Strain differences in the response to morphine on incorporation of 3H-lysine into rat brain protein. The effect of morphine on the specific activity (SA) of lysine in the plasma free amino acid (FAA) fraction and in the cerebral cortical FAA and protein fractions, as well as on the specific accumulation and incorporation, was determined in male Sprague-Dawley and Wistar rats at various time intervals after intravenous injection of drug and amino acid into unanesthetized animals. The lysine SA was higher in Sprague-Dawley than in Wistar rats in the plasma and brain FAA fraction and in the protein fraction. In the SD strain, morphine decreased the SA of plasma FAA significantly, but had only slight effects in the Wistar strain. In the cortical gray matter, morphine elevated the SA of lysine significantly in both strains, although the rate of decrease of SA with increasing time after injection was different in the two strains. SA of the lysine in cerebral cortical protein increased in both strains with time, but did so more rapidly in the Sprague-Dawley strain. When the data for the free amino acids were expressed in terms of specific accumulation, the observed rates were higher in the Sprague-Dawley animals and reached a point of maximal concentration, which was not observed in animals of the Wistar strain. Morphine elevated the levels of specific accumulation of lysine into the cortical free amino acid pool in both strains of rat. However, specific incorporation of lysine into the cerebral gray cortical protein in control animlas was essentially similar in both strains. Despite the similarity in specific incorporation of lysine into brain protein in both strains of control rat, morphine treatment caused a much more marked inhibition of incorporation of lysine in the Wistar rats. Thus, it is concluded that Sprague-Dawley and Wistar rats are not equivalent in relation to the accumulation of an amino acid in the brain FAA pool from the plasma and that the effect of morphine on specific incorporation of lysine into brain protein is greater in Wistar rats.


Lack of effect of clonazepam on serum levels of diphenylhydantoin, phenobarbital and carbamazepine. The influence of clonazepam on steady-state serum levels of diphenylhydantoin, phenobarbital and carbamazepine was studied in 22 patients with epilepsy receiving one or two of these drugs. Clonazepam was given in slowly increasing doses for 2 weeks until a maximum dose of 4-6 mg per day was reached; thereafter the dose was kept constant. The serum levels of diphenylhydantoin, phenobarbital and carbamazepine were determined once a week for at least 6 weeks. During clonazepam medication in ordinary doses the serum levels of the drugs in question were unaltered. Thus, it is unlikely that the antiepileptic effect of clonazepam in these patients even partly may be due to increased serum levels of these other drugs mentioned.


The effect of anticonvulsant drugs which induce liver microsomal enzymes on derived and ingested phenobarbitone levels. A comparison was made between the levels of derived Phenobarbitone in three groups of patients who were taking Primidone as a single drug, Primidone with Phenytoin and Primidone in combination with Phenytoin and Carbamazepine. The levels of ingested Phenobarbitone when this drug was taken as a single drug were compared with the levels when Phenobarbitone was taken in combination with Phenytoin in two other groups of patients. A significant increase in derived Phenobarbitone levels occurred when Primidone was used in combination with Phenytoin alone or with Phenytoin and Carbamazepine. The highest level occurred in a group of patients taking the three drug combination. There was no significant difference between the levels of ingested Phenobarbitone when this drug was used as single therapy or in combination with Phenytoin. We suggest that the increase in derived Phenobarbitone levels relates to the effect of Phenytoin on liver enzyme systems, and that the greater increase with triple therapy was related to the combined effect of Carbamazepine and Phenytoin on microsomal enzymes. As there was no increase in ingested Phenobarbitone levels when this drug was taken in combination with Phenytoin, we were unable to confirm previous suggestions that Phenytoin either inhibits the hydroxylation of Phenobarbitone or impairs its renal excretion.


Theophyllamine and the antiparkinsonian response to levodopa treatment. In an open preliminary study theophyllamine (theophylline-ethylenediamine) was administered to eight patients with idiopathic parkinsonism showing residual signs of parkinsonism though already in treatment with levodopa. Although theophyllamine in preclinical studies was found effective in potentiating the response to central dopamine stimulation, the drug in the present clinical study was without effect on idiopathic parkinsonism. After a loading dose of aminophylline, 5.6 mg per kilogram given intravenously, a maintenance dose of 0.9 mg per kilogram per hour infused during 2 h resulted in serum levels of theophylline of 23.5 +/- 3.9 mg per liter. 3-methyl-xanthine, a pharmacodynamic active metabolite of theophylline was analyzed in the serum samples. Less than 0.5 mg per liter was found.


Aphasia and epilepsy in childhood.

Aphasia and epilepsy in childhood. The syndrome of progressive aphasia and epilepsy in childhood is delineated. Four cases are presented, three of which show the typical gradual onset, fluctuating course and EEG changes with bilateral foci of spike and spike-wave activity, and, finally, normalization after some years of the EEG. Also the aphasia tends to subside, but often with considerable delay in relation to the other features. Neuropsychological assessment showed varying residual defects mainly on language functions. The aetiology is unknown. No pathoanatomical data on this disorder has hitherto been published. In one of the present cases a cortical biopsy was performed on suspicion of a left temporal tumour. The biopsy showed changes indicative of a slow virus infection. It is therefore suggested that the newly established language function in children particularly is vulnerable to a subchronic viral encephalitis affecting both hemispheres.


Diagnostic value of visual evoked response, clinical eye examination and CSF analysis in chronic myelopathy. The results of neuro-ophthalmological examination, visual evoked responses (VER) to pattern reversal stimulation and cerebrospinal fluid (CSF) analysis were compared in 25 patients with myelopathy of unknown etiology and without subjective symptoms of involvement of CNS outside the spinal cord. Delayed latencies of VER indicating a disseminated disease were found in 76 per cent of the patients. In 64 per cent of the patients, CSF showed abnormalities similar to those found in MS. Pathological findings at the clinical eye examination consistent with such an etiology was found in 36 per cent of the cases. It is suggested that a large proportion of patients with myelopathy of unknown etiology suffer from a disseminated demyelinating disorder similar to MS. By a combination of neuro-ophthalmological, VER and CSF examinations such as etiology can be established with reasonable certainty, and more troublesome investigations such as myelographies and spinal angiographies may be restricted to patients in whom the etiology still remains unclear.


Neurological and motor functioning of 10--12-year-old children who showed mild transient neurological symptoms in the first five days of life. This study concerns itself with the neurological functioning of 11-year-old children who neonatally presented a variety of shortlived or transient symptoms. These symptoms, while shortlived, are similar in nature to symptoms which other authors have shown to be correlated with later increased rate of neurological deviance. By using the data from a birth cohort of 9,006 consecutive deliveries, we attempted to discover whether such symptoms, when only transiently present in the newborn, are correlated with later neurological functioning. Results indicate that the subjects with transient neonatal symptoms presented more neurological deviance at age 10--12 than did matched controls.


Does O-methyl-dopa play a role in levodopa-induced dyskinesias? Clinically scored levodopa-induced dyskinesias were correlated with plasma dopa and O-methyl-dopa levels determined every hour during one day in 30 Parkinsonian-treated patients. In patients treated with a combination of L-dopa and a peripheral decarboxylase inhibitor (PDI), those with dyskinesias have very high plasma O-methyl-dopa levels compared with those who have no dyskinesias. In contrast, no significantly different plasma dopa levels are found in these two subgroups of patients, leaving open the question of the possible involvement of such elevated plasma O-methyl-dopa levels in favouring dyskinesias.


Lysosomal enzymes in the lymphocytes and granulocytes of patients with multiple sclerosis. The activities of three lysosomal enzymes were measured from the lymphocytes and granulocytes of patients with multiple sclerosis and of controls. The activity of acid phosphatase was increased in the granulocytes and that of beta-glucuronidase in the lymphocytes of MS patients in remission, as compared to those in relapse. No marked increases were observed in the activity of acid proteinase. These findings suggest that a number of lysosomal enzymes in both lymphocytes and granulocytes can be activated during demyelinating processes for reasons unknown at the moment.


Subclinical myopathic findings in patients affected by malignant tumours. An autopsy study. Histoenzymologic studies on representative muscles and the peripheral microcirculation from selected autopsies of non cachectic patients dying of neoplasms, without signs of neuromuscular involvement, demonstrate a high incidence of neuromuscular and microcirculatory changes. A correlation between neuromuscular changes and the peripheral microcirculation particularly evident in myopathic cases is discussed.


Nervous lesions in a case of local gigantism. A case of local gigantism of the thumb was studied by light and electron microscopy. In the lesion, proliferation of fibroadipose tissue and typical alterations of the nerves were found. The alterations in the nerve were isolated hypertrophy of the perineural cells. The relation of the changes to other peripheral nerve tumours especially in neurofibromatosis, is discussed.


Early stages of status marmoratus.

Early stages of status marmoratus. Basal ganglionic lesions in three young infants were found in a prospective search for early stages of status marmoratus. The lesions had formed and had passed into glial scars well before myelination of the basal ganglia commenced. The myelinating fibers crossing the scarred tissue were disoriented; however, fiber structure was normal, and the numbers of myelin lamellae did not differ significantly between scars and non-scarred tissue. There was no indication of a derangement of the process of myelin formation or of the formation of anomalous myelin sheaths around non-neuronal processes.


The pathophysiology of the blood-brain barrier dysfunction induced by severe hypercapnia and by epileptic brain activity. The cerebrovascular permeability to protein was studied in hypercapnic rats and in rats with epileptic seizures induced by bicuculline and homocysteine. Despite the differences of the basic pathophysiological mechanisms involved in these models, the blood-brain barrier (BBB) dysfunction was clearly related to the combined effects of high blood pressure and cerebral vasodilatation, thus indicating mechanical factors to be predominantly involved. The BBB changes were most frequent in central and basal regions in contrast to those induced by acute hypertension, which are most common in cortical areas.


[Neuropathological study of incontinentia pigmenti. Anatomical case report (author's transl)]. Report of a case of Incontinentia pigmenti (IP) of the Bloch-Sulzberger type, with neurological features, in a 3 month-old deceased infant. The neuropathological examination revealed signs of a destructive process which had occurred in the perinatal period: ulegyria, cavities of white matter and patchy scar softening of the cerebellar cortex. In addition, there was a diffuse inflammatory process involving the pia-arachnoid and brain tissue: perivascular cuffs of lymphocytes, histiocytes and eosinophilic polymorphs, and mononuclear nodules. No prenatal malformations or vascular lesions were found. These findings are discussed in the light of both the relevant literature on neurological abnormalities in IP and the only already reported neuropathological examination by O'Doherty and Norman (1968). Two main hypotheses might account for the frequency of neurological disturbances in IP, 1. a peculiar sensitivity of the brain to anoxia and/or ischemia: 2. its involvement by the specific inflammatory process which occurs both in the skin as other tissues in this genetically determined disease (Perié et al., 1976).


[Progressive multifocal leucoencephalopathy. Observation with predominant pontocerebellar lesions and association with congenital immune deficiency]. A young woman presented a mixed congenital and familial immunodeficiency syndrome consisting in an absence of IgA and lowered levels of IgG and IgM, with a defect in cellular immunity. She had a mild malabsorption syndrome with slight alterations of the jejunal mucosa. Non-caseating tuberculoid granulomata were found in skin lesions, in lymph nodes and in the spleen. At age 27 the patient died of a neurological disease of 4 months duration. Autopsy revealed a very widespread demyelinating process involving mainly the right cerebellar hemisphere but also most of the pons and left cerebellum, with the typical morphologic characters of PML. In the hemispheres lesions were limited to microscopical "microglial nodules" with discrete demyelination. A review of 86 published cases of PML revealed 9 other cases in which lesions showed a strong predilection for the subtentorial territories. This sampling allows for tha assumption that some 11% of the cases of PML have this particular lesion distribution. Other pertinent features of this case are briefly discussed.


Changes of placental site diagnosed by repeated ultrasonic examination. Over a period of two years, 7 137 localisations of placenta were performed. In 67 patients on the first examination it was found that the lower margin of placenta reached the internal os of the uterus. All these patients were followed up by examinations every two or four weeks. In 63 of the 67 patients, placental migration was found involving a change in the level of the lower placental edge from the cervix towards the fundus. The change in this position varied from 3 to 9 cm. All four cases where the placenta extended from anterior to posterior wall ended as placenta praevia. Ultrasonic proof of placental migration shows the necessity for ultrasonic examination shortly before the birth, as only then is the final diagnosis of placenta praevia possible.


The myometrial response to intra-uterine administration of PGF2alpha and PGE2 in dysmenorrheic women. Serial recordings of uterine contractility during different phases of the menstrual cycle were carried out in five dysmenorrheic women, and in two subjects during the acute stage of severe dysmenorrheic pain. The sensitivity and reactivity of the uterus to intrauterine administration of small doses of PGF2alpha and PGE2 were studied. A relative insensitivity of the uterus was found in the proliferative phase and around ovulation. The uterus was highly sensitive to the stimulatory effect of PGF2alpha in the secretory phase and at menstruation but probably not more sensitive than in normal women. The corresponding results with PGE2 were rather variable in that small doses did not induce any response or slight stimulation whereas high doses occasionally caused an inhibition in the secretory phase and during menstruation. The results indicate that PGF2alpha may be a significant factor in eliciting uterine hypercontractility and dysmenorrheic pain. Whether the occasional inhibitory effect of PGE2 is of any significant importance in the pathogenesis of dysmenorrhea cannot be stated.


Evaluation of fetal maturity by amniotic fluid creatinine concentrations and lecithin/sphingomyelin ratio. In a material of 144 samples of amniotic fluid from the last trimester, creatinine concentration, lecithin/sphingomyelin (L/S) ration and their correlation, have been examined. Amniotic fluid creatinine concentration (a.f.c.) increased gradually through the last trimester up to 39 weeks (273-279 days p.m.) with median values of 2 mg/100 ml at 37 weeks and 2.5 mg/100 ml at 39 weeks gestation. The great range makes a.f.c. of doubtful value in assessment of gestional age in individual samples. The correlation between a.f.c. and L/S ratio was highly significant (Kendall's T=0.56). Even so lung maturity cannot be predicted from a.f.c. A low L/S ratio with a.f.c. larger than or equal to 2 mg/100 ml was found in 8-9%, while a.f.c. 1.1-1.9 mg/100 ml was combined with L/S ratios larger then or equal to 2 in a great number of cases. A.f.c. less than 1.1 mg/100 ml was invariably correlated with low L/S ratios.


Neonatal and prospective follow-up study of infants delivered by vacuum extraction (VE). Forty infants delivered by vacuum extraction have been studied in the neonatal period--neurological examination, neonatal CSF-examinations, skull X-ray examination, transillumination and sonoencephalography --and at 14 months of age--developmental and behavioural evaluation, neurological examination, skull X-ray examination, sonoencephalography and electroencephalography. Two infants died in the neonatal period but in both cases a life-threatening situation of the fetus required immediate delivery. CSF cytological signs of haemorrhage were observed in 42% of the 26 infants who had a successful lumbar tap, compared to 10% found in normal deliveries. The result of the neonatal neurological study did not differ from that in a control group. The result of the skull X-ray examination and sonoencephalography were also within normal limits. In the follow-up study behavioural problems were found in 25%, but otherwise very few abnormalities were found. The deviatiosn found do not for the present indicate any later signs of brain lesions. It is concluded that this prospective study has shown that VE-delivery in fullterm babies seem to imply no risk fo serious cerebral sequelae. Further follow-up studies at a later age in order to evaluate the incidence of so-called minimal brain damage in VE-delivered children are required.


Quantification of fetal heart rate variability in relation to oxygenation in the sheep fetus. Beat-to-beat variability has been suggested as a sensitive indication of fetal well-being. The suggestion originates from case reports of observed decrease in variability preceding clinical signs of fetal asphyxia and fetal death. Against this background a study was performed to evaluate possible changes in heart rate variability in relation to changes in fetal oxygenation. Chloralose-anesthetized sheep were used. Short-term hypoxia was produced without acidosis. The FECGs were recorded on magnetic tape and later analysed by scrutinizing each QRS complex prior to the trigger of a rate meter. The differential index (DI) described by Yeh and co-workers was chosen because it is easily computed and reflects the variability of coefficient of variation for two successive R-R intervals. In contrast to the generally held view of a progressive diminution of variability during the development of asphyxia, the variability was found to increase parallel with a decrease in fetal arterial PO2 determined on blood samples withdrawn at intervals and ranging between 26 and 10 mmHg. The correlation between variability and PO2 in the range below 8-10 mmHg is still to be determined.


Changes of bone mineral content during pregnancy and lactation. In order to study changes in the calcium depots of the body during pregnancy and lactation, bone mineral deteminations were performed on fourteen pregnant women and eighteen mothers post partum by X-ray spectrophotomeyry. Pregnant women exhibited a loss in trabecular bone but not in cortical bone when measured once during late first or early second trimester and again one week post partum. Lactating women who nursed less than three months lost mineral during the first three months and than regained it while those who nursed for longer than three months had no losses during six months of study.


Renin-angiotensin--aldosterone system and sodium in normal pregnancy: a longitudinal study. Plasma renin activity, the concentration of angiotensin I and the urinary excretion of aldosterone and sodium were studied longitudinally in 10 healthy primigravidae from the 10th week of pregnancy monthly until the 7th puerperal day. Plasma renin activity and angiotensing I levels were significantly elevated throughout pregnancy and showed maximal mean values at the 10th week, gradually returning to the level of nonpregnant women 7 days after delivery. They daily urinary excretion of aldosterone was also increased throughout pregnancy, but the mean values showed an increasing trend until 34th week. They returned to nonpregnant levels 7 days after delivery. There were no significant changes in the urinary excretion of sodium during pregnancy but the mean value was lower than in the nonpregnant control group. There was a significant positive correlation between urinary aldosterone and sodium values, while an almost significant negative correlation existed between urinary aldosterone and plasma renin activity, suggesting the priority of natriuresis in the regulation of aldosterone secretion during pregnancy. No corrleation was found between plasma renin activity and urinary sodium excretion values.


Hysterectomy in central recurrence of carcinoma of the uterine cervix. Central recurrence was recorded during 1963-1972 in 136 patients (14%) out of a group of 977 cases given radiation therapy for carcinoma of the uterine cervix (Stages I and II). Fifty of these patients (i.e. 37%) showed indications for surgery. In 12 of them only explorative laparotomy was performed. Radical hysterectomy was carried out in 14 cases, combined vaginal and abdominal wide extrafascial hysterectomy in 13 cases and ordinary extrafascial hysterectomy was chosen in 11 cases. The cellmorphology in the squamous-cell cancers, classified according to Reagan et al., was proportionally the same in these patients as in the series as a whole. The patients operated on by combined vaginal and abdominal hysterectomy had the same rate of survival, but fewer complications, than those given radical hysterectomy.


Water and ion metabolism in placenta. I. water and ion content of rabbit placenta in different periods of gestation. Total tissue water of rabbit plancenta decreases by 18% between the 9th day and the end of gestation. In the same period intracellular water decreases by 40% and the extracellular compartment swells. Total tissue sodium and chloride content increase by 34% and 27% respectively from the 16th to the 33rd day while potassium decreases by 30%. The intracellular concentration of these ions does not vary greatly during gestation. Moreover the total tissue magnesium content decreases by about 23% at the end of gestation while its intracellular concentration does not show marked changes. Calcium content of rabbit placenta substantially increases during gestation and intracellular calcium shows a fivefold increase from the 16th to the 33rd day of gestation. The results are discussed in terms of relation between water and ion content and placental tissue growth and aging.


Testicular femininization with intraperitoneal disseminated mesothelial cysts. A case report is given of a patient suffering from testicular femininization, a 13.5 l mesothelial-lined cyst associated with the right gonad, and several small intraperitoneal mesothelial cysts. No malignant changes were found, and no remnats of the Mullerian duct system were detected.


Coronary artery changes in newborn babies. A histological and electron microscopical study. The main branch of the left coronary artery of 14 autopsied newborn babies was studied both in light and electron microscopy. Intimal and medial changes of varying severity were found in most cases. The lesions show edema and suggest insudation of the blood solutes into the vessel wall. The edematic phase is followed by proliferation of smooth-muscle and undifferentiated cells, leading to a thickening of the arterial wall. The structure of the lesions resembles the so-called preatherosclerotic changes found frequently in adults. The relationship of the neonatal coronary changes to arteriosclerosis is discussed.


On the effect of vinblastine on ameloblasts of rat incisors in vivo. 2. Protracted effect on secretory ameloblasts. A light microscopical study. The effects of vinblastine sulphate at a dosage of 0.2 mg per 100 g body weight on the secretory ameloblasts of rat incisors were studied 3, 6 and 24 hours and 3 and 7 days after administration of the drug. The vinblastine affected the secretion profoundly, caused a reduction in size of the cells and death of many ameloblasts. Most of the surviving ameloblasts restored initially-induced loss of polarity. Many also resumed secretion and deposition of enamel matrix. The Tomes' processess were extremely sensitive to vinblastine and all matrix deposited after administration of the drug appeared abnormal in structure. Ameloblasts not resuming secretory activity were less than half the size (height) of normal cells. In some areas all the ameloblasts were destroyed with the exception of a varying number of surviving ameloblasts parts consisting only of a nucleus and a small amount of cytoplasm. The ameloblasts which had re-established secretory activity, and most of the ameloblasts which had not, retained their ability to transform into transporting ameloblasts. Large amounts of ameloblast debris present 3 and 6 hours after administration of the vinblastine were effectively engulfed and digested by the cells of the striatum intermedium within 24 hours.


On the effect of vinblastine on ameloblasts of rat incisors in vivo. 3. Acute and protracted effect on differentiating ameloblasts. A light microscopical study. The acute effect of vinblastine sulphate at a dosage of 0.2 mg per 100 g body weight on ameloblasts in the progress of differentiation in rat incisors, and the ability of these cells to develop into secretory ameloblasts after exposure to the drug, were studied under the light microscope. In the early stages of differentiation (exclusively dividing cells) no changes were seen. In more advanced stages of differentiation the cell apices were altered and the nuclei normally placed near the cell base were located at all levels in the ameloblast layer. These changes were reversible and the cells developed into secretory ameloblasts of normal appearance and function. Ameloblasts in the most advanced stage of differentiation in which secretion had begun were severely damaged, and the mature secretory ameloblast population derived from these cells was decimated and produced enamel matrix with abnormal structure. It is concluded that differentiating ameloblasts are relatively invulnerable to vinblastine, whereas in secretory ameloblasts the organelles directly engaged in the secretory processes are particularly exposed to damage from the drug.


The ultrastructure of macrophages found in contact with plasma cells in the bone marrow of patients with multiple myeloma. The ultrastructure of a macrophage found in the bone marrow of 15 patients with multiple myeloma is described. The macrophage is designated the dendritic bone marrow macrophage, due to the various branching cell forms in which it can be found. It is further distinguished by having contact with plasma cells. At the contact zones a thickening of the inner leaflet of the cytoplasmic membrane of the plasma cells is observed, whereas no morphological changes are present in the adjoining membranes of the macrophage. These macrophages show a great variation in their phagocytic capacity, and only few show morphological evidence of being actively phagocytic. A few dendritic bone marrow macrophages show a localized thickening of the inner leaflet of their cytoplasmic membrane, but this thickening is never found in the regions of contact with plasma cells.


The ultrastructure of contact zones between plasma cells and macrophages in the bone marrow of patients with multiple myeloma. The ultrastructure of intercellular connections between plasma cells and dendritic bone marrow macrophages found in bone marrow aspirations from 15 patients with multiple myeloma is described. Two types of cell-to-cell contact were observed: 1) a juxtaposed type and 2) a mortise-joint type. In both types the zones are characterized by an amorphous electron dense layer adherent to the inner leaflet of the cytoplasmic membrane of the plasma cell, whereas no morphological changes are present in the macrophage. The thickness of the electron dense layer in the plasma cell was found to range from 11 to 33 nm and its extension along the membrane fron 0.2 micronm to 2--3 micronm. The distance from plasma cell surface to the surface of the macrophage was found to range from 11 to 27 nm, but the two cell membranes were always parallel at the contact zone region. At the contact zones small amounts of electron dense material were generally present in the interspace between the cells, and sometimes fine bridges of this material were seen to connect the two cells. The cytoplasm of the plasma cell was sparse in organelles at the contact zone region except for cytoplasmic filaments (7--9 nm in diameter). However, more than 50 per cent of the plasma cells did show a few electron dense, membrane-bound granules close to the contact zones. In some plasma cells a few coated vesicles were also found adjacent to the dense layers of the contact zones.


Quantitative studies of the renal corpuscles IV. Determination of normal values in various age categories, and an analysis of the possible influence of physiological degrees of arteriolosclerosis. A quantitative study including total and differential counts of nuclei and determination of mesangial and total glomerular area was carried out on kidney tissue from 21 persons without renal disease, in order to determine the normal values of glomerular parameters and to estimate the possible influence of age and physiological degrees of arteriolosclerosis. No age dependency was found to exist for the glomerular parameters within the age category of 17 to 45 years. Above the age of forty-five a rise in mesangial area per cent of total area and mesangial nuclei per cent of total nuclei was found on increasing age, while a decline on increasing age was demonstrated for epithelial nuclei per cent of total nuclei. The mean value of mesangial nuclei per 1000 micron2 of mesangial area was found to be significantly higher in the older age category than in the younger. Arteriolosclerosis did not appear to influence the parameters. The study also attempted to describe the three variance components: interrenal, interfocal and interglomerular variation. Interfocal variation was the smallest part of the total variation, and interrenal plus interfocal variation was at most of the same size os interglomerular variation.


Effect of cell aggregation on intravenous tumor transplantation. We have studied how the presence of cell aggregates affects the pattern of intravenously induced "experimental metastases" from two syngeneic murine tumors. Aggregates were produced mechanically by centrifugation, or chemically by a lectin (wheat-germ agglutinin). Compared to well-dissociated suspensions, aggregated suspensions tended to give a greater total metastasis volume in the lungs of recipient mice. Disaggregated suspensions, on the other hand, gave rise to more extrapulmonary metastases. Presumably, aggregates are preferentially retained in lung vessels, while single cells are let through to other sites. Nor are aggregates superior to single cells in producing tumor growth when the total metastasis yield is considered.


Abnormal mitochondria in hepatocytes in human fatty liver. Liver biopsies from fatty livers in thirty patients whose daily alcohol consumption was excessive, or they were in a diabetic state or overweight, and liver biopsies from seven control patients not presenting the above disorders, were studied by light microscopy 0.75 micronm EPON embedded, toluidine blue stained sections, and electron microscopy. Abnormal mitochondria were rarely found in normal liver tissue and, if present, they were found only in periportal hepatocytes. The frequency of hepatocytes containing abnormal mitochondria was significantly higher in fatty liver than in normal liver (p less than 0.01). These cells were usually localized periportally, practically never in the centre of the lobule (p less than 0.01). The occurrence of abnormal mitochondria was not correlated with the degree of steatosis, and the increase in number of abnormal mitochondria was equally high in alcoholists, diabetics, and overweight subjects. The ultrastructural appearance and the periportal localization suggest a hyperfunction of the mitochondria, which may prevent a development of steatosis in these areas.


Ultrastructure of periportal and centrilobular hepatocytes in human fatty liver of various aetiology. The ultrastructure of periportal and centrilobular hepatocytes of fatty liver from 2 alcoholic patients, 2 diabetic patients and 2 obese patients is described and compared with that of hepatocytes in 2 patients with normal liver. A striking difference between periportal and centrilobular hepatocytes in all cases of fatty liver is deomonstrated. The periportal hepatocytes contain abnormal mitochondria, while centrilobular hepatocytes have normal mitochondria, but fatty vacuoles, peroxisomes and lysosomes are more abundant. The nature and degree of ultrastructural changes showed no correlation with aetiology of the fatty liver. The normal livers showed no such changes or distinct differences between periportal and centrilobular hepatocytes.


The prostatic lobes and the seminal vesicles in non-diabetic and alloxan-diabetic castrated adrenalectomized rats injected with cortisone. The growth of the prostatic lobes and the seminal vesicles was studied morphologically in alloxan-diabetic and non-diabetic castrated adrenalectomized rats. In non-diabetic but not in alloxan-diabetic rats cortisone in daily doses of 3 or 6 mg induced growth and secretory activity in the epithelium of the dorsolateral prostate, the coagulating glands and the seminal vesicles. Insulin administration to alloxan-diabetic rats could restore the effect of cortisone on these glands. This indicates that insulin deficiency per se was the main reason for the failure of cortisone to induce secretory activity of the prostatic lobes and the seminal vesicles of alloxan-diabetic rats.


IgA levels and carrier rate of pathogenic bacteria in 27 children previously tonsillectomized. The object of the present paper is to present laboratory and clinical data on 27 children of ages between 6 and 11 years, who in connection with tonsillectomy 2 1/2 years earlier had been found to have low serum and saliva IgA levels, low serum IgE levels, and a considerable lack of IgA and IgE plasma cells in the excised tonsils; correlation between deficiency in IgA and culture of pathogenic bacteria from the tonsils was significant. From a clinical point of view, 22 of the children had benefit of the tonsillectomy and had no longer a tendency towards a development of recurrent infections. The remaining 5 patients continued to complain of recurring respiratory infections; in addition, levels of serum and saliva IgA were low. Furthermore, 4 or these 5 children harboured pathogenic bacteria in their throats. Many of the 27 patients still had low serum IgA and IgE levels as compared with levels in healthy, age-related controls; in 3 patients, however, the IgE levels in serum had risen considerably parallel with the development of atopic diseases. Saliva IgA was rather constant after tonsillectomy as compared with the preoperative levels, though it had risen in some of the children. As regards serum IgG and IgM, these immunoglobulins had decreased significantly, and the question is raised, whether it might had been due to the tonsillectomy, either by the removal of chronically infected organs or by the removal of important immunological tissue.


Delayed hypersensitivity and borderline essential hypertension. By means of the leucocyte migration technique, it has been demonstrated that the migration indices from 19 patients suffering from borderline essential hypertension are significantly different from those of 19 normal persons. These results support the view that delayed hypersensitivity directed against arterial wall components is a possible pathogenetic factor in patients suffering from essential hypertension.


Hydro- and hemodynamic effects of catheterization of vessels. III. Experiments with a rigid-walled model. An experimental and a theoretical investigation has been performed on some essential factors influencing the volumetric flow rate through and the static pressure in a catheterized, rigid-walled vessel model. These factors comprise: (a) the length of the catheter introduced into the vessel, (b) the catheter diameter, (c) the vessel diameter, (d) the dynamic viscosity of the liquid and (e) the mode of catheterization. Theoretical expressions for pressure and volumetric flow rates have been observed for laminar and turbulent flow in even, concentric annuli, and the influence of eccentricity is discussed. A good agreement found between the experimentally and the theoretically obtained values of static pressure and the volumetric flow rate in catheterized vessels elucidates a series of features of interest for catheterization praxis and it emphasizes the applicability of relatively simple fluid mechanical equations in flow conditions of medical interest.


Radiologic technique for measuring instability in the knee joint. The measurement of anteroposterior instability as well as lateral and medical instability in the knee joint based upon radiologic films exposed while forces are being exerted on the patient in a specially constructed stress apparatus is described. Measurements on the films require detailed knowledge of the landmarks of the joint, alignment of baselines to special points, especially on the lateral projection, where anterior and posterior displacement should be measured for each tibial condyle to calculate the mean.


Hydro- and hemodynamic effects of catheterization of vessels. IV. Catheterization in the dog. In four dogs the hemodynamic effects of renal artery catheterization has been analysed. Aortic and renal arterial blood pressure and renal blood flow were determined and injection of contrast medium made before during, and after the catheterization maneuver, using catheters with different outer diameters. No effect on the blood pressure or the mean renal blood flow was found until catheters were used with the outer diameter close to the inner diameter of the renal artery.


Metrizamide in angiography I. Femoral angiography. In 20 patients the non-ionic Amipaque (metrizamide) and the ionic Isopaque Cerebral (meglumine/calcium-metrizoate) were injected into the femoral, brachial internal iliac or external carotid arteries. Strain gauge plethysmography of the lower leg demonstrated less increase in blood flow following injections of Amipaque (25%) than following injections of Isopaque Cerebral (95%). None of the 20 patients complained of pain following injection af Amipaque; 15 experienced pain following Isopaque Cerebral.


Subintimal injection of contrast medium as a complication of selective abdominal angiography. The frequency, cause and sequelae of subintimal injection of contrast medium as a complication of selective abdominal angiography have been evaluated. The frequency increased considerably with the degree of superselectivity. The risk of total occlusion and clot formation in the renal artery after subintimal injection is high. Injury and total occlusion of the celiac and hepatic arteries have better chance for healing than of the renal arteries. A subintimal injection in the proximal part of the superior mesenteric artery may result in the development of an aneurysm.


Brain scan as an aid in the diagnosis of acoustic neuroma recurrence. Brain scans using 99Tcm were performed on 34 patients from whom acoustic neuroma had been removed. The age range was 19 to 66 years at the time of operation. The scans were carried out at intervals up to 13 years postoperatively. There were 4 positive. 3 doubtful, and 26 negative scans. A policy is formulated for periodic scanning as an integral part of the follow-up programme of acoustic neuroma patients.


Postoperative kinematics in structural scoliosis. Three cases with idiopathic, structural scoliosis were examined postoperatively with a roentgen stereophotogrammetric method. Curvatures developed in both the frontal and sagittal planes. Axial rotation also occurred. In addition, residual mobility was demonstrated and quantified one year postoperatively.


Roentgen stereophotogrammetry for determination of bone growth. Comparison with the tetracycline method. Two different methods for determination of leg growth, the tetracycline method and roentgen stereophotogrammetry, were applied simultaneously in 41 young rabbits and compared 1 and 2, and 21 and 22 days after insertion of pins or balls of tantalum as markers. The tetracycline method gave slightly higher values than the other method, the difference varying between 77 and 6 micrometer/d on the first 2 days after marker insertion and between 32 and 1 micrometer/d after 3 weeks. When ball markers were used, agreement between the two methods was obtained 3 weeks after insertion. The difference between the methods used is due to that the two methods did not measure growth in precisely identical regions.


High-density failure of radiographic films. The recording of weak signals of high spatial frequency emanating from intensifying screens has been analysed in different films at varying densities. Even if the gamma value is kept constant over a wide range of densities, the recording of these signals is impaired at high densities above a certain optimum density, coinciding with the lower part of the straight part of the characteristic curve. The recording of these signals appears to be related to the number of silver halide grains per unit area available for signal recording rather than to the contrast as represented by the gamma value. When the density of the image is increased more grains are precipitated in creating the background density, leaving a smaller number of grains unaffected for the signals added on top of the background. If the signal frequency is high and the amplitude is low the remaining grains appear to become too few and too scattered for a proper recording, so that the signal cannot appear in the image. Since this occurs at densities where the film is not usually considered to be overexposed the phenomenon is called high-density failure. Different films may display great differences in high-density failure even if the sensitivity is the same.


ADP-induced platelet aggregation in vitro in patients with ischemic heart disease and peripheral thromboatherosclerosis. ADP-induced platelet aggregation in vitro has been studied in 90 normal controls and in 30 patients with ischemic heart disease (IHD) and 22 with peripheral thromboatherosclerosis (PTA). The sensitivity to ADP was defined by the threshold concentration which produced secondary aggregation with an amplitude corresponding to not less than 80% of the transmission obtained by platelet-poor plasma. In the normal controls the threshold concentration was significantly lower in women aged 50 or more than in women under that age. The geometric means were lower in the patients than in the controls. Significantly lower threshold concentrations than in the corresponding age groups of controls were found in the following age groups of patients: Men and women greater than or equal to 50 years with IHD (p less than 0.005 and p less than 0.001, respectively), men and women under 50 with IHD (p less than 0.05). Men and women greater than or equal to 50 years with PTA (p less than 0.002 and p less than 0.01, respectively), men and women under 50 with PTA (p less than 0.005).


The peripheral platelet count in response to intravenous infusion of salbutamol. Five healthy male volunteers received i.v. infusions of salbutamol, a relatively selective beta-2-receptor-stimulating agent, in doses of 0.03, 0.06, 0.09 and 0.27 microgram X kg-1 X min-1 over a period of 6 min. At the three low doses the heart rate remained essentially unchanged and no significant decrease in the platelet count occurred. However, in response to 0.27 microgram X kg-1 X min-1 of salbutamol the heart rate increased by 25% over basal value (p less than 0.01) and a significant lowering (p less than 0.005) of the platelet count was obtained. The present findings suggest that the drop in the peripheral platelet concentration in response to adrenergic beta-receptor stimulation is mediated via beta-1-receptors.


Raynaud's phenomenon. Photoelectric plethysmography of the fingers of persons with and without Raynaud's phenomenon during cooling and warming up. A study has been made of the changes in the amplitudes shown on photoelectric plethysmographs of the fingers of one hand of controls (17 men and 17 women without Raynaud's phenomenon) during cooling and warming up of the hand. This is called the cooling and warming up test. The hands of the women appeared to cool more quickly than of the men, besides getting warm more quickly and remaining warm for a longer period. This difference is already apparent at the lowest water temperatures (6 and 3 degrees C) and may be ascribed to a difference in hand volume, with a hunting reaction due to extreme cold. The lowest values of controls appear to be useful for the clinical differentiation of patients with a serious Raynaud's phenomenon. The test is said to be positive when the values are below the lowest values of the controls. The test was performed on 50 of 58 out-patients suffering from Raynaud's phenomenon. In serious cases the severity of the disease could be assessed objectively. In less serious cases the test was sometimes negative.


Significance of enzyme release from ischemic isolated rat heart. Whole-heart ischemia has been induced in isolated working rat heart. The distribution of the reduced coronary flow was even, as judged by 3H-antipyrine autoradiographs. Reducing the coronary flow resulted in myocardial ischemia, as indicated by a lowered tissue content of glycogen, ATP and creatine phosphate and accumulation of lactate. After a reperfusion period of 30 min there was a restoration of glycogen, ATP and creatine phosphate for hearts that were ischemic for 5 and 10 min, with a concomitant normalization of tissue lactate. Hearts that were ischemic for 30 min did not show restoration of high energy phosphates and glycogen. There was a leakage of ASAT, CK and LD in all groups of hearts, suggesting that a release of these enzymes does not necessarily indicate an irreversibly damaged myocardial cell.


Factors modifying ischemic injury in the isolated rat heart. The extent of ischemic injury has been studied in the isolated working rat heart utilizing an aortic ball valve that reduces the coronary flow. A number of factors were tested including high heart rate, noradrenaline, acidosis, alkalosis, high afterload, beta-blockade, glucose-insulin-potassium (GIK), palmitate and methylprednisolone. Mechanical performance, myocardial contents of ATP, creatine phosphate, glycogen and lactate and the leakage of creatine phosphokinase (CK) from the myocardium to the perfusion buffer were measured and used for determination of the ischemic injury. Tachycardia, noradrenaline and palmitate are factors that markedly increase the ischemic injury in this preparation. GIK and probably metoprolol decrease the release of CK compared with the controls.


Electrocardiographic changes in massive pulmonary embolism. I. Analysis of the changes in P wave and QRS complex. A retrospective analysis of ECG changes during lung embolism has been made in 35 patients (16 male, 19 female) who died of massive lung embolism. The presence of lung embolism or infarct was confirmed at autopsy. According to the ECG the mean heart rate increased from 91 to 106. The amplitude of the P wave increased in leads I, II, III and aVL and decreased in all precordial leads. A small increase in the O wave occurred in leads II, III, aVF, V1, V2 and V6. Only a small decrease in the R wave occurred in leads I, II and aVL. A small increase in the S wave occurred in leads I, II, V2-V6 when compared with the controls. None of the differences was, however, statistically significant.


Electrocardiographic changes in massive pulmonary embolism. II. Analysis of the changes in ST segment and T wave. A retrospective analysis of the changes in ST segment and T wave has been made in 35 patients (16 male, 19 female) with massive pulmonary embolism in whom the diagnosis was confirmed at autopsy. Parameters of the last two ECGs available were measured and compared. It was found that during massive pulmonary embolism the most characteristic abnormalities were a decrease in ST segment, which took place in about 70% in leads I and V5-V6. Another common change was the inversion of the T wave, which took place in 43% in aVF, and in 37% in lead II. None of the changes, however, was statistically significant.


Coffee consumption and coronary heart disease in middle-aged Swedish men. The possible association between coffee and myocardial infarction (MI) has been studied both prospectively in a random population sample of Swedish men aged 50 years (n=834) and with case control methodology in non-selected male patients surviving a MI (age 40-57 years, n=230). Coffee consumption was significantly associated with two other important risk factors for MI, namely smoking and alcoholic intemperance, but weak (non-significant) relationships were found with serum cholesterol, serum triglycerides, systolic or diastolic BP, and dyspnoea on exertion. In the prospective study there was no significant relationship between coffee and MI, either with univariate or multivariate analysis. The retrospectively reported coffee consumption of MI patients was higher than of those who later suffered a MI (the population sample). With the aid of non-parametric multivariate analysis of the combined population sample and the series of MI patients, a significant association was found between coffee consumption and MI. The experience of having had a MI may have affected the patients' rating of coffee consumption, or their consumption may have really increased during some months or a few years before the MI.


Sudden coronary death in Scandinavia. A report from Scandinavian coronary heart disease registers. All cases of acute myocardial infarction (AMI) and sudden death due to coronary heart disease have been registered in two Swedish and two Finnish cities during a 1-year period. The incidence increased steeply with age in both sexes and was in all age groups far higher in males than in females. The age-related incidence in both Finnish cities was definitely higher than in Gothenburg, Sweden, while the other Swedish register city, Boden, had an intermediate position. fatality rate within one year was 44.2% for males and 37.4% for females. This difference was already apparent in the first hour after the onset of the attack, when the case: fatality rate was 15.5% for males and 9.3% for females. A history of previous cardiovascular disease was much more common in AMI patients than in the general population. It was also slightly more common in subjects who died suddenly than in AMI patients who did not die suddenly.


Oesophageal acid perfusion test as a complement to work test in patients with chest pain. Out of 121 patients referred to a work test on account of chest pain, 67 with a case history typical for oesophageal dysfunction have been further investigated with an acid perfusion test during continuous ECG monitoring. Neither arrhythmias nor ST-T changes were induced by the procedure. Of the 67 patients, 6 had a "positive related" acid perfusion test, 23 a "positive unrelated" and the remainder a negative test. Five of the 14 patients with pathological effort ECG belonged to the group with a positive acid perfusion test. The acid perfusion test, as a safe routine in close connection with the effort ECG in selected patients, is a useful technique for establishing whether or not the patient's symptoms have an oesophageal component.


A family with dominantly inherited mild juvenile diabetes. A family of 53 members is described in which mild diabetes in young, non-obese subjects is transmitted through four generations from parents to children, the ratio diabetic/non-diabetic offspring of diabetic parents being 3:2 and all affected individuals having a diabetic parent. In this family, mild juvenile diabetes thus appears to be inherited as an autosomal Mendelian dominant.


Prevalence of angina pectoris and myocardial infarction in a general population sample of Swedish men. A primary preventive trial against cardiovascular diseases has been in progress since 1970 in Göteborg, Sweden. The study population comprises all men in the city born in 1915-22 and 1924-25, a total of about 30 000 men. One third of this population constitutes the intervention group. The prevalence of angina pectoris and myocardial infarction among men aged 47-53 years has been studied in this group. The cases were identified by means of a postal questionnaire, direct interview at screening examination and by clinical examination. A validation of the postal questionnaire technique gave a sensitivity of 74% and a specificity of 94%. The minimum prevalence of angina pectoris amounted to 4.3% and the prevalence of myocardial infarction to 1.6%. In the angina series, 22% had suffered a myocardial infarction that preceded angina pectoris in 9%.


Swallowing syncope. A case report.

Swallowing syncope. A case report. A previously healthy man complained of syncopes and convulsions during meals. Despite thorough gastroenterologic, neurologic and cardiologic examination, the condition was misinterpreted as a psychiatric disorder for 13 years. Then ambulatory ECG, using a casette recorder, revealed periods of 2nd degree AV block during swalllowing. Pacemaker implantation prevented the attacks.


Primary purulent meningococcal pericarditis with tamponade. A case of primary purulent meningococcal pericarditis, presenting with hemodynamic derangement due to tamponade, is reported. Treatment was successfully fulfilled with antibiotics and surgical drainage, using continuous percutaneous subxiphoidal catheter drainage with the Seldinger technique. Less than ten cases of this potentially lethal entity have been reported in the literature.


A case of severe compression of the coeliac artery. A man, aged 42 years, presented as an emergency with a history of stabbing upper abdominal pain, nausea and diarrhoea of two weeks' duration. Apart from abnormal transaminase and alkaline phosphatase values, the routine clinical and laboratory examinations did not reveal any abnormality. As the abdominal pain increased in severity, particularly in association with eating, and projectile vomiting supervened, aortography was carried out and showed severe stenosis of the coeliac axis, involving about 1 cm of the  artery. At operation a thick fibrous band, which originated from the median arcuate diaphragm, was seen to constrict the point of origin of the artery and to compress the vessel against the aorta. The band was divided, whereupon the coeliac artery immediately showed strong pulsations and adequate filling. Microscopic examination of the fibrous band revealed, among other structures, those characteristic of a ganglion. The symptoms disappeared after operation.


[The microsurgical treatment of the so-called tuberculum-sellae-meningiomas (author's transl)]. Experience from five cases operated on within one year (among 50 microsurgical operations at the base of the brain) persuades us to discuss the topical relations of the meningiomas of the tuberculum sellae and the modifications in operating techniques necessary. For the two contrasting types of tumour found, which are:-- 1. Tumours en plaque with osseous reactions, particularly of the sphenoidal ridge, in which the exact predetermination of the positions of the optic nerve and of the carotid artery is facilitated by means of measurement and by fronto-temporal approach (which does not preclude a frontal or a bifrontal approach). 2. Suprasellar tumours whose topical relationships to the posterior surface of the chiasma, the pituitary stalk, the big vessels, and the perforating arteries increase the risk of operation. Radical operations for tumours near the pituitary stalk are not always advisable. Pre- and postoperative analysis of the anatomical characteristics of the individual case is essential before microsurgical intervention.


Spinal dissemination following operation on cerebral oligodendroglioma. This paper concerns two cases of cerebral oligodendroglioma (intraventricular in one case, right temporal in the other), with spinal dissemination (cervical and upper thoracic respectively), manifested clinically 2 years and 14 months respectively after removal of the cerebral tumour. Anatomical examination confirmed the diagnosis of disseminated oligodendroglioma in the leptomeninges in both cases and also in the parenchyma in the second case.


Radiation-induced meningeal sarcoma. A case report with a review of the literature. A case is reported of a 21 month old boy from whom a 357 g ependymona was removed. Postoperatively, radiation therapy (Co60) was administered, and the central dosage was estimated to be 4,350 r given over 46 days. Seven and a half years later craniotomy was again performed because of a supposed recurrence. However, a meningeal sarcoma weighing 370 g was found. Tumour induction by radiotherapy is discussed on the basis of published reports, and the need of estimating tumour dose in relationship to the age of the patient is stressed.


Cerebral blood flow in patients with subarachnoid haemorrhage studied with an intravenous isotope technique. Its clinical significance in the timing of surgery of cerebral arterial aneurysm. The cerebral blood flow state has been evaluated in a series of 207 patients suffering from subarachnoid haemorrhage and with proved arterial aneurysms. Particular interest was focussed on 160 in grade I or II according to Botterell. An intravenous isotope method was used with 131-I Hippuran or 99-Tc pertechnetate as indicators. 133 of the 160 patients were operated on. 78 were also examined postoperatively. The radioactivity was recorded by two gamma detectors place bilaterally over the skull. The heights of the curves were taken as an index of the cerebral blood flow. Transit time was determined by dividing the area of the curve by its height. The results showed that even patients with no or slight neurological symptoms could have a depressed cerebral blood flow. Alterations in the blood flow seemed to precede a change in the clinical picture. Postoperatively, most patients had a further decrease in flow, but some others remained unchanged or even improved. With a normal or only slightly disturbed cerebral blood flow in the preoperative period, the morbidity and mortality of intracranial aneurysm surgery was estimated at 8%. For patients with a low preoperative blood flow value, i.e. more than a 40% reduction, the morbidity and mortality was much higher, about 30%. The results indicate that an analysis of the cerebral blood flow status represents an additional diagnostic parameter of great clinical significance, increasing the possibility of predicting to outcome of the operative treatment of an intracranial arterial aneurysm.


Fibrinolytic activity in the walls of cerebral saccular aneurysms. The fibrinolytic activity of 28 cerebral saccular aneurysms from 24 patients and of controls consisting of 10 cerebral arteries has been studied by Todd's autography technique. An increased activity was seen in the minute adventitial vessels and in the endothelium in ruptured cerebral saccular aneurysms, but the aneurysms showed somewhat less activity than the surrounding arteries. Seven patients with subarachnoid haemorrhage had the same increase in fibrinolytic activity in the aneurysmal wall despite antifibrinolytic therapy ante mortem. This finding has been discussed.


Longitudinal extension of oedema in experimental spinal cord injury--evidence for two types of post-traumatic oedema. As in brain, another, obviously hydrostatic, type of oedema develops in the acutely injured spinal cord of the rabbit in addition to vasogenic oedema. The authors arrived at this finding by means of fluorescent tracer studies histological examinations, and measurements of tissue water, sodium and potassium. Longitudinal spread of vasogenic oedema remained limited to the zone of the epicentre and its surroundings. Hyperhydration, which appears gradually in the remote segments and is associated with increased sodium content, has the characteristics of plasma-ultrafiltrate.


Administrative receivership and troika management. The authors describe the use of troika management and administrative receivership to upgrade a unit in a state mental hospital. The experiment included a three person unit chief, transitional leadership, and collective decision making.


Psychiatrists in community mental health centers. A study of 20 community memtal health centers indicates that of all staff, psychiatrists are least identified with the ideology of community mental health.


Developing human service administrators: the educational challenge. The author reports the results of a survey on the education of human service administrators and concludes that an interdisciplinary approach is most desirable. A model curriculum in human service administration is outlined.


The conflict between research and mental health services. Serious friction often results from the association between social scientists and providers of mental health care. Understanding the nature of this association and the types of conflict that exist may result in improved research and services.


Staff participation in governance.

Staff participation in governance. Staff participation in the governance of a mental health organization can be implemented through a governing council. The author describes the functions of such council and recommends it as a vehicle for the improvement of mental health services.


The mental health administrator and evaluation. The administrator is responsible for ensuring that evaluation is an integral part of mental health programs. To do this, several important factors such as staff resistance must be considered.


PERT in patient placement.

PERT in patient placement. The use of PERT as a standardized process for the placement of patients in community facilities is illustrated and advocated by the authors.


Pathogenesis of food and gastrointestinal atopy. The pathogenesis of gastrointestinal and alimentary atopy is an unclear problem. The reason of respiratory or gastrointestinal location of atopic symptoms is unknown. The density of intestinal IgG, IgM, IgA and IgE forming cells (Ig F.C.) was measured in 23 atopic and 16 non atopic children. The IgM F.C. was found to be increased in atopic children up to two years old (p less than 0.05). The IgE F.C. was increased in atopic patients (p less than 0.05), specially over two years old (p less than 0.001). The ratio IgA F.C./IgE F.C. was decreased (p less than 0.02) and we assume it is the more significant index. The same modifications were found in alimentary or gastrointestinal atopic patients and the location of allergic symptoms did not change the IgE F.C. density. We suggest the local increase of IgE F.C. does not play an important role on the type of clinical atopic disturbance. May be it only reflects the "atopic state" and the progressive systemic overstimulation by allergens.


Recognizing the allergic person.

Recognizing the allergic person. Recognition of the allergic individual is facilitated by an awareness of certain characteristic actions and various facial lesions which may be clues to other allergic problems. A gaping expression, clearing of the throat and rubbing or mashing of the eyes and nose may indicate significant rhinitis. Dark circles and bags under the eyes, long, silky eyelashes and injected conjunctivas are other signs. Bruxism and malocclusion may also be related to an allergic diathesis.


Estrogen and the menopause.

Estrogen and the menopause. Currently popular dosage schedules of estrogens are not physiologic. Daily large peak fluctuations of circulating estrogen may induce unfamiliar patterns of target cell stimulation which may ultimately be expressed in abnormal cellular activity. For women who require estrogen to control menopausal symptoms, ethinyl estradiol or 17 beta-estradiol is recommended in small daily doses for three weeks (followed by one week off), with the addition of medroxyprogesterone in a small dose in the third week of estrogen treatment.


Tennis elbow.

Tennis elbow. The evidence that tennis elbow is caused by poor muscle strength and improper tennis stroke is strong. The lesion may be at the lateral epicondyle (70 to 80% of patients), at the musculotendinous junction at the level of the radial head or, rarely, at the medial condyle. Anti-inflammatory steroid injections in the condylar lesions are helpful. Sinusoidal wave stimulation of the affected muscles, or repetitive active wrist dorsiflexion, is important in the early stages. The recurrence rate drops sharply when patients adhere to a progressive exercise program.


Frequency and significance of conduction defects in acute myocardial infarction. The frequency of intraventricular conduction defects was determined in 556 consecutive patients with proven acute myocardial infarction. Complete left bundle branch block was present in 23 patients and carried a high mortality rate (61 per cent). Complete right buldle branch block was the rarest defect to be seen in isolation (8 patients) and carried a lower mortality rate (38%). Lone left anterior hemiblock was present in 72 patients and was associated with a low mortality rate (13 per cent); left posterior hemiblock occurred in 32 patients (mortality rate 19 per cent). In a further 59 patients right bundle branch block with left anterior or posterior hemiblock in addition was present and these patients had a high mortality rate which was greater than isolated right bundle branch block or hemiblock alone. Complete atrioventricular block developed in 51 patients, 26 of whom had prior evidence of intraventricular conduction defect. Despite the use of temporary transvenous pacing, mortality in patients who developed complete heart block was significantly increased whether or not an intraventricular conduction defect was already present. The significance of these findings for the management of patients with myocardial infarction is discussed.


Cardiovascular effects of dobutamine in severe congestive heart failure. The effects of continuous infusion of dobutamine 5 to 15 microgram/Kg./min. were studied in 17 patients using right heart catheterizations, echocardiography, and/or the Systolic Time Intervals. HR increase was dose-related, but insignificant (p less than 0.05) rate increase was obtained at infusion rates below 15 microgram/Kg.)min. C.O. increased from 2.9 +/- 0.7 to 5.0 +/- 1.2 liters/min. (p less than 0.001), and the stroke volume from 30 +/- 6 to 49 +/- 14 ml./min. (p less than 0.005). The mean BP did not change, P.A.W.P. decreased from 30 +/- 7 to 20 +/- 8 mm. Hg (p less than 0.001) and R.A.P. from 20.0 to 12.0 mm. Hg (p less than 0.005). The P.E.P.I. decreased from 160.93 +/- 54.91 to 133.4 +/- 28.7 msec. (p less than 0.050). Echo-determined mean VCf increased from 0.387 +/- 0.14 to 0.537 +/- 0.13 cm. (p less than 0.010), diastolic diameter did not change significantly, but the end systolic diameter decreased from 6.020 +/- 0.69 to 5.750 +/- 0.70 cm. (p less than 0.025). During a mean infusion period of 75 hours, the only side effects noted were transient nausea and/or vomiting at 15 microgram/Kg./min. dose range in two patients, and multifocal P.V.C.'s following 68 hours of infusion in another patient. It is concluded that in the dose range of 5 to 15 microgram/Kg./min., dobutamine is well tolerated and is a very potent inotropic agent with only minor effects on the heart rate and blood pressure.


A comparison of the response to arm and leg work in patients with ischemic heart disease. An exercise test based on arm work was evaluated in a series of 33 male patients, mean age 52 years, with ischemic heart disease. The responses to arm exercise on a modified table-mounted bicycle ergometer and to standard bicycle exercise were compared. Twenty six of 33 patients (79 per cent) had identical end-points with both tests. Three patients had an ischemic response, i.e., significant ST abnormality and/or angina pectoris during leg work only, and four patients during arm work only. 41 per cent of the peakload during leg exercise. Mean values were 181 and 439 kpm./min. (p less than 0.001). Comparison of individual data on peak load demonstrated only a weak correlation between arm and leg work capacity (r = 0.37, p less than 0.05). Peak heart rate was slightly higher during leg work, 129 compared to 122 beats/min. (p less than 0.05) but the mean heart rate-systolic blood pressure products were not significantly different. A subgroup of seven patients had a history of angina pectoris preferentially precipitated by arm work but their physiological responses did not differ significantly from those of patients without a history of arm work sensitivity. The data indicate that arm work is a satisfactory alternate diagnostic test method with respect to myocardial ischemia, but measurements of physical work capacity defined as aerobic capacity, cannot be based on arm work.


Respirable dust sampling in Czechoslovak coal mines. The paper contains a brief survey of the airborne dust concentration measuring methods presently used in Czechoslovak coal mines, their comparison and the evaluation of their contribution to the determination of the dust workings hygienic risk. Moreover, attention is directed to the newly developed two-stage dust sampler, DP 50.


Expirical relationships among heat stress indices in 14 hot industries. This study develops empirical relationships between several indices of heat stress derived from a series of studies in 14 representative, hot industries. With particular emphasis on Wet Bulb-Globe Temperature, the analysis verifies and supplements certain relationships between heat stress indices developed by other investigators. Because of its large industrial data base, the study also provides a reliable basis for interrelating heat stress indices in future standard-setting procedures.


The prediction of WBGT from the Botsball. This study investigated the relationship between the Botsball (BB) and WBGT in varied environmental conditions. Two levels of radiant heat, two levels of air movement, three levels of relative humidity, and dry bulb temperatures ranging between 17.2 and 42.8 degrees C (63 and 109 degrees F) yielded 210 different environmental conditions. The results indicate that if good estimates of wind speed, humidity and radiant heat are available, BB can predict WBGT with +/-0.4 degrees C (90% confidence level). Only when there is limited knowledge of the type of environment does the predictability fall to +/-2.9 degrees C (90% confidence level).


An extraction method for determination of benzene in tissue by gas chromatography. An extraction procedure has been developed for the determination of benzene by gas chromatography in tissues following inhalation. Results are reproducible using very small quanities of sample (0.05 g for tissue and 0.02 ml for blood). The procedure has been applied to the analysis of blood and tissue of A.K.R. mice following a single exposure to levels similar to those that may be found in industrial hygiene atmospheres.


The filtration efficiency of organic vapor sampling tubes against particulates. The particulate filtration efficiency of industrial organic vapor sampler tubes is of interest for air sampling in work environments containing toxic materials as both vapor and particulate, or where inert particles contain adsorbed toxic material. Particulate collection efficiencies, measured with dioctylphthalate and polystyrene latex aerosols ranged from 70-90%. However, only 20% of this total is deposited on the active sorbent (charcoal granules). Considerable variability in collection efficiency between tubes was observed. Recommendations are made for obtaining improved contaminant estimates using these tubes.


Occupational dust exposures in West Texas cotton gins. Total and elutriated dust concentrations were measured by four methods for typical ginning situations. Total and elutriated levels were 0.73 and 0.47 and 0.59 and 0.26 mg/m3 per bale/hr by the gin stands and bale press, respectively. Limited data show the corresponding mass media diameters are 9.2-14.8 and 9.6-18.5 micrometer.


Blood pressure, renin activity and heart rate changes during propranolol therapy of hypertension. To investigate the importance of plasma renin activity in determining the antihypertensive action of propranolol and of heart rate in guiding propranolol therapy, the effect of a graded oral dose of propranolol on blood pressure, plasma renin and heart rate was studied in 24 men with essential hypertension and differing initial levels of renin activity. Although plasma renin decreased substantially in patients with normal and high renin levels tasking a small dose of propranolol (40 mg/day), blood pressure was unchanged in the normal renin group, and a small decrease in systolic pressure alone was noted in those with high plasma levels of renin. Patients with low renin levels had no reduction in blood pressure with small doses of propranolol, but as a group they responded well to a dose of 320 mg/day. Standing heart rate decreased maximally at plasma propranolol concentrations greater than 25 ng/ml, and did not exceed 72 beats/min with plasma concentrations above that level. Overall, the observed responses for plasma renin and heart were more pronounced at lower plasma propranolol concentrations than those for blood pressure.


Echocardiographic diagnosis of left anterior descending coronary artery disease. To determine the usefulness of the standard echocardiogram in the diagnosis of left anterior descending coronary artery disease proximal or distal to the first septal branch, coronary arteriograms and echocardiograms were performed in 77 patients with a chest pain syndrome. Seventy-nine percent of patients with proximal disease (15 of 19) had an abnormal septal motion measured as a posterior wall/interventricular septal (PW/IVS) excursion ratio greater than or equal to 2.5 compared with 10% of patients with distal disease (2 of 20) who had abnormal septal motion. Only 5% of patients without obstructive disease of the left anterior descending coronary artery (2 of 38) had abnormal septal motion. Proximal disease was found in 79% with abnormal septal motion in the echocardiogram (15 of 19) but in only 7% of patients with normal septal motion (4 of 58). Therefore, abnormal septal motion as measured by the PW/IVS excursion ratio in the echocardiogram is a useful index for the diagnosis of disease of the left anterior descending coronary artery when that disease is proximal to the first septal branch.


Mitral valve aneurysm after infective endocarditis in the billowing mitral leaflet syndrome. Mitral valve aneurysm is an uncommon complication of infective endocarditis. This report describes a patient with severe regurgitation due to perforations in a mitral aneurysm who required mitral valve replacement 9 years after a staphylococcal infection was superimposed on a billowing mitral leaflet. The unusual auscultatory signs and angiographic appearance could have led to diagnosis of the aneurysm.


Echocardiographic observations in opiate addicts with active infective endocarditis. Frequency of involvement of the various values and comparison of echocardiographic features of right- and left-sided cardiac valve endocarditis. Echocardiographic observations are described in 25 opiate addicts with active infective endocarditis involving apparently previously normal valves. Infective endocarditis was isolated to the tricuspid valve in 11 patients, involved both right- (tricuspid valve) and left-sided valves in 7 and was isolated to the left-sided valves in 7 (mitral valve in 6). Twenty patients (80%) had tricuspid valve regurgitation, 12 had mitral regurgitation, 3 had aortic regurgitation and none had pulmonary valve regurgitation. Considering the 75 cardiac valves (excluding the pulmonary) in the 25 patients, echocardiographic abnormalities consistent with active infective endocarditis were detected in 26 (74%) of the 35 clinically incompetent valves but in none of the 40 competent valves. Comparison of the 20 incompetent tricuspid valves with the 12 incompetent mitral valves indicated that (1) the echocardiogram was less sensitive in detecting tricuspid valve lesions, (2) rupture of tricuspid valve chordae tendineae was absent or not detectable, and (3) tricuspid valve vegetations tended to be larger.


New endomyocardial biopsy catheter for the left ventricle. A new biopsy catheter specifically made for left ventricular endomyocardial biopsy is described. The biopsy catheter is equipped with a device enabling one to bend the tip at will by rotating a knob on the operating handle. The rate of success in obtaining left ventricular biopsy specimens was very high (100%) and there were no serious complications in a group of 10 dogs and in five patients with cardiomyopathy.


Surgical correction of atrioventricular canal during the first year of life. Eight infants less than 1 year of age with an atrioventricular (A-V) canal defect (five with the complete form and three with the partial form) had definitive surgical correction performed because of intractable congestive heart failure. At operation, the infants weighed 2.9 to 6.5 kg. There was one operative death and one late death. The six surviving children were all doing well when followed up 10 months to more than 4 years postoperatively. This small series demonstrates that complete connection of A-V canal is possible even in very small infants and that chances of success are excellent. The infant with this defect who is not progressing with medical management should undergo definitive surgical correction, and a strong argument can be made for elective complete repair in all patients with this lesion, who have severe pulmonary hypertension, during the first 1 or 2 years of life.


Congenital pulmonary atresia with tricuspid insufficiency: morphologic study. In an anatomic study of 21 cases of pulmonary atresia with tricuspid insufficiency (pulmonary atresia with intact ventricular septum, type II), the morphologic features of the tricuspid valve and the right ventricle were found to differ greatly from those seen in pulmonary atresia with tricuspid stenosis (pulmonary atresia with intact ventricular septum, type I). Morphologically, pulmonary atresia with tricuspid insufficiency (type II) has a greater resemblance to Ebstein's disease with pulmonary atresia than to type I pulmonary atresia. The anomaly may be more amenable to surgery than pulmonary atresia with tricuspid stenosis because the right ventricle in the former may be converted into a functional chamber by a valvotomy combined with a shunting procedure and atrial septostomy.


Altered hemoglobin-oxygen affinity with long-term propranolol therapy in patients with coronary artery disease. Pharmacologic agents that alter hemoglobin affinity for oxygen may affect systemic or myocardial oxygen delivery. In vitro, and in normal man propranolol shifts the oxyhemoglobin equilibrium curve to the right, thus increasing the partial pressure of oxygen at which hemoglobin is 50% saturated (P50) and enhancing oxygen delivery. The effect of propranolol on hemoglobin P50 was evaluated in 12 patients with angina pectoris and documented coronary artery disease. Determinations were made during oral propranolol therapy (mean daily dose 152 mg) of at least 3 months' duration and after administration of propranolol had been discontinued for at least 4 days. Hemoglobin P50 and erythrocyte 2,3-diphosphoglycerate (DPG) were measured. Data in 12 patients were: the mean P50 after discontinuation of propranolol was 28.2 mm Hg+/-0.9 (standard error of the mean) and during propranolol therapy 31.7+/-0.7; P less than 0.001; red blood cell 2,3-DPG did not change to explain the increase in P50. This demonstrated shift could increase systemic oxygen delivery and thus benefit marginally perfused myocardium while sparing coronary flow. Propranolol, in addition to its negative chronotropic and inotropic effects, may increase tissue oxygen delivery in patients with the anginal syndrome.


Effects of propranolol on the hemodynamic, coronary sinus blood flow and myocardial metabolic response to atrial pacing. The hemodynamic, coronary sinus blood flow and myocardial metabolic effects of 0.15 mg/kg body weight of intravenously administered propranolol were studied in 19 patients with coronary artery disease and 6 normal patients. Atrial pacing was performed in all patients and produced angina in 15 of the 19 patients with coronary artery disease. In these patients propranolol reduced heart rate from 78 to 69 beats/min, cardiac index from 3.0 to 2.6 liters/min per m2 and left ventricular stroke work index from 47 to 43 g-m/m2; it increased total peripheral resistance from 24 to 28 units and lactate extraction from 16.3 to 22.5%. There was no significant change in mean arterial pressure, left ventricular end-diastolic pressure, coronary sinus blood flow or myocardial oxygen consumption. During a second pacing stress propranolol produced clinical improvement in 9 of the 15 patients who experienced angina initially. The improvement was associated with less severe abnormalities in S-T depression and left ventricular end-diastolic pressure, increased lactate extraction and no significant change in coronary sinus blood flow or myocardial oxygen consumption. Thus, propranolol appears to be capable of modifying the anginal threshold as determined with atrial pacing, and the clinical response appears to be independent of global changes in coronary sinus blood flow and myocardial oxygen consumption.


Imaging of the inflammatory response in ischemic canine myocardium with 111indium-labeled leukocytes. Myocardial leukocyte infiltration is one hallmark of acute myocardial infarction. In order to detect noninvasively this inflammatory response associated with acute myocardial infarction, we produced coronary occlusion in eight dogs, intravenously administered autologously labeled indium-111 (111In) leukocytes and scintigraphically monitored accumulation of radionuclide in myocardium. Seventy-two hours after coronary occlusion, 111In-labeled white cells accumulated in regions corresponding to myocardial infarcts, and positive images with 111In-labeled leukocytes correlated well with images obtained with technetium-99m pyrophosphate and computer-reconstructed tomograms obtained with nitrogen-13-labeled ammonia. In contrast, two control dogs subjected to sham operation did not exhibit positive 111In-leukocyte images. Scintigraphic results with 111In-labeled leukocytes were verified in vitro by analysis of radioactivity in normal myocardium and in infarcts. Thus, leukocytic infiltration associated with acute myocardial infarction can be detected noninvasively in vivo.


Systolic honks in young children.

Systolic honks in young children. Three children with loud systolic honks were studied noninvasively with phonocardiography and echocardiography. It was shown that the precordial honk, like the late systolic mitral murmur and the clicking apical systolic sound, is part of a continuum of auscultatory sounds that result from a defect of mitral valve support and are classified under the general heading of mitral valve prolapse syndrome. Prolapse of one or both of the mitral valve leaflets is believed to cause the characteristic auscultatory findings of click, murmur or honk. The timing of these sounds in systole varies with different physiologic or pharmacologic maneuvers. Variations in the onset of prolapse are associated with changes in left ventricular end-diastolic dimensions.


Hemodynamic benefits of atrioventricular sequential pacing after cardiac surgery. The hemodynamic effects of atrioventricular (A-V) sequential pacing were assessed and compared with those of ventricular and of atrial pacing in 10 patients with and without heart block after cardiac surgery. Ventricular pacing alone was either hemodynamically detrimental or of no benefit in six of the eight patients who initially had sinus or accelerated junctional rhythms. Atrial pacing alone produced significant improvement in cardiac output in all patients who were not pacemaker-dependent. However, five of the eight patients with intact A-V conduction had further increases in cardiac output through A-V sequential pacing at shorter than intrinsic A-V intervals. Optimal A-V intervals for maximal cardiac output could be identified in all patients and varied widely. Significant changes in cardiac output occurred with relatively small diviations in the A-V interval. In selected patients after cardiac surgery, temporary A-V sequential pacing is a workable and valuable adjunctive form of hemodynamic support and is preferable to ventricular or atrial pacing.


Exercise testing in the diagnosis of coronary heart disease: a perspective. The methods of assessing the diagnostic usefulness of exercise testing in detecting coronary obstructive disease are examined. The limitations of long-term clinical follow-up and coronary angiography as standards for the determination of disease are described as are the effects of test methodology, criteria for positivity, prevalence of disease in the study population, reliability of the standard and recognition of false positive and false negative results in determining reliability of such testing. High values were found for sensitivity and specificity for exercise testing of patients with coronary artery disease referred for consultation to medical center cardiology services. Maximal exercise testing and consideration of symptomatic and hemodynamic as well as electrocardiographic criteria for identification of myocardial ischemia are helpful in improving reliability. Diagnostic accuracy is greatly enhanced by recognition of known causes for false positive and false negative results.


Thallium-201 imaging with color display computer system in old myocardial infarction. In 13 patients with old myocardial infarction diagnosed with use of the electrocardiogram, coronary angiogram and left ventriculogram and in 11 patients without infarction, thallium-201 imaging with a color display computer system was carried out. In the group without infarction the average ratio of activities in two regions of interest within the myocardial wall, excluding the apex, was 1.14 (1.08 to 1.23). In the group with infarction the average ratio of noninfarcted to infarcted areas was 1.44 (1.23 to 1.78). Objective detection of infarction was possible in 12 patients (92 percent) in the group with infarction. In two patients, the earlier electrocardiographic pattern of infarction had resolved by the time of imaging. These results suggest that the sensitivity of thallium-201 imaging in the diagnosis of old myocardial infarction may be greatly enhanced by objective and quantitative analysis using a color display computer system.


Cardiac death in mucocutaneous lymph node syndrome. A 12 year old boy had 4 symptom-free years after hospitalization for acute febrile mucocutaneous lymph node syndrome before he died suddenly from extensive myocardial infarction. Current evidence suggests that many patients with this syndrome have coronary artery disease and that those with significant cardiac findings should be studied with coronary angiography. Serial studies are recommended because of the danger of sudden death.


Fine structure of spermatozoa of the Asiatic musk shrew, Suncus murinus. The fine structure of spermatozoa of the Asian musk shrew, Suncus murinus, has been investigated using air-dried and critical-point-dried replicas in addition to freeze-fractured specimens. Asymmetry in the structure of the head, notable the acrosome, can be recognized in critical-point-dried replicas as a slight dorsoventral convexity not apparent in air-dried specimens. Freeze-etching reveals a dense accumulation of intramembranous particles just anterior to the posterior ring, but relatively few other characteristic membrane conformations associated with the head. Gelatin smears visualized with the light microscope show a vigorous lytic response, but preliminary efforts to remove the acrosome by physiological or enzymatic incubation have thus far not been successful.


The interaction of clomiphene, estradiol, and progesterone in the control of rat uterine glycogen metabolism. Uterine glycogen accumulation was studied in ovariectomized rats treated with all combinations of clomiphene citrate (0.25 mg/kg) estradiol (1.0 micron g) and progesterone (5.0 mg). The rats were given three consecutive daily dosages and killed 24 hours after the final dosage. Based on biochemical data, either estradiol or clomiphene increased uterine glycogen concentration and total glycogen, but progesterone did not. Progesterone significantly suppressed both the estradiol and clomiphene-induced glycogen increases. Based on the histochemical results, progesterone also suppressed the estradiol and clomiphene-induced glycogen responses, but the tissue affected differed. Clomiphene markedly increased luminal epithelial glycogen whereas estradiol induced primarily myometrial glycogenesis. Progesterone completely suppressed the clomiphene-induced epithelial effect and partially suppressed the estradiol-induced myometrial effect. Clomiphene also suppressed the estradiol-induced myometrial response. The results indicate that progesterone does have a significant interaction with clomiphene in the control of uterine morphology and biochemistry. The results also stress the importance of correlated histochemical and biochemical studies in the study of clomiphene-induced uterine glycognesis.


The comparative fine structure of the interhemal membrane of chorioallantoic placentas from six genera of myomorph rodents. In order to extend the cytological information available on the structure of the interhemal membrane in cricetid rodents, in particular, and myomorph rodents, in general, we have examined the fine structure of the placental labyrinth in five genera of cricetid rodents (Lemmus, Dicrostonyx, Clethrionomys, Microtus and Peromyscus) and one genus of murid rodent (Acomys). Small pieces of labyrinth from near-term placentas were fixed in glutaraldehyde and osmium tetroxide and processed for electron microscopy. The interhemal membranes of all the species examined were hemotrichorial. The outermost layer of trophoblast, bordering the maternal blood spaces, was cellular and often contained some patent fenestrae, whereas the middle and linner trophoblastic layers were apparently syncytial. The outermost trophoblastic layer of all the species contained abundant granular endoplasmic reticulum. The intercellular space between the outer and middle layers was variable in width, primarily due to the complex folding of the surface of the middle layer. The surfaces of the middle and inner layers were closely apposed. The middle trophoblastic layer in several species contained filamentous "glomerular bodies" and the innermost layer, particularly of Peromyscus, contained smooth membranous whorls. A basal lamina separated the innermost trophoblastic layer from the fetal capillary endothelium. The endothelial cells in most of the species contained fenestrated regions. These observations are compared to those on other hemochorial placentas, and common features of cricetid (and myomorph) rodent placental find structure are emphasized.


Regeneration of tooth development in vitro following sodium fluoride treatment. Mandibular incisors were dissected from the jaw of 15- and 16-day C57BL/10 mouse embryos and cultured on agar-solidified Eagle's basal medium supplemented with fetal calf serum, an antibiotic, and glutamine, The experimental medium was the same as the control except that fluoride was added such that the final concentrations ranged from 2.0-8.0 mM NaF. Control and experimental explants were recovered after two, four and six days of incubation and studied histologically. After two days of fluoride treatment (3.0 mM NaF), cellular degeneration was observed in the dental papilla mesenchyme while the enamel organ epithelium appeared more resistant. Prolonged treatment or treatment at higher concentrations resulted in destruction of the dental papilla. The enamel organ was still present but was abnormal and reduced. Older tooth germs were less affected overal when incubated at the same fluoride dosage and time of treatment. When explants subjected to limited exposure (2 days) to fluoride were placed on control medium, the suppressed tooth germs recovered. The recovery was enhanced by grafting untreated mesenchyme to the treated explants followed by incubation on control medium. The observations indicate that NaF can suppress the development of tooth germs in vitro and that recovery from the suppresion does occur. The more severe inhibition observed in the mesenchymal component when compared to the response of the epithelial component of the treated explants suggests that fluoride may alter the ultimate morphology of the tooth crown by disrupting the normal epithelial-mesenchymal interaction which occurs during early tooth development.


Observation on the morphological heterogeneity of WI-38 cells. WI-38 cells of intermediate and late-passage cultures were examined by light microscopy, scanning, conventional transmission and high voltage electron microscopy for evidence of heterogeneity among the cells within a single culture. Two morphologically distinct cell sizes and shapes were noted in all passages, (1) a typical fibroblastic type, and (2) a much larger, non-fusiform type. The larger cells generally had a nucleus that was positioned to one side of the bulk of the cytoplasm. The smaller was consistently fusiform with a centrally placed nucleus. The surfaces of intermediate-passage cells were uniform in showing small microvilli and corticall pits but were otherwise smooth and with out distinctive featues. The late-passage cells, on the other band, were consistent in showing numerous blebs and marginal ruffing. The internal structure of these cells in all passages studied was complicated by many age-related changes. The observations indicate that there is in WI-38 cells a high degree of intraculture heterogeneity. An awareness of this is important in studies which characterize the biochemical properties of this cell strain.


Pathogenesis of osteopetrosis in the microphthalmic mouse: reduced bone resorption. Bone resorption, stimulated by injection of parathyroid extract, was measured in vivo in microphthalmic mice as the rate of release of 3H from bone after incorporation of 3H-proline. Bone resorption in these mice, which inherit osteopetrosis, was less than 10% of the in normal litermates. Autoradiography confirmed the reduction in removal of radioactive bone matrix and in bone growth in microphthalmic mice. The ability of these mice to raise the serum calcium concentration in response to PTE was also reduced. These results, that bone resorption is reduced in microphthalmic mice, are discussed in relation to the pathogenesis and cure of the disease.


The fenestrated collar of mammalian cardiac sarcoplasmic reticulum: a freeze-fracture study. Freeze-fracture studies of papillary muscles from cat, rabbit and dog reveal the presence of a fenestrated collar of the sarcoplasmic reticulum (SR) in the region of the M band. This membrane specialization is structurally similar to that observed previously in skeletal muscle. This report includes mammalian cardiac muscle on the list of those muscles containing this SR membrane structure.


Ultrastructural identification of the Sertoli cell in the testis of the northern pike, Esox lucius. Identification of the intralobular Sertoli cell in the testis of Esox lucius is based upon residual body phagocytosis. Formerly, this lipid-containing cell type was refereed to as the "lobule boundary cell" and erroneously believed to be homologous to the interstitial Leydig cell.