decreased, even when most of the other biological tests of lead intoxication remained negative. Below the level of 150 microgram of lead per 100 ml of blood, the magnitude of the red-cell Py5N decrease was roughly proportional to the level of lead in peripheral blood. We conclude that red-cell Py5N is a convenient, reliable and sensitive index of lead exposure.


Cholesterol balance during pregnancy.

The possibility was examined that the hyperlipidaemia of pregnancy may reflect abnormal cholesterol metabolism, as occurs in some other hyperlipidaemic states. Seven women were studied during the three trimesters of pregnancy and the increase in their plasma lipid concentrations was compared with their sterol balance, measured over 8-day periods in each trimester. Dietary intake of cholesterol was identical during the three study periods. Faecal bile acid excretion peaked during the second trimester and this coincided with the initial rise in plasma triglyceride levels. However, the rise in bile acid output was counter-balanced by a fall in neutral steroid excretion, so that the net cholesterol balance throughout pregnancy was not dissimilar to that reported in healthy non-pregnant women. The hyperlipidaemia of pregnancy is therefore not associated with an increase in cholesterol synthesis, although the altered ratio of bile acids to neutral steroids resembles that reported in other hypertriglycerdaemic states.


Carboxypeptidase A activity of cultured skin fibroblasts and relationship to cystic fibrosis.

Properties of carboxypeptidase A of cultured skin fibroblasts from control and cystic fibrosis patients were studied using alpha-N-carbobenzoxy-L-glutamyl-L-tyrosine as substrate. Carboxypeptidase A was inhibited by thiomersal, cyanide, iodoacetate and N-ethylmaleimide in a similar manner for control and cystic fibrosis fibroblasts. Both trypsin and dithiothreitol treatment activated the enzyme, but 1,10-phenanthroline inhibited only in the presence of dithiothreitol. Both Zn2+ and Co2+ reversed this inhibition. Trypsin treatment of carboxypeptidase A produced a form of the enzyme having a higher KM value for both control and cystic fibrosis fibroblasts. Dithiothreitol treatment of control fibroblasts resulted in a form with similar properties to the trypsin activated form, but cystic fibrosis fibroblasts yielded a variant form with even higher KM and Vmax values. Since other properties were similar, it seems likely that this difference reflected binding of a molecule to the enzyme rather than of a defect in the enzyme.


A new micromethod for colorimetric determination of zinc in serum.

A simple micromethod with a colorimetric reagent of high sensitivity was developed for the determination of zinc in serum. For the color reagent 2-(2-pyridylazo)-5-dimethylaminophenol (PADAP) was used. Coefficients of variation of the within-day precision were 6.65 and 2.24% for zinc standard at concentrations of 0.1 and 0.5 microgram/ml, respectively. The mean recovery by this method was 101.2% (S.D.: 3.56%). Zinc concentrations measured by the above method showed good agreement with those by atomic absorption spectrophotometry, with a correlation coefficient of 0.934. Serum zinc values of 50 healthy adults (38 females, 12 males) ranged from 63 to 116 microgram/100 ml (mean: 89.68 microgram/100 ml, Sd.: 13.28 microgram/100 ml).


The association between lead concentrations in teeth and domestic water lead concentrations.

Tooth lead levels have been measured in 109 children living in Glasgow. A significant association has been demonstrated between molar tooth lead concentrations and domestic drinking water lead concentrations. Tooth lead concentrations were found to be greater the longer a child had liver in older housing with lead plumbing during foetal life and following birth. Tooth lead concentrations were also found to be age-related although no difference with respect to social class could be found.


Concentrations of polyamines in renal cell carcinoma.

In order to obtain biochemical indicators for histopathological, biological and clinical malignancy of renal cell carcinoma (RCC), concentrations of protein, RNA, DNA and polyamines in 14 samples of RCC were measured and examined on their histopathological properties and clinical malignancies. The concentration of spermidine in RCC was significantly higher than that in normal renal tissue and a statistically significant difference was not detected between the concentrations of the other compounds in RCC and normal tissue. The concentration of spermidine and the ratio of spermidine/spermine were found to increase in the order of normal tissue, the well-differentiated type and the poorly-differentiated type of RCC while no significant difference was detected between the concentrations of the other compounds in these types. There was no difference in the concentrations of the compounds examined among the non-metastasis and istant-metastasis groups of RCC.


The turnover time of calcium in the exchangeable pools of bone in man and the long-term effect of a parathyroid hormone fragment.

(1) A non-compartmental method is described for analysing the kinetics of the exchange of calcium between the bloodstream and the exchangeable bone pools. (2) This method has been applied to studies on osteoporotic patients treated with low doses of an active fragment of human parathyroid hormone. The data of Phang et al. (1969), who studied the effects of dietary calcium peturbation on normal volunteers, were also analysed. (3) It was found that in response to chronic PTH treatment the transit time of calcium in the exchangeable pools decreased. This could not be explained by the observed changes in the calcium accretion rate to the fixed bone pools, and it was necessary to postulate an alteration in the ratio of the rate constants governing the interchange of calcium between bloodstream and exchangeable pools. (4) The changes in the behaviour of the exchangeable pools in response to dietary perturbation could not be explained by the postulated increase in endogenous PTH secretion rate in response to dietary calcium restriction.


Glucagon response to arginine in growth hormone deficient children before and after treatment with growth hormone and in children with non-endocrine short stature.

In order to assess the role of growth hormone in the modulation of alpha cell function, the plasma pancreatic glucagon response to intravenous arginine (0.5 g/kg) was determined in thirty-two children with non-endocrine short stature and in eighteen growth hormone deficient children. 60 min after arginine infusion, the growth hormone deficient children had significantly higher (P less than 0.05) plasma glucagon values than the children with non-endocrine short stature. Following short-term growth hormone therapy (2 iu qd or bid for 5 days) in eleven of these growth hormone deficient children, plasma pancreatic glucagon response to arginine was diminished, and there was a significantly (P less than 0.02) more rapid return to basal values than in the untreated group. The same trends persisted after long-term growth hormone therapy (2 iu three times per week for 12-30 months) in ten children but were not statistically significant. We conclude that growth hormone may play a role in modulating plasma pancreatic glucagon response. The persistent glucagon response to arginine noted in growth hormone deficient children might reflect a greater gluconeogenic stress imposed upon these children during fasting or decreased catabolism of glucagon in the growth hormone deficient state.


Measurement of thyroid size by ultrasound, palpation and scintiscan.

Thyroid gland size was calculated from grey-scale ultrasound images in twenty patients with goitre. Results were compared with measurements by palpation and in some cases with measurements by scintiscan and at operation. There was a good correlation between ultrasound measurements and both the size of surgical specimens and clinicians' estimations, although clinicians under-estimated the size of large (greater than 40 ml) goitres compared with ultrasound and surgical specimens. Gland size calculated from scintiscan did not correspond well with measurements by ultrasound or palpation.


Protein hormones in cerebrospinal fluid: evidence for retrograde transport of prolactin from the pituitary to the brain in man.

Plasma and cerebrospinal fluid (CSF) levels of two hormones of similar molecular size, pituitary prolactin (PRL) and human chorionic somatomammotropin (hCS), and of the bigger hormone human chorionic gonadotropin (hCG) were measured in six pregnant women without pituitary disease. For all three hormones, the plasma and CSF levels were closely correlated. The plasma/CSF concentration ratio for hCG (571 +/- 378, mean +/- SD) was significantly different (P less than 0.01) from the hCS ratio (24.6 +/- 6.1); the hCS ratio was significantly different (P less than 0.005) from the PRL ratio (7.2 +/- 1.5). We conclude that (1) the CSF concentration of a protein hormone depends on the plasma concentration and on its molecular size, and (2) pituitary hormones reach the CSF not only via filtration of peripheral blood at the choroid plexuses, but also more directly via retrograde transport from the pituitary to the brain.


A radioimmunoassay for 3,5-diiodothyronine.

A radioimmunoassay for the measurement of 3,5-diiodothyronine (3,5-T2) using a 3H-labelled derivative of 3,5-T2 as tracer has been developed. The cross-reactivity of the antiserum was relatively high for T3 (3.1%) and low for T4 (less than 0.0015%). 3,5-T2 serum concentrations measured after fractional enrichment of 3,5-T2 were near or below the detection limit of 0.1 nmol/l in ten normal subjects and 0.38 nmol/l in five hyperthyroid patients. 3,5-T2 was also detected in thyroid tissue. The serum half-time of 3,5-T2 estimated after injection of 2 mg 3,5-T2 in three normal volunteers was 4.5 h.


Differential diagnosis of neoplasia of the palatine tonsil.

The differential diagnosis of approximately 2000 cases of palatine tonsillar malignancy contained in the Otolaryngic Pathology Registry of the Armed Forces Institute of Pathology are presented to include basic statistics of age, race and sex. These statistics and others from the World English language medical literature are compared and discussed briefly. Pertinent information points out the overwhelming predominance of squanmous (epidermoid) carcinoma, the delayed medical attention of patients and hence the advanced clinical state of the disease when first diagnosed, the involvement of cervical lymph nodes in the majority of cases and the causative relationship of alcoholism. A discussion of the various histological types of tonsillar carcinoma suggests a simplification of the current microscopic classification.


Results of radiotherapy for carcinoma of the oropharynx.

One hundred and forty-four patients with carcinoma of the oropharynx were seen at the South Wales Radiotherapy Centre between 1960 and 1971. The median age was 67 years. Curative treatment by external beam radiotherapy was attempted in three-quarters of the patients, resulting in a local cure rate of 58% and a crude 5-year survival of 37%. Radiotherapy was equally effective in controlling primary growths and lymph node metastases. Distant metastases in the absence of local recurrence in the head and neck occurred very rarely. There are now several new techniques available which offer the possibility of improving local cure without increasing morbidity, but their value must be assessed by careful comparison with existing methods of treatment, preferably by prospective controlled trials.


Visual suppression test.

The visual suppression test is one of the visual fixation tests. It is performed by recording caloric nystagmus by ENG, and the maximum slow phase velocity of caloric nystagmus in darkness is compared with the slow phase velocity in light with eyes open. Visual suppression of slow phase velocity of caloric nystagmus is 54 +/- 12% in 52 normal adults ageing from 21 to 40. Visual suppression in normal subjects is not influenced by water temperature used for the caloric test and not changed by background illumination in light. Visual suppression is stronger when the target is closer to the eyes of the subjects. The following abnormalities have been diagnosed by this test: flocculus and nodulus lesions on the side of the lesion; inferior olive lesions; parietal lobe lesions; compensation after unilateral sudden loss of inner ear function.


Cholesterol granuloma of the maxillary antrum.

Five cases of cholesterol granuloma in the maxillary antrum are described. The lesion takes place in the mucosa. It seems likely that filtration and haemorrhage are the 2 main ways in which cholesterol is concentrated in certain tissues. The maxillary antrum provides a clear illustration of these 2 mechanisms at work.


Perennial rhinitis: an analysis of skin testing, serum IgE, and blood and smear eosinophilia in 201 patients.

Allergen skin testing, eosinophil counting in blood and nasal smear and serum IgE determination were performed in patients with simple perennial rhinitis, and in patients with rhinitis and asthma. The results were compared with those obtained in normal controls. As a positive skin test was demonstrated in 40% of patients with simple rhinitis and in 88% of patients with rhinitis and asthma, skin testing is considered relevant in all patients with perennial rhinitis. While blood eosinophil count and serum IgE level were elevated in a fair proportion of asthmatic patients, only a few subjects with simple perennial rhinitis had an elevated level, and the diagnostic values of these tests is questionable. On the other hand, examination of a nasal smear for eosinophils could usually separate the patients from the controls. The study emphasizes the importance of making a distinction between simple perennial rhinitis and perennial rhinitis associated with other symptoms and diseases.


Genetic epidemiology of an institutionalized cohort of mental retardates.

By criterion scaling and principal component analysis of performance, social class, symptoms, institutionalization, and medical history, a cohort of mental defectives has been divided into medical, biological, and sociofamilial categories. This division, corresponding to differences in etiology and severity, reveals changing patterns of admission and provides evidence that male excess is not primarily due to sex linkage. The incidence of mental retardation increases about 5% with first-cousin marriage, in agreement with other studies. The decline of IQ with inbreeding appears to be due entirely to rare recessive genes, not to dominance deviations of polygenes.


Ichthyosis vulgaris showing features of the autosomal dominant and X-linked recessive variants in the same family.

A family in which the mother and six of her sons present an ichthyosis of the vulgaris type has been analysed clinically, histologically and electron microscopically. Phenotypically the ichthyosis in the mother is purely of the dominant type, while that in all the affected sons shows, to varying degrees, features of both the dominant and X-linked recessive variants. The findings are interpreted as reasonably good evidence that the mother has transmitted to all her affected sons both the autosomal dominant and the X-linked recessive genes for ichthyosis. Although genetically this is a most unusual situation, it corresponds best to our findings.


Familial occurrence of lumbar spondylolysis and spondylolisthesis.

In a Finnish kindred consisting of 192 descendants from two marriages of a male ancestor born in 1868, the lumbar spines of 105 of the 170 living members were X-rayed. Spondylolysis was found in 22 individuals. In addition, six of them had spondylolisthesis, four had spina bifida occulta, and two had a transitional lumbar/sacral vertebra. Seven members of the kindred without spondylolysis had spina bifida occulta and 10 had transitional lumbar vertebrae. The pedigree is consistent with autosomal dominant inheritance and incomplete (about 75%) penetrance for spondylolysis. It raises the question of a common aetiology for several congenital disturbances in the formation of lumbar vertebrae and possibly supports the concept of variable expressivity of a "spondylolysis gene".


Prenatal diagnosis of an XXY foetal karyotype in a woman with a previous 21-trisomic child.

Prenatal chromosome analysis revealed that a 34-year-old, gravida 2 mother was pregnant with a XXY foetus. She had previously given birth to a 21-trisomic boy with another spouse. Both parental karyotypes were normal, but a high frequency of associations between satellited chromosomes was observed in maternal lymphocytes. The possibility that increased satellite associations may predispose to aneuploidy in the offspring is discussed. The finding of normal testicular histology in the aborted XXY foetus provides evidence that the characteristic XXY testicular dysgenetic lesions are likely to occur not earlier than in the late prenatal period.


2:2 and 3:1 meiotic disjunctions in a carrier of a reciprocal 10/14 translocation.

The offspring of a female with a reciprocal whole-arm translocation between a chromosome No. 10 and a chromosome No. 14 is described. She gave birth to three cytogenetically different children: one with a normal, one with an abnormal but balanced, and one with an unbalanced karyotype. In these three cases, 2:2 disjunctions must have occurred during maternal meiosis. She also had a trisomy 14 abortion, which is assumed to have been caused by a 3:1 meiotic disjunction.


Incomplete prenatal diagnosis of G-trisomy mosaicism.

Chromosomal mosaicism is difficult to detect in prenatal diagnosis, and it seems even more difficult to predict its significance correctly. We present a case, in which G-trisomy mosaicism was diagnosed prenatally but was not verified in the aborted fetus. A practical approach to suspected fetal mosaicism in prenatal diagnosis is proposed.


Association of interstitial nephritis with tubule cell injury and proliferation in NZB/NZW mice.

The relationship between renal interstitial mononuclear cell infiltration and renal tubule cell (TC) proliferation has been examined in (NZB X NZW) F1 hybrid (B/W) and control mice. TC proliferation was measured by tritiated thymidine ([3H]TdR) injection, autoradiographic examination of kidney sections and enumeration of labelled tubule cells. In B/W mice interstitial infiltration began at 5 months and reached a peak at 9 months. Proliferation of TC began at 7 months and also reached a peak at 9 months. Control mice consisting of NZB, CBA/J and C57Bl/6J mice showed no increase with age. When the percentages of labelled TC in areas adjacent to interstitial infiltrates and distant from them were compared, the TC adjacent to infiltrates showed an approximately four-fold greater amount of labelling. Ultrathin light and  electron microscopic sections demonstrated TC injury in areas in close proximity to infiltrates. These studies suggest that mononuclear cells in the interstitial infiltrate may be injurious to TC, leading to a sequence of injury and subsequent regeneration of these cells. In diseases in which interstitial nephritis is present, such as Sjögren's syndrome, the interstitial infiltrate may contribute to the observed TC dysfunction.


Comparative clinical study of protein SAP (amyloid P component) and C-reactive protein in serum.

The serum concentration of protein SAP (amyloid P component) has been measured for the first time in a substantial series of normal individuals and patients with various diseases, and the results contrasted with the levels of the related protein C-reactive protein (CRP). The mean +/- s.d. concentration of protein SAP was 43 +/- 14 microgram/ml in seventy-six normal men, 33 +/- 10 microgram/ml in eighty-six normal women and 4 +/- 2 microgram/ml in thirty-six normal cord sera. Unlike CRP, whick is a major acute phase reactant, protein SAP was only slightly elevated in inflammatory and neoplastic diseases in which CRP was greatly increased. The level of protein SAP was significantly depressed in patients with hepatic disease, suggesting that its measurement might be of value in their management.


Spontaneous lymphocyte proliferation and depressed cellular immunity in Hodgkin's disease.

Patients with Hodgkin's disease have increased numbers of spontaneously proliferating circulating lymphocytes. In order to test the relationship between this phenomenon and the in vitro mitogenic response, both spontaneous lymphocyte proliferation and the response to stimulation with phytohaemagglutinin were quantified. In addition, the proliferating lymphocytes were identified autoradiographically and characterized for the presence of lymphocyte surface markers and monocyte markers. Spontaneous thymidine incorporation by lymphocytes from patients with Hodgkin's disease was increased compared with normal controls, and the phytohaemagglutinin response was depressed. A significant inverse relationship was demonstrated between the spontaneous thymidine incorporation on day 0 and the phytohaemagglutinin response on day 3 (P is less than 0.01). The activated lymphocytes were heterogeneous with respect to both morphology and surface markers. These data suggest that the circulating proliferating lymphocytes in Hodgkin's disease are reactive cells and that the quantitative depression in cellular immunity demonstrable in these patients may be related to this chronic reactivity.


Comparison of the relative cytotoxic effector cell capabilities and the proportions of cells bearing various surface markers in human tonsil and peripheral blood mononuclear cells.

The relative cytotoxic effector cell capabilities and the proportions of cells bearing various surface markers in human tonsil and peripheral blood mononuclear cells has been studied. The peripheral blood contained a substantial proportion of monocytes (22 +/- 2.9%) compared to tonsil cell suspensions (2.5 +/- 0.3%). The percentages of T lymphocytes was significantly higher in the blood than in the tonsil (P is less than 0.01); however, the percentages of cells forming rosettes with 7S EA were not significantly different in each group (P greater than 0.5). Mitogen-induced cellular cytotoxicity by blood and tonsil mononuclear cells against Chang cells was proportional to the percentages of T lymphocytes in these cell suspensions, and both antibody-dependent and mitogen-induced cellular cytoxicity against sheep red blood cells was proportional to the percentages of monocytes in these suspensions. Tonsil mononuclear cell suspensions were incapable of mediating antibody-dependent cellular cytotoxicity against Chang cells, whereas blood mononuclear cells functioned normally. These findings are in contrast to the findings of similar percentages of Fc receptor-positive lymphocytes in blood and tonsil mononuclear cell suspensions. Previous studies have shown that the effector cells against antibody-coated Chang cells are Fc receptor-positive lymphocytes. These studies show that in the case of cytotoxicity mediated by an Fc receptor-bearing lymphoid cell, there may be a clear discrepancy between the relative proportions of Fc-bearing lymphoid cells in different organs and the relative levels of cytotoxicity.


Cutaneous necrotizing venulitis: a sequential analysis of the morphological alterations occurring after mast cell degranulation in a patient with a unique syndrome.

An unusual patient, with dermal nodules, flexion contractures of the fingers and toes, cold-induced urticaria, dermographism and serum hypocomplementaemia, had necrotizing cutaneous venulitis underlying the spontaneous lesions. Since necrotizing cutaneous venulitis could be experimentally induced by the physical stimuli of cold or trauma, the time-course of histopathological events was documented in the skin of this patient. The histopathological alterations were studied in 1 micron thick, Epon-embedded skin biopsy specimens over an interval of 6 days. The early massive degranulation of the mast cells was followed by the sequential infiltration of neutrophilic, eosinophilic and basophilic polymorphonuclear leucocytes, by the development of venular endothelial cell necrosis and by the deposition of fibrin. The persistent serum hypocomplementaemia involved the classic activating and amplification pathways. It seems possible that the unusual combination of pathobiological processes involving the mast cells and the complement system in this patient has created a unique syndrome, in which venules are damaged and the sheaths of the extensor tendons of the hands and feet become affected in time.


The role of complement in Ascaris suum induced histopathology.

The role of complement in the histopathology of primary and challenge re-infection by Ascaris suum was assessed. Guinea-pigs deficient in C4 or depleted of the terminal components C3 to C9 by cobra venom factor (CVF) were employed. Pathological changes in the livers of complement-deficient guinea-pigs differed slightly from controls. The most striking findings were in the lungs of CVF-treated infected animals, where marked eosinophilic abscesses were observed following either a primary or repeat infection with Ascaris suum. Additionally, greater numbers of larvae were harvested from the lungs of both CVF-treated and C4-deficient infected guinea-pigs as compared with controls. Serum C4 levels varied over the first 7 days after primary infection, declining in several of the normal and CVF-treated animals, but remaining stable in others. The C4 levels remained unchanged in re-infected animals. The C3 to C9 levels remained within the normal range in both primary and re-infected guinea-pigs. The data suggests that complement is involved in the host responses to infection with Ascaris suum. In the absence of complement (C3 to C9), enhanced pulmonary eosinophilic infiltration and eosinophilic granuloma formation occur in both primary and re-infected animals.


Serum complement pattern in essential mixed cryoglobulinaemia.

In twenty-six patients affected by essential cryoglobulinaemia, 188 determinations of serum complement components (SCC) were made. A peculiar pattern was observed which was characterized by: (a) low levels of early components (Clq, Cls and C4), (b) normal levels of C3 and high concentrations of late components (C5, C9) and (c) CH50 values significantly lower than normal. No relationship could be observed between early SCC and C3 levels. Thirty-three crossed immunoelectrophoreses were performed in thirteen patient's blood samples. The C3c peaks were not different from normal. Follow-up data (156 serum samples from twenty-four patients) during a 6-40 month period showed a non-homogeneous SCC behaviour. However, no relationship was found between the complement concentrations and clinical score. These findings suggest that SCC abnormalities are related to a complement hyposynthesis, which could be caused by a reduced C2 production or by a negative feedback effect of active components or their fragments.


Evaluation of isoniazid-associated hepatitis by immunological tests.

In a retrospective study of patients developing hepatitis or persistent serum glutamic oxaloacetic transaminase (SGOT) elevations while receiving isoniazid, it was found that the lymphocyte transformation test (LTT) was positive in nineteen cases (95%) in response to stimulation by isoniazid, isonicotinic acid and conjugates of these compounds with human serum albumin. However, no significant amount of antibody against isoniazid was detected in the sera of these patients by a sensitive radioimmunoassay. By contrast, no positive LTT was seen in normal controls or in patients receiving isoniazid without evidence of liver damage, while in patients with transient SGOT abnormalities, the LTT was positive only at the time of liver dysfunction. There was no correlation between the degree of lymphocyte transformation and the severity of liver damage. However, there were differences in the patterns of response to the four stimulatory preparations used. Thus patients with overt hepatitis most frequently responded to isoniazid, while individuals with only SGOT abnormalities showed stimulation in the LTT more often with a conjugate of isonicotinic acid and human serum albumin. It appears, therefore, that the presence of isoniazid-induced liver damage is associated with the presence of cellular hypersensitivity to the drug. The differences in lymphocyte reactivity in the two groups might indicate a potential means of predicting which individuals are at increased risk of developing overt hepatitis when exhibiting evidence of minor liver dysfunction while receiving isoniazid.


Circulating soluble immume complexes in recurrent oral ulceration and Behçet's syndrome.

Circulating IgG immune complexes were assayed by means of agglutination inhibition of IgG-coated latex particles to human IgG by rabbit IgM antibodies. Sera from thirty patients with Behçet's syndrome, thirty patients with recurrent oral ulcers and thirty healthy control subjects were analysed. The results showed raised levels of immune complexes in 60% of patients with Behçet's syndrome and 40% of patients with recurrent oral ulcers. There were significant differences in the levels of immune complexes between the neuro-ocular and arthritic types of Behçet's syndrome as compared with the muco-cutaneous type of Behçet's syndrome or recurrent oral ulceration. A close association was found between the disease activity and the amount of immune complexes. These results suggest that immune complexes may play a part in the transition from the epithelial involvement of mucosa or cutaneous tissues to the neuro-ocular and arthritic types of Behçet's syndrome. Another factor in tissue distribution might be the size of immune complexes, as multi-focal involvement of tissues in the neuro-ocular type of Behçet's syndrome is associated with a broad range of immune complexes from 3 X 10(5) to 3 X 10(6) daltons.


Complement-fixing material in ther sera of patients with rheumatoid arthritis.

We investigated the properties of the complement-fixing material in samples of sera from fifteen patients with rheumatoid arthritis having low levels of C4, in order to determine its possible relationship to the immune complexes and rheumatoid factors. The complement-fixing material in most sera was of high molecular weight, 19s or greater, but in two sera it was also present in an intermediate zone (about 12s--15s). Cryoprecipitation did not remove the complement-fixing material except from serum with a elevated content of cryoglobulin. Analysis of the sera by analytical ultracentrifugation for the content of rheumatoid factor IgG complexes did not show a close relationship between the content of these complexes and the amount of complement-fixing material present in the sera. The responsible material could be absorbed by IgG-Sepharose together with the removal of rheumatoid factor. It was, however, possible to absorb the complement-fixing material from most sera with unconjugated Sepharose without significantly affecting the rheumatoid factor titres. Thus the complement-fixing material in the rheumatoid sera closely resembles an immune complex. It very likely contains rheumatoid factor, but it is not certain whether the material consists entirely of rheumatoid factors complexed to IgG or whether other antigen-antibody systems may also be present.


Treatment of Goodpasture's disease by plasma exchange and immunosuppression.

Three cases of Goodpasture's disease are described who were treated with intensive plasma exchange and immunosuppression. There was no improvement in renal function and the patients required chronic haemodialysis, but renal function did recover with treatment for recurrence of disease in a transplanted kidney. Anti-GBM antibody levels were not controlled and substantial reduction in fibrinogen and complement were only achieved with daily treatment. A controlled trial of this regime is urgently required.


Stimulation of antibody synthesis induced by surgical trauma in rats.

The effect of a standard laparatomy on antibody synthesis was studied in Wistar R/A rats recieving an intravenous injection of 10(9) sheep red blood cells (SRBC) during the surgical procedure. Anti-SRBC antibody titres were significantly higher in operated animals than in controls. When SRBC were given 2 hr after the surgical procedure, stimulation of antibody synthesis still persisted, but when the antigen was administered 24 hr after laparotomy, no significant difference could be detected between the operated animals and controls. Surgery also enhances the secondary humoral response.


Refractoriness to anaphylactic shock after continuous feeding of cow's milk to guinea-pigs.

Further studies have been undertaken on the anaphylactic sensitization to cows' milk in guinea-pigs given cows' milk to drink instead of water. With continuous feeding over a prolonged period of time (over 70 days), about 70% of the guinea-pigs became refractory to intratracheal challenge of cows' milk and about 30% to intravenous challenge. Some guinea-pigs given cows' milk from the second day of life appeared not to undergo an early sensitization at all and may have been displaying a tolerance to anaphylactic sensitization. The degree to which this was shown may be genetic. The anaphylactic sensitivity, particularly as regards intravenous challenge, could be assessed by examining the sera for IgGl a antibodies to cows' milk by passive cutaneous anaphylaxis.


The occurrence and nature of alveolitis-inducing substances in Aspergillus clavatus.

Five groups of antigens were identified in culture filtrates and extracts from spores and mycelia of Aspergillus clavatus fractionated by gel filtration, affinity chromatography, electrophoresis in polyacrylamide gels and chemical analysis. Some particulate and soluble fractions given by nasal inoculation provoked murine allergic alveolitis in non-sensitized and sensitized precipitin-negative, and sensitized, precipitin-positive, animals. Alveolitis-inducing substances appeared to be glycoprotein precipitinogens, which withstood proteolysis, were preferentially adsorbed by concanavalin A, but which were rendered almost inert by sodium periodate oxidation. Spore walls were particularly rich in allergenic substances extractable by alkaline hydrolysis. Delipidated dead spores provoked more severe disease in all immunological groups of mice than live spores. Polysacchraride extracts and acid hydrolysates of spore walls were unreactive.


Anaphylactic bronchoconstriction in rats immunized with antigen-coated latex particles.

Studies have been carried out on the immunization of rats with antigen-coated latex particles. These studies confirmed that a significant lung blood eosinophilia is induced by a repeat intravenous injection of antigen-coated latex particles. Rats treated with antigen-coated latex particles also become sensitive to antigen such that on antigen challenge the animals show bronchoconstriction. Studies show that the bronchoconstriction is specific for antigen, but is unlikely to be mediated by tissue-fixing antibodies. Experiments comparing different immunization schedules involving latex particles indicate a strong association between the level of eosinophilia and degree of antigen-induced bronchoconstriction. These studies suggest that eosinophils may contribute to the anaphylactic bronchoconstriction.


Detection and separation of two serum factors responsible for depression of lymphocyte activity in pregnancy.

Studies using the rosette inhibition test have demonstrated a depression of lymphocyte activity in pregnant mice which occurs as early as 6 hr after fertilization and persists until just before delivery. This depression of lymphocyte activity is induced by two serum factors, the relative contributions of which vary with the time of gestation. The first, a high molecular weight early pregnancy factor, appears within hours of fertilization and then slowly declines in activity as gestation proceeds. The second, a lower molecular weight substance which cross-reacts with antiserum to human chorionic gonadotrophin, appears after the formation of the trophoblast at 4--5 days and persists until parturition.


Effect of sport stress on lymphocyte transformation and antibody formation.

The effect of a heavy (marathon, 2.5 hr) and moderate (35 min of running) sport stress on the number and function of lymphocytes, and on the plasma cortisol and leucocyte levels was investigated. Marathon running had a profound effect on the lymphocytes. Though the total number of lymphocytes did not change, their responsiveness to PHA and Con A, especially to PPD, was clearly depressed. The suppression of lymphocyte transformation was transient, the recovery occurring in 24 hr. The marathon running had no effect on antibody-forming capacity when the antigen was given immediately after the performance of the marathon, i.e. at the time when the response of lymphocytes to PHA, Con A and PPD stimulation was impaired. A clear-cut granulocytosis and elevation of plasma cortisol was seen in all the marathon runners. The 35 min of running also resulted in granulocytosis and an increase of plasma cortisol, but it did not cause any impairment of the lymphocyte function.


A new approach to the autoradiographic study of proliferating lymphocytes.

An adaptation of a cell filtration method for the autoradiographic study of cultured lymphocytes has been developed. The percentages of labelled cells are very similar in the filtered cell population to those obtained from replicate cultures processed by centrifugation. The filter method permitted a higher recovery of cells from small numbers in culture with better cytological detail than seen when cells were washed by repeated centrifugation, then suspended and smeared.


A microtest for rosette formation.

The microrosette formation test described is carried out in tissue-typing microplates under paraffin oil. Only 8000 lymphocytes in a volume of 2 microliter are required for one assay. This system is very suitable for investigating biopsy-extracted lymphocytes. Furthermore, rosette inhibition can be carried out even when the amount of inhibitory substance tested is minimal.


L-Tryptophan-induced depression of the pressor response to clinidine in anaesthetized rats.

1. The interaction of serotonin precursor L-tryptophan with the pressor responses of the anaesthetized rat to the intravenous injection of clonidine, adrenaline and angiotensin has been studied. 2. Pretreatment of rats with L-tryptophan (100 mg/kg) depressed the pressor response to clonidine but had no effect on the responses elicited by adrenaline or angiotensin. 3. The L-tryptophan-induced depression of the clonidine response was prevented by pretreating rats with either Rö 4-4602, carbidopa, BW 172C58, methysergide or by pithing. 4. Intravenous infusions of serotonin depressed the pressor responses to clonidine, adrenaline and angiotensin in both intact anaesthetized and pithed rats. 5. It is concluded that the depressant action of L-tryptophan is dependent on its conversion within the periphery to serotonin. This action is also dependent on or mediated by the sympathetic nervous system.


The effects of adrenalectomy on the cardiovascular responses to delta 1-tetrahydrocannabinol in rats.

1. In urethane anaesthetized sham-operated rats, intravenous administration of delta 1-THC (1 mg/kg) caused an immediated and prolonged fall in blood pressure, with a concomitant reduction in pulse rate. 2. In rats which had been adrenalectomized 24 h previously, delta 1-THC (1 mg/kg, i.v.) also caused a depressor response, but it was significantly shorter in duration than that observed in sham-operated animals. The durations of the cardiac slowing effect were similar in both groups of rats. 3. Hydrocortisone pretreatment (25 microgram/kg, i.v.), given 45 min before delta 1-THC, restored the duration of the depressor response to delta 1-THC in adrenalectomized rats, but it did not have any effect on the bradycardia induced by delta 1-THC. 4. Hydrocortisone did not produce any significant effect on the hypotensive action of delta 1-THC in sham-operated rats, but the cardiac slowing effect was markedly potentiated. 5. These results suggest a lack of correlation between the hypotensive and cardiac slowing actions of the drug and that a certain level of adrenal steroids is necessary for the maintenance of the depressor response to delta 1-THC.


Measurement of 42K concentration in the mucosal portion of the intestine without tissue samples: an approach to the measurement of mucosal blood flow in the dog.

1. The concentration of 42K within the jejunal mucosa was measured by intraluminal miniatrue Geiger-Müller tubes shieleded with platinum foil. 2. Isotope concentration measured by tissue assay of jejunal mucosa gave similar results to that obtained by the Geiger-Müller tubes. 3. Isotope measurement by shielded Geiger-Müller tubes obviates the need for tissue samples and permits repeat measurement in the same animal. This should find physiological application in measuring the mucosal portion of total intestinal blood flow by the indicator fractionation technique.


The effect of spontaneous diabetes mellitus on fatty acid oxidation, beta-hydroxybutyrate dehydrogenase activity and respiratory coupling of hepatic mitochondria in the guinea-pig (Cavia porcellus).

1. The purpose of this study was to determine whether hepatic mitochondria of guinea-pigs with spontaneous diabetes mellitus differ from those of non-diabetic guinea-pigs in the oxidation of fatty acids, the activity of beta-hydroxybutyrate dehydrogenase, or respiration-linked oxidative phosphorylation. During the course of the study, a third group of animals (referred to as the unclassified group) was discovered which, on the basis of the clinical chemistry and histological changes in the pancreas, appeared to be in a pre-diabetic or post-diabetic state. 2. No differences in the respiratory control ratios were found between any of the three groups. Fatty-acid oxidation in hepatic mitochondria was greater in both the unclassified and diabetic groups than in the non-diabetic group. Beta-Hydroxybutyrate dehydrogenase activity, however, was increased only in the diabetic group. These findings suggest that increased fatty acid oxidation is probably an intermediate change in the development of or the recovery from diabetes mellitus, whereas the activity of beta-hydroxybutyrate dehydrogenase is affected only in more advanced stages.


Henoch-Schoenlein syndrome: a clinical and morphological study of renal biopsies.

Twenty-four patients, 12 children and 12 adults, with the Henoch-Schoenlein syndrome had their renal biopsy specimens studied by light and electron microscopic and immunofluorescent antibody techniques. The principal glomerular lesion was  a focal and segmental proliferative glomerulonephritis in 15, a diffuse proliferative glomerulonephritis in 6 and a animal or minor change lesion with mesangial hypertrophy in 3 cases. The proliferation of the cells was mainly mesangial. Renal biopsies taken earlier in the course of the disease showed a greater number with a focal lesion. Electron dense deposits with cellular proliferation and increased matrix were seen in the mesangium. Less frequent subendothelial and occasional subepithelial deposits were found. Capillary loop changes were seen more frequently in the later stages of the disease. Heavy deposits of IgA were found in the mesangium in all cases, and less intense deposits of IgG in 60%. beta 1 C globulin and fibrinogen were found in 80% and IgD and IgM less frequently. Complement activation was via the alternate pathway as early complement components C1q and C4 were absent. Overt allergies, streptococal infections and the HBsAg could not explain the pathogenesis of the disease. Henoch-Schoenlein syndrome is a chronic disease of the mesangium; only 5 patients showed complete recovery, 15 had persistent microscopic hematuria and 3 died or developed renal insufficiency within 8 years. The prognosis was worst with diffuse proliferative glomerulonephritis, widespread focal glomerulonephritis or epithelial cresents formation.


Focal segmental sclerosis or scarred focal proliferative glomerulonephritis?

We have made a blind retrospective analysis of 334 renal biopsies, each containing more than 10 glomeruli, from adults and children with glomerulonephritis, in order to assess the clinicopathological significance of segmental lesions. These were defined as endocapillary proliferation and/or sclerosis involving capillary loops, and a less than half the glomerular tufts. On optical microscopy of paraffin-embedded material, 57 biopsies containing segmental lesions were independently classified by two observes as "focal proliferative glomerulonephritis" or "focal segmental glomerulosclerosis". These results were then reviewed with immunofluorescence, electron microscopic and clinical data and an "executive" diagnosis reached. Scarred focal proliferative glomerulonephritis could not be reliably distinguished from focal segmental glomerulosclerosis by optical microscopy alone. Some cases of focal proliferative glomerulonephritis are not associated with systemic disease and may have negative immunofluorescence findings, and we were unable to distinguish scarring in these patients from the lesion of focal segmental glomerulosclerosis with any of the tools at our disposal. Some patients with scarred focal proliferative glomerulonephritis showed profuse proteinuria, a nephrotic syndrome and progression to renal insufficiency. These cases cannot therefore be differentiated from focal segmental glomerulosclerosis by their clinical features. It would seem that the morphological lesion of focal segmental glomerulosclerosis should be regarded as focal segmental glomerular scarring from a variety of insults, rather than a distinct disease entity.


Renal disease in infectious mononucleosis.

Evidence of mild renal involvement is present in approximately 16% of patients with infectious mononucleosis as gauged by abnormalities in urinary sediment. Serious renal involvement including renal failure is very rare, our incidence was only 1.6%. There are only six cases reported in the literature during the last 25 years. The mechanism of renal involvement is probably multifactorial and includes both a direct viral cytopathic effect with other factors including hemolysis, hyperuricemia, and nephrotoxic drugs playing an important role. Interstital nephritis is the most common histologic abnormality. Chronic renal failure has been reported in only one case of infectious mononucleosis.


Oral essential amino acid supplementation in patients on maintenance hemodialysis.

Sixteen patients with chronic renal failure on maintenance hemodialysis were studied before and during oral treatment with essential amino acids. The patients received their usual diets (60-100 g protein/day) throughout the study. Plasma amino acids were studied pre-dialysis before supplements were started, after one month and after three months treatment; some measurements were also carried out post-dialysis. Before treatment 63% of patients pre-dialysis, and 82% post dialysis, had at least one essential amino acid value which was lower than our normal range. After one month of treatment 38% of patients pre-dialysis, and 67% post-dialysis, had one or more low essential amino acid value. After 3 months only 2 patients had an abnormal essential amino acid chromatogram pre-dialysis. Changes in non-essential amino acids, blood urea, serum proteins and hemoglobin are also reported. The data show that low plasma essential amino acid concentrations are frequently present in patients on maintenance hemodialysis even when the diet contains theoretically adequate amounts of protein. This deficiency can be corrected successfully with oral essential amino acid supplements.


Post meningococcal acute glomerular nephritis.

A case of meningococcal meningitis is described in which 10 days later there developed the histological lesions of acute exsudative proliferative glomerular nephritis without proteinuria, hematuria, hypertension or salt and water retention. The relationship between structural and functional changes in the kidney in glomerular nephritis is discussed in the light of these findings.


Exacerbation of hepatic encephalopathy by chronic renal failure: response to maintenance hemodialysis.

The consequences of chronic renal insufficiency relevant to hepatic failure are not well appreciated. We describe a patient with chronic cirrhosis and marked porto-systemic shunting who, after the onset of chronic renal failure, developed intractable encephalopathy which improved markedly during an eight month period of maintenance hemodialysis.


Obstetric anesthesia.

In this article, we have presented an overview of obstetric  analgesia and anesthesia. If one central theme could be developed, it shoud be that analgesia either for labor and delivery or cesarean section must be chosen and performed with absolute exactness and safety. There is no margin for error. The ultimate goal should be delivery of obstetric anesthesia in such a way that the best qualified professional is responsible for establishing the services in the hospital. Such service must provide contiguous around-the-clock coverage for tertiary hospital centers. On the one hand, most anesthesiologists are not well suited to many of the special demands of the obstetric suite, and, on the other hand, many obstetricians lack the full understanding and capabilities that the anesthesiologists possess. One solution for this dilemma might be to encourage obstetric colleagues to seek anesthesia training in order to organize obstetric anesthesia coverage.


Prevalence of childhood allergy in a subtropical environment: data from Dade County, Florida.

Other prevalence studies of allergy in school children have been limited to temperate zones only. The aims of this computerized investigation were wholly focused on South Florida, located in a subtropical climate. The occurrence of allergy in relation to marked geographic variations was surveyed to evaluate the prevalence of allergy in connection with these topographic differences.


Renin release from renin granules in the dog.

1. Renin release from isolated dog renin granules was limited to within 20% of the total renin during incubation at 37 degrees C in isotonic medium and did not depend on the external concentration of renin. 2. Although the renin granules were osmotically and mechanically fragile, they were quite stable at 0 degrees C in isotonic medium. 3. The bulk of renin activity appeared in the supernatant when the granules were ruptured by osmotic lysis. About 8% of the total renin still remained in the membrane fraction of the granules after treatment by freezing and thawing. 4. Therefore stored renin in the granules can be described as comprising three components: a readily released soluble form; a soluble but hard-to-release form; a membrane-bound form.


Effects of concentration-polarization on the filtration of proteins through filters constructed from isolated renal basement membrane.

1. Filters comprising multiple layers of rabbit renal tubular basement membrane were constructed with conventional pressure filtration chambers. The effects of concentration-polarization on the behaviour of these filters was assessed by studying the filtration of proteins and of serum under turbulent (stirred) and unstirred conditions. 2. With stirring bovine serum albumin was effectively rejected by the filter barriers (sigma = 0.95) but rejection was diminished (sigma = 0.18) without stirring. The hydraulic permeability of the filters also fell without stirring. 3. In the presence of horse immunoglobulin G, a wholly rejected protein, the rejection of cytochrome c was increased and hydraulic flux was reduced. 4. Filtration studies of serum showed that serum protein was effectively rejected with stirring (sigma greater than 0.999) but rejection diminished when stirring ceased (sigma = 0.98). Albumin was the only protein detected in the filtrate with stirring but alpha- and beta- globulins appeared when stirring ceased. 5. These results show that concentration-polarization markedly affects the behaviour of these basement membrane filters in vitro, since without stirring a polarization layer of rejected protein is formed, which reduces hydraulic permeability and results in increased protein permeation through the filter.


Parallel changes between lipoprotein lipase activating capacity and lipid concentrations in the serum of rats and ferrets during development and dietary manipulation.

1. The lipoprotein lipase activating capacity of serum from 5 to 22 day old rats and male ferrets fed on diets rich in either beef tallow or maize oil was significantly correlated with the triglyceride concentration in the serum. 2. These increases in activating capacity associated with increased serum triglyceride concentrations were similar to those reported for human serum.


Revised standards for normal resting dead-space volume and venous admixture in men and women.

1. Data have been combined from three previous series to provide revised standards for the prediction of physiological dead-space volume (VD), arterial oxygen tension (Pa,O2), alveolar-to-arterial oxygen-tension difference (PAO2--Pa,O2) and venous admixture fraction (QVa/Qt) in the sitting position. 2. These standards, based on measurements in 96 healthy men and women aged from 20 to 74 years, largely confirm conclusions drawn from the first series of 48 subjects. 3. VD is best predicted on age, height, tidal volume and the reciprocal of respiratory frequency. Pa,O2,(PA,O2--Pa,O2) and Qva/Qt are adequately predicted on age alone.


Lack of effect of blood-volume expansion on short-circuit current across an isolated toad skin incorporated in the circulation of a rat.

1. Evidence for the existence of 'natriuretic hormone' resides, in part, in the demonstration that blood volume expansion in the dog is followed by a transient fall in short-circuit current (SCC) across a frog skin incorporated within its circulation. 2. We have attempted to confirm this effect in the rat, with a toad skin (Xenopus laevis) incorporated within the circulation. The skins, bathed in whole rat blood, displayed low SCC; skins bathed in 'mammalian' Ringer solution displayed equally low SCC, but responded normally to pitressin or amiloride. 3. When volume expansion was induced in ten rats by infusion of equilibrated whole blood (28 ml/kg body weight) there was a brisk rise in systemic blood pressure, diuresis, natriuresis and kaliuresis. 4. This blood-volume expansion was without detectable effect on the SCC across the skins incorporated within the rats' circulations.


Urinary kallikrein excretion and plasma renin activity in patients with essential hypertension and primary aldosteronism.

1. The 24 h urinary excretion of kallikrein has been studied in 40 normotensive control subjects and in 74 age-matched patients with essential hypertension under similar conditions. By use of the renin-sodium index, hypertensive patients were divided into two subgroup: low-renin hypertension and normal-renin hypertension patients. Urinary kallikrein determinations were also obtained from six hypertensive patients with primary aldosteronism. 2. Urinary kallikrein was significantly lower both in patients with normal-renin and low-renin essential hypertension. Urinary kallikrein excretion was very high in the patients with primary aldosteronism. 3. In nine hypertensive patients beta-adreno-receptor-blocking therapy caused a significant decrease of plasma renin activity, but had no significant effect on urinary kallikrein excretion. 4. The results support the concept that low urinary kallikrein is likely to be a marker of essential hypertension. Under certain conditions its excretion is positively related to mineralocorticoid hormone concentrations but it is not primarily related to the renin-angiotensin system.


Blood alcohol and impairment of judgment.

1. The cerebral depressant effect of 30 ml of aqueous ethanol diluted to 25% and administered orally to 16 volunteer subjects was compared with a control group of 15 volunteer subjects. 2. The two parallel forms of the Watson--Glaser Critical Thinking Appraisal tests were employed as a measure of cerebral function. 3. The control group showed a small but statistically insignificant improvement on retesting with Watson--Glaser test form ZM after preliminary administration of form YM. 4. The relationship between the blood alcohol time curve and the alcohol effect was analysed for each individual subject, each subject being used as his own control. 5. The main peak cerebral depressant effect was substantial and occurred on average 25.5 min before the attainment of the peak blood alcohol concentration. 6. There was no significant correlation between blood alcohol concentration and contemporaneous cerebral impairment (r = -0.01). 7. There was a highly significant correlation (r = 0.60) between the effect upon cerebral function and the gradient of the blood alcohol curve at that time.


Definition of a conjugation of dysfunction in Gilbert's syndrome: studies of the handling of bilirubin loads and of the pattern of bilirubin conjugates secreted in bile.

1. Intravenous doses of bilirubin (3.4 mumol/kg) were given to normal subjects and patients with Gilbert's syndrome. Both groups displayed an identical initial disappearance of a substantial proportion of the bilirubin but, late in time, the Gilbert's patients exhibited reduced clearance with a sustained elevation of the plasma bilirubin and no reflux into the plasma space of conjugated bilirubin. Increasing the dose in normal subjects (by factors of 3 and 6) failed to reproduce the response found in the Gilbert's patients. 2. In the the bile-containing duodenal aspirates of Gilbert's patients the average proportion of bilirubin found as bilirubin diglucuronide was 68% (normal 88%) and of bilirubin monoglucuronide, 23% (normal 7%). Both differences were significant at the P less than 0.001 level. In the Gilbert's patients restriction of caloric intake to 1569 kJ/day for 2 days characteristically raised the serum bilirbuin with no modification of the biliary pigment pattern; phenobarbital (180 mg/day for 2 weeks) decreased the plasma bilirubin to the normal range with, concomitantly, a reversion of the biliary pigment pattern towards normal. 3. We conclude that there is no hepatic uptake defect in Gilbert's syndrome but that there is decreased activity in the conjugation process underlying the addition of the second glucuronic acid moiety to bilirubin, to form bilirubin diglucuronide.


Determinants of high blood pressure in salt-deprived renal hypertensive rats: role of changes in plasma volume, extracellular fluid volume and plasma angiotensin II.

1. Rats with indwelling aortic and right atrial cannulae were maintained on a sodium-free diet before and after renal arterial constriction combined with contralateral nephrectomy. Control animals underwent the same protocol except that non-constricting clips were used. 2. Plasma volumes in the salt-deprived animals were lower than previously determined values in animals with free access to sodium. After clipping plasma volume increased in the hypertensive animals. Extracellular fluid volume was increased equally in both normotensive and hypertensive animals on the second postoperative day only. 3. Before clipping and contralateral nephrectomy plasma angiotensin II values were higher than normal. After the operation angiotensin II concentrations fell to normal over a period of 14 days without significant differences between experimental and control groups. 4. It is concluded that high blood pressure after clipping may be in part maintained by increases in plasma volume. However, the results strongly suggest that other renal mechanisms are likely to be of major pathogenic importance.


Gastric ulcers with and without associated duodenal ulcer have different pathophysiology.

1. Maximal acid output after pentagastrin stimulation, and fasting and postprandial serum gastrin concentrations were determined in 25 normal subjects, 30 patients with corpus gastric ulcers, 10 patients with prepyloric ulcers and 30 patients with both duodenal and gastric ulcers. 2. Corpus ulcers and prepyloric ulcers formed one distinct group. Maximal acid output was abnormally low in the corpus ulcer patients and no different from normal in prepyloric ulcer patients, whereas fasting serum gastrin and postprandial integrated gastrin response was abnormally high in the former and no different from the normal in the latter. Furthermore, as in the normal subjects, a significant negative correlation between maximal acid output expressed in mmol h(-1) kg(-1) body weight and postprandial integrated gastrin response was observed in the corpus and prepyloric ulcer patients taken as a group. 3. In complete contrast patients with both duodenal and gastric ulcers, in whom postprandial integrated gastrin response was statistically highest amongst the three types of gastric ulcers, had a significantly positive correlation between maximal acid output and the integrated gastrin response. 4. These findings suggest the operation of different pathophysiological mechanisms in gastric ulcers with and without associated duodenal ulcers.


Antisecretory and antiulcer properties of prostaglandins.

Certain prostaglandins inhibit gastric secretion and exert an antiulcer activity. These properties, first discovered in animals, were confirmed in humans and are likely to be useful in the treatment of peptic ulcer. On the other hand, several prostaglandins given at high doses favor the passage of water and electrolytes into the intestinal lumen. This accumulation of fluid seems to be the cause of the diarrhea observed on occasion after prostaglandins are given.


Intestinal angina.

The outlook for chronic ischemic disease of the intestine must stress several factors: (1) the clinical entity is uncommon, (2) vascular occlusion is common, (3) diagnosis is most difficult, and (4) angiography is indispensable for diagnosis, but the procedure is not without hazard. Proper evaluation of all factors, with proper selection of patients who would benefit from revascularization procedures, is essential. The future evaluation and alleviation of ischemic bowel disease may well depend on skills of the past, i.e., a thorough, painstaking history of the existing illness.


Prostaglandin therapy for peptic ulcer disease.

The demonstration of inhibition of acid secretion in man or cytoprotection in animals is not proof of efficacy in clinical disease. Indeed, there has been continued debate up to now as to whether any of our previous standard therapies for peptic ulcer disease did more than alleviate symptoms. The use of the fiberoptic endoscope to locate and measure ulcers precisely and evaluate the progress of ulcer healing may finally allow us to assess the efficacy of new therapy. Several endoscopically controlled studies abroad have found PG analogs to be effective in both gastric and duodenal ulcer disease. Clearly, well-controlled, large clinical trials are needed to assess the efficacy of these compounds when compared to placebo and other modes of therapy. A close watch must be kept to detect the possible development of toxicity or other unwanted effects. We are still at an early stage in the development of the specific PG molecule that will affect only the stomach and duodenum in a favorable way, while having no effect on other tissues. When we come close enough to this goal, a PG may be the drug of choice for peptic ulcer disease in man.


Computer-assisted method for intracavitary radiotherapy of cancer of the uterine cervix.

This paper describes a simple computer system for calculating the radiation dose rate to selected points in the pelvis of a patient treated by gynaecological insertion of applicators loaded with radioactive sources. The calculations are performed on the basis of radiographs made before the sources are placed in the applicators. The system consists of a minicomputer, a teletype and a digitizer. The method allows an optimum loading distribution to be determined within a few minutes once the radiographic images are available.


Interactive control of graphic output devices.

A software package for the support of graphic output was developed. The main feature is the capability to draw graphs in a Cartesian coordinate system. With up to 60 variable parameters, it is problematic to change them interactively. Classical program languages do not support interaction. Subroutines for various kinds of input had to be written. Most important are other subroutines for reading, writing or erasing datasets at runtime, the name of which need not be known before starting a program. According to the problems, different appropriate methods of dialogue were used: the simple sequential dialoque, command languages and, for more complex input, a syntax analyser. The resulting dialogue is very simple and self-explanatory. The users need not have previous experience with computers; the package was accepted quickly and is now in extensive use.


A computer program for stepwise logistic regression using maximum likelihood estimation.

A computer program has been written which performs a stepwise selection of variables for logistic regression using maximum likelihood estimation. The selection procedure is based on likelihood ratio tests for the coefficients. These tests are used in a forward selection and a backward elimination at each step. The use of the program is illustrated by several examples.


Program to estimate parameters of linear systems without numerical differentiation.

This paper describes a computer program for estimating the parameters of a linear differential equation systen with constant coefficients by use of a nonlinear least-squares method. For minimization the sum of squares of an existing standard program, the Gauss-Newton gradient procedure, is employed. The differential equation system is solved by the Taylor expansion method. The advantage of this approach is that the derivatives with respect to the parameters are available without numerical differentiation. Therefore the inaccuracy inherent in numerical differentiation and the problem of choosing the modification of the parameters are eliminated. The given procedure is applicable for all the first order gradient methods. The presented method was tested with generated data from a four-compartmental model.


Interactive graphical isolation of homogeneous data subgroups.

A method is described for compacting homogeneous and separating heterogeneous data subcomponents. Allowance is made for heterogeneity due to a concomitant variable. When used with a large sample size, the major component of bivariate normal data will tend to be compacted to a single point. By applying the algorithm twice, the major component of bivariate lognormal data will tend to be compacted to a single point. These procedures have been implemented as part of an interactive graphical system for convenient use by biomedical researchers.


A simulation program examining the use of ratios as raw variables in analyses of variance.

An interactive, BASIC-PLUS, simulation program is described for performing a large number of multivariate analyses in accord with, or in violation of, known underlying models. Using a PDP 11/40 computer, random numbers are generated and converted into bivariate normal observations X and Y. These data are then analyzed according to three models. The three analyses are: (1) a standard analysis of variance ignoring the concomitant variable; (2) an analysis of covariance; (3) an analysis of variance on the ratio Y/X. The program can be used to examine the effect of performing multivariate analyses on data transformed into ratios. The utility of the program is the simplicity with which one can alter the underlying models and/or the mathematical relationships between X and Y. Output provides comparisons between models by accumulating rejections and other statistics on critical F-values for each model.


Treatment of radioimmunoassay data: a computer program for curvefitting and dose interpolation using orthogonal polynomials.

We propose a method allowing the automatic exploitation of radioimmunoassay results. The standard curve is calculated according to two models; a linear model by Logit-Log transformation of data and another one using Fisher's orthogonal polynomials. The computer programs are written in FORTRAN IV.


Concentrations of patch test allergens: are we comparing the same things?

A new way of expressing the concentrations of patch test allergens solutions (or emulsions) is proposed. From these new expressions it can be seen that apparently similar concentrations (0.5% chromium, 2% formaldehyde) can actually be in the ratio 1 to 15 as expressed at the molecular level.


Nickel excretion in urine after oral administration.

In recent years the importance of internal exposure to nickel in patients with recurrent hand eczema and nickel allergy has become evident. The present study was performed in order to investigate the value of urinary nickel determinations as an index of oral nickel intake. After oral administration of 5.6 mg nickel (as the sulfate), increased nickel excretion was found over the following 2-3 days. We conclude that consecutive urinary nickel determinations are able to disclose variations in oral intake of nickel.


Contact urticaria provoked by balsam of Peru.

Six patients with chronic urticaria are described in whom immediate type hypersensitivity to balsam of Peru was proven by patch test.


Simple methods for demonstration of epoxy resins of bisphenol A type.

Low molecular weight oligomers of epoxy resins of bisphenol A type are common sensitizers. For demonstrating the presence of sensitizing oligomers of these resins, two simple methods are described. The first one, a colour reaction, demonstrates the presence of the bisphenol A skeleton. If this test is positive, thin-layer chromatography is carried out to demonstrate the presence of low molecular weight oligomers of epoxy resins. Some practical applications are reported.


An investigation of the possible immunological relationship between allergen extracts from birch pollen, hazelnut, potato and apple.

In a retrospective study on selected group of patients, the coincidence of birch pollen allergy and a clinically relevant positive prick test reaction to apples and potatoes was confirmed. Immunochemical comparison using the crossed line immunoelectrophoresis technique (CLIE) confirmed partial identity between birch pollen and hazelnut. By the same method no partial immunological identity between birch pollen and extracts and fresh peel from apples and potatoes was found. However, both apples and potatoes gave rise to non-immunological affinity precipitates. On this basis it is discussed, whether the active agents from apples and potatoes were extremely labile allergens, plant lectins, or low molecular weight substances with a direct or indirect histamine release effect.


Sensitization and testing of guinea pigs with cobalt chloride.

The guinea pig maximization test was used to study the sensitizing potential of cobalt chloride; 1 % CoCl2 was used for injection and 5 % for topical application. The animals were challenged twice; in series I epicutaneous testing was performed 3 weeks after sensitization and intradermal testing after yet another week. In series II the reverse schedule was used, i. e. intradermal testing after 3 weeks and epicutaneous after 4 weeks. CoCl2 was found to be a grade V allergen. The differences between cobalt-exposed and control animals (which had been treated with Freund's adjuvant, petroatum, occlusion, etc.) were statistically significant (P less than 0.001). however, the administration of cobalt at the first challenge testing caused this difference to diminish.


Immediate and delayed allergic contact reactions to polyethylene glycol.

The lower molecular weight liquid polyethylene glycols (PEG) varying from 200 to 700 are extensively used as solvent vehicles in topical medicaments. Four patients showed allergic reactions to these liquid polyethylene glycols in topical medications. Two had immediate urticarial reactions to PEG 400. Two other patients had delayed allergic eczematous reactions, one to PEG 200, and one to PEG 300. Cross reactions occurred between PEG 200, 300 and 400, but not between these liquid polyethylenes and the higher molecular weight solid polyethylenes from 1000 to 6000.


Day 7 (D7) patch test reading - valuable or not?

Day 7 (D7) reading of 15,469 patch tests was carried out in 499 patients. In one fifth of them, positive reactions were observed at D7 having been judged negative at D2. The significance of the findings is discussed.


Factors influencing nickel dermatitis. I.

The nickel concentrations in urine and blood plasma of a very hypersensitive female patient have been followed during two periods of 34 and 42 days each. A limited degree of correlation was found between the course  of the nickel concentration in plasma, the nickel concentration in urine and the clinical activity of the dermatitis. Evidently other factors also influence the activity of the dermatitis; among these menstruation and stress might be expected to play a role.


Factors influencing nickel dermatitis. II.

The nickel concentrations in urine and other data of a very hypersensitive female patient have been followed during two periods exceeding 30 days each. Only a limited degree of correlation was found between the course of the nickel concentration in urine and the clinical activity of the dermatitis. In order to better evaluate the measure of the correlation and the influence of some other factors upon the activity of the dermatitis, a pathway analysis scheme has been constructed. Consideration of this scheme reveals the need for more extensive data regarding the nickel ion climate in the body.


Cosmetic regulatory activities in the United States: past, present and future.

To protect consumers from unsafe or decptively labeled cosmetics, the Food and Drug Administration promulgates regulations, conducts factory inspections, investigates mardeted products, evaluates consumer complaints, maintains registries of voluntarily submitted formulation and adverse reaction information, and carries out analytical, microbiological and toxicological studies. There has been a significant shift in program priorities from surveillance activities to scientific research and the determination of systemic hazards to health. Major scientific efforts involve studies to determine the dermal toxicity of cosmetics, develop methods for predicting the efficacy of preservatives, and answer questions about the skin penetration and carcinogenicity of nitrosodiethanolamine. A further issue of concern is the carcinogenic hazard of hair dyes.


Bacteriologic culture results obtained before and after elective midtrimester urea abortion.

Twenty patients undergoing elective midtrimester abortion by urea amnioinfusion had bacteriologic culture data obtained before and after the procedure. Despite the presence of pathogens in the vagina and cervix prior to the procedure, only 20% of patients exhibited endometrial growth following abortion. Factors that seem to favor such endometrial growth include increased injection-abortion intervals and the requirement for curettage to manage incomplete abortion.


No increase of the fibrinolytic activity of the human endometrium by progesterone-releasing IUD (progestasertR).

An increase in menstrual blood loss is one of the most common side effects of plastic IUDs and, though less often, also of copper IUDs. This has been explained by the observation that IUD enhances the fibrinolytic activity of the endometrium. A progesterone-releasing IUD (ProgestasertR) does not increase menstrual bleeding. The fibrinolytic activity of the endometrium was studied in 17 women before and after insertion of a progesterone-releasing IUD. It did not enhance the histochemically determined fibrinolytic activity in the endometrium.


Pathogenesis and renal function in acute toxic nephropathies.

Acute toxic nephropathy may be produced by a variety of poisons and drugs. Cellular poisons, such as mercuric bichloride, produce tubular necrosis. Many drugs induce an immunologically mediated response presenting as interstitial nephritis, glomerulonephritis or angiitis. Substances, which are not primarily nephrotoxic but induce dehydration, shock, hemolysis, rhabdomyolysis and/or electrolyte disturbances may also lead to secondary acute renal failure. Reduced renal blood flow, suppressed glomerular filtration, increased tubular pressure due to obstruction, and tubular leakage are responsible for the functional breakdown. In addition, specific tubular functions may be impaired. Complete or incomplete recovery is the rule.


Nephrotoxicity of gentamicin. Action on subcellular organelles and pharmacokinetics in the kidney.

Our findings on the renal pharmacokinetics of gentamicin explain why: (1) gentamicin concentrations in the kidney reach levels high enough to provoke injuries to the organelles; (2) the morphological manifestations of toxicity involve primarily the convoluted proximal tubule (which constitutes the largest part of the cortex), since antibiotic concentrations in this area are especially high; (3) nephrotoxicity is related to duration of treatment; (4) urine may contain small quantities of gentamicin up to 3 weeks after the end of therapy (14, 22, 30); (5) nephrotoxicity continues after discontinuance of the treatment, and (6) the hepatocytes, whose lysosomes are very sensitive to the action of gentamicin, show no obvious signs of toxicity, since the antibiotic never attains a high enough concentration in this organ.


Nephropathies due to analgesics.

Analgesic drugs causing kidney functional disturbances and histologically evident kidney derangements are reviewed. Today, not the pathological changes, which have dominated the scene of pathogenesis for analgesic nephropathies are in the foreground of investigative interest, but rather the biochemical interactions of analgesics or their metabolites in the renal cell and prospective epidemiologic studies. As the term 'phenacetin nephropathy' has been replaced by 'analgesic nephropathy', it seems likely that metabolic activation responsible for renal injury caused by analgesic mixtures will be of primary importance in furture investigations as well as the unravelling of immunogenic processes for a variety of analgesics and their metabolites.