Effects on the child of alcohol abuse during pregnancy. Retrospective and prospective studies.

Retrospective and prospective investigations of children to alcoholic women gave an incidence of fetal alcohol lesion of one per 300 deliveries of whom half had the complete fetal alcohol syndrome. Perinatal and infant mortalities were increased seven to tenfold and low birth weight (less than or equal to 2 500 g), preterm deliveries (less than 37 weeks) and smallness for gestational age (less than -2 S.D.) were increased eightfold, threefold and twelvefold, respectively. Small size at birth correlated with reduced mental performance later in life, 58% had IQ below 85 and 19% below 70.8% had cerebral palsy. The incidence of cerebral palsy associated with maternal inebriety was 1/5 000 deliveries, i.e. every sixth case of cerebral palsy. Tracing of alcoholic women during pregnancy and treatment gave favourable effect on intrauterine growth when sobriety could be induced early in pregnancy but could not protect from functional brain disturbance measured by neurological performance and be evoked response electroencephalography. Damage to the fetus by alcohol is now the largest known health hazard by a noxious agent that is preventable.


Breast feeding trends and recent information activities in Sweden.

The breast feeding rate has been declining steadily in Sweden since the 1930's up to the early 1970's. It is suggested that this was linked to the changing role of women, the development towards the nuclear family, the changing way of living, the influence of strict routines at the maternities and many other factors. A Committee was appointed in 1973 by the National Board of Health and Welfare, which initiated a number of breast feeding promoting activities: the editing of a Manual for health personnel, and booklets for mothers, the systematic arranging of workshops for key personnel in each county, stimulation to more flexible and breast feeding favouring maternity routines, backing of working groups of La Leche League-type, etc. Coinciding with these activities and probably a result of changed breast feeding attitudes among mothers, the breast feeding rate has increased considerably--at 2 months from an all time low of 31% in 1972 to 62% in 1976/77, and at 6 months from 6% to 20%.


Collaboration in practice. Experiences from a multidisciplinary research project on child abuse and neglect.

This paper describes experiences from a three-year research project concerning questions of child abuse and neglect. The emphasis is placed on an attempt to define the real difficulties that have arisen during the course of this work, e.g. group pressure, breaks in continuity, goal heterogeneity, role conflicts and differences in frames of reference. Collaboration problems must be taken seriously and deserve systematic investigation. Multidisciplinary collaboration in different connections within medical, health and social care is of particular importance at this time when the care resources are limited. At the same time it is of decisive importance that the members of the team clarify their attitudes towards certain fundamental questions.


Perinatal mortality in Sweden. Analyses with international aspects.

The perinatal mortality in Sweden has been decreasing during the last four decades. From available vital statistics in 1976 Sweden's figures are the lowest internationally. The decline continues and in 1978 the figure was as low as 10.0 per thousand. The five-year period 1973--1977 has been specially analysed using medical birth records from all births. Data from an international perinatal study in 1973 coordinated by WHO have been treated in the same way. With birth weight (BW) specific mortality rates in groups of 250 g it is shown that late fetal deaths (LFD) are related to BW only for high BW and that early neonatal deaths (END) are inversly related to BW. There is no sex difference in LFD but a marked male dominance in END, with one third higher rate for the boys. BW specific mortality rates in BW groups of 250 g, separated in LFD and END can be used as a tool for evaluating the quality of perinatal care. The influence oof factors related to patterns and standards of living is emphasized. It is suggested that perinatal mortality should be given in its two components separately late fetal death rates (LFD) and early neonatal death rates (END).


Analysis of perinatal mortality rate in the Stockholm area.

During the period 1973--1976, a significant decrease in perinatal mortality from 14.2 to 10.4/10 newborns occurred in Sweden. In the Stockholm area, the mean perinatal mortality during the same period varied significantly between the different maternity hospitals, even when pre-term and high risk pregnancies were excluded from the comparison. The majority of hospitals with fewer deliveries and without pediatric wards had a perinatal mortality above the mean. Some explanations of these differences were also looked for in differences between the total population of the referral area of each maternity hospital. In the referral areas of the hospitals with a perinatal mortality above the mean, there were higher percentages of low-income households and over-crowded dwellings and fewer professional people than in the other area. The results suggest a need for analysis of individually-based data to find etiological factors which account for differences in perinatal mortality.


Perinatal mortality among children of immigrant mothers in Sweden.

The perinatal mortality among the infants of foreign and Swedish mothers was studied with the help of the data submitted to the medical birth register in 1973--1976. Unexpectedly, the perinatal mortality was slightly lower among the infants of the immigrant mothers. This difference could not be explained by differences in the distribution by age or parity of the mothers or by the length of gestation of the infants. A conceivable explanation is that the foreign mothers constituted a favorably selected group.


Paediatric services within the primary health care system in suburban areas.

Results from a few studies on community paediatrics in suburbs of Stockholm are presented. Pattern of diagnoses, utilization of care and social and psychological team work are discussed. Goals of the paediatric service in the primary care are set up and a distribution of duties between different professionals is suggested.


Case report of a Swedish school health clinic.

The work in the school health services, which, according to regulations, should be only preventive, has developed into a mixture of preventive and curative care with strong features of social paediatrics and treatment of minor complaints. Together, the nurse and the physician make an important contribution to pupil welfare in school, providing a sense of security for children, teachers and parents. On the other hand, it is evident that the resources are not used optimally. Too much time and effort are spent on routine class examinations, which yield very little benefit, while other important tasks are neglected, e.g. co-ordination of treatment and education of chronically ill or handicapped children and health education of children and teachers. This study reports the health problems that a physician and nurse encounter during one year in their daily work at a medium sized school in a medium sized city in Sweden.


Dealing with suspicions of malformation frequency increase. Experience with the Swedish register of congenital malformations.

Strategies in dealing with data obtained from malformation monitoring based on experiences with the Swedish monitoring systems, operating since 1965 (Register of Congenital Malformations) and 1973 (Medical Birth Register) are discussed. The importance of checking data that have sounded an alarm is stressed. Experience has shown that false alarms due to artefacts, such as changed diagnostic routines, changed reporting or registration of malformations, or random fluctuations, comprise most suspected changes in incidence. If a true increase in malformation frequency or a local cluster is observed, a hint of possible aetiological factors can be obtained from studies of maternal age distribution, seasonal viriation, geographical distribution, etc. The last step of the analysis consists of a case-control or a cohort study, aimed at revealing a specific teratogen. The importance of locating limited research resources to well-defined problems using high quality data is stressed.


Mentally retarded children and young people in Sweden. Integration into society: the progress in the last decade.

The services for the mentally retarded follow the principle of normalization, with integration as the most important means towards achieving this goal. A total of 0.44% of the population are mentally retarded. This number is decreasing. Only 23% of these are midly mentally retarded. The number living in different forms of institutions, is given by age and grade of retardation as well as the number of integrated school classes, and the changes in these respects since 1970 are described.


Social adaptation in juvenile diabetes.

A sample of 36 juvenile diabetics, age 19--28 years, and with a duration of diabetes of 14--17 years were interviewed with regard to their social adaptation. Five patients could not be traced and six patients did not want to participate. Educational and professional careers were normal. However, none had received individual diabetes-oriented vocational guidance. A majority of patients was unsatisfied with the information given at the diabetic clinics, and a negative attitude towards society and its institutions was common. Patients often felt that as children they had been neglected by the diabetic team, while their parents received all information. It is concluded that diabetic children and adolescents require continuous socio-psychological support, that psychologists and/or social workers should be permanent members of the diabetic teams, and that paediatricians should follow diabetic patients until they are fully grown up.


Prevention of childhood accidents in Sweden. With special attention to the Work of the Joint Committee for Prevention of Accidents.

In the industrialized countries accidents constitute one of the greatest threats to children and Sweden was no exception to this. A joint committee was thus formed in 1954 to co-ordinate preventive work. Official bodies for health and education, safety organizations, some professional groups and voluntary organizations, were members of the Committee from the beginning. The Committee's role has been to stimulate investigations and research in safety, to work for a safer environment through planning and safety regulations and to provide information to parents and other key-groups. An important part of the preventive effort has been research, which has emphasized the seriousness of the problem and provided a basis for sefety work and subsequent information. Information has been channeled through the mass media as well as child welfare centres, schools and local groups which have become involved in safety matters. In order to make the environment safer the Swedish Board for Consumer Policy has a programme to test household equipment. The National Board of Urban Planning has drawn up regulations for the design of homes and their immediate surrounding. There seems to be a better understanding today of this important health problem. A tendency toward a lower number of fatal accidents can also be seen through the last few decades.


Accidental poisoning in pre-school children in the Stockholm area. Medical, psychosocial and preventive aspects.

Accidental poisoning in pre-school children requiring hospital admission has increased sixfold from 1955 to 1975 in the Stockholm area. The mortality from this accident has decreased from 0.5 to less than 0.1 per 100 000 pre-school children in the whole of Sweden during the same period. Medical and psychosocial background factors were investigated in 104 consecutive in-patients (0--6 years old) with accidental poisoning and compared to an out-patient group, a group of patients who only had called the poison control centre, and a matched control group from Child Health Centres. There were no difference between the groups regarding health and history of earlier accidents except that 20--25% of the families of the poisoned children and 7% of the control families had called the Poison Control Centre before. Change of residence during the last 6 months was much commoner among families of poisoned children than of nonpoisoned. Other social stress factors were more common among in-patients than out-patients. The measures taken by the parents to combat the poisoning were adequate in most cases. The decrease in mortality inspite of the increase in potentially dangerous accidental poisonings may be attributed to a good knowledge among parents about adequate measures and where to seek advice resulting in early treatment, and to intensive care and antidote therapy.


Studies on vagal activation of gastric acid secretion in man.

Vagal activation produces a gastric acid secretory response by direct nervous stimulation of the parietal cell area and, at least in dogs, by gastrin released mainly from the antrum. In duodenal ulcer (DU) patients antrectomy reduces the acid response to sham feeding slightly more than the maximal acid output in response to pentagastrin, indicating that an antral factor contributes to the acid secretion induced by sham feeding. The marked acid response to sham feeding in antrectomized patients suggests that the direct nervous stimulation of the acid-secreting glands is the predominating stimulus in the vagal activation of acid secretion in man. In the present study vagal activation has been induced by adequate and modified sham feeding and insulin hypoglycemia in DU patients and healthy subjects. The acid response to adequate and modified sham feeding amounted to about 50% of the peak acid output in response to pentagastrin and corresponded to the acid response to an insulin dose of 0.1 U/kg b.w. Modified sham feeding seems to be a simple method of inducing physiological vagal activation of acid secretion. Sham feeding for 15 min increased only insignificantly the plasma concentrations of total gastrin immunoreactivity or heptadecapeptide gastrin. Prolonged sham feeding during intragastric neutralization or sham feeding after proximal gastric vagotomy did not significantly increase the plasma gastrin concentrations. Sham feeding is obviously a poor stimulus for release of gastrin in man. Either release effect of very small amounts of gastrin-17 or release of non-established gastrins may explain the biological effect of an antral factor. Pretreatment with benzilonium, an anticholinergic drug with minimal cerebral actions, increased the gastrin concentration after sham feeding in about half the experiments. This heterogeneous effect supports a non-cholinergic vagal release of gastrin and a cholinergic inhibition of gastrin release but also indicates a complex interaction at the level of the gastrin cells during vagal activation. Evidence for an inhibitory vagogastrone mechanism in DU patients has been found but its effect is weak and transient. Proximal gastric vagotomy abolished the acid responses to both insulin hypoglycemia and sham feeding, in accordance with the view that the direct nervous excitation of the acid-secreting glands is the predominating stimulus in the vagal activation of gastric acid secretion in man. Atropine in low doses or benzilonium inhibited the acid response to sham feeding by only 65%. This finding suggests that the direct vagal excitation of the acid-secreting glands is mediated only partially by cholinergic neurotransmission. Gastric acidification inhibited the gastric acid secretory response to insulin hypoglycemia both in healthy subjects and in DU patients. The inhibitory effect was significantly less in DU patients, however, supporting the concept of a defective inhibition by antral acidification in DU patients.


Kallikrein system during treatment of hematological malignancies.

Factors of the plasma kallikrein system have been evaluated following the course of 48 patients with hematological malignancies which consisted of 15 cases of AML, 6 cases of myeloproliferative disorders, 14 of lymphoproliferative disorders, 8 of multiple myeloma and 5 of bone marrow carcinomatoses. Normal range of spontaneous activity was 11.4 +/- 3.0 micronM/ml TAMe hydrolyzed, kallikreinogen was 115.8 +/- 26.2 micronM/ml.h and enzyme inhibitor was 1.02 +/- 0.37 unit. Lower kallikreinogen level of the range was from 77.2 to 93.1; higher spontaneous activity, 8.4 to 18.0 and lower enzyme inhibitor activity of 0.46 to 0.92 was seen before treatment. Kallikreinogen increased up to the range of 95.6 to 120.1 at complete remission and decreased down to 63.1 - 76.5 prior to death. The causes of the change in these factors were discussed.


Influence on thromboxane and malondialdehyde synthesis in human thrombocytes by various inhibitors of platelet function.

The effects of various inhibitors of platelet function have been compared with respect to the minimal effective concentration required to inhibit platelet aggregation and the thromboxane (TXA2) and malondialdehyde (MDA) synthesis in washed platelets. The potencies of the agents in the different platelet function tests showed no consistent correlation. The most striking difference was found between the prostaglandins and the adenine nucleotides. The prostaglandins PGE1 and PGI2 inhibited all platelet reactions (10(-7) - 10(-8) g/ml) which may be explained by their stimulation of adenylcyclase. In contrast, the adenine nucleotides adenosine and AMP which are supposed to raise cAMP platelets via the same mechanism and strongly inhibited primary and secondary platelet aggregation (3 x 10(-6) - 3 x 10(-7) g/ml) had no effect on TXA2 and MDA synthesis. The results suggest that the pharmacological inhibition of platelet function may not act via a uniform mechanism controlled by the arachidonate pathway.


Arachidonic acid induced mortality in animals - an appropriate model for the evaluation of antithrombotic drugs?

Sodium arachidonate (1.1 mg/kg b.w.) was injected into a marginal ear vein of rabbits according to SILVER M.J. et al. (1). 94% of the animals died within a few minutes. We investigated to what extent these lethal effects of arachidonic acid (possibly caused by embolizing platelet thrombi) can be prevented by potential antithrombotic drugs. As indicated in the tables the animals are protected by some compounds, especially the nonsteroidal anti-inflammatory agents, in a dose-dependent manner. However, the results of this in vivo model showed no correlation with the potency of the drugs for inhibiting platelet aggregation and inhibition of experimental thrombosis. It is therefore reasonable to assume that the drug effects in this model reflect an overall inhibition of prostaglandins including thromboxanes.


Mechanism of glucocorticoid-induced inhibition of prostaglandin synthesis.

In order to study the mechanism of steroid-induced inhibition of prostaglandin (PG) secretion, we have used rat renomedullary interstitial cells grown in tissue culture as an in vitro model. These cells have been shown by radio-immunoassay to produce high amounts of prostaglandins, mainly PGE2 and PGF2 alpha. Using (3H) dexamethasone, we have demonstrated in our cultures the existence of glucocorticoid binding sites which exhibit all the characteristics of physiological glucocorticoid receptors. Comparison between the biological activity (i.e. the ability to inhibit PG secretion) of the various steroids tested (dexamethasone, corticosterone, aldosterone, progesterone and estradiol) and their affinities for the glucocorticoid binding sites reveals a striking correlation between these two parameters. Steroids which bind to the receptors also inhibit prostaglandin secretion whereas testosterone and estradiol, which have a very weak affinity for the glucocorticoid binding sites do not inhibit PG secretion. In addition, actinomycin D (0.1 microgram/ml) and cycloheximide (0.1 microgram/ml) are able to abolish the inhibitory effect of dexamethasone on PG secretion. Our results indicate that the action of corticosteroids on prostaglandin secretion, which is believed to be the basis of their anti-inflammatory properties, is mediated through receptor occupancy and requires RNA and protein synthesis.


Nonspecific esterases in leukemic blasts. Characterization by isoelectric focusing in polyacrylamide gel.

Using high-resolution technics of isoelectric focusing in polyacrylamide gel, isoenzymatic components of nonspecific esterases extracted from various cytologic types of leukemic blasts were visualized using alpha-naphthyl acetate and alpha-naphthyl butyrate as substrates. For each cytologic type of leukemic blast, consistent and distinctive patterns of nonspecific esterase activity were visualized. These studies provide further evidence for heterogeneity of nonspecific esterases, and for elaboration of isoenzymatic components as a reflection of cellular differentiation.


Childhood leukemia-lymphoma. Heterogeneity of phenotypes and prognoses.

Results are reported on 724 children and adolescents with acute leukemia-lymphoma. One hundred patients had immunologic marker analysis that defined the major phenotypic groups, i.e., T-cell, B-cell (Burkitt), myeloid, and the most frequent form, non-T, non-T "common" or "undifferentiated" acute leukemia. Pre-T, pre-B, and "null" leukemias are included in the latter group. Response to therapy and survival was best in non-T, non-B acute lymphocytic leukemia, intermediate in T-cell disease, and worst in B-cell (Burkitt) disease. Additional factors resulting in decreased survival include elevated peripheral leukocyte count, presence of enlarged nodes, less depression of hemoglobin and platelets, and age greater than 7 years (all associated with 'lymphomatous" disease). Other factors resulting in decreased survival include age under 3 years and depression of serum immunoglobulins. Definition of the heterogeneity of childhood leukemia-lymphoma dictates differing forms of therapy for the various types of these diseases.


Reversible respiratory failure due to intravascular leukostasis in chronic myelogenous leukemia. Relationship of oxygen transfer to leukocyte count.

In a 49 year old man with blast crisis and massive leukocytosis due to chronic myelogenous leukemia, severe hypoxic respiratory failure developed despite a normal chest film. Correction of hypoxemia was observed after reduction of the white blood cell count by hydroxy-urea therapy. A similar episode occurred prior to death, and necropsy examination revealed extensive plugging of the pulmonary vasculature by leukemic blast cells but no infection or pulmonary edema. An inverse linear correlation was demonstrated between the peripheral white blood cell count and the efficiency of oxygen transfer in the lung as determined by the arterial to alveolar oxygen tension ratio. We postulate that mechanical obstruction and/or leukocyte mediated capillary endothelial injury caused the severe leukocyte mediated capillary endothelial injury caused the severe hypoxemia. Abnormalities of pulmonary gas exchange may be common in leukemic patients with markedly increased leukocyte counts.


Spontaneous remission in acute myelogenous leukemia in the adult.

A spontaneous complete remission of 17 months duration was observed in a patient with acute myelogenous leukemia. Resolution of all clinical and morphologic abnormalities occurred. The remission was apparently associated with an acute pulmonary infection. At relapse, remission induction was accomplished with cystosine arabinoside and daunorubicin therapy. In vitro granulocyte-macrophage agar culture studies (CFU-c) showed an abnormal growth pattern at presentation, which persisted during the period of spontaneous remission. Reports of spontaneous remissions of acute myelogenous leukemia in adults have become increasingly rare, and the remissions themselves are short-lived. Despite the association between spontaneous remissions and acute infections or febrile episodes, attempts at remission induction with infectious agents have been unsuccessful. Spontaneous remissions are an uncommon variant of the natural course of acute myelogenous leukemia in the adult.


Computed tomography: a three-dimensional study of the nasal airway.

1. Accurate volume measurement of the nasal airway based upon computed tomography images sequentially generated along the length of the airway is possible. 2. The cross-sectional area of the airway at any position along its length can be determined. 3. The most constricted part of the airway is not necessarily at the location of the turbinates. 4. Details of hard- and soft-tissue anatomy not otherwise discernible can be detected with computed tomography imaging.


Single arch extraction--upper first molars or what to do when nonextraction treatment fails.

The logical goal of treatment must be to correct a malocclusion to the nearest possible approach in all respects to a normal condition as we understand it. When extraction within the upper arch only is the desired treatment plan, removal of two upper first molars will produce the closest approach to normalcy in terms of the dentition's function, its health, its influence on facial features, and its appearance. With the removal of upper first molars for treatment purposes, the result will be a dentition that has all the magnificent appearance of a dentition that never had any extractions at all. It will be a dentition that can have good functional movements at the end of treatment and on into the posttreatment period.


An electromyographic and roentgen cephalometric study of occlusal morphofunctional disharmony in children.

In a sample of children with dual bite and symptoms in the masticatory system, the activity of the anterior temporal and masseter muscles was studied electromyographically during clench and light tapping in the posterior occlusal contact position and centric occlusion and in protrusive bite on the incisors. The findings indicated that the optimal muscle function during maximal clench and tapping with displayed in the posterior occlusal contact position, which in the present subjects was situated, on the average, 0.5 to 1 mm. anterior to the centric jaw relation. It should therefore be recommended that, in orthodontic treatment of children with dual bite, the intercuspal position (centric occlusion) should be established in the posterior occlusal relationship. This is in accordance with the opinion of several authors who have emphasized the use of the retruded contact position (the centric jaw relation) as key reference position in orthodontic treatment and occlusal rehabilitation. These authors have further emphasized the importance of stable occlusal contacts in centric relation, centric occlusion, and the various jaw excursions in obtaining and maintaining a harmonious function between the dentition, the temporomandibular joints, and the neuromuscular system.


Treatment of class II malocclusions by jumping the bite with the Herbst appliance. A cephalometric investigation.

The purpose of this study was to investigate the effect of continuous bite jumping with the Herbst appliance on the occlusion and craniofacial growth. The material consisted of twenty growing boys with Class II, Division 1 malocclusion. Ten of the boys were treated with the Herbst appliance for 6 months. The other ten boys served as a control group. Dental casts, profile roentgenograms, and TMJ radiographs were analyzed before and after 6 months of examination. The following treatment results were found: 1. Normal occlusal conditions occurred in all patients. 2. Maxillary growth may have been inhibited or redirected. The SNA angle was reduced slightly. 3. Mandibular growth was greater than average. The SNB angle increased. 4. Mandibular length increased, probably because of condylar growth stimulation. 5. Lower facial height increased. The mandibular plane angle, however, remained unchanged. 6. The convexity of the soft- and hard-tissue profile was somewhat reduced.


Surgical closure of diastema of central incisors.

In spite of the success and excellent results orthodontists have had in correcting dental abnormalities, one particular area which lends itself to relapse is the diastema between the incisors. The surgical correction of a diastema has been successfully accomplished without orthodontic treatment in patients interested in a rapid correction. The correction of functional problems was not a part of this treatment. Rapid correction is usually sought by adults who are self-conscious about their appearance and are unable to have corrections done for various personal reasons.


[A newly developed ventilator driven by a microprocessor (author's transl)].

The A4/6 is a newly developed ventilator, which may be used in the operating theatre or in the intensive care unit. The machine is electronically driven (microprocessor) and is characterised by a highly sensitive triggering mechanism. It is designed for the ventilation of the newborn (including premature infants) and children up to approximately 5 years. The significant and important features of its control design including its triggering mechanism will be described.


Pseudochloroma: extramedullary hematopoietic nodules in chronic myelogenous leukemia.

Five patients with chronic myelogenous leukemia had multiple hemorrhagic soft tissue lesions at the time of diagnosis. Histologic examination of tissue removed by biopsy and at autopsy revealed extramedullary hematopoietic nodules with associated hemorrhage and necrosis. No evidence of either blastic transformation or systemic bleeding diathesis was found. Pseudochloroma is a treatable although potentially fatal complication of uncontrolled chronic myelogenous leukemia and should not be confused with myeloblastomas occurring with blastic transformation. Early recognition of the syndrome, prompt treatment with intensive chemotherapy, and radiation therapy of intracranial lesions seem to provide effective control of this complication and reversion to a status that is responsive to conventional treatment of chronic myelogenous leukemia.


Cell surface coat of hamster fibroblasts.

The UHF fraction from NIL 8 hamster embryo fibroblasts contains the LETS protein and several other major proteins. It exhibits three enzymatic activities in significant amounts: 5'-nucleotidase, alkaline phosphatase, and galactosyl transferase. The latter two appear to be different from the membrane-bound enzymes. This fraction is heavily stained with ruthenium red, a dye specific for the cell coat in intact cells. A comparable fraction from hamster sarcoma virus-transformed cells exhibits a similar overall protein composition but lacks at least three major proteins, including the LETS protein. Compared to NIL 8 cells, the distribution of alkaline phosphatase in fractions from these cells is different, and the level of galactosyl transferase in the UHF is much reduced.


Identification and characterization of normal and malignant human blood leukocytes by surface glycoprotein patterns.

We have labeled surface glycoproteins of normal and malignant human blood leukocytes by the galactose oxidase-NaB3H4 and periodate-NaB3H4 labeling techniques. The labeled glycoproteins were separated by slab gel electrophoresis in the presence of sodium dodecyl sulfate and visualized by fluorography. The different types of normal blood cells could be distinguished by their surface glycoprotein patterns. The surface glycoproteins of cells from patients with acute lymphoblastic, myeloid, or monoblastic leukemia were different from those of normal cells. The leukemic cells could be classified by their surface glycoprotein patterns with respect to their relationships to normal blood cells, and an estimation of their degree of differentiation was obtained.


Transformation-sensitive cell surface protein: isolation, characterization, and role in cellular morphology and adhesion.

Cell surface protein is the major cell surface glycoprotein of chick embryo fibroblasts. We have isolated and purified this glycoprotein and find that it is an adhesive protein that increases cell-cell and cell-substratum adhesiveness in a variety cellular adhesion assays. Transformation of chick fibroblasts results in decreased quantities of CSP due primarily to a fivefold reduction in CSP biosynthesis, although increased proteolytic degradation and shedding from the cell surface also contribute. The decreased biosynthesis is apparently due to a fivefold reduction in translatable mRNA for CSP. Reconstitution of isolated purified CSP on 14 transformed cell lines from several species results in reversion to a more normal fibroblastic morphology, adhesiveness, cell surface architecture, microfilament bundle organization, motility,  and alignment at confluence. Cell surface protein does not restore growth control. The effects of CSP appear to be due to at least two actions, increased cell-substratum adhesion plus altered cell-cell interactions. Untransformed chick cells treated with affinity-purified antibodies to CSP develop the rounded morphology characteristic of many transformed cells that are deficient in CSP (LETS protein). Cell surface protein is found primarily in fibrillar aggregates on the cell surface. These CSP fibrils are relatively immobile and do not affect the mobility of other cell surface components. However, CSP can be eventually redistributed to caplike structures with anti-CSP. Isolated CSP consists of highly asymmetric disulfide-linked dimers and multimers. The interchain disulfide bridges are confined to a short terminal fragment that is readily removed by trypsin. Cell surface protein and cold-insoluble globulin have similar compositions but differ in solubility and amino termini. Cell surface protein contains primarily asparagine-linked oligosaccharides that appear to be responsible for CSP's concanavalin A receptor activity. Inhibition of CSP's glycosylation by treatment with tunicamycin results in decreased CSP due to marked increases in its degradation rate, without inhibition of synthesis or secretion. Studies of this major cell surface glycoprotein have provided insight into the biochemical mechanisms of cellular adhesion, morphology, and social interaction and provide an approach to analyze the dynamics and regulation of protein synthesis, glycosylation, secretion, and turnover.


Are lobster fibrinogen and cold-insoluble globulin related molecules?

Several of the molecular properties of lobster fibrinogen and CIg have been compared. There are some significant similarities between these two proteins; however, to date, no direct experiments have demonstrated molecular homologies. Studies involving cyanogen bromide mapping, additional immunologic probing, and modifications of cell morphology effected by lobster fibrinogen are currently in progress. It is anticipated that these and other experimental approaches will provide direct evidence to answer the question, posed by the title of this paper.


Fibronectin and the pericellular matrix of normal and transformed adherent cells.

Fibronectin is a major glycoprotein component of normal fibroblasts in culture. External fibronectin is predominantly present in a pericellular fibrillar matrix that mediates distant cell-cell and cell-substratum contacts. A small proportion of external fibronectin is closely associated with the plasma membrane. In the matrix, fibronectin is partially disulfide bonded into complexes. Plasma transglutaminase, activated by thrombin, also cross-links external fibronectin into high-molecular-weight covalent complexes. In cultures of normal fibroblasts, pericellular matrix fibronectin displays extensive codistribution with (pro)collagens types I and III. Transformed adherent cells show decreased formation of the fibronectin-collagen matrix. The deficient synthesis of fibronectin and other matrix components and abnormal interactions with the matrix may account for several phenotypic characteristics of transformed cells. The pericellular matrix structure has been prepared by use of deoxycholate and hypotonic medium to solubilize the cells. The matrix contains glycosaminoglycans, procollagens, and fibronectin. The fibronectin codistributes with the procollagens. The matrix may be considered to be an in vitro equivalent of the connective tissue matrix and basal laminae found in vivo. Human sarcoma cells spread rapidly on the prepared matrix and assume an elongated morphology characteristic of normal fibroblasts. The prepared matrix may provide a general tool to study the effects of matrix on cellular behavior and differentiation.


Distribution of cold-insoluble globulin in plasma and tissues.

Cold-insoluble globulin is normally present in plasma and serum at concentrations of 27.52 +/- 4.60 and 23.46 +/- 5.18 mg/dl, respectively (means +/- SD). The concentration of CIg in blood samples was significantly decreased in DIC syndromes (14.69 +/- 6.55 mg/dl; p less than 0.001). A strong, positive correlation was found with AT-III (r = 0.68) and a less striking one with Plg. Although alpha 2-PI was shown to be significantly decreased in DIC syndromes (p less than 0.001), a weak, inverse correlation was found between CIg and alpha 2-PI (r = -0.29). Immunologically cross-reactive substances were found to be widely distributed in association with the cells and tissues of mesenchymal origin, including fibroblasts, adipose cells, smooth muscle cells, and basement membranes. The glomerular basement membrane was an exception and is currently believed to be of different origin. In the kidney, fluorescence was found in the mesangium. Cold-insoluble globulin is also present as a component of cryofibrinogen that forms a solid gel at low temperatures. Sodium dodecyl sulfate polyacrylamide gel electrophoresis revealed that CIg in this fraction was rather homogeneous. Although closely migrating doublets were occasionally seen in the 440,000-dalton region on gels of unreduced samples, monomeric derivatives with a molecular weight of 220,000 or less, which have been claimed to occur in circulating plasma, were not observed. Thus, intact dimeric CIg appears to be the form of the molecule that complexes with fibrinogen. Cold-insoluble globulin is the fraction that was shown to exist as an independent entity from fibrinogen at an ambient temperature by immunoelectrophoresis and ultracentrifugation. However, very rapid formation of highly polymerized complexes in the sol phase at low temperatures was manifested by the finding of a sharp increase in light-scattering intensity using the technique of quasielastic light scattering. A control study on a mixture of normal CIg and fibrinogen disclosed no appreciable change in the temperature range between 37 and 8.5 degrees C. A comparative study on a mixture of cryofibrinogen-derived CIg and normal fibrinogen revealed an intermediate light-scattering pattern. After 2 hr at 8 degrees C, this mixture reached a state of equilibrium, where no further polymerization occurred. The secondary structures of normal and cryofibrinogen-derived CIg, determined by circular dichroism, showed no appreciable difference. A noteworthy finding was the almost complete absence of alpha-helices and a relatively high proportion of beta-structure in both forms of CIg. Amino termini of the fibrinogen moiety of cryofibrinogen were found to consist of alanine, tyrosine, and a small quantity of aspartic acid, consistent with the NH2 terminal moiety composition of normal fibrinogen but not of soluble fibrin monomer complex.


Electromyographic abnormalities in osteosarcoma arising in Paget disease of the vertebral column.

The case of a patient with low back pain and Paget disease of the L5, S1 vertebrae is presented. Electromyography revealed dysfunction in both the paraspinal and gluteal muscles. Postmortem examination showed sarcomatous transformation of the vertebrae with nerve root compression and skeletal muscle infiltration by tumor. The electromyographic abnormalities are correlated with the pathologic findings. The clinical features of neurologic dysfunction in Paget disease of the vertebral column and in osteosarcoma arising in Paget disease of the vertebral column are reviewed. Electromyography can provide valuable information in the evaluation of the patient with Paget disease of the vertebral column who is suspected of having neurologic dysfunction.


Fusion of a third molar to a supernumerary tooth with an associated dentigerous cyst.

During a routine oral examination of a 19 year-old Black male, a bony impaction of his mandibular left third molar fused to an inverted supernumerary tooth with a cystic cavity was found. Histologic examination confirmed the presence of a dentigerous cyst.


55 Nitinol wire: force developed as a function of "elastic memory".

Closing spaces is done either by translation of the edgewise brackets over an archwire or by the use of closing loops of some common design. This investigation suggests the concept of the further refinement of the "wire rubber band" as a means of closing spaces. Advantages of such a wire hypothetically would be to level the dentition, align the dentition, and condense spaces in the dentition with only one or two stretched nickel titanium wires having the proper temperature transition range (TTR). The temperature of the mouth would make such wires return to their original prestretched length. A correctly-sized wire would have sufficient stiffness at mouth temperature, and it would be kept at or above its TTR. The system eliminates friction from edgewise bracket translation and also the use of many auxiliary closing devices as well as reducing the number of archwire changes, thus saving chairside time.


Suppression of phytohemagglutinin response by fungi from a "leukemia" house.

Fungal isolates from the house of a husband and wife who both developed acute myelomonocytic leukemia were assayed for effects on the in vivo response to phytohemagglutinin in guinea pigs. Skin responses to intradermal phytohemagglutinin were measured following injections of sterile fungal extracts. Isolates of Penicillium canescens, Curvularia, Fusarium sambucinum, Fusarium equiseti and Trichoderma koningii from the leukemia-associated house depressed the responses to phytohemagglutinin, but none of the fungal isolates obtained from a nearby control house depressed responses to phytohemagglutinin. Such environmental agents may contribute to development of malignancy by suppression of immune responses.


The ultrastructural localization of the corrosion products of dental amalgam.

The ultrastructural localization of corrosion products released from dental amalgam implants in rat subcutaneous tissue was studied by means of a sulphide-silver technique. Implants stimulated a prolonged inflammatory response with delayed granulation tissue formation and slow and faulty collagen formation. The metallic corrosion products were found both in cells and in association with matrix components. Intracellular metal deposits were predominantly in the cytoplasmic matrix and in vacuoles in the early (19 day) lesions, but at 60 days there was metal in many nuclei, both viable and dead. Collagen fibrils had metal on the surface and vascular basement membranes had granules of bound metals.


Delayed diagnosis of carcinoma of the rectum and sigmoid.

In a large series of patients with carcinoma of the sigmoid colon and rectum there was a delay in diagnosis due to misinterpretation of the physical signs in 36 cases (2.3%). The causes of the misdiagnosis were haemorrhoids, radiological misinterpretation, and chronic inflammatory disease. A miscellaneous variety completed the series. A study of the survival of those patients in whom there was a delay in diagnosis shown that it is most unlikely that it actually affected adversely the prognosis of these patients.


Work loads of a sample of general surgeons in N.S.W.

The work loads of 34 general surgeons in New South Wales during a six week period in 1977 have been determined. Data was obtained on the number of elective, emergency and supervised procedures, and of elective and emergency first consultations. The operative work loads were assessed by a simple grading system, and also by the "hernia-equivalent" method which relates the work involved in a given operation to that for an adult unilateral inguinal herniorrhaphy. The latter is arbitrarily given a score of one. The hernia-equivalent scores for academics, country and city surgeons were similar. The mean hernia-equivalent rating for the 2,321 operations assessed was 1.1; thus, the "typical" operation was equivalent to a herniorrhaphy. The mean number of operations per week was 11.4, or 12.6 hernia-equivalents. Assuming a 48-week working year, these figures represent an annual work load of 547 operations, or 605 hernia-equivalents. Comparison of these results with those obtained in the U.S.A. (the "SOSSUS" report) indicates that these work loads are almost three times those found for board-certified general surgeons in the U.S.A.


Head injuries in a general surgical unit.

A five years' experience of the care by general surgeons of patients with severe head injuries in a general surgical unit with inferior facilities was retrospectively reviewed. It was concluded that the mortality compared favourably with that in similar patients managed by neurosurgeons in specialized centres. The still inadequate understanding of primary diffuse brain damage in head injuries is suggested as the cause for this lack of significant improvement in results over the years. Certain guide-lines, however, exist to allow prediction of the eventual outcome in these patients.


Pulmonary hydatid cyst: a 25-year experience.

This study reviews our experience with 102 patients operated on for pulmonary hydatid cysts during a 25-year period. The sex incidence was approximately equal. All subjects except three were symptomatic. The diagnosis was made on the radiographic findings. Early surgery is advised for complicated cysts in view of their increased postoperative morbidity and mortality. Surgical treatment included Barrett's enucleation for uncomplicated cysts and resection for complicated ones.


Operative ultrasonic bile duct scanning.

The concept of operative echography is introduced. A technique of operative ultrasonic bile duct visualization is presented as an alternative to contrast cholangiography during surgery. The technique is rapid, sensitive, provides immediate results, and does not involve the use of ionizing radiation.


Rubber sump drainage of enterocutaneous fistulae.

Effective sump drainage of high enterocutaneous fistulae, together with alimentary rest and total parenteral nutrition, is now an integral part of the modern management of patients with this condition. The low tissue reactivity of the plastic and polymer materials currently used in most drainage tubes appears however, to be counterproductive to the establishment of a discrete fistula track and control of the fistula. A case is made for the use of red rubber sump drains for enterocutaneous fistulae. The greater tissue reactivity of rubber is reviewed and confirmed by animal experimentation. A method of rubber sump drainage of enterocutaneous fistulae developed during the management of 83 such fistulae is described.


Postoperative pancreatitis as a complication of biliary surgery.

Forty patients who underwent biliary surgery were investigated for postoperative pancreatic disturbance as measured by the amylase creatinine clearance ration (ACCR). Its relevance to preoperative pancreatitis, exploration of the common bile duct, and operative cholangiography were examined. The results suggested that a recent clinically proven episode of pancreatitis did not predispose to a postoperative recurrence following biliary surgery. Similarly, cholecystectomy alone did not produce a postoperative pancreatic disturbance. However, exploration of the common bile duct did frequently cause a postoperative elevated ACCR, and hence we recommend that duct exploration should be performed as carefully and as atraumatically as possible. The small number of patients who did not have operative cholangiograms prevented statistical evaluation of the effect of this procedure on the pancreas. However, information from elsewhere suggests that the plasma amylase level is not likely to be raised by cholangiography.


Diagnostic pneumoperitoneum in traumatic rupture of the right diaphragm.

The diagnosis of diaphragmatic rupture following blunt trauma is difficult and often delayed. Introduced pneumoperitoneum can provide important diagnostic information. Its use is illustrated in a case of massive rupture of the right diaphragm where diagnostic pneumoperitoneum was valuable in distinguishing recent rupture from preexisting pathology.


The performance of multiple joint procedures at one operation in a patient with haemophilia.

A haemophiliac patient with crippling degenerative joint disease is described in whom arthrodeses of the left knee and right ankle and total replacement of the left ankle were performed in the course of one operation. The reasons for this and for using a total ankle replacement are discussed.


Mesenteric-cervical vascular anastomosis as an adjunct to oesophageal bypass surgery for carcinoma.

Dysphagia is the most disabling symptom for patients with carcinoma of the oesophagus. Bowel segment bypass surgery offers satisfactory relief, but is often complicated by anastomotic leakage with its associated high mortality. Poor vascular perfusion of the cervical end of a bypass segment is an important cause of breakdown and leakage. A technique of cervical-mesenteric vascular anastomosis to improve the blood supply of the bypass is described and a case is reported.


Epidural abscess: a hazard of spinal epidural anaesthesia.

Two cases of spinal epidural abscess following prolonged epidural anaesthesia are presented. The clinical features included fever, malaise, and signs of nerve root compression; backache was not marked. Prompt surgical drainage and appropriate antibiotics are required to avoid the costly sequelae of bladder and leg paralysis from spinal cord compression. Both infections were caused by bacterial contamination of catheter, and although this complication is uncommon, it emphasizes that strict asepsis is essential during continuous epidural anaesthesia.


Y incision for median sternotomy.

Between July 1968 and June 1977, in the University of Hong Kong Department of Surgery, 1,083 patients underwent operations via a median sternotomy using a Y incision. Of these patients, 1,070 had open heart surgery, eight had total thymectomy and in five patients pericardectomy was carried out. The overall wound complication rate was 2.31%, with a wound infection rate of 1.24%. The main advantage of a Y incision is that it leaves a better cosmetic appearance than the usual vertical incision because the upper end of the scar is at a much lower level. The incidence of subcutaneous haematoma and subsequent wound infection is much lower with the Y incision, whereas the T incision is associated with a high rate of both these complications due to the large upper flap that one has to create and mobilize to expose the suprasternal area. While using the Y incision, one only requires a small V-shaped upper flap to obtain access to the suprasternal space.


Neurosis and social bonds in an urban population.

The hypothesis that a deficiency in social bonds is a significant causal factor in neurosis was examined in a sample of an urban population (N = 756). The General Health Questionnaire was used as a measure of morbidity while social bonds were measured by the Interview Schedule for Social Interaction. An association was found between neurosis and a deficiency, particularly a perceived deficiency, in social bonds. Attention is now being directed to the interpretation of this association and to establishing the direction of causality.


Sex differences in non-clinical depression.

Two recent reviews have suggested that the prevalence of depression is higher in women than in men. In one review Weissman and Klerman cited several United States community studies, and claimed that findings reveal a female excess in the 'true prevalence' of depressive syndromes. Their interpretation of those studies allowed them to reject the artefact hypothesis that women perceive, acknowledge, report and seek help for stress and symptoms differently to men. The present paper questions their interpretation of those studies. In addition, results from a recent study of depressive experience in a non-clinical group, where no sex difference was found, are presented.


Munchausen syndrome in a psychiatric setting: three case reports.

A primarily psychiatric presentation of Munchausen Syndrome has only rarely been reported and has been assumed to be unusual. Three patients presenting to psychiatric hospitals are discussed. These patients were found to demonstrate the salient features of Munchausen Syndrome: repeated simulation of illness requiring hospital admission, pseudologia phantastica, wanderlust and the use of aliases. It is our view that such presentations are not uncommon.


Urbanization and mental health: psychiatric morbidity, suicide and violence in the State of Victoria.

Australia is one of the most urbanized countries in the world with over 85% of the population living in metropolitan and other urban areas. More important, the change from a predominantly rural society to an urbanized society has occurred within the last 100 years. To assess the effects of urbanization on mental health, rates of admissions to psychiatric institutions, suicides and violent crime in Victoria have been analysed for the last hundred years. Data on admissions to psychiatric facilities in Victoria from metropolitan, other urban and rural areas, as well as results of community health surveys carried out in metropolitan and rural areas were compared to examine for evidence of urban-rural differences in psychiatric morbidity. The findings do not support the notion that the level of psychiatric and psychosocial disorders in Victoria are related to urbanization or to urban living.


Assessment of suicidal intent by a visual analogue scale.

The use of a visual analogue scale to assess feelings about living and dying at the time of suicidal acts is described. It appears to have face validity, and the results obtained correlate significantly with those of a validated suicidal intent scale. Of note, is the significant correlation between the visual analogue score and that part of the suicidal intent scale which rates the objective circumstances of the attempt, suggesting that suicidal subjects are aware of their mixed feelings of living and dying, and that their actions approximate these feelings. These findings, coupled with its ease of administration and scoring, suggesting that it has a place in the screening of suicidal patients.


Mental symptoms and electrolyte imbalance.

A 75-year-old woman on long term diuretic therapy presented with depression. She was found to have hyponatraemia and hypochloraemia. There was no improvement in her condition with antidepressant medication but she responded promptly to cessation of spironolactone and prescription of potassium chloride.


The new patient in San Francisco.

This paper describes an increasingly prevalent type of patient seen in San Francisco, a city which is often regarded as a social trend-setter. Such patients are characterized by social and material success, diffusion or reversal of traditional sex roles, acceptance of any sexual behaviour and instability of all relationships. The resultant insecurity leads to heavy reliance on self-help books and pseudo-therapies, often with disastrous results. Conventional therapeutic methods seem inapplicable, the task being apparently more one of education than therapy.


Attitudes of medical practitioners to mental illness.

The O.M.I. Scale was used to evaluate the attitudes to mental illness of a sample of 50 Australian medical practitioners. Although the scores of the Australian subjects did not differ from those of previously-tested British medical practitioners, they were significantly different to those obtained in a study of Czechoslovakian practitioners. The Australian, British and Czechoslovakian medical practitioners scored similarly on Mental Hygiene Ideology which reflects a medical model of mental illness. It was suggested that there were several disadvantages in supporting the medical model and that, through undergraduate and continuing education programs, medical practitioners should be exposed to alternative models of mental illness.


A lod score method for detecting linkage on the X chromosone between a marker locus and a major gene locus for a quantitative.

A sequential lod-score method is proposed for detecting linkage on the X chromosome between a marker locus and the locus of a major gene influencing a quantitative trait, The method uses information from sons of doubly heterozygous mothers. The average number of families required to detect linkage is substantially less than that of the fixed sample-size method proposed by Hill.


Pharmacokinetics of cytosine arabinoside in patients with acute myeloid leukaemia.

1 The pharmacokinetics of cytosine arabinoside were studied after a single i.v. bolus of 2 mg/kg ara-C in patients with newly diagnosed untreated AML, using a bioassay and GC-MS method to measure the plasma concentrations. 2 Most patients showed a bi- or tri-phasic decline in plasma concentrations with time. Plasma clearance was 3.9 to 18.1 l/min as measured by the GC-MS method, and terminal half-lives varied from 7--107 min. 3 There was poor correlation of the GC-MS assay with the bioassay, probably because the latter was interfered with by the release of endogenous nucleosides from blasts after after ara-C. 4 Plasma concentrations were measured by GC-MS during continuous infusions in 14 patients. Plasma clearances were much lower than after a bolus, 0.39 to 5.25 l/min. 5 There was no correlation of response (remission or fall in peripheral blast count) with exposure to ara-C calculated from infusion dose, clearance and duration of infusion. 6 This study shows that ara-C pharmacokinetics varies markedly from patient to patient and that there is a wide range in the plasma concentrations associated with therapeutic response.


The significance of Ph1 mosaicism: a report of six cases of chronic granulocytic leukaemia and two cases of acute myeloid leukaemia.

Six cases of chronic granulocytic leukaemia (CGL) and two cases of acute myeloid leukaemia (AML) with dual populations of karyotypically normal and Philadelphia (Ph1) chromosome-positive cells are described. GTG and QF-banding characterized the Ph1 as resulting from a 9/22 translocation in all eight cases. Four of the patients suffering from CGL presented with 100% Ph1-positive bone marrows, and after receiving intensive chemotherapy, karyotypically normal cells were demonstrated. The other two patients with CGL showed Ph1 mosaicism at presentation. The two patients with AML exhibited Ph1 mosaicism at presentation and throughout the course of the disease. In both of these patients, a marker No. 10 chromosome was found in some of the Ph1-positive cells and in one hyperdiploidy was observed to have developed only in the clone with the additional chromosome anomaly.


37 degrees CE rosettes in various malignant and non-malignant disorders.

T lymphocytes, forming sheep erythrocyte rosettes at 37 degrees C, have been described in thymus glands, mitogen and allogeneic cell stimulated lymphocyte cultures, and acute T cell lymphoblastic leukaemia. This paper describes the finding of such lymphocytes in lymph nodes of a variety of disorders including Hodgkin's disease, Lennert's lymphoma, malignant lymphoma of large transformed T lymphocytes, immunoblastic lymphadenopathy, metastatic carcinoma, and other disorders. A large number of tonsils, but not reactive lymph nodes, also contained a significant number of those T lymphocytes. The significance of these findings in relation to interpretation of immune red cell rosettes and to the subclasses of T lymphocytes is discussed.


Acute myeloid leukaemia occurring in untreated chronic lymphatic leukaemia.

A case of acute myeloid leukaemia (AML) occurring in a patient with untreated chronic lymphatic leukaemia (CLL) is presented. The diagnosis of two simultaneous leukaemic processes is based on morphological, cytochemical and immunological findings. The significance of the development of AML in patients with CLL is discussed.


Premature chromosome condensation studies in human leukemia. I. Pretreatment characteristics.

The phenomenon of premature chromosome condensation (PCC) was used to compare the bone marrow proliferation characteristics of 163 patients with various forms of leukemia prior to the initiation of new therapy. The proliferative potential index (PPI, or fraction of G1 cells in late G1 phase) and the fraction of cells in S phase was determined and compared to the type of disease and the bone marrow blast infiltrate for each patient. Previously untreated patients with acute leukemia exhibited an average PPI value three times that of normal bone marrow (37.5% for acute myeloblastic leukemia [AML], acute monomyeloblastic leukemia [AMML], or acute promyelocytic leukemia [APML] and 42% for acute lymphocytic leukemia [ALL] or acute undifferentiated leukemia [AUL]). Untreated chronic myelogenous leukemia (CML) patients showed intermediate PPI values (25.2%), whereas CML patients with controlled disease exhibited nearly normal PPI values (14.6%). On the other hand, blastic-phase CML patients exhibited PPI values closer to that observed in patients with acute leukemia (35.4%). Seven patients with chronic lymphocytic leukemia (CLL) exhibited even higher PPI values. No correlations were observed between PPI values, fraction of cells in S phase, and marrow blast infiltrate. For untreated acute disease patients, PPI values were prognostic for response only at low and high PPI values. These results suggest that the PCC-determined proliferative potential is a biologic reflection of the degree of malignancy within the bone marrow.


Induction of erythropoietic colonies in a human chronic myelogenous leukemia cell line.

The ability of cells derived from the K562 cell line to generate erythropoietic colonies was studied. The K562 cell line was derived from a patient with chronic myelogenous leukemia 8 yr ago by Lozzio and Lozzio. Rare benzidine-positive colonies formed when these cells were cloned in plasma clots (3 +/- 1/10(4) cells), and their number was not substantially increased by the addition of erythropoietin (9.5 +/- 1/10(4) cells). Sodium butyrate was capable of markedly enhancing the number of benzidine-positive colonies (19.5 +/- 1/10(4) cells) formed, while the combination of sodium butyrate plus erythropoietin exerted a synergistic effect on erythropoietic colony formation (57 +/- 4/10(4) cells). The K562 cell line is a long-term culture system that contains human erythropoietic stem cells. This cell line should be useful in future studies on the cellular and molecular events associated with human erythroid cell differentiation.


[Multidrug chemotherapy of osteogenic sarcoma (author's transl)].

Osteogenic sarcoma may be treated effectively by radical surgical removal of the primary tumor and combined chemotherapy, including Adriamycin and high dose Methotrexate. In order to render any protocol a safe procedure, strict precautions are required to avoid drug toxicity. We present a protocol, "COSS 77", presently employed in several university hospitals of West Germany and Austria. Final results concerning long term prognosis and long term side effects are not yet available.


Osteosarcoma in Manitoba: review of 95 patients.

A retrospective review of all recorded cases of osteosarcoma diagnosed and treated in Manitoba from 1930 to 1977 was carried out. There were 95 patients (64 males, 31 females). The peak age was 10 to 19 years. The most common sites of osteosarcoma were the femur (38 patients), tibia (14 patients), humerus (13 patients) and pelvis (9 patients). The survival rate (excluding parosteal and periosteal types) was 28% at 2 years and 16% at 5 years. Patients who were operated upon had a somewhat better prognosis than those who had radiotherapy. Initial results of chemotherapy are encouraging. Patients with distal limb tumours had a better prognosis than those with more proximal neoplasms. Patients with tumour secondary to Paget's disease and to irradiation did poorly, those with parosteal and periosteal osteosarcoma did better. Thirteen patients had 31 thoracotomies for pulmonary metastases; their average duration of survival after this procedure was 9.3 months.


Septicemia due to Streptococcus equisimilis in a child with acute lymphoblastic leukemia.

A 4-year-old boy with acute lymphoblastic leukemia in relapse with documented septicemia due to group C Streptococci (Streptococcus equisimilis) is described. The patient responded well to therapy with appropriate cytotoxic and antimicrobial agents. There is a general lack of recognition of the pathogenicity of group C Streptococci in man. The potential opportunistic nature of these organisms in immunocompromised hosts and the need for early recognition and appropriate treatment of such infection is emphasized.


Chromosomes and causation of human cancer and leukemia. XXXIV. A case of "hypereosinophilic syndrome" with unusual cytogenetic findings in a chloroma, terminating in blastic transformation and CNS leukemia.

A 47-year-old white male developed massive hepatosplenomegaly, a pleural effusion, leucocytosis, and a left parasternal mass following a relatively symptom-free persistent hypereosinophilia for about 5 years. Bone marrow aspiration and biopsy and peripheral blood differential showed eosinophilia and a shift to the left with immature cells. A high serum B12 vitamin level and low LAP activity were found. Biopsy of the soft tissue mass revealed a granulocytic sarcoma (chloroma) with a hyperdiploid karyotype (49,XY, + 10, + 15, + 19,3q-), whereas the bone marrow cells had a normal male karyotype. The patient responded temporarily to chemotherapy but eventually developed CNS leukemia and went on to terminate in a frank blastic phase. This case illustrates hypereosinophilia and a myeloproliferative syndrome characterized by a somewhat indolent chronic course evolving into "eosinophilic leukemia" and granulocytic sarcoma, CNS involvement by leukemic cells and, finally, blastic transformation. It is possible that this case represents a variant of Ph1-negative CML to which the term "chronic eosinophilic leukemia" could be justifiably applied.


Impaired bone marrow lymphocyte proliferation in acute myelogenous leukemia.

Bone marrow cells were cultured in liquid media with and without phytohemagglutinin (PHA) to test bone marrow lymphocyte response during the remission period of acute myelogenous leukemia (AML). Mitogen-stimulated cultures from nine leukemic patients while in complete remission showed high percentages of morphologically transformed lymphocytes, but proliferation of these cells was significantly decreased (p less than 0.02) in cultures from six patients who subsequently relapsed (mean remission duration 10 months) and died. In contrast, lymphocyte proliferation in cultures from three AML patients with long remission (greater than 30 months) was comparable to controls. Parallel cultures without added PHA showed a progressive decrease in total viable cell number with time, but an increasing percentage of macrophages in both control and AML cultures. These studies suggest that bone marrow lymphocyte proliferation, but not morphologic transformation, is impaired in some patients with AML, and that identification of this defect may be of prognostic value.


A large parosteal osteosarcoma with transformation to high-grade osteosarcoma: a case report.

This case of a large (31 cm) parosteal osteosarcoma had x-ray documentation 4 1/2 years before treatment. When the tumor began enlarging rapidly, treatment was sought. The tumor histologically showed typical parosteal osteosarcoma as well as malignant cartilage, osteoid, and undifferentiated sarcoma. The case shows one course a parosteal osteosarcoma can take over a 7-year untreated period. The significance of high-grade sarcoma and intramedullary involvement is discussed. When unequivocal high-grade osteosarcoma is present, it should be treated with radical resection and adjuvant multi-drug chemotherapy.


Leukemia in a black child with Bloom's syndrome: somatic recombination as a possible mechanism for neoplasia.

A 5 1/2-year-old child with Bloom's syndrome developed acute lymphocytic leukemia (ALL). Bloom's syndrome is associated with chromosomal aberrations, and affected individuals have an increased incidence of leukemia and solid tumors. The skin on our patient had adjacent areas of decreased and increased pigmentation similar to the "twin-spots" seen in Drosophila. "Twin-spots" are the manifestation of somatic cell DNA recombination and provide evidence that clones of cells in Bloom's syndrome have become homozygous for a particular gene. Somatic cell recombination is proposed as a mechanism to explain the increased incidence of neoplasia in Bloom's syndrome and supports the hypothesis that cancer may be a recessive disorder at the cellular level.


Leukemic iritis with hypopyon.

A patient with acute lymphoblastic leukemia who had received CNS sanctuary treatment with cranial X-irradiation and intrathecal methotrexate displayed his first sign of relapse as iritis with malignant hypopyon. Treatment included topical and subconjunctival corticosteroids and local X-irradiation. Leukemic infiltration of the iris may be the first sign of leukemic relapse. Slit-lamp examination should be performed in all leukemic patients with ocular symptoms.


Loss of terminal deoxynucleotidyl transferase (TdT) activity as a predictor of emergence of resistance to chemotherapy in a case of chronic myelogenous leukemia in blast crisis.

A 46-year-old female with chronic myelogenous leukemia (CML) in blast crisis was monitored for terminal deoxynucleotidyltransferase (TdT) activity of marrow and peripheral blood throughout the course of her illness. TdT was elevated at the time of diagnosis of blastic transformation, and the patient easily obtained remission after therapy with hydroxyurea, 6-mercaptopurine and prednisone. The patient enjoyed a remission of eight months duration, and at time of relapse, marrow TdT was again elevated. The patient again obtained complete remission with the same regimen, with the addition of vincristine, given weekly. This second remission was shortlived, however, and at relapse marrow TdT activity was undetectable. Subsequently, the patient failed to achieve remission, despite the use of a wide variety of chemotherapeutic agents. This case suggests that loss of TdT activity in blastic CML cells marks the emergence of cells resistant to existing chemotherapeutic agents.


Anthracycline cardiomyopathy in children: report of two cases.

Two children with leukemia are presented, each demonstrating an unusual aspect of anthracycline-induced cardiomyopathy. In the first patient (a 7-month-old female with acute monocytic leukemia) extremely young age and previous chemotherapy with a podophyllotoxin derivative, VP-16, may have prediposed the patient to fatal congestive heart failure at a total Daunorubicin dose of only 225 mg/m2. In the second patient, a delay of 4 1/2 years was not sufficient in preventing congestive heart failure resulting from the administration of additional anthracycline chemotherapy. We conclude that extremely young age and, possibly, prior therapy with VP-16 may be addition risk factors in the development of anthracycline cardiomyopathy. Also, we suggest that once an anthracycline agent has reached a toxic threshold for the myocardium, the heart may always be at risk to injury from additional Adriamycin or Daunorubicin therapy.


Sudden death during doxorubicin administration.

Three patients are described who either died suddenly or had severe, life-threatening arrhythmias during or immediately after doxorubicin administration. Since doxorubicin and daunorubicin administration is known to be associated with acute EKG abnormalities, the acute decompensation in these patients appeared to be caused by the administration of these agents. The importance of careful observation of patients receiving doxorubicin, because of the possibility of acute cardiac arrhythmias, is stressed.


The gingival platinum line: a new finding following cis-dichlorodiammine platinum (II) treatment.

Cis-dichlorodiammine platinum (II) (DDP) is the salt of a heavy metal with a wide spectrum of antineoplastic activity. Its toxicity is multisystem and similar to that of other heavy metals, including lead and thallium. A young man being treated with primary adjuvant Adriamycin and DDP for osteogenic sarcoma is described who developed a gingival line which temporally was related to DDP administration. Although not chemically or histologically analyzed, we believe this to be a new finding related to DDP which corresponds to the lead line of plumbism and other heavy metal intoxication.


Childhood leukemia as a model for cancer research: the Richard and Hinda Rosenthal Foundation Award Lecture.

Childhood acute lymphocytic leukemia (ALL) is a model for the study of disseminated cancer. It is always disseminated and relatively uniform, it is accessible to repetitive tissue sampling, and we have highly effective chemotherapy for it. The first systematic, controlled trials of cancer therapy were designed for patients with ALL by physicians with the courage and audacity to aim for cure of a "hopeless" disease. The concept of leukemia cell subpopulations in each patient received major clinical support from ALL. The pharmacological sanctuary, typified by the meninges, was first discovered and specifically attacked in ALL. Combination therapy, aggressive therapy during remission, phase-specific therapy, and the interrelationships of phases of therapy were developed first in ALL. Since leukemia cell features, such as T-cell characteristics, correlate with responsiveness to therapy, powerful new tools may be developed to improve the biological specifically of therapy. In addition to the gratifying results of therapy over the past two decades, childhood ALL continuity offers opportunities for biological research as well as improved therapy for ALL and other forms of disseminated cancer.


Cytotoxic thresholds of vincristine in a murine and a human leukemia cell line in vitro.

L1210 murine leukemia and CEM human lymphoblastoid leukemia cells were exposed to vincristine sulfate in vitro. The response of these cell lines to this agent was measured by the colony-forming ability of L1210 cells in soft agar and inhibition of growth of CEM in suspension culture. Incremental increases of vincristine concentrations in excess of 2 x 10(-9) M produced a progressive reduction of survival of L1210 cells and suppression of CEM growth under the condition of constant drug exposure. A maximum cytotoxic effect was reached with drug concentrations between 10(-8) and 10(-7) M. When L1210 cells were exposed to vincristine for a variable length of time ranging from 0.5 to 24 hr, 10(-7) M produced a noticeable cytotoxic effect following an incubation of only 30 min. A 50% cell kill of L1210 cells and a 50% reduction of CEM cell growth were produced by 10(-7) M following a 1- to 3-hr period of exposure; 6 to 12 hr were required to produce a similar effect at a vincristine concentration of 10(-8) M. Therefore, the antitumor effect of vincristine is critically dependent on both concentration and duration of exposure. These data suggest the possibility that the effectiveness of vincristine as an antitumor agent could be enhanced if methods are developed to prolong exposure of neoplastic tissues for longer periods of time than currently produced by conventional methods of administration.


Cytogenetic analysis of human renal carcinoma cell lines of common origin (NC 65).

Cytogenetic analyses were performed on 3 clonal cell lines derived from a human renal cell carcinoma and its lymph node metastasis, two long-term tissue culture cell lines (NC 65-Sp and NC 65-R) and a serially transplantable tumor line growing on nude mice and brought into culture at the fifth animal passage (NC 65-V). Karyotype were established using banding techniques. Most of the marker chromosomes could be identified and were derived by deletion, inversion, translocation, or isochromosome formation of Chromosomes 1, 3, 4, 5, 8, 9, and 17. These markers were different from HeLa markers. NC 65-Sp had a near diploid chromosome number, NC 65-R a hypotetraploid number, and NC 65-V had a bimodal chromosome number, and NC 65-V had a bimodal chromosome number. Three chromosome markers were shared by the three cell lines; NC 65-R and NC 65-V shared an additional set of four markers. Markers specific to each line were also observed; they demonstrated the independent derivation of the lines and eliminated laboratory cross-contamination. Common markers between the lines confirmed their common tumoral origin.


Enhancing effect of phorbol esters on induction of differentiation of mouse myeloid leukemia cells by human urinary protein and lipopolysaccharide.

12-O-Tetradecanoylphorbol-13-acetate, a potent promoter of carcinogenesis in mouse skin, enhanced differentiation of cultured mouse myeloid leukemia cells (M1) induced by human urinary protein or by lipopolysaccharide from Salmonella typhosa. 12-O-Tetradecanoylphorbol-13-acetate enhanced differentiation of all the markers tested, such as phagocytosis, Fc rosette formation, lysozyme activity, and morphological change. Other potent tumor-promoting macrocyclic plant diterpenes also enhanced the induction of differentiation, but no-tumor-promoting diterpenes did not. These findings were in marked contrast with generally accepted findings on the inhibitory effect of 12-O-tetradecanoylphorbol-13-acetate on terminal differentiation observed in other cell culture systems but consistent with the observations with some kinds of leukemia cells.


cis-Dichlorodiammineplatinum(II): combination chemotherapy and cross-resistance studies with tumors of mice.

cis-Dichlorodiammineplatinum(II) (cis-platinum) has no more than additive, and often much less than additive, lethal toxicity for mice when given in combination with other anticancer agents representing several of the major functional classes of clinically useful anticancer drugs. The previously reported broad spectrum of anticancer activity of cis-platinum against tumors in laboratory animals has now been extended to promisingly useful therapeutic synergism in combination with other active anticancer drugs, including advanced-staged tumors in mice; eg, cis-platinum plus cyclophosphamide against advanced Ridgway osteogenic sarcoma and advanced P388 leukemia, and as surgical adjuvant chemotherapy against advanced colon tumor 26; cis-platinum plus Adriamycin against advanced P388; and cis-platinum plus VP-16-213 against advanced P388. Therapeutic synergism was also seen with cis-platinum plus carminomycin (an Adriamycin analog) against early colon tumor 26. Resistance and cross-resistance studies using sublines of L1210 and P388 selected for resistance to various alkylating agents (cyclophosphamide, melphalan, BCNU, or cis-platinum) indicate a variety of resistance and cross-resistance patterns which further support the growing body of evidence that wide differences in mechanism of cytotoxic activity exist among alkylating agents having experimentally and clinically useful anticancer activity. These data support the observed therapeutic synergisms with combinations of alkylating agents seen against a broad spectrum of murine tumors, and they suggest other drug combinations that might be considered for experimental and clinical trial based on a growing number of logical differences in biochemical mechanism of action of alkylating agent anticancer drugs that have been reported.


Platinum analogs of clinical interest.

Eight platinum analogs including complexes containing two isomeric forms of 1,2-diaminocyclohexane have received preliminary clinical trials. Dosage and limiting toxicity have been identified for racemic malonato-1,2-diaminocyclohexaneplatinum(II) (PHM) and its trans(-)-1,2-diaminocyclohexane isomer (neo-PHM). Dosage and toxicity for racemic sulfato-1,2-diaminocyclohexaneplatinum(II) have been identified and preliminary dosage data for the trans(-)-1,2-diaminocyclohexane isomer are presented. Of the four remaining compounds, three have been abandoned due to toxicity or lack of promise as antitumor agents and the fourth is not being pursued actively at the present time. Further trials of PHM, and especially the neo-PHM isomer, in combination with standard agents seem indicated and are underway. The search for platinum analogs of clinical interest may yet identify analogs significantly superior in effectiveness and safety to cis-dichlorodiammineplatinum(II).


Evaluation of cis-dichlorodiammineplatinum(II) in children with advanced malignant diseases: Southwest Oncology Group Studies.

Two schedules of cis-dichlorodiammineplatinum(II) (cis-platinum) were evaluated for therapeutic efficacy and toxicity in children with malignant diseases resistant to standard therapy. Initially, cis-platinum was given as a rapid iv bolus injection at a dose of 15 mg/m2/day for 5 days every 3 weeks. The second schedule of cis-platinum was a dose of 1 mg/kg/week administered as an 8-hour infusion with mannitol. furosemide, and hydrating fluids. Using the daily schedule, no responses were seen among 23 children with acute lymphatic leukemia and only eight responses were noted among 47 children with solid tumors. Using the weekly schedule, three responses were noted among 25 children with solid tumors. Responses were observed in seven children with neuroblastoma, two with osteosarcoma, one with embryonal testicular carcinoma, and one with an endodermal sinus tumor. With one exception (a 4-year-old child with neuroblastoma), all responses were of short duration. The most common side effects with both schedules were nausea and vomiting which were usually controlled with antiemetics. The dose-limiting toxicity, especially on the 5-day schedule; was renal function impairment. Only one child who received cis-platinum weekly as an 8-hour infusion with diuresis had elevation of the serum creatinine level. Protocols are being initiated to determine the therapeutic effectiveness and toxicity of combination therapy with cis-platinum in children with neuroblastoma and osteosarcoma.


cis-Dichlorodiammineplatinum(II) in childhood cancer.

cis-Dichlorodiammineplatinum(II) (cis-platinum) was evaluated in three separate studies at Roswell Park Memorial Institute in children and adolescents with cancer. In the first study, 16 patients with a variety of solid tumors were treated. Objective responses were seen in patients with neuroblastoma, osteogenic sarcoma, seminoma, and medullary carcinoma of the thyroid. In the second study, five of eight patients with far-advanced osteogenic sarcoma showed objective responses to cis-platinum. In the third study, cis-platinum and Adriamycin were employed as primary adjuvant chemotherapy along with surgery in osteogenic sarcoma. Nine of ten patients have remained disease-free from 8 to 31 months (mean, 19 months). cis-Platinum is an active agent in pediatric tumors.


Clinical and pharmacologic studies with adriamycin-DNA complex in children with malignant disease.

During the last 4 years, we have studied the adriamycin-DNA complex originally developed by Trouet and co-workers (1972). This paper summarizes the results of our pharmacologic and clinical studies. The complex is taken up by cells through an adsorptive pinocytosis, with DNA as the binding molecule. Excess DNA prevents uptake of the drug. Administration of the drug as the complex results in much higher serum concentration and a reduced urinary excretion. The complex is well tolerated, but side effects are probably of the same order as those seen with the free drug. An exception may be the heart. The acute toxicity is not seen when infusing the complex. Our experience with 20 children who have received more than 500 mg/m2 indicates that the chronic cardiac toxicity may be reduced, too. Spectacular, but anecdotal, results have been observed in a variety of solid tumors. Of 16 children with acute myelogenous leukemia, 14 went into a complete remission on a protocol of cytosine arabinoside in combination with the complex. Three of these children are now off therapy, with the longest observation period being 4 years and 4 months.


The mean corpuscular volume (MCV) in children with acute lymphoblastic leukemia.

Although most children with acute lymphoblastic leukemia (ALL) are anemic at the time of diagnosis, the cause of this anemia remains obscure. In an effort to characterize the anemia, we analyzed the mean corpuscular volume (MCV) at the time of diagnosis. The MCV was selected because of the observation that older erythrocytes have a reduced MCV and an anemia presumably related to decreased red blood cell production should be reflected by a reduced MCV. A total of 54 patients fulfilled the criteria for analysis. Of this group, 33 per cent had an increased MCV, 61 per cent had a normal MCV, and 6 per cent had a decreased MCV for age. Patients with an increased MCV were found to have a significantly lower hemoglobin and platelet count. The number of females in the group with the increased MCV was 83 per cent as contrasted with 43 per cent in the group with a normal MCV. At relapse, 71 per cent of patients with an initially increased MCV had an elevated MCV as contrasted with only 23 per cent in the group with an initially normal MCV. These observations suggest that in patients with ALL and an increased MCV, a maturation defect may be present that affects all cell lines and may be the result of a diffusible substance released from the leukemic cells. The MCV cannot be used as a reflection of mean cell age in patients with ALL and does not support the belief that the anemia in ALL is merely the result of a "crowding-out" process.


Use of biofeedback in weaning paralyzed patients from respirators.

Two paralyzed patients who were being treated with mechanical respirators and in whom weaning with intermittent mandatory ventilation failed were treated with regular sessions of biofeedback. Their respiratory volumes were displayed to them on oscilloscopes at bedside. A plastic (Plexiglas) template was placed on the face of the oscilloscope with two horizontal strips of adhesive tape affixed to it; the patient had to achieve a certain tidal volume (TV) to push the tracing outside the space between the horizontal lines. During each session the highest TV achieved determined the target TV to be maintained during the next session. The application of treatment coincided with improved ventilation; both patients were eventually weaned.


[Pseudo-hyperkalaemia in myeloproliferative diseases (author's transl)].

In two patients in the blast phase of chronic myeloid leukaemia there was a marked rise in serum potassium levels, while plasma potassium was at the lower range of normal and there were no signs of hyperkalaemia clinically. After reduction of the pathological cells under cytostatic treatment the serum potassium levels returned to normal. This in-vitro phenomenon seems to be more common in patients with marked thrombocytosis and leukaemia than has previously been thought. In such patients hypokalaemia may be undetected because serum potassium levels arenormal. Pseudo-hyperkalaemia exists when the potassium level is normal in plasma obtained by centrifugation immediately after the blood sample has been taken, without addition of plastic spheres and at once separated from the blood cells.


Investigation of the human macrophage. II. The in vitro cytotoxicity of macrophages.

Macrophage-mediated cytotoxicity in vitro was studied by a tritiated thymidine incorporation inhibition assay as well as by microscopic examination and optical transmitance determination. It was found that macrophages from patients with malignant diseases showed cytotoxic effects on two malignant human cell lines. The cytotoxic activity was more marked in patients who were clinically tumor-free. Some patients with benign diseases and normal subjects also exhibited cytotoxic macrophages. Macrophage-mediated cytotoxicity (MMC) was thus nonspecific in nature. Cell-free exudate from cancer patients did not influence MMC appreciably. The experimental methods and the possible significance of MMC are discussed.


Management of acute psychologic problems in pediatric oncology.

Several psychologic issues in pediatric oncology are addressed and case illustrations of psychologic intervention for selected problems are offered. Psychologic intervention must take into account the patient's perception of his illness, the patient's developmental level, the parents' coping mechanisms, the dynamics of the child's emotional and behavioral responses, the staff's perception of the problems, and the community's capacity for reintegration of the patient. Each of these issues is addressed by use of case examples to demonstrate important aspects of psychosocial intervention.


[Determination of Streptomyces coelicolor A3(2) resistance to erythromycin].

Resistance to erythromycin is genetically unstable in strains of Streptomyces coelicolor A3(2). The frequent loss of resistance as well as reversion of sensitive variants to the original unstable resistance phenotype excluded the possibility that plasmid elimination is involved. The spontaneous frequency of occurrence of sensitive clones was 0.14 to 1.5%, the rate of reversion ranging from 1.10(-6) to 1.10(-8). Resistance to erythromycin has been mapped on the chromosomes of two S. coelicolor A3(2) derivatives in different sites: between markers adeC (v 10) and ArgA1 in the strain A617, between pheA1 and SCP1 in the strain S18. It is suggested that genetic instability of erythromycin resistance determinants having chromosomal location is due to transposition of genetic material.


[ZNS complications in children with acute lymphatic leukemia. Computer tomographic studies].

78 children with acute lymphoblastic leukemia or non-Hodgkin-lymphoma were treated at the Children's Hospital of the University of Heidelberg from December 1971 to April 1979. Following cytostatic treatment and irradiation of the skull 11 children developed CNS-symptoms (mainly seizures and paresis) which were caused by intracerebral hemorrhage, infectious or degenerative CNS-diseases. Cranial axial tomography (CAT) was helpful in finding the cause of the CNS-complication. We recommend routine CAT in the beginning and during the course of treatment of leukemia to document CNS-changes as early as possible and to prevent further damage by alterations of therapy.


Peer review for nonphysicians.

The inclusion of nonphysician health care practitioners in hospital quality assurance programs is being called for by the new JCAH standards and PSRO regulations/PSRO guidelines require that nonphysicians be reviewed by peers.


Hypereosinophilia syndrome or eosinophilic leukaemia. A case report of a one-year-old infant.

The case history of a one-year-old girl, who suffered from a fatal hypereosinophilia syndrome (HES), is presented. It is demonstrated that in this particular patient the origin of the HES has been a variant type of juvenile chronic myeloid leukemia. Clinical and pathologic data are presented. This is the youngest patient ever described as having suffered from fatal HES caused by a leukemic process.


Analysis of genetic control of chylous ascites in ragged mice.

Chylous ascites is a disorder visible as a white fluid in the peritoneal cavity of suckling mice. It is due to inadequate lymphatic drainage from the small intestine. An initial genetic study showed it to be a pleiotropic effect of ragged, Ra. There were four main studies. These involved seven major mutants segregating with ragged. Four of the mutants had no effect on chylous ascites, but two mutants linked with ragged, and one unlinked, showed a complex situation involving enhancement, inhibition, epistacy and other interactions. The overall phenotypic effects which these mutants are known to have do not explain how they produce their interaction with ragged in terms of chylous ascites. The studies also indicate the existence of a single major modifier controlling penetrance and expression, and there is evidence for cumulatively acting minor modifiers. In neonates the male sex is more liable to chylous ascites, and in adults this condition affects fertility and fecundity.


Multiple skeletal metastases of osteogenic sarcoma in a dog.

A 9-year-old male German Shepherd Dog with osteogenic sarcoma involving the right humerus was treated by scapulohumeral disarticulation and adjuvant chemotherapy. Doxorubicin was used, at a dosage of 30 mg/m2 of body surface. Chemotherapy was unsuccessful, and 4 months after surgery, the dog developed multiple metastases of osteogenic sarcoma in the appendicular skeleton, a metastatic pattern rarely observed with primary bone tumors.


Regulation of acid phosphatase activity in human promyelocytic leukemic cells induced to differentiate in culture.

Induction of differentiation of a human promyelocytic leukemic cell line (HL60) in culture is accompanied by changes in acid phosphatase (Acpase) activity. The increase in activity is less than twofold when the leukemic cells are stimulated by dimethylsulfoxide (DMSO) to differentiate into metamyelocytes and granulocytes but is eightfold when the cells are stimulated by the tumor-promoting agent 12-0-tetradecanoylphorbol 13-acetate (TPA) to differentiate into macrophage-like cells. Five different isozymes of Acpase were separated by acrylamide gel electrophoresis. Isozyme 1, the most anodal isozyme, was found to be present in undifferentiated, DMSO-treated and TPA-treated cells; isozyme 2 was a very faint band observed both in DMSO- and TPA-treated cells, the isoenzymes 3a and 3b were present only in TPA-induced cells; and isozyme 4, the most cathodal isozyme, was present both in TPA- and DMSO-induced cells. A time sequence study on the appearance of the various forms after TPA treatment indicated that the expression of the isozymes is regulated in an uncoordinated fashion. Acpase activity has been shown by ultrastructural cytochemistry to be localized in the entire rough endoplasmic reticulum (RER) and in areas of the smooth endoplasmic reticulum (SER) located near the Golgi complex in differentiating cells but to be extremely weak, if at all detectable, in undifferentiated promyelocytes.


Erythroid progenitors (BFU-e and CFU-e) in acute leukaemia.

Bone marrow erythroid progenitor cells were examined from 50 cases of acute leukaemia and from 20 normal subjects using an in vitro semisolid culture method. Numbers of both primitive erythroid progenitor cells (BFU-e) and later-stage erythroid progenitor cells (CFU-e) were remarkably depressed in patient with acute leukaemia in active phase. However, both BFU-e and CFU-e recovered to within normal range when the patients achieved remission. Peripheral blood BFU-e of children with acute lymphocytic leukaemia in remission were also examined and found to have values not significantly different from those of control subjects. There was no distinct correlation between the numbers of erythroid bursts or colonies and the duration of remission in patients with acute leukaemia in remission. The reduction of BFU-e and CFU-e in active acute leukaemia suggests the involvement of erythropoietic progenitors in the pathophysiology of this type of leukaemia.


The influence of functional use of endosseous dental implants on the tissue-implant interface. I. Histological aspects.

The tissue-implant interfaces of functional and non-functional endosseous dental implants were compared histologically for up to one year post-operatively. Nonmineralized connective tissue zones (a "fibrous capsule") existed in all functional interfaces. Direct, or nearly direct, bone apposition to implants occurred in non-functional interfaces. The origin of this result and its significance in dental implantology is discussed.


The influence of functional use of endosseous dental implants on the tissue-implant interface. II. Clinical aspects.

Functional and non-functional endosseous dental implants were clinically compared in beagle mandibles for up to one year post-operatively. Differing biomechanical conditions led to clinical differences between functional and non-functional implants. Typical clinical tests, however, did not always reveal detailed histological differences between implant-tissue interfaces of functional and non-funcional implants.


A new composite restorative based on a hydrophobic matrix.

A hydrophobic restorative composite based on a fluorocarbon analog of an alkyl methacrylate and a bisphenol adduct was formulated into a one-paste system, which polymerized in the presence of blue light. Physical, mechanical and water-related properties were determined. High contact angles and low water sorption were shown by the experimental composite. Capillary penetration of oral fluids around restorations, therefore, could be prevented in the presence of this highly hydrophobic surface. The physical and mechanical properties of the experimental composite were either comparable to or somewhat less favorable than commercial Bis-GMA composites.


New amine accelerators for composite restorative resins.

The overall characteristics of the composites cured with a number of newly synthesized, tertiary aromatic amines compare favorably to those of resins polymerized with commonly used accelerators. Maximum compressive and tensile strength for the composites are obtained only over a narrow concentration range of accelerator used.


Viscosity of dental porcelain as a function of temperature.

A method for viscosity measurement is described and representative data are given for opaque, gingival, and incisal porcelains. The significance of viscosity in annealing and in stress development due to thermal expansion mismatch is discussed. Thermal history of the porcelain is shown to be important only over a relatively small temperature interval in affecting residual stresses.