Mechanism of human lymphocyte stimulation by concanavalin A: role of valence and surface binding sites. A monovalent form of concanavalin A (m-Con A) has been prepared to determine the importance of valence for human lymphocyte surface binding and subsequent lymphocyte stimulation as measured by blast transformation and cytotoxicity. Concanavalin A (Con A) was fragmented by a proteolytic process and the m-Con A) derivative was isolated by elution with an ascending D-glucose gradient on a Sephadex G-200 column. The molecular weight of m-Con A was 18,000 by sodium dodecyl sulfate-polyacrylamide electrophoresis. Equilibrium dialysis with alpha-methyl D-glucoside and subsequent Scatchard plot analysis revealed an association constant (Ka) of 1.2 X 10(3) liters/mol and a valence of 1.1. Incubation of lymphocytes with 125I-labeled m-Con A demonstrated surface binding at 1.21 X 10(6) molecules per cell, which was comparable to the binding of [3H] Con A (1.02 X 10(6) molecules per cell). However, in contrast to the intact lectin, m-Con A had a markedly reduced capacity to agglutinate rabbit erythrocytes and human lymphocytes and did not stimulate lymphocyte blast transformation or cytotoxicity at 1 and 10 mug/ml. Finally, pretreatment of lymphocytes with m-Con A blocked blast transformation induced by Con A. These observations demonstrate that m-Con A binds to lymphocyte surface receptors but does not stimulate blast transformation or cytotoxicity, suggesting that Con A must bridge binding sites on the lymphocyte surface to induce lymphocyte activation.


Immunological cross-reactivity of antibodies to a synthetic undecapeptide analogous to the amino terminal segment of carcinoembryonic antigen, with the intact protein and with human sera. A peptide corresponding to the 11 amino acid residues of the NH2-terminal portion in the sequence of carcinoembryonic antigen(CNTHETIC CEA(1-11) peptide was attached by means of a water-soluble carbodiimide reagent to multichain poly(DL-alanine( as well as to bovine serum albumin. Both macromolecular conjugates provoked in rabbit anti-CEA(1-11) peptide antibodies. The specificity of this immunological system and the crossreactivity between the peptide and intact CEA were investigated by two methods--passive hemagglutination and modified bacteriophage inactivation. Hemmagglutination experiments showed that not only anti-CEA(1-11) sera, but also anti-CEA sera, agglutinated CEA(1-11)-coated sheep erythrocytes, and both these reactions were inhibited with CEA(1-11) peptide. In experiments with the chemically modified bacteriophage technique CEA(1-11)-coated phase was efficiently inactivated with antisera against the CEA(1-11) conjugates, and the inactivation reaction could be totally inhibited with the free peptide. The semipure CEA, but not the pure protein, could also inhibit the phage inactivation, even though less efficiently. On the basis of the above results, sera of some cancer patients were tested for their capacity to inhibit the inactivation of CEA(1-11)-coated phage by means of anti-CEA(1-11) antiserum. The results indicate that sera from a large proportion of patients with adenocarcinomas of the digestive tract, pancreas, and breast are capable of inhibiting the above inactivation, whereas most normal sera do not inhibit.


Soluble dextran-hemoglobin complex as a potential blood substitute. A complex between soluble dextran and human hemoglobin has been synthesized by two different methods. In the alkylation method, hemoglobin was allowed to react with bromoacetyl groups incorporated into the dextran; the yield of the complex was about 80% in terms of the hemoglobin used. In the dialdehyde method, hemoglobin was allowed to react with dialdehyde groups on the dextran generated by periodate oxidation; the yield of the complex was about 60%. Both soluble dextran-hemoglobin complexes could bind and release oxygen reversibly, but the oxygen-binding curves were shifted to the left relative to that of free hemoglobin. In the rabbit, the complex obtained by the alkylation method was excreted by the kidneys and cleared from the circulation much more slowly than free hemoglobin.


Antibodies as a means of isolating and characterizing biologically active substances: presence of a non-peptide, morphine-like compound in the central nervous system. Antibodies generated against small molecular weight substances such as drugs are being used to isolate and characterize biologically active agonists. A morphine-like compound can be extracted from brain of various species which has determinant groups that are recognized by specific morphine antibodies. It has a regional distribution which can be quantitated as immuno-equivalents. Immunological, chemical and chromatographic tests show great similatiries of the compound to morphine. This morphine-like compound has biological activity as it inhibits the electrically induced contractions both of the guinea pig ileum and mouse vas deferens but the inhibition is not reversed by naloxone or naltrexone.


Mapping of the influenza virus genome: identification of the hemagglutinin and the neuraminidase genes. Polyacrylamide gel electrophoresis of the RNA of influenza A/PR/8/34 (H0N1) and A/Hong Kong/8/68 (H3N2) viruses and recombinant viruses derived from them revealed that each contains eight RNA segments, the fourth of which codes for hemagglutinin. (The largest RNA of the segmented genome is counted as band 1.) The neuraminidase gene was identified as the sixth segment in the RNA pattern of influenza A/PR8 virus and as the fifth segment of A/Hong Kong virus. The molecular weights of the RNAs for the hemagglutinin and the neuraminidase genes lie in the range of 600,000-700,000.


beta-Lipotropin as a prohormone for the morphinomimetic peptides endorphins and enkephalins. The hypophysial homomeric peptide beta-lipotropin (beta-LPH-[1-91]) has no morphinomomimetic activity in a bioassay (myenteric plexus-longitudinal muscle of the guinea pig's ileum) or binding assays with stereospecific opiate-receptors of rat brain synaptosome preparations. Incubating beta-LPH-[1-91] at neutral pH with the supernatant aqueous extracts of rat brain generates (fragments of beta-LPH with) morphinomimetic activity in the same assay systems. These results are related to the recently recognized structural relationships between beta-LPH, the newly isolated peptides met-enkephalin (beta-LPH-[61-65]) and alpha-endorphin (beta-LPH-[61-76]) and also to the biologically active fragments of analogs: beta-LPH-[61-64], beta-LPH-[61-65[-NH2, (Met(O)65)-BETA-LPH-[61-65], beta-LPH-[61-69], and beta-LPH-[61-69]. Enzymatic biogenesis of these morphinomimetic peptides would preclude localizing them as such in cellular or subcellular elements with currently available methodology.


The role of radiation therapy in the treatment of osteosarcoma. Seventy patients received primary surgical or radiotherapeutic treatment for osteosarcoma at the University of California-San Francisco between 1950 and 1974. Twenty-two received surgery alone and 27 received preoperative irradiation followed at varying intervals by surgery. Twenty-one patients received irradiation alone because of tumor location, refusal of recommended surgery, or development of metastatic disease. The results are analyzed and the role of radiation therapy in the primary management of osteosarcoma is discussed. The authors believe that irradiation without chemotherapy offers little in terms of palliation or enhanced survival in patients who are able to undergo radical surgery.


Multiple chromosomal associations and paracentromeric region instability in a case of acute leukemia. A case of acute myelomonocytic leukema is described, which was characterized cytogenetically by the presence of centromeric elongations, somatic crossovers, selective endoreduplication figures, and multiple chromosomal clusters. The demonstration of these phenomena by selective staining techniques for the chromosome bands (Q, C, G and S) and the nucleolar areas (acridine-orange, amido black B 10) raises some biological aspects involved in the proliferation of leukemic cells, such as nucleolar persistance during the metaphase and the non-separation of chromatids in the clusters during the anaphase. These structural abnormalities may represent the background for the explanation of the appearance of subclones in neoplastic disorders.


Serum iron increase as a measure of iron absorption - studies on the correlation with total absorption. The correlation between the magnitude of the increase of serum iron after an oral dose of iron and the total absorption of iron was studied in 51 healthy subjects and 10 patients with iron deficiency anaemia. 59Fe-labelled solutions of ferrous sulphate (25-100 mg iron) were administered to the fasting subjects. The serum iron concentration was followed for 4-6 hours and the absorption was measured in a whole-body counter. Good correlation was found between the maximal increase of serum iron and the total amount of iron absorbed after a dose of iron given as a solution. The serum iron method may be used for comparisons of the absorbability of different doses of iron by performing cross-over studies in groups of subjects. However, it was found that in an individual subject the serum iron method could not be used to determine the amount of iron absorbed from an oral dose of iron.


Absorption from different types of iron tablets - correlation between serum iron increase in total absorption of iron. The absorption of iron from three different iron tablets - rapidly-disintegrating ferrous sulphate and ferrous carbonate tablets and slow-release ferrous sulphate tablets - was studied in healthy subjects with a serum iron technique and by whole-body counter measurements. A solution of ferrous sulphate was used as a reference. There were no differences in the absorption from the ferrous sulphate preparations, but the ferrous carbonate tablets were less well absorbed. Good correlation was found between the maximal serum iron response and the total absorption of iron and it was concluded that serum iron studies may be used for semiquantitative measurements of iron absorption in comparative studies on different iron preparations.


Influence of a liquid antacid on the absorption of different iron salts. The influence of a liquid antacid on the absorption of iron from iron tablets was studied in healthy volunteers using a serum iron technique. Tablets containing ferrous salts (carbonate, fumarate, sulphate) with different in-vitro dissolution properties were studied. Co-administration of the antacid and the iron tablets resulted in a marked reduction of the absorption of iron from all preparations studied. The lowest absorption was found when ferrous carbonate was given with the antacid. This was ascribed to the fact that ferrous carbonate is almost completely insoluble at pH-levels near neutral. This was confirmed in a series of patients with achlorhydria in which the absorption from ferrous carbonate was virtually nil. It was concluded that iron tablets and antacid preparations should not be administered at the same time and that ferrous carbonate tablets should not be used in patients with achlorhydria.


Influence of food on the absorption from different types of iron tablets. The influence of a standardized breakfast meal on the absorption of iron from two types of iron tablets - rapidly-disintegrating and slow-release tablets - was studied in 24 healthy subjects, using a serum iron technique and whole-body counter measurements. The meal markedly reduced the absorption of iron from both types of tablets. An 8-fold reduction was found with the rapidly-disintegrating tablets and a 3-fold reduction with the slow-release tablets. Under fasting conditions the rapidly-disintegrating tablets were significantly better absorbed than the slow-release tablets, whereas the reverse was found when the tablets were given with the meal.


Absorption of iron from slow-release and rapidly-disintegrating tablets - a comparative study in normal subjects, blood donors and subjects with iron deficiency anaemia. The absorption of iron from slow-release and rapidly-disintegrating ferrous sulphate tablets has been compared using a double radioiron isotope technique. The studies were performed in 15 normal subjects, 20 blood donors and 10 patients with iron deficiency anaemia. The preparations containing 100 mg of ferrous iron were given twice daily on alternate days for 10 days. The absorption differed significantly between the three groups of subjects, being highest in the anaemic patients and lowest in the normal subjects. In all groups, significantly more iron was absorbed from the slow-release tablets compared to the rapidly-disintegrating tablets. The mean absorption ratios were 1.3 in both normal subjects and blood donors. In patients with iron deficiency anaemia the ratio was 1.4.


Blast crisis of chronic myeloid leukaemia: the effect of intensive chemotherapy. 24 patients with Philadelphia chromosome positive chronic myeloid leukaemia (CML) in blast crisis were treated with intensive chemotherapy. 16 patients showed either partial or complete response to this treatment, but median survival remained short (13 weeks), and much of this time was spent in hospital. These results were not significantly better than those obtained by others using vincristine and prednisolone alone, and this combination of drugs can often be given on an outpatient basis. It is concluded that until more effective intensive therapy becomes available patients in CML blast crisis should be managed in such a way that the quality of life is not impaired; and that at present vincristine and prednisolone appears to be the most impaired; and that at present vincristine and prednisolone appears to be the most appropriate initial treatment, though even this is far from satisfactory.


The penetration of trimethoprim into seminal fluid and serum. A series of determinations of the concentrations of trimethoprim in seminal fluid and serum was made during the treatment of 18 men. Trimethoprim could be demonstrated in an average concentration in serum of 1.8-2.0 mug per millilitre and in seminal fluid of between 1.0 and 1.5 mug per millilitre. At the same time it was demonstrated that the combination of trimethoprim and sulphamethoxazole (co-trimoxazole) has no effect on genital mycoplasma species.


Co-trimoxazole in the long-term treatment of pyelonephritis with normal and impaired renal function. The effect of co-trimoxazole was studied in 29 cases of acute or chronic pyelonephritis. The therapy produced the desired effect in 22 out of 23 cases and in the 6 cases treated prophylactically. We used a special dosage schedule for the combination of sulphamethoxazole and trimethoprim in the treatment of patients with normal renal function and with varying degrees of renal impairment. The results show that the plasma concentrations were at satisfactory therapeutic levels, with no accumulation of the three substances and without causing any toxic side effects, even in patients with severe impairment of the renal function. The mean duration of the treatment was 12.3 months. The material is, however, not largelu enough to warrant the recommendation of standardized treatment according to the schedule described, in spite of the favourable experience gained. It does, however, permit us to recommend that the plasma concentrations should be determined, particularly of the total sulphamethoxazole in patients with severely impaired renal function.


The treatment of meningitis in infants with co-trimoxazole administered parenterally. We found that co-trimoxazole had a good clinical and antibacterial effect when given parenterally to infants with infections of the central nervous system. We showed good concentrations in the serum and satisfactory penetrations into the cerebrospinal fluid. In one case, there was a side effect which may have been due to the sulpha or to the solvent. We think that at present the preparation should not be given to very premature babies or to babies with icterus, for the same reasons that we avoid using sulpha preparations in these conditions, but otherwise it may be of great use in difficult cases of meningitis caused by Gram-negative bacteria in infancy.


The intravenous infusion of co-trimoxazole in cases of septicaemia: tolerance and results of treatment. The tolerance to co-trimoxazole given by intravenous infusion was investigated in 25 patients suspected to be suffering from septicaemia. One patients developed allergic skin manifestations and two had increased difficulties with cardiac insufficiency, probably on account of the infusion. The other patients tolerated well. The results of treatment of 11 patients with septicaemia were good in 8 cases. In 2 cases, the poor results of the treatment can be explained by the presence of undrained abscesses  in these patients. Good concentrations of the components in the serum were achieved by the treatment.


[A new device for the positioning of lateral teeth in complete dentures]. A new instrument for the arrangement of the posterior teeth in complete dentures is introduced. The instrument consists of a device to attach a transparent base-plate reproducing the morphology of the jaw to an articulator. During the set up the base-plate is fixed to the articulator at the level of the occlusal plane. So the morphological features of the edentulous jaw are three-dimensionally reproduced by the base-plate at the occlusal level. The advantage of the instrument is to allow a better, immediate and direct control of the occlusal configuration of the posterior teethe in relation to the morphology of the jaw.


[Functionally stable osteosynthesis and simulography in sagittal osteotomy of the ascending ramus. A comparative clinical study]. Sagittal mandibular osteotomy is a well-founded means to correct various dysgnathias. The method is enhanced by the possibilities of fixation which osteosynthesis has offered to the treatment of bone fractures. The success of using osteosynthesis in osteotomy depends partly of preoperative planning combined with simulography which allows for orthograde adaptation of the proximal fragments and the proper localization of the traction screws. 75 sagittal osteotomies were checked. They had all been operated the same way, but the fixation was varied: without fixation, fixation by wiring, fixation by Kirschner wire, fixation by bilateral traction screws, 1 each, 2 each, 3 each. The evaluation was made by using many criteria. It was found that without functionally stable osteosynthesis, inspite of 2-3 months immobilization a recurrence occurred in most cases and that postoperative treatment by activator or by head-chin appliance was necessary. With 3 screws on each side and preoperative planning with simulography no recurrence was found in 30 cases. Also, the hospitalization could be shortened and with it the working incapacity. These patients could be left without intermaxillary fixation and late postoperative treatment.


[The possibility of a standardization of clinical trials concerning materials for root canal obturation]. Clinical trials constitute epidemiologic experiments, in comparable groups of human populations designed to assess the preventive of curative effects of agents or measures. International organizations (FDI, WHO, CIOMS, ISO) have been instrumental in creating uniform methods, so that the findings from different sources can be validly compared. The need for a standardization of clinical trials in dentistry is particularly felt: - by the dental profession in order to make the choice of materials with the best clinically proven qualities - by the manufacturers in order to develop materials of improved clinical quality - by the public health administrators (or social security agencies), in order to either evaluate the benefit of instituted preventive and curative measure or to ascertain the best possible services A centennial history of efforts is shown to have resulted today in a broad international understanding (Table III). 1. The first chapter of this paper presents a review of the principal requirements for controlled clinical trails [8] such as officially adopted by FDI (Table V). 2. The second chapter offers a first-hand apercu of impending recommendations proposed by COMIET in two protocols [11] for the uniform conduct and evaluation of clinical trials of restorative techniques and materials. 2.1 Three standardized forms (A, B: Table IX, and C) serve to uniformly record data of the operative procedures. 2.2 The proposed standardized criteria (Tables X, XI) for the clinical appraisal of distinct materials give the advantage of having been tested already very extensively. 3. A critical review of the proposed protocols [11] reveals the necessity of: 3.1 referring to and coordinating with the already adopted principal requirements for controlled clinical trials. 3.2 generally adopting the excellent guidelines for the  conduct of the study and the evaluation of observations (Tables X, XI) 3.3 taking advantage of the possibilities for reducing the recommended sample of 100 paired restorations (200 cavities)--difficult to implement in many countries--by certain measure such as preliminary in-vitro experiments, consideration of results already reported in the literature and a more systematic use of a standardized photographic serial documentation, a topic which will be the object of an ensuing paper.


[The Sjögren-Gougerot syndrome].

[The Sjögren-Gougerot syndrome]. The Sjögren-Gougerot syndrome represents a rare disease of the collagenous tissue characterized by the three symptoms Xerophtalmy, Xerostomy, polyarthritis. Women after the menopause are the most affected. Oral symptoms addup to diverse dermatological manifestations. The bilateral parotidic swelling and systemic complications accompany the disease, and the immunological disorder is coupled with hypergammaglobulinemia. Prognosis is very reserved and treatment delicate.


The problem of splenectomy in a leukemic patient population. An attempt has been made in an experimental group of 20 patients, with leukemia or one of the myeloproliferative disorders, to devise a safe method of splenectomy by timing the operation to coincide with optimal response to chemotherapy, preoperative bowel preparation with antibiotics to minimize infections, and availability of platelet concentrates, matched for HL-A antigens when possible, to control massive hemorrhage. The results in this experimental group were compared with a historical control group of 26 patients. Two-thirds of all the patients had chronic myelocytic leukemia, and the mean weight of the spleens removed was just over 1,800 grams. Operative mortality was 35% in the historical group and zero in the more recent group, six of whom were operated on while in blastic crisis. Splenectomy can be done safely in leukemic patients, and is not contraindicated. Future planned studies will determine its possible therapeutic role in reducing tumor burden.


Hypoventilation after high unilateral cervical chordotomy in a patient with preexisting injury of the phrenic nerve. Unilateral cervical chordotomy for the relief of intractable pain is a well accepted procedure but is not without hazard. Postoperative respiratory failure is not an uncommon occurrence, but the likelihood increases with a number of factors, particularly preexisting pulmonary abnormalities or previous contralateral cervical chordotomy. Preoperative assessment of the pulmonary function of patients who are about to have cervical chordotomy is emphasized to predict and anticipate potential postoperative respiratory failure.


Splenectomy in chronic myelogenous leukemia. There were no deaths or major complications in three chronic myelogenous leukemia patients in group 1 who were selected under well controlled conditions and had the spleen removed. Intensive chemotherapy in the treatment of chronic myelogenous leukemia patients who undergo splenectomy remains to be resolved. Well controlled prospective clinical trials are now being conducted to evaluate the value of splenectomy in chronic myelogenous leukemia.


Clinical assessment of the hypertensive fundus. This brief paper attempts to place some of the pieces of the jig-saw of hypertensive retinopathy together, and to emphasize the value of fundus photography including stereoscopic pictures in reducing the subjective element in the clinical assessment of these cases.


An ophthalmic genetics clinic.

An ophthalmic genetics clinic. The results are presented from the first year of our clinic in Edinburgh. These were included in the setting up of a computerized Register of Ascertainment and Prevention of Inherited Disease ('RAPID') in the Department of Human Genetics. A total of 45 relatives who had greater than 10% risk were ascertained from fifteen families with hereditary diseases; 24 relatives had 10% risk of retinitis pigmentosa. The pupils at the Royal Blind School, Edinburgh, were surveyed and it was found that 40% of the 100 pupils had definitely inherited severe eye disease. Only 31% , had definitely non-genetic disease, for which reassuring counseling can be given. In 29% we could not be sure. From those with hereditary disease we ascertained 51 relatives at greater than 10% risk. Any patient with a fairly symmetrical 'quiet' eye disease, especially if congenital, should be suspected of having an hereditary disease--presumably due to a recessive gene, even if the parents are not consanguineous, but possibly due to a mutation which could prove dominant; a search of the literature in such cases is useful. Although patients with a 'recessive' disease can be reassured that the (extra) risk to their children is small, it is worth warning them that in their families a consanguineous marriage is more liable than usual to produce affected children. A case of oculo-pharyngeal muscular dystrophy was seen and two cases of Leber's congenital amaurosis: the commonest diagnosis was retinitis pigmentosa, and there were several cases of Marfan's syndrome. The Royal Blind School takes both boys and girls and one couple have recently married, the male with X-linked retinitis pigmentosa and the female with dominantly inherited retinoblastoma.


Ultrasonic cataract extraction with acoustic horn. An ultrasonic lens-disintegrations system is added to the aspiration side of an irrigation-aspiration system. It incorporates an acoustic horn of which one part is a stainless steel cone 4 cm long with a 1 cm diameter base. From the apex of the cone projects the other part, viz. a 22 gauge needle, which is inserted into the anterior chamber at the limbus temporally (left eye) and which carries aspirated lens fragments with saline out into a duct drilled 2 cm into the cone along its axis. At that point the duct turns at right-angles to leave the cone; a polythene tube connects the duct with the aspiration syringe. A vibration generator (sandwich transducer) initiates ultrasonic vibrations which the needle-cone combination magnifies about 100-fold at the tip of the needle. Saline input to and output from the anterior chamber are maintained exactly equal (and simultaneous) by means of a 'push-pull' system of twin reciprocating hand-driven 30 ml. syringes (Fig. 7). Saline input is through a 25 gauge needle at the limbus at 6 o'clock (left eye).


Colour stereociné photography with twin cameras through the operation microscope. Two Beaulieu R16 cinecameras attached toa Zeiss operation microscope, OP Mi2, one for each side, produced colour cine films. When these were projected through polarizing filters on to a silver screen, the audience (wearing appropriately oriented polarizing spectacles) achieved a stereoscopic view.


Diabetic retinopathy. Review of 82 patients presenting with unilateral blindness. Of the 82 patients who presented to our clinic with unilateral blindness secondary to diabetic retinopathy, 76% had PDR in the blind eye, 4% had non-proliferative retinopathy, and 20% had macular exudates. The second eye, in most instances, had or developed the same pathology as the first eye. Visual prognosis was poor for the 59 patients who had PDR in the second eye; 24 became blind at an average of 15-7 months after presentation. Those patients who were treated seemed to fare better than those not treated. Only three of the fourteen patients who had pituitary ablations became blind, but the average age of this group was, of course, significantly lower than that of the others. Nine of the 22 patients who received photocoagulation became blind in the second eye. Twelve of the 24 patients who received no treatment became blind in the second eye. Visual prognosis for patients with non-proliferative retinopathy was much better; ten patients maintained useful vision for an average of 4 years follow-up. Of the twelve patients with macular exudates in the second eye, three became blind at an average of 34 months after presentation.


[Slow-virus "encephalitis" following measles in a child with cytostatically-treated leukaemia (author's transl)]. A child with acute infantile lymphoblastic leukaemia in remission after cytostatic therapy contracted apparently uncomplicated measles. 8 weeks later, an acute neurological syndrome developed, which led to death within 2 weeks. At autopsy, a peculiar type of inclusion body "encephalitis" almost without signs of inflammatory infiltration was found. Electron microscopic examination showed changes of paramyxovirus infection, which were attributable to slow measles virus disease of the CNS. There was evidence of disturbed nucleocapside synthesis, which is considered to be one of the basic defects in the development of slow-virus processes and their altered viral maturation. Possible pathogenetic factors are discussed in the light of our case.


[Current problems of childhood and juvenile neuropsychiatry]. In the submitted study a short historical review intends to point out the roots and mode of formation proceeding the new medical branch "Neuropsychiatry for children and juvenils", trying to emphasize interdisziplinary work as basic point of conception. Aspects in regard to the development of higher human functions will be discussed in the second part of the paper, whereby the common approach of Neurophysiologist and psychoanalytical oriented Psychologist accentuated is. In connection with the therapeutical consequences of such physio- and psychological development consideration questions regarding the neuropsychiatric welfare service for children and juveniles will be taken.


Giant millipede burns in Papua New Guinea. Three patients with superficial burns to the face and neck from benzo-quinone derivatives in the excretions of giant millipeds of the Spirobolus family are reported from the Northern District of Papua. A review is made of the clinical features and treatment of these burns.


Traditional medicinal plants used in the treatment of malaria and fevers in Papua New Guinea. Plants have been used as traditional medicine in many areas of Papua New Guinea. Over thrity different plants used to treat malaria and fevers have been collected and their uses recorded. Many of the plants taken internally, but few others, are found to contain alkaloids.


Pharmacological investigations of virosecurinine. This study reports some biological studies on the alkaloid virosecurinine isolated from the plant Securinega Virosa. Virosecurinine is an isomer of the securinine group of alkaloids present in plants used in traditional medicines in many areas, including the Central District of Papua New Guinea. Virosecurinine is mildly toxic to mice with an LD50 of 73 milligrams per kilogram body weight. Death results from violent tonic convulsions and paralysis similar to those observed with strychnine poisoning. Virosecurinine had no effect on the growth of the following bacteria, E. coli, S. aureus, and B. subtilis, or the fungi, F. monoliforme, P. viridicatum, A. niger, R. solani, R. stolonifer and C. lunata.


The social consequences of accidental injury. A case history is presented showing how traditional beliefs affect the understanding of accidental injury. The impact of such an event on the life of a particular village is also described, and certain implications for medical workers are noted.


Motivation, crime, and cultural change: a review of fifteen years experience in the law courts. The author's forensic experience among the different cultural groups of this country stress the doctor's twin obligations as physician as well as witness. Provisional definitions of psychiatric disorder and criminality in this context are given. The medicolegal aspects of cargo cult, customary land rights, and the incest taboo transgression are discussed, and suggestions made that the law can act as an educational force, as well as having a social control function, and that legislation could be prepared with this additional end in view.


Orderlies as interpreters in Papua New Guinea. The medical orderly as a linguistic intermediary is performing the function of interpreter for which he has not been trained. However, it is found that he almost always achieves an adequate equivalence between the source language and the target language. One strength of the system is that the orderly has medical training but this is also a basic weakness since if a more complex situation arises in which the patient wishes to convey information heregards as relevant but the orderly regards as irrelevant, the communication process may break down into a mass of misunderstandings.


[McArdle's disease (a familial case)].

[McArdle's disease (a familial case)]. The author describes a family (48 year old mother and 15 year old son) with the muscular variant of glycogenosis-McArde's metabolic myopathy. The mother has been ill since 22 years old, the son--since 7. The disease had a slowly progressive development. The clinical picture was characterized by convulsions of the type of cramps following physical loadings on muscles of the body and extremities. Convulsions were accompanied by pain, an induration and enlargment of the muscles, muscle fatigue and increased significantly in an artifical ischemia of the extremities. A histochemical study of the muscle revealed a pathological accumulation of glycogen. The content of lactic and pyruvic acid in the blood after work in ischemic conditions did not change significantly. A study of the sugar curve in the blood with a loading with glucose and a parallel determination of insulin by a radioimmune method found hyperinsulinemia and a dysfunction of the pancreas.


Cytologic features of seminal vesicle epithelium in aspiration biopsy smears of the prostate. To determine the rate of occurrence of cells derived from seminal vesicles in routine needle aspirates of the prostate, the smears of 853 aspirates were reviewed. The cytologic features of cells originating from the seminal vesicles were described using air-dried smears stained by the May-Grünwald-Giemsa method. The differential diagnosis with malignancy is discussed.


Cytologic examination of post prostatic massage specimens as an aid in diagnosis of carcinoma of the prostate. The results of cytologic examination fo post-massage prostatic secretion from symptomatic and asymptomatic subjects were evaluated by comparison with available tissue diagnosis. Specimens studied consisted of post-prostatic massage secretion and urine. The latter specimen gave much superior results. Although possibility of the cytologic diagnosis in prostatic carcinoma cases was limited, it proved to be reliable. Presently available short follow-up data indicate that this technique may play a role only as a diagnostic aid, however, its real value in prostatic cancer detection, could be only evaluated by long term follow-up of the "high risk" group.


[Intravascular disseminated coagulation syndrome in patients with acute leukemias]. The author discusses the occurrence of disseminated intravascular clotting syndrome in patients with acute leukaemias in the light of personal material comprising 9 cases. The syndrome may appear as a complication of the main disease or of chemotherapy applied in it. It is most frequent in acute promyelocytic leukaemia and this fact may suggest that promyelocytes play a role in initiation of blood clotting. The problem of diagnosis and treatment of this syndrome in patients with acute leukaemia is discussed.


Rapid cytologic diagnosis of surgical specimens. The application of a rapid cytologic procedure for examination of tissue submitted for immediate frozen section diagnosis is reported. Its use in various anatomical locations is described briefly. It is apparent that this technic has wide applicability in the cytologic diagnosis of lesions from all organs. It has been used by the author for the past twenty years and has been found applicable to all types of lesions from all organs.


3H-thymidine incorporation into mammary carcinoma cells obtained by needle aspiration before and during endocrine therapy. 3H-thymidine autoradiography was used to evaluate DNA-synthesis in carcinoma cells obtained by fine-needle aspiration biopsy from mammary carcinomas. Needle aspirates were analyzed before and after oophorectomy, and before and during treatment with oestrogen or anti-oestrogen (tamoxifen). Tumor regression occurred in 18 patients-in one of four following oophorectomy, in 15 of 38 treated with tamoxifen and in two of three given oestrogen. Seven tumors remained stationary for long periods-up to a year. In 20 cases there was tumor progression. Regression of tumors was preceded by a decrease in the fraction of 3H-thymidine-labeled cells (s-phase cells). The tumors that remained stationary or progressed retained significant levels of 3H-thymidine incorporation. This study thus showed that 3H-thymidine autoradiography can give an early estimate of tumour response to endocrine therapy. Considerable differences were found between the carcinomas in regard to proportions of S-phase cells. Further insight into this parameter may be useful for planning chemotherapy with S-phase specific agents.


[The lipid metabolism of the small intestine and its correlation to the lipid and lipoprotein metabolism of the total organism]. It is attempted to discuss the intestinal lipid metabolism particularly as it relates to systemic lipid and lipoprotein metabolism. In an introductory review of recent concepts of intestinal fat absorption special reference is given to the significance of the mixed lipid micelle during the intraluminal phase of fat absorption, to special morphological and functional features of the lumen-absorptive cell interface and to the proposed role of a fatty acid binding protein in the intracellular transport of long chain fatty acids. Furthermore the metabolic fate of absorbed fatty acids within the absorptive epithelial cell is reviewed and pointed out, that certain proteins (f.i. apoprotein B) are of crucial significance for the export of intestinal lipids into lymph. Absorption of dietary fat, however, is not the only function of the intestine in lipid metabolism. Intestinal mucosa is also capable of de novo synthesis of lipids, a function which is elaborated upon in the discussion of intestinal biosynthesis of cholesterol. Since in addition biosynthesis of cholesterol in the liver has been shown to be under sensitive control of cholesterol in intestinal lymph lipoproteins and the intestine represents the only organ, in which serum cholesterol can be excreted (after conversion to bile salts in the liver), the intestine occupies the central role in cholesterol metabolism. The intensive interrelation of intestinal functions and systemic lipoprotein metabolism is underscored by the more recent finding, that the intestine also synthesizes endogenous lipoproteins, which are secreted constantly into intestinal lymph even in the fasting state, thus contributing to plasma very low density lipoproteins. The intestine is the only organ, in which extrahepatic production of endogenous lipoproteins has been demonstrated. In the special section of this paper own original work is presented, elaborating on intestinal metabolism of plasma free fatty acids (FFA) and dealing with the important question, whether plasma FFA are incorporated into intestinal lymph lipoproteins. Studies were conducted in rats initially, which were given a rapid i.v. injection of labelled fatty acids. Mucosal radioactivity of the small intestine was greatest 2 minutes after i.v. 14C-palmitate, and accounted for 1% of administered isotope. Of mucosal 14C, 42% were present in water soluble metabolites, including CO2 and ketoacids, 28% in phospholipids and only 16% in triglycerides. The specific activity of mucosal triglyceride fatty acids (TGFA) was 11 times that of serum TGFA, confirming triglyceride synthesis by intestinal mucosa. The unexpectedly low percent incorporation of 14C-palmitate into triglycerides and its preferential conversion to water soluble metabolites, reflecting oxidation, were confirmed in double label experiments (3H-palmitate intraluminally, 14C-palmitate i.v.), which showed marked differences in the metabolism of fatty acids entering mucosa simultaneously from the two sources. While i.v...


The exfoliating cervical epithelial surface in dysplasia, carcinoma in situ and invasive squamous carcinoma. I. Scanning electron microscopic study. The exfoliating epithelial surface in cone specimens of the human cervix with histologically normal epithelium, squamous metaplasia, dysplasia, carcinoma in situ and in cervical biopsies with invasive squamous carcinoma was studied by scanning electron-microscopy (SEM). A cobblestone-like surface with anisovillosis seems to herald the appearance of malignant cells on the exfoliating epithelial surface. Post-scanning histologic examination served as a diagnostic reference for the SEM findings.


Comparison of cellular recovery rates and morphologic detail obtained using membrane filter and cytocentrifuge techniques. Two methods commonly used for collecting cells from a large volume of fluid-membrane filters (Millipore, Gelman, and Nuclepore) and cytocentrifugation-were compared for percentage of cell recovery and degree of cell preservation. Twenty samples of body cavity fluid were centrifuged, and the buffy coat of each was resuspended in a balanced electrolyte solution. The cellularity of each suspension was determined using both Coulter Counter and hemocytometer. Exact aliquots of each sample were collected on Millipore, Gelman, and Nuclepore filters and on slides by cytocentrifugation (Shandon). The resultant material was fixed in alcohol (95% ethanol), stained by the Papanicolaou method, mounted, and then evaluated with respect to the number of cells present and the diagnostically significant morphologic detail of the cells. Cell recovery was estimated by counting cells in known areas of each preparation and then ascertaining the total area. The Millipore filter technique consistently recovered the highest percentage of cells and preserved the best morphologic detail.


Migraine in children and adolescents.

Migraine in children and adolescents. Although migraine has been considered in the past to be uncommon in children and adolescents, there is mounting evidence that it is not, and that it produces significant childhood morbidity. However, the clinical picture varies from case to case, and often from attack to attack in the same patient. Stress plays a most important role in triggering attacks of this familial disease, and the physician must be aware of this if his treatment is to be successful. In adolescent girls, falling estradiol plasma levels are apprently important in triggering attacks of migraine associated with menstruation. In an attack, the initial vasoconstrictive phase, mainly intracranial gives way to a vasodilative phase, mainly extracranial, which results from withdrawal of the vasoconstrictive support from the extracranial arteries which is normally provided by serotonin. The plasma level of the latter drops sharply during an attack, and its excretion product, 5-hydroxy-indole acetic acid, appears in increased amounts in the urine. Laboratory investigations, after a most careful, detailed history, and physical examination, should include an EEG, skull films and possibly a brain scan. Management includes prophylactic measures, both environmental and pharmacologic, and treatment of the attack itself, where promptness is the watchword.


The impact of illness in adolescence and coping behavior. The emotional impact of serious illness or injury bears just as much potential for being disabling to an adolescent as does the condition itself. It is also these concerns and the possibilities for difficult behavior on the part of teenagers on the ward which frequently cause staff members to feel at a loss when caring for this reputedly difficult age group. But if one carefully examines the specific developmental stresses of illness and the various coping mechanisms by which the youth may counter them, a logical management approach emerges. To a large degree this approach depends on compensation, intellectualization, displacement and constructive denial but also recognizes that destructive denial, regression and projection do normally and naturally occur at various points in the course of illness and hospitalization and that panic and acting out may also readily occur, but less frequently. The deterence of the more deleterious responses and promotion of the more felicitious dependes on a ward setting which provides for the adolescent's growing need for independence and self-determination; for continued reassurance about body image integrity, for resumption of mastery and control; and for the maintenance or restoration of his sense of self-worth. These goals are achieved by encouraging the youth to be an active partner in his own care; to share in decisions made about his condition; to pursue just as much independent self-management as he can; to actively engage in establishing a peer group with other adolescents in the ward; to continue with his education, socialization, personal interests and outside peer contacts as much as possible; and to feel that the staff respects his dignity and privacy, likes him as a person and appreciates the courage and effort with which he is facing a difficult time.


New approaches to the delivery of health care to adolescents. Adolescents are a new population group showing certain common characteristics which transcend the confines of geography, economics, education, culture and race. Certain health problems have emerged which are closely related to the life style of teenagers. These health needs are not met by existing health care delivery systems, and future planning must take into account the morals of young people. At present there is no unified approach to the development of health care programs for adolescents, but important explorations of effective methods are are taking place in a fragmentary way. The challenge is to provide the necessary technology and professional expertise in an accessible setting and then to weld these services into programs which will become cohensive and stable. Analyses of data show that adolescents seek help more often for primary and preventive care than for serious ilnesses. Services are particulary needed for addictive problems, emotional disorders, suicidal states, and conditions related to  sexual activity. Consideration of the effect of adolescent behavior on the reproductive cycle is of the utmost importance. These sequelae of conception and veneral disease can be extremely serious for the immature girl and her baby. Therefore the opportunity for birth control, health education, abortion and prenatal care for teenagers should be priority goals in any program for adolescents. The provision of services for the young mother and her baby should be included in the overall plan. New approaches in the ambulatory care of adolescents include an age-specific operation, satellite clinics with hospital backup, and the inclusion of young people in the planning services. Care should be comprehensive and continuous, and a multi-disciplinary staff team would permit a more effective approach. The involvement of other teenagers as assistants in counseling has been found an effective method of communication; this relaitonship may bridge the generation gap when highly personal experiences must come to the surface. Financial and legal barriers should be removed so that care is available to all. Social systems which affect the adolescent should coordinate their activities at all levels. Examples of some innovative methods are available. The ideal approach to health care delivery for adolescents is not yet established; but it must obviously do more than merely cope with a series of crisis oriented episodes. A recognition of underground self-help methods is needed, even if in the last analysis these methods are found to be irrelevant and are discarded. The health of teenagers automatically and immediately affects the well being of the following generation. No effort to improve the situation should be spared.


The adolescent with a learning problem. Experience and insight with delinquent boys. Twelve teenaged boys referred by a juvenile court clinic because of delinquent behavior and academic failure were examined by an experienced team of pediatricians, neurologists, psychologists, social workers, nurses, and occupational, physical, recreational, speech and hearing therapists. Two boys came from troubled families with long histories of legal problems, had behavior problems antedating their school difficulties and had no evidence of perceptual handicaps. The remaining ten were the family blacksheep whose academic problems began early and whose behavior decompensated later. They all had perceptual handicaps and both groups of boys had intense psychological reactions to their school difficulties. The learning disabled require a flexible team approach in school together with individual, group and family therapy in order to achieve success.


Proceedings: Persepectives on adolescent medicine: concepts and program design. The concepts and goals of a program in adolescent medicine should include development of a capability to focus on current health needs of youth in a variety of settings; to plan clinical services to meet those needs with the flexibility necessary to respond to changing future requirements; and to deliver service within such a context while simulataneously creating a milieu conducive to education and investigation into the very process and definition of adolescence. The Division of Adolescent Medicine at Montefiore Hospital and Medical Center was designed 7 years ago to fulfill these goals and consequently may serve others as a functional model for health care delivery to teenagers. The Division is comprised of: (1) a 37 bed in-patient unit; (2) a hospital-based ambulatory program including general diagnostic and follow-up services, as well as a speciality service capability in the areas of gynecology and family planning, cardiology, gastroenterology and nutrition; (3) primary care health services within teenage dentention and prison facilities; (4) addictive disease diagnostic and treatment programs; (5) school health programs from intermediate school through college levels, and (6) the division also performs supportive and consultative functions for a variety of community-based agencies. Within the programatic design approximately 70,000 adolescents have been served. The cornerstone of the educational and investigative efforts has been the concept that all the above six functional units are clinical laboratories and classrooms so that training and research activities are integral parts of each of the service areas. This program design is continually undergoing revision and refinement so as to remain ever-responsive to new and emerging problems to meet additional training demands and, most importantly, to permit and encourage creativity and growth patients and staff.


Management of hallucinogen abuse.

Management of hallucinogen abuse. Most street hallucinogens contain either LSD or phenycyclidine HCl (PCP). Because the acute phase of LSD and PCP mimic several other drugs and conditions, it is important to exclude these other possibilities. When faced with LSD or PCP, "talking down" usually suffices for the mild case; management becomes more complex should hyperpyrexia, coma, seizures or a hypertensive crisis ensue. Diazepam, not a phenothiazine, is preferred for sedation.


Immune markers in adult acute leukemia.

Immune markers in adult acute leukemia. Three cases of adult acute leukemia were examined for immunologic markers. Incubation of leukemic cells with anti-D (IgG)-coated erythrocytes was used for the identification of monocytes; sheep erythrocytes were employed for T-cells and fluorescein-conjugated anti-mixed immunoglobulins for B-cells. It was shown that IgG receptors (monocytes) were present on immature cells with predominant monocytic components; T- and B-cell markers were absent in the mono- and myelocytic leukemias.


Evaluation of the Lung Ventilator Performance Analyser. The characteristics of the Lung Ventilator Performance Analyser (LVPA) have been compared with the model lung defined in the proposed ISO standard for Breathing Machines. The different characteristics of the two models lead to marked differences in the pressure, flow and volume curves obtained during a standard procedure. The LVPA is a useful teaching tool, but it is recommended that ventilator testing should be performed on a lung model which fulfills the requirements of the proposed International Standard.


A disconnection alarm for the Bennett BA-4 ventilator. A simple warning device is described to attach to a Bennett BA-4 Ventilator. It has proved reliable in practice when the ventilator is operated on pressure limit.


Malaria complicating neoplastic disease. Two patients with neoplastic disease had transfusion-induced malaria. In a patient with acute myelogenous leukemia infected with Plasmodium vivax, neither his underlying disease nor intensive cytotoxic chemotherapy appeared to ameliorate or worsen the clinical course of his infection. In a splenectomized patient with metastatic carcinoma of the colon, P malariae infection was associated with a fulminant course simulating cerebral malaria. Despite delay in diagnosis, both patients responded dramatically to antimalarial chemotherapy and both developed appreciable antibody responses.


Partial deletion of long arm of chromosome 17: a specific abnormality in acute promyelocytic leukemia? Two patients with acute promyelocytic leukemia had an identical chromosomal abnormality detected by fluoresecence banding. In each case, the clinical course was rapidly fatal, and was characterized by a lack of response to chemotherapy with cytarabine and thioguanine, and was complicated by disseminated intravascular coagulation. Bone marrow cells from each patient contained 46 chromosomes; in each instance, however, one chromosome 17 had a deletion of almost one half of the proximal portion of the long arm [del(17)(q11q21 or 22)].


[Changes in the proteins of erythrocyte membrane in polycythemia vera]. Red cell membrane protein behaviour was studied in patients with polycythaemia vera, polyglobulia secondary to cardiorespiratory disorders, chronic myeloid leukaemia and acute granuloblastic leukaemia. Electrophoretic pictures were examined after solubilisation in urea or SDS and on various supports. Chromatographic analysis was also made of acid, neutral and basic amino acids obtained by hot-acid hydrolysis of the stromas. Protein electrophoretic changes in polycythaemia differed from those observed in  granuloblastic leukaemia and chronic cor pulmonale. Different stromal protein amino acid percents were also noted, with marked variations between each disease.


[Juxtacortical osteosarcoma (author's transl)]. Juxtacortical osteosarcoma should be considered a very rate distinctive entity under all malignant bone tumors. The tumor has a remarkable tendency to grow from the periostal tissues peripherally with a usually marked degree of ossification without primary medullary involvement. It's different und characteristic behavior in clinical, roentgenographic and microscopic findings from that of other types of bone-forming sarkomas is discussed by means of a just treated case. In contrast to osteogenic osteosarcoma the prognosis for early well treated juxtacortical osteosarcoma is much better.


Effects of occlusal instability.

Effects of occlusal instability. Changes that may occur in an occlusion are basically either horizontal or vertical. Horizontal changes need not be damaging and may be readily accommodated. Vertical changes can be more damaging and require a more extensive treatment procedure.


Research into mastication.

Research into mastication. An electronic method of recording displacement was used to study mandibular movement during mastication. The technique enables the parameters of muscle activity, the sound of tooth contact, the force developed between opposing teeth, and the displacement of the mandible to be recorded at the same time on a single U/V chart. Previous reports on mandibular movement using cine-photographic techniques were confirmed in relation to mastication, but additional information was obtained in relation to muscle activity in the final closing movements. It appears that tooth contact initiates a latent-silent period in masseter and temporalis which occurs before movement is arrested in the final intercuspal position. It is considered that the kinetic energy of the mandible on closing is reduced by the cessation of activity in these two muscles during the silent period and finally absorbed by the crushing of food during the terminal intercuspal slide to rest. A description of mastication is given and a theory advanced that this may be controlled by a central clock mechanism.


Vasoactivity of local anaesthetic solutions. The basic mechanisms responsible for effects of vasoconstrictors in local anaesthetic solutions are not fully understood. In this paper the interactions of the various ingredients of local anesthetic solutions are considered. Some of the author's work in this field is summarised and current research is discussed.


Cryosurgery.

Cryosurgery. Cryosurgery offers a means of destroying tissue by subjecting it to extreme cold. The mechanisms by which cells die are as yet poorly understood, but reliable and predictable clinical results have been obtained in the treatment of a wide range of benign and premalignant oral lesions. Its effectiveness in the primary treatment of malignant oral lesion has not been adequately assessed but at least it offers palliation and relief of intractable pain where conventional cancer therapy has failed. The use of carbon dioxide 'snow' has been tested and found to be a simple and effective means of treating superficial benign lesions of the mouth.


Medico-dental dilemmas.

Medico-dental dilemmas. Patients with a variety of diseases in the oro-facial region are frequently confused when trying to decide from which of the professions of medicine and dentistry to seek treatment. Furthermore, during the process of arriving at a diagnosis, numerous practitioners and specialists in both professions may be called in for consultation, thus adding to the dilemma. Four cases are reported in this article to illustrate the problem, and some conclusions are drawn as to how it may be minimized albeit not completely solved.


Gastric glycoproteins in chronic peptic ulcer. The output and concentration of gastric glycoproteins in gastric juice from patients with chronic duodenal and gastric ulcer and from controls, have been determined in the basal state and following pentagastrin stimulation. Patients with gastric ulcer had a significantly higher basal glycoprotein output, basal glycoprotein concentration and stimulated glycoprotein concentration than patients with duodenal ulcer or controls. The basal and stimulated glycoprotein output in gastric juice from patients with duodenal ulcer and controls was independent of ABO blood group and secretor status. The carbohydrate composition of the gastric glycoproteins has also been determined in the basal state, and following stimulation of gastric juice by pentagastrin, which did not influence the carbohydrate composition of the molecules. The principal carbohydrate components were galactose, N-acetylglucosamine, fucose, N-acetylgalactosamine, and sialic acid. Small amounts of mannose and glucose were detected in some gastric glycoprotein samples. The carbohydrate composition of the glycoproteins varied according to the ABO blood group and secretor status of the individual. Glycoproteins form stimulated gastric juice from non-secretors of groups A and O had a higher sialic acid content than glycoproteins from secretors of the same blood groups. There were no significant differences in the carbohydrate composition of glycoproteins from patients with chronic gastric and duodenal ulcer compared with gastric glycoproteins from control subjects of the same blood group and secretor status.


Serum gestrin in Chinese patients with peptic ulcer. Fasting serum gastrin was determined in 30 Chinese patients with duodenal ulcer, 43 Chinese patients with gastric ulcer, 23 Chinese control subjects, 14 European control subjects and ten Indian control subjects. Basal and pentagastrin-stimulated peak acid outputs were also determined in the Chinses patients with duodenal or gastric ulceration. The mean (+/- SD) basal serum gastric level for Chinese controls and Chinese patients with duodenal and gastric ulcer were 24-6 pg/ml (+/- 13.7 pg/ml), 18-5 pg/ml (+/- 8-9 pg/ml), and 33-9 pg/ml (+/- 27-7 pg/ml), respectively. Statistical analysis showed no significant difference between the Chinese control subjects and the Chinese patients with duodenal or gastric ulcer, but the mean fasting serum gastrin level of Chinese gastric ulcer patients was significantly higher than that of Chinese duodenal ulcer patients. Comparison of the mean fasting serum gastrin level of the Chinese, European, and Indian control subjects showed no significant difference. Statistical analysis also showed no significant correlation between fasting serum gastrin level and both basal and peak acid outputs, in Chinese patients with duodenal or gastric ulcer.


Salicylate therapy and drug interaction in rheumatoid arthritis. Salicylates form the basis of drug treatment in rheumatoid arthritis. Despite their use for many decades, there is considerable confusion about what constitutes a regime which will ensure anti-inflammatory properties. We have found that blood vessels in the proposed therapeutic range can be maintained overnight on a four times daily dose regime, using either soluble aspirin (in the form of "Disprin") or aloxiprin ("Palaprin Forte"), and on a 12 hourly regine using an aspirin-sustained release aspirin combination ("BiPrin"). Because of variation in the levels reached using a fixed dosage schedule, treatment should be individualised. No correlation was found between dosage levels and either disease activity or serum albumin levels. No significant alteration in free or total salicylate levels was found following the addition of indomethacin to therapy.


What is tertiary hyperparathyroidism?

What is tertiary hyperparathyroidism? Five patients who had gross abnormalities of calcium and phosphorus metabolism due to long standing renal failure are described to illustrate the difficulties with the term "tertiary hyperparathyroidism". One patient who had unequivocal biochemical tertiary hyperparathyroidism was found histologically to have nodular hyperplasia of all four glands even though one gland weighed twice as much (12g) as the combined weight of the other three. Another patient was not hypercalcaemic but had all the other features of the condition including rapid onset of osteitis fibrosa, vascular calcification and a probable parathyroid adenoma, with hyperplasia of the three glands. The other three had hypercalcaemia only after a reduction in the plasma inorganic phosphorus due either to renal transplantation or aluminum hydroxide therapy. The bone histology of the five patients varied from severe osteomalacia to severe osteitis fibrosa. A consideration of the factors involved in causing hypercalcaemia in these patients and a review of the literature leads to the conclusion that the term tertiary hyperparathyroidism is often misleading and best avoided.


Rapid correction of water intoxication by hypertonic saline and frusemide. A case of profound hyponatraemia with severe cerebral dysfunction, induced by excess water intake and exacerbated by smoking, is described. Rapid correction with hypertonic saline infusions and frusemide allowed a negative fluid balance and elevation of serum sodium concentration to be achieved without precipitating acute pulmonary oedema.


Paget's disease in identical twins.

Paget's disease in identical twins. Paget's disease of bone was found in each of elderly monozygotic twin sisters. Apart from the skull, which was affected in each twin, different bones were involved by Paget's disease. This is the fifth pair of identical twins reported with Paget's disease of bone.


The use of high calcium dialysate in the treatment of renal osteomalacia. Four chronic haemodialysis patients suffering from osteomalacia were treated by increasing their dialysate calcium concentration from 1-40 to 2-15 mM/I. Bone biopsies were taken before and after 22 weeks of this treatment and a further biopsy was taken in one patient after 52 weeks. Symptomatic cure occurred in one patient with mild osteomalacia and some improvement osteomalacia and hyperparathyroidism. Bone biopsies showed slight improvement in the patient with mild osteomalacia after 22 weeks, and considerable improvement after 25 weeks. In the patient with mixed histology, the osteitis fibrosa subsided and the osteomalacia became a little worse after 22 weeks. There was no histologic improvement in the two patients with  severe osteomalacia after 22 weeks. It is concluded that high calcium dialysis is not an effective treatment for renal osteomalacia.


Regional differences in lactate concentration in experimental myocardial infarction. Lacate concentrations were measured in blood from (a) coronary veins within ischaemic myocardium and (b) veins nearer to the coronary vein, for periods of up to 2 1/2 hours after ligation of the left anterior descending artery in dogs. Concentrations at (a) were three to four times higher than at (b), while blood sampled simultaneously from two veins at (a) yielded similar concentrations of lactate. At 2 1/2 hours after ligation the veno-arterial difference of lactate concentration in blood from (a) was about one half of the difference at 15 minutes. Lactate concentration at (a) was approximately twice as great when the area of ischaemic myocardium drained by the vein was large (18 not equal to 1% of heart weight) than when it was small (6 not equal to 1% of heart weight). No close correlation was apparent between the height of epicardial ST-segment elevation and the level of lactate release. These experiments extend previous observations that changes in lactate concentration at a given site may reflect changes in venous dilution, rather than in the rate of production of lactate, and emphasize that caution is necessary in interpretation of changes in concentrations of metabolites in coronary sinus blood after acute myocardial infarction in man.


The significance of chest pain occurring with the Master two step test. This study has assessed whether chest pain occurring during or after a step test could improve the accuracy of exercise testing in the diagnosis of coronary artery disease (CAD). One hundred and fifty-three consecutive men underwent the double Master two-step test prior to diagnostic coronary arteriography. On hundred and twenty-five had CAD, 28 insignificant disease (NCA). The post-exercise ECG showed at least 0-5 mm of ischaemic ST depression in 71 (57%) of the men with CAD and in five (18%) with NCA. Ischaemic ST depression of at least 2-0 mm occurred in 24 men, all of whom had CAD. Chest pain occurred during or after the test in 78 (62%) men with CAD and in nine (33%) with NCA. The accuracy of diagnosis of CAD could be improved by combining the occurrence of chest pain in the test with a positive post-exercise ECG. Either a 2 mm positive post-exercise ECG with or without test angina or 0-5 mm to 1-9 mm positive post-exercise ECG with test angina was found in 56 (45%) of men with CAD and one (4%) with NCA. Thus the concurrence of chest pain during or after a double Master two-step test, together with ischaemic ST segment depression after the test, strongly suggests the presence of CAD.


Diazoxide-induced renin release in diagnosis of remediable renovascular hypertension. In hypertensive patients with unilateral renal artery stenosis, intravenous diazoide increased renal vein renin activity more on the involved side than on the contralateral side, whereas, in a group with predominantly unilateral renal parenchymal disease, the increase in renal vein was similar for both kidneys. In patients with bilateral renal artery stenosis, the use of diazoxide was helpful in lateralizing the dominant ischaemic lesion. Diazoide administration appears to be a safe, rapid and convenient method of increasing the sensitivity of the renal vein renin test used in predicting the outcome of surgical treatment of renovascular hypertension. Bilateral renal vein renin determination of established value in the diagnosis of functional renal ischaemia. 1-4 However, in the use of this procedure to predict the efficacy of corrective surgery, false positive and false negative results still occur. Thus, various manoeuvres which stimulate renin release have been employed to  improve the sensitivity of the test. 5-7 We report a new application the practical approach to of this procedure in the diagnosis of renal hypertension, which both basal and stimulated levels of renal venous renin activitity can be measured during a brief period of bilateral renal vein catherization.


Haemolysis in liver disease: relationship to erythrocyte membrane function, serum bilirubin concentration and plasma electrolyte disturbances. The pathogenesis of the mild to moderate haemolysis that is almost universal in patients with liver disease was investigated to determine if it was related to dysfunction of the red blood cell (RBC) membrane resulting from abnormalities in plasma electrolyte, urea or bilirubin concentrations. Thirty-nine patients with various forms of liver disease were investigated as well as six with miscellaneous diseases associated with plasma electrolyte disturbance. RBC membrane permeability was measured by the rate of 22Na influx. The results showed that the shortened RBC survival in liver disease is not related to morphological changes in the RBC or altered membrane integrity as measured by osmotic fragility, mechanical fragility, autohaemolysis, membrane ATP and membrane permeability.


Hereditary thrombocytopathy: a familial bleeding disorder due to impaired platelet coagulant activity. A family with a bleeding disorder due to congenital thrombocytopenic thrombocytopathy is described, with ten affected members in three generations. The disorder is inherited as an autosomal dominant trait and is characterized by thrombocytopenia, morphologically abnormal platelets, prolonged bleeding time, platelet coagulant activity deficiency and abnormal platelets, prolonged bleeding time, platelet coagulant activity deficiency and abnormal platelet aggregation. Patients' platelets adhered to collagen, but aggregation was reversible and the release of platelet constituents was minimal. Aggregation with ADP was similarly reversible, but the platelet response to thrombin was normal. These defects in platelet aggregation and release were not corrected by addition of normal plasma indicating an intrinsic abnormality of platelets. By definition thrombocytopathy consists of a deficiency in platelet coagulant activity. It was shown that the deficiency of platelet coagulant activity caused a delay and decrease in the conversion of prothrombin to thrombin, and it is proposed that the lack of thrombin accounts for the defective release reaction and the reversible aggregation. An adequate haemostatic plug due to decreased release of ADP, together with instability of the plug provide an explanation for the bleeding tendency in thrombocytopathy.


Evaluation of an enteric coated aspirin preparation. The bioavailability and gastrointestinal site of release of enteric coated aspirin tablets ("Rhusal", G.P. Laboratories) were investigated following dosage with single tablets. A delay of one to more than eight hours was observed between dosage and the appearance of salicylate in plasma or saliva. This delay was decreased by pretreatment with metoclopramide. No aspirin or salicylate was detected in gastric aspirates. The mean urinary recovery of salicylate was equivalent to 92% of the administered dose. All these tests were consistent with the designed function of the enteric coating. The time course of concentrations of salicylate in saliva rather than in plasma was confirmed as a useful technique for the evaluation of different formulations of aspirin. The acceleration of gastric emptying by metoclopramide is a useful technique for the evaluation of enteric coated tablets.


Spirometric values for normal Perth children aged six to twelve years. The purpose of this study was to construct tables and nomograms of spirometric norms for Perth children aged between six and 12 years. These norms were to be based on anthropometric measurements and age. A sample of 623 children was tested of which 556 were analysed and comprised 289 boys and 267 girls. All testing was carried out in the child's own school. The spirograms were recorded with a dry spirometer from which the FVC, FEV1, and FMF were measured. Correlation coefficients were established between each of these ventilatory parameters and anthropometric measurements of height, mass, arm span and age. The findings of the study revealed high correlations for both boys and girls between ventilatory parameters of FVC and FEV1 and height, mass, arm span and age. Moderately high correlations were found for both sexes between FMF and height, mass, arm  span and age. Height correlated best with each of these ventilatory measures. It was also established that significant improvement in some correlations was obtained when anthropometric values were used in multiple correlation analysis. The use of height plus mass proved to be best when predicting FVC and FEV, for boys and girls, and for predicting FMF of girls. FMF for boys could be best predicted by using height alone. The limits of normality for ventilatory parameters of FVC, FEV1 and FMF were found to be best defined by the per cent standard error of the estimate. Tables and nomograms were established from regression and multiple regression equations in order to predict normal values in children. The findings of this study revealed that little difference existed between the ventilatory values of children tested in Perth, Europe and the Eastern States of Australia. However, the differences that were found to exist could be due to the age group which was sampled or possible environmental and genetic differences.


Cardiovascular complications due to pheniramine overdosage. Cardiovascular toxicity including ventricular extrasystoles associated with pheniramine overdosage has been documented in the absence of factors recognised to aggravate this toxicity. The presence of pheniramine and the absence of other compounds was established using analytical techniques. It is concluded that patients with pheniramine overdosage should be treated exercising the same precautions as with tricyclic overdosage. Several sudden and unexpected deaths have occurred due to pheniramine overdosage in both adults and children. The cause of death in each case was not known. The purpose of this report is to document clinical features of pheniramine overdosage, in particular previously unsuspected cardiovascular toxicity manifesting as clinically significant ventricular arrhythmias. Pheniramine was positively identified in the overdosed patient, and the presence of other agents excluded.


Recurrent ventricular tachycardia in hypothyroidism. Ventricular tachycardia associated with myxoedema is rare. Only two cases have so far been documented. In the report by Hansen, the patient had recurrent chest pain which suggested coexisting coronary heart disease. In the second case, the patient developed recurrent ventricular tachycardia only after intravenous triiodothyronine was given. This paper reports a further case of hypothyroidism with recurrent episodes of ventricular tachycardia and ventricular fibrillation which was not associated with any of the established causes of this arrhythmia.


Detection of hepatitis b surface antigen in patients with acute viral hepatitis. The relative value of solid phase radioimmunoassay and counter immunoelectrophoresis for the detection of hepatitis B surface antigen in the serum, was studied in 1401 patients with acute viral hepatitis. When specimens were obtained early in the illness, counter immunoelectrophoresis was found to be a reliable test for the diagnosis of hepatitis B, detecting 95.6% of patients found to be antigen positive by radioimmunoassay. The additional sensitivity of radioimmunoassay was of particular value for detecting antigen later in the illness and in patients with post-transfusion hepatitis in which the titre was frequently below the level detectable by counter immunoelectrophoresis. Radioimmunoassay was also of value in testing sera which had been stored for many years, detecting up to 3-3 times as many patients with hepatitis B as did counter immunoelectrophoresis.


Gangrene following intra-arterial injection of procaine penicillin. Irreversible ischaemic gangrene of the upper limb developed in a one-year-old child after an unintentional intra-arterial injection of procaine penicillin. The hand needed amputation. Arterial embolization phenomenon along with intense vasospasm appears to have been responsible for this rare complication. Unintentional intra-arterial injection of penicillin intended for intra-muscular use may lead to disastrous consequences. Regional tissue necrosis has been described previously but ischaemia leading to gangrene of an extremity has not been reported. The following is a case report of a child who developed such a gangrene in his hand which had to be amputated.


Neuroendocrine identification of depressed patients. Recent studies of hypothalamo--pituitary--adrenal (HPA) suppression in depressed patients indicate that these subjects often show abnormal early escape of plasma cortisol levels following an initial suppression. Non-depressed psychiatric inpatients usually show normal sustained HPA suppression. The responses of 49 depressed and 30 non-depressed patients have been analysed to develop criteria which can make the dexamethasone suppression test suitable for outpatient studies. The cortisol levels measured in a 24-hour urine collection and a single blood sample post-dexamethasone were sufficient to enable 61% of the depressed patients to be identified correctly at a confidence level of 90%, on the basis of at least one abnormal cortisol value. When both cortisol values were abnormal 35% of the depressed patient were identified correctly at a confidence level of 100%. Patients with "endogenous" depressive profiles had the most abnormal results. A normal response to this test will not necessarily exclude the diagnosis of primary depressive illness. An abnormal response to the test may be of help in confirming the diagnosis. With the simplified procedure outpatient studies may become possible.


The great debate.

The great debate. A.R. Jensen's hypothesis concerning genetically-determined differences in intelligence between North American blacks and whites is summarised. Problems involved in the application of heritability statistics to IQ data are discussed. The concept of "intelligence" is reviewed from a cross-cultural perspective, and an alternative model of potential, competence and performance is proposed. Finally, the questions of scientific freedom and social responsibility are touched upon, and the implications of the great debate for scientists and educators discussed.


A scale to measure the stress of life events. A comprehensive life event inventory suitable for questionaire or interviewer administration has been constructed. Two sets of matched scalings of these life events have been derived from the responses of an Australian urban population. Each of the scalings were consistent across the sociodemographic groups in the population. The two scales allow the significance of life events to be scaled in conceptually different ways. The first follows Holmes concept of the extent of life change produced by the event, the second the Paykel concept of the amount of distress caused by the event. The inventory and the scalings are suitable for use in an Australian urban population.


Good death: responsible choice in a changing society. Revolutionary advances in social and medical knowledge and technology have radically changed the conditions which precede death for an increasing number of people. The fear of death is being replaced by the dread of too-prolonged life, a feature of which is a widely documented incidence of both pain and physical and mental distress. This situation has produced the accelerating social demand for euthanasia (a painless inducement of death, preferably by medical means) to be legally available to a suffering person earnestly desiring it. The attitudes of medical workers are ambivalent, trapped as they are between a changing society and intransigent law. Psychiatry, however, and its concern for the whole person, is potentially an ally of those who desire to educate the community to a healthier view of death, even a planned death, as a part of life and a responsible conclusion to it.


Lithium neurotoxicity.

Lithium neurotoxicity. One of the most alarming and potentially serious complications of Lithium Carbonate therapy is the emergence of central nervous system toxicity. This paper discusses the clinical changes that may occur with illustrative case histories. The role that such factors as serum Lithium levels, sodium balance, organic brain damage, clinical typology, concurrent physical illness and drug interaction play in the genesis of this disorder is discussed. Permanent neurological damage following Lithium poisoning is discussed and guidelines for appropriate use and monitoring of Lithium in psychiatric disorders is outlined.


Concepts of mental illness amongst the rural Xhosa people in South Africa. The rural Xhosa people of South Africa have retained social cohesion through traditional custom, purity of language and the dominant role of ancestor worship, traditional medicine and witchcraft in life-style, beliefs and ceremonies. Abstract concepts are limited and ego defence mechanisms include projection, displacement and rationalization but cognitive disturbances per se are not regarded as important. Major attention is paid to severe conative and affective disturbances, ascribed to object or spirit intrument by a traditional "witchdoctor". Therapy is community orientated as far as possible unless uncontrollable violent behaviour necessitates referral to a mental hospital.


Rating scales as predictors of response to tricyclic antidepressants. Fifty-three patients suffering from depressive illness were classified as 'responders' or 'non-responders' on the basis of an "amelioration score" of the Hamilton Rating Scale for depression after six weeks treatment with nortriptyline hydrochloride at 150 mgs. daily. A multivariate analysis of variance was performed on the four psychological rating scale scores used, to determine whether rating scales could predict treatment response to tricyclis antidepressants was found to be at 75% probability.ic anti-depressants was found to be at 757. probability.ic antidepressants. There was a significant difference between the two groups after adjustment for age. Subjects were then classified as 'non-responders' and 'responders' on the basis of their discriminant scores. The prediction of response to tricycl


An evaluation of evidence on depressive classification and some alternative suggestions from physiology. The wealth of material on depressive classification provides both researcher and clinician with a sorting task of monumental proportions. Moreover the criticisms which have been fired at studies of depressive classification using symptoms as a data base, also require systematic sorting and elucidation. An attempt has been made to review the major studies of depressive classification in a systematic way, together with the principal criticisms which have been made of them. The survey is not exhaustive but aims at providing a relatively ordered overview of the area. The most critical issue, that of subjectivity of data collection is taken up, and it is suggested that biological measures may form a more objective data base for studies of depressive classification than ratings of symptoms and behaviour.


The measurement of plasma levels of tricyclic antidepressant drugs. A double-isotope derivative dilution procedure for measuring plasma levels of Nortriptyline is described. The assay is specific, sensitive, precise and reproducible. Studies on the variation in steady-state plasma levels are described on a fixed oral dosage of nortriptyline. Between individual variations in steady-state plasma levels are large. Between day within individual variation is 15-20%. Dosage regime, time of blood sampling after last oral dose and the method of blood handling are unlikely to affect the steady-state plasma levels. Within an individual, the oral dose, duration of treatment and concomitant drug treatment are all important determinants of the steady-state plasma level.


Taboo and Malay tradition.

Taboo and Malay tradition. According to Malinowski there are no peoples, however primitive, without religion and magic; nor are there any societies lacking either in the scientific attitude or in science (Blumberg 1963). Magic and taboo are resorted to when through the normal use of science, or rational techniques, man is unable to control unpredictable events important to him. Where there is difficulty in predicting the outcome of behaviour, where the results of action are not consonant with effort, where there are great limitions on man's knowledge of vital issues, magical techniques are employed--in short, where circumstances of life are uncertain, uncontrolled and unknown. Magic and animism are systems of thought which give not only the explanation of a single phenomenon, but make it possible to comprehend the totality of the world from one point, as a continuity. Of the three systems of thought--animistic, religious and scientific--animism is perhaps the most consistent and the most exhaustive, the one which explains the world in its entirety.


Psychotherapeutic management of a potential spirit medium. Psychotherapeutic management of a potential spirit medium (shaman) in a modern University Hospital setting in Malaysia is described. Magical thinking, projection and spirit possession (trance state) occur during management. Discussion of management was based on what Heinz Wolff described as the psychotherapist's functions of (1) psychodynamic understanding; (2) the therapeutic function; and (3) the developmental function. This patient did not conform to the general criteria of a suitable patient for psychotherapy. But her willingness to engage in therapy contributed to a satisfactory outcome. The therapist's growth in cross-cultural therapeutic encounter seems to be prominent.


Meth-drinkers and lotus-eaters: some educational aspects of transcultural psychiatry in Papua New Guinea. The rapid development of Third-World societies in the Pacific Region, as elsewhere, involves modern, traditional and idiosyncratic factors. Often this complex of interaction is expressed or symbolically exemplified in aberrant behaviors. The paper presents some examples from Papua New Guinea, including methyl-alcohol poisoning amongst students and cargo cults, as part of an interface between traditional and modern. Such aberrant and psychotic behaviors provide a datum for curricula and clinical services. Psychiatric efforts via related disciplines such as anthropology, can provide dramatic pan-human insights into development for contemporary educational and health-delivery services, ultimately with more meaning for recipients, practitioners and research.


Associative illness among aboriginals.

Associative illness among aboriginals. Associative mental illness occurring in close relatives is described from Numbulwar and Yirrkala Missions, two Aboriginal communities in Eastern Arnhem Land. Since it is a clear example of the influence of culture on mental illness, these factors which facilitate the production of the illnesses are examined. They are (1) cross-identification between members of the clan group; (2) the assumption that mental illness is caused by sorcery which acts to detriment of all the relatives in a clan group, not only on the individual; (3) the belief that mental experiences in general are not private and may be shared by close relatives.


Psychiatry in Bali.

Psychiatry in Bali. Since the advent of modern psychiatry to Bali in 1968, great strides have been achieved, but based on the above field study it is found that a large part of the mentally disturbed still rely upon traditional psychiatry, a fact which sould be kept in mind when planning future mental health activities.


The attribution of mental illness by rural Balinese. This paper is based on the answers of 208 Balinese rural respondents to the question "What makes you think person X is mentally ill?" The responses are tabulated by age and sex and a cluster analysis is carried out on them. It is shown that the rural Balinese view interference with others and threatening behaviour as prime indicators of mental illness, but that different indicators are commonly used for women, men, the old and the young. The results are discussed with reference to a sociological model and a medical model of diagnosis.


Influence of exogenous tRNA on growth of transplantable 32P-induced osteosarcomata. The weights of osteosarcomata that arose 22 days after the s.c. injection of cell suspensions (of whold tumours) that had been exposed in vitro to tRNA were significantly different from the weights of those arising from untreated cells. The tRNA was isolated by phenol extraction and DEAE-cellulose chromatography from eviscerated full-term rat embryos, from rat mesenchymal (granulation) tissue and from rat anaplastic osteosarcomata. Tumours developing from osteosarcoma cells treated with either embryonic or normal mesenchymal tRNA were reduced in weight by 76% and 60% respectively. These effects could not be explained as a toxic consequence, because tumour weight was increased by 128% after exposure of cells to osteosarcoma tRNA. In this osteosarcoma model it appears that tumour weights can be influenced in different ways by tRNA from different sources.


A mathematical model of the acute myeloblastic leukemic state in man. A dynamical mathematical model of the acute myeloblastic leukemic state is proposed in which normal neutrophils and their precursors, and leukemic myeloblasts, proliferate as distinct but interacting cell populations. Each population has a Go compartment, consisting of resting cells, that acts as a control center to determine the rate of proliferation. These rates are assumed to depend on the total number of cells in the combined populations. The presence of the leukemic population destabilizes the homeostatic state of the normal population, which is stable in the absence of leukemic cells, and drives the system to a new stable state consisting entirely of leukemic cells and no normal cells. Calculations based on the theory suggest that it is able to simulate the kinetic features of this disease state, at least in its typical manifestations.


Accelerated myeloblast destruction and abnormal lysosome disruption in cultured bone marrow: association with indolent acute myelogenous leukemia. Despite no chemotherapy and a marrow morphologically typical of frank relapse, an acute myelogenous leukemia (AML) patient survived for nearly 1 yr. During this time she remained asymptomatic and maintained nearly normal levels of platelets and hemoglobin. Cytochemical and electron microscopic studies of her bone marrow in liquid culture revealed on several occasions a unique maturational sequence in that leukemic cells differentiated to form morphologically abnormal primary granules which appeared to rupture and cause cytolysis of these cells. In these cultures, blasts rapidly disappeared and were replaced by more mature granulocytes, in contrast to observations in cultures derived from five other patients with AML in relapse which showed persistently elevated blast counts with no evidence of maturation in vitro. These findings support the concept that in AML cell maturation is regularly impaired and in some cases also aberrant. In addition, the abnormal granule formation with autolysis of the leukemic cells observed in one patient may explain both the early cell death in vitro and this patient's relatively indolent clinical course. Similar in vitro studies may help predict atypical clinical courses in patients with AML and facilitate design of appropriate chemotherapy.


Further characterization of the circulating cell in chronic lymphocytic leukemia. Peripheral lymphocytes from normal individuals and from patients with chronic lymphocytic leukemia (CLL) were cultured in vitro for 1-7 days. The growth response to phytohemagglutinin (PHA) was quantitated by the incorporation of tritiated uridine into RNA nucleotide during a 2-hr pulse with the radioisotope. While the maximum response in PHA-stimulated normal cultures appeared at 2-3 days, CLL cultures required 5-7 days to develop their maximal response, which was 50%-60% of the normal magnitude. Dilution of the number of normally reactive lymphocytes by culturing them with totally unreactive, mitomycin-treated cells produced a normal 72-hr maximal response, no matter what proportion of unreactive cells was included in the PHA-stimulated cultures. In addition, the response of peripheral lymphocytes from patients with myeloblastic leukemia, where large numbers of unreactive myeloblasts diluted the normal small lymphocytes, a depressed reaction occurred at the anticipated 2-3 days. Nylon fiber-adherent lymphocytes consisting of 85% immunoglobulin (Ig)-bearing cells responded minimally to PHA, but showed no evidence of a delay. When isolated from CLL patients, both fiber-adherent cells (Ig-bearing) as well as non-fiber-adherent (sheep erythrocyterosetting) cells responded to PHA in a delayed fashion. Similarly, a case of CLL, in which 93.5% of the circulating lymphocytes bore sheep red blood cell receptors, showed its peak response to PHA at 7 days. Therefore, using surface marker criteria considered characteristic of normal T cells and B cells, the delayed response to PHA on the part of CLL lymphocytes was independent of thymic or nonthymic origin.


DNA histogram analysis of human hemopoietic cells. The proliferative activity of human neoplasms may be an important determinant for therapeutic management. The advent of automated flow-through systems measuring cellular DNA content by means of fluorescence has considerably facilitated the analysis of cellular kinetics. Using a pulse cytophotometer ICP-11 (Phywe Co., Göttingen, Germany), three different fluorescent staining techniques for DNA histogram measurement on human hemopoietic cells were tested: mithramycin, ethidium bromide, and a combination of ethidium bromide and mithramycin. Employing the tritiated thymidine labeling index as reference standard for comparison with the DNA histogram-derived S-phase fractions, linear correlations were obtained using ethidium bromide alone and ethidium bromide in combination with mithramycin as staining techniques. The fluorescence intensity was increased fourfold to fivefold by the use of the two-dye combination, resulting in a substantial decrease in the coefficient of variation of DNA histograms to 1.5%-2%. This augmented histogram resolution is an important codition for detecting small-degree numeric chromosomal aberrations and discrete drug perturbation effects.


Therapeutic irradiation of the central nervous system using intrathecal 90Y--DTA. The erdication of established neuroleukaemia is often difficult, and with subsequent relapses even harder. The use of an intrathecally-injected beta emitting isotope has the advantage of preserving the bone-marrow of the vertebral column and cranium whislt irradiating the meninges. The value of intrathecal 90Y-DTPA(diethylene-triamine penta-acetic acid) has been investigated in nine patients with neuroleukaemia or CNS involvement in malignant lymphoma. Measurements of retention of the isotope in the whole body, spinal, and intracranial subarachnoid spaces have been made, together with blood levels, and are reported. The clinical results are presented. In three out of five evaluable patients 90Y-DTPA failed to maintain a chemotherapy-induced CNS remission and in two out of two evaluable patients malignant cells were not dispersed from the CNS with a single intrathecal injection of 90Y-DTA. It is concluded, therefore, that with this agent and the doses used no useful clinical result is gained.


Arteriography in bone tumours.

Arteriography in bone tumours. The usefulness of arteriography in the diagnosis and management of bone tumours has been evaluated in 78 cases (49 malignant neoplasms, 17 benign tumours and 12 inflammatory lesions). Using well-defined criteria, of which the presence or absence of tumour vessels is of decisive importance, arteriography represents - not as a routine procedure but in selected cases - a most useful guide to establishing the diagnosis, by adding important information to standard radiography, by defining the extent of the lesion and by assisting in the selection of the best site for biopsy.


The multiple sclerotic osteogenic sarcoma of early childhood. Two cases of sclerosing osteogenic sarcoma that occurred in early childhood are reported. They and the similar cases reviewed are unusual in their development at an unusually early age, their multicentric presentation and their densely sclerotic nature. These are uncommon manifestations of osteogenic sarcoma and are considered due to proliferative metastatic osteoid formation in areas of rapid bone growth.