[New directions in radiotherapy. The use of fast electrons]. The post-surgical radiotherapy of breast cancer and its problems are discussed and an account is given of recent trends in this field. The use of fast electrons is regarded as an optimal form of management for the chest wall, and the ipsilateral subscapular and internal mammary lymph gland chains.


[Erythrocyte protective synergism of ascorbic acid and alpha-mercaptopropionylglycine]. The antitoxic action of 1-ascorbic acid and alpha-mercaptopropionyl glycine was examined via the formation of Ehrlich-Heinz bodies in human venous red cells following in vitro intoxication with 100 mg/ml acetylphenylhydrazine. Marked synergism was noted, especially when small amounts of glucose were added. Both substances displayed a marked affinity for red cells and penetrated them on contact without an incubation period. Optimum amounts for maximum synergy were alpha-mercaptopropionyl glycine 0.01-0.02, 1-ascorbic acid 0.01-0.02 ml and glucose 40 mg per ml of blood. At this dose, appearance of Ehrlich bodies was appreciably retarded. In addition, changes in the size and quality of such bodies pointed to enhanced cell resistance to the poison used.


[Circadian variations in glycemia and IRI in normal subjects, young and adult diabetics and in obese subjects]. Blood sugar and IRI were followed for 24 hr in healthy patients, young and adult diabetics, and in subjects with apparently primary obesity on a standard, normal calorie diet. Morning and nocturnal insulin positivity peaks were noted in the normal subjects, though circadians variations in these parameters were mainly related to meals. This periodicity was altered in young diabetics, for whom insulin responsivity was ruled out, and in the adult diabetics, who displayed deficient insulin secretion in the morning, and delayed secretion after the afternoon meal, and in the obese subjects, the quality of whose response was close to that of the previous group. The usefulness of this type on examination in the planning of diet and drug management, quite apart from diagnosis and prognosis, is stressed.


[Pseudo-tumoral calcinosis universalis]. Marked deposits of calcium salts were noted in the triceps and gluteal and peritrochanteric areas in a 16-yr-old girl. Blood calcium values basal and after stimulation were normal. The classification of the case as a form of pseudotumoral calcinosis universalis is discussed.


[Sporadic persistence of amebic hepatitis]. A case of classical colliquative amoebic hepatitis, documented with aspiration of abundant amoebic pus by means of hepatocentesis and treated with chloroquine and haematin, is reported. This type of amoebiasis is rare nowadays, it is pointed out. Present-day clinico-epidemiological features are outlined: reduction in official cases, reversal of the ratio between colitis and hepatitis (the latter is on the increase), disappearance of acute dysenteric forms, less tendency to colliquative development in cases where the liver is involved, an involvement which is seen most frequently with an atypical chronic-type imprint. Mention is finally made of the reasons behind this cliniqo-epidemiological shift.


[A case of pulmonary eosinophilia with protracted and benign course]. A case of corticosteroid-sensitive pulmonary eosinophilia with protracted course, followed up for more than years, is reported. After highlighting the diagnostic difficulties of such clinical pictures and their as yet ill-defined nosological contours, the comparative benignity of most of such forms is stressed.


[Basic aspects and current trends in iatrogenic kidney diseases. Correlations between their physiopathological mechanisms and clinical findings for the general practitioner]. Iatrogenic origins may be assigned to any form of kidney disease. Of the pathogenetic mechanisms involved, increasing importance is now attached to immunological responses and intravascular coagulopathies, though other processes long known to medicine have not ceased to play their part. Moreover, recent advances in the improvement of drugs and the standardisation of their use have given a better idea of the potential damage to the kidneys from many substances. A re-examination is made of the main findings in this field with a view to offering a simple summary of the underlying physiopathogenetic mechanisms, and drawing the diagnostic and clinical conclusions therefrom, so as to aid the general practitioner rather than the specialist. An account of the various medical interventions that may lead to kidney lesions, and the circumstances in which such interventions are most likely to be harmful, is followed by an analysis of recent opinions on the correct way of administering drugs in patients with kidney disease, so as to limit their potentially harmful effects as far as possible.


[Indirect immunoelectrophoresis in the study of urinary proteins]. The indirect immunoelectrophoresis applied to the proteinurias is a simple and quick method, of usual execution, that makes use of not concentrated urines and discriminant between physiological and pathological proteinurias. The results obtained from a various casistic, collected in many years are presented. For the correlation which exist between morphological isototype and immunoelectropherogram, sometimes, it is possible to go up to the diagnosis of nephropathy also without applying to the renal biopsy.


[The value of electrophoretic studies of urinary proteins in clinical practice]. A brief account of the physiopathology of proteinuria is followed by a description of the diagnostic routine to be followed in such cases, with particular reference to the electrophoretic study of urinary proteins. In many cases, this simple method gives information on a par with that offered by biopsy, especially insofar as the planning of treatment is concerned. Several clinical cases are cited by way of illustration.


[Incidence of skin changes during active chronic hepatitis and liver cirrhosis. Comparison with normal controls]. The frequency of the principal skin changes held to be typical of chronic diseases of the liver has been evaluated together with the frequency of diseases of primarily dermatological interest in a group of 116 chronic liver patients (73 with cirrhosis, 43 with active chronic hepatitis) and in a group of 90 controls comparable by sex and age. The frequency of skin changes secondary to liver disease was statistically higher in the patients with respect to the control group. The incidence of primarily skin diseases associated with liver disease was, by contrast, extremely rare. The simultaneous presence of spiders, hepatic palms and white nails was observed in 21% of the chronic liver patients, while it was never encountered in the controls. Clinical observation of these changes (particularly the triad mentioned) is therefore highly indicative of chronic liver disease, even without a significant clinical history.


[Senile liver and its repercussions on cerebral activity]. On the basis of previous personal data regarding glycidic, lipidic and protein metabolism in groups of young-old-cirrhotic and hypoglycaemic subjects, a correlative study has been carried out for the purpose of highlighting dependence situations between reduced cerebral activity in the elderly and liver-dependent metabolic changes. Specifically as regards protein metabolism, it is shown that all amino acids dependent on the senescence process (glutammic acid, cystine, thyrosine, histidine, threonine, serine) are related to those involved in altered consciousness states (hepatic and hypoglycaemic coma). It is thus possible that in the elderly too there may be some correlation between liver function deficiency and senile encephalopathy.


[Angina syndromes. Clinical data and case contributions from an emergency ward]. The Authours wish to do a personal contribution to the anginosis syndromes. We have a series of fifty-two cases divided in various syndromes. We have, then, examined the possible factors of coronary risk, such as arterious hypertension, smoke, diabetes, hypercholesterolaemia.


[The chordoma. Description of 2 clinical cases and results of oncolytic chemotherapy]. Only seven hundred cases of chordoma approximatively are reported in medical literature from 1850 to date. We now describe two cases recently observed at our Medical Division, one of sacro-coccigeal chordoma and the other developed from clivus of Blumenbach. Their peculiarities are briefly discussed and compared with a rapid revision of the literature on this argument. The results of antiblastic therapy are presented and its opportunity in addition to Roentgenologic and surgical therapy is discussed.


[Pelger-Huet leukocyte anomaly. A clinical case of acquired and transient anomaly]. A survey of the relevant literature is followed by the presentation of a case of transient, acquired Pelger-Huët anomaly observed in a patient operated for Crohn's disease.


[An elderly patient with symptoms of dehydration]. In connection with serious dehydration symptoms in an elderly patient, which appeared to be attributable to a hypersmolar nonketoacidotic diabetic syndrome, a comprehensive study of this syndrome is made with reference to a study of pertinent literature. Possible causes, pathogenesis, clinic and treatment are extensively dealt with. The seriousness of this clinical picture, the high rate of mortality and the favourable prognosis if immediate action is taken are pointed out.


[We all will age].

[We all will age]. In 1977/78 the American Research-plan toward understanding aging 'Our future selves' was published. In this article the report of the panel on biomedical research is reviewed. The report appears to be very comprehensive and to give a carefully detailed research plan. It will certainly take many years to realise all the plans. Part of the research could very well be done in the Netherlands although only to a limited extent. The governmental planning-group, which is developing a research plan for gerontology in the Netherlands, should make a sensible selection out of the many items mentioned in the American plan. After all, it is of vital importance to all of us, our future selves.


[Our future selves: individual behavioral aspects. Discussion and comments]. We will summarize this part of the plan against a historical background (Havighurst, 1969, 1071; the second White House Conference on Aging, 1971) and compare some parts (personality and adaptation, death and dying) with the list of priorities in the 'summary report'. Policy- making and planning research appear to be too different tasks. Our comments concern especially: - the choice of the design for the research-plan; - too little is said in the plan on the conditions (money, research centers, education, necessary for realization); - themes missing: the meaning of old age, given by the individual older person in connection to time-experience; sexuality and aging; suicide and pre-aging mortality; - the splitting of the research-plan in three parts has advantages but also disadvantages. There are three (independent) fields with not enough overlap, i.e. not enough interdisciplinary research-proposals; - another point is the unequal level of testability of the different proposed themes; - the last point is, that the concept of aging, which forms the background, [corrected] is a rather negative one. Therefore, few proposals concern the positive aspects of growing older and being old. This is perhaps related to the handicap, that there is not one general theory on aging (if that is possible?).


[What is at stake? 'Our future selves'!]. The sociological questions in the gerontological research-plan 'Our future selves', developed in the USA for stimulating and co-ordinating the research in this field, are shortly summarized. It concerns demographic studies, age as dimension of the social structure, social-cultural comparative studies, social roles and social networks and the aging problems in different sectors of the society. After this summary some critical remarks are made and some points are mentioned that seem more or less fundamental in this field, namely the societal orientation on youth, the long term orientation that is needed because of the changing demographic structure, the problem of the 'social construction' of aging and the interdependency between the development of the sciences and characteristics of modern society (especially for the situation of old people).


[Services for the aged in the new world. Comments on 'Our future selves: research-plan towards understanding aging']. A comment is given on the report 'Our future selves; a research-plan towards understanding aging', concerning the human services and delivery systems. The title of the report seems to promise a picture of the aged in the future. It is regretted that the contents of the report only gives some ideas to improve the current services for the elderly. About the procedure in which the report was achieved is said, that the use of a panel of experts requires a very careful choice of the experts. Next to that, you cannot use the saying of a panel as they are, but you have to work them up, if you want to make a research-lan. As it seems that this is not sufficiently done, the results is not a plan, but a mere collection of subjects. Out of this collection five subjects are described (cultural factors, religion-ethics, nutrition, legal services, commerce), on which in the Netherlands little or no research is done. Participation in geronotology by anthropologists, theologians, and jurists is pleaded.


['Our future selves'. Comments on "Human services and delivery systems']. A description is given of the recommended research topics on Human Services and Delivery Systems for the Aging. Fifteen different fields of research attention are described. It is stated that there is a lack of a frame of reference for the different attention fields. This frame of reference is necessary for a more systematic approach towards the age specific problems and the age specific services, needed to solve those problems. The systematic approach can be found in a three-dimensional scheme in which the fifteen attention fields have their logical place. The recommanded research topics have to be assessed in this frame: 1. Socio-cultural aspects. Culture, religion, ethics, communication, education, recreation, civic participation. 2. Socio-economic aspects. Economic support, employment, legal services, commerce. 3. Physical environment. Physical Environment, nutrition, transportation. 4. Human environment. This aspect is not mentioned in the report. 5. Psychological aspects. 6. Physical aspects. These aspects are not explicitly mentioned in the report, but implicitly in the chapter about Health. Some of the recommendations are also relevant for the situation in the Netherlands. The recommended research on the health care system is critisized, because the items are too complex. For the Netherlands it is more worthwhile to do fundamental research on the age-specific vulnerability in relation to social, psychological and physical aspects. The results of that research can be used for a reconstruction of the whole health care system for the aged.


[Vitamin and mineral needs of the aged]. With increasing age the need of vitamins and minerals is very probably not less than at a younger age. On the other hand, based on a lowered caloric intake and/or a one-sided diet, the possibility of the occurrence of deficiencies will be greater. Resorption disturbances, less body activity, misuse of laxantia and other factors may also be of a negative effect. Quite a number of publications point to the possibility of latent deficiencies, as shown by lowered vitamin and mineral blood levels. Although the available data are scare, older people are certainly a very vulnerable group, in need of special care with regard to their diet, quantitatively as well as qualitatively.


[Fluid deficiency in the older person].

[Fluid deficiency in the older person]. With reference to the frequent occurrence of dehydration in elderly patients, after a discussion of the causes, the various methods of research are pointed out to determine the lack of moisture, the method of treatment and the prophylaxis of this disorder in the urinary organs.


Effect of different dietary fats on daily loss of sterols from the skin of man. We studied the effect of polyunsaturated dietary fat upon the 24-hour loss of cholesterol and other sterols from the skin surface of 4 human subjects. They were fed cholesterol-free diets which provided 40% of the total caloric intake from saturated fat (cocoa butter) and then a highly polyunsaturated fat (corn oil). In both dietary fat periods, the daily loss of cholesterol through the skin was similar, 91 and 87 mg in the saturated and polyunsaturated fat periods, respectively. 87 and 89% of the total cholesterol were in the esterified form in the saturated and polyunsaturated dietary fat periods. The sterol composition of the skin surface lipid was not altered. The study suggests that the plasma cholesterol-lowering effect of dietary polyunsaturated fat was not mediated by a change in the loss of cholesterol through human skin.


Simultaneous correction of Ca deficiency and acidosis in fasting obese patients as a prevention of bone demineralisation. Short-term starvation in the obese induces metabolic acidosis and increased calciuria resulting in severe negative Ca balance. Oral administration of 5 g Ca-lactate daily is capable of correcting acidosis, reducing calciuria and providing the body with 650 mg Ca daily, thereby maintaining a positive Ca balance throughout the period of starvation. We therefore propose administering this amount of the preparation to obese individuals during starvation as a simple and cheap preventive measure against bone demineralisation.


Effect of indigestible polysaccharides on protein digestibility and nitrogen retention in growing rats. The effect of five indigestible polysaccharides (IP) of different origin and chemical structure on N balance and dry matter digestibility was studied in growing rats. The diets contained 10% of gum guar (GG), carob bean gum (CBG), Na-alginate (Na-A), agar-agar (AA) or carrageenan (C), respectively. Dry matter digestibility and apparent protein digestibility were significantly decreased below control values by all 5 IP. N retention was significantly lower after ingestion of AA or C. In the rats receiving GG, CBG or Na-A urinary N excretion was reduced, thus compensating for increased fecal N losses by these animals. The different effects of the 5 substances on N balance are attributed to their partial breakdown through the action of intestinal microflora and/or their ability to partially inhibit the activity of proteolytic enzymes in the gastrointestinal tract. Trypsin inhibition in vitro was observed for C only. Suitability of the various IP as bulking agents in reducing diets is discussed.


Adenine nucleotide translocation in liver mitochondria isolated from rats deficient in essential fatty acids. Adenine nucleotide content and adenine nucleotide transport were evaluated in rats deficient in essential fatty acids (EFA) and in control rats. ADP uptake by EFA-deficient mitochondria was altered in a manner similar to the alteration produced by treatment of normal mitochondria with uncoupler. The uptake of ATP by EFA-deficient mitochondria was more rapid than that of normal mitochondria, but similar to that of normal mitochondria treated with uncoupler (DNP). Both uptake of ADP and uptake of ATP by EFA-deficient mitochondria were atractyloside sensitive. Total adenine nucleotide content of liver mitochondria from EFA-deficient rats was similar to that of liver mitochondria from control animals, but the content of ATP in EFA-deficient mitochondria was significantly higher than that of normal mitochondria. There was a negative correlation between the concentration of linoleic acid in total mitochondria lipids and ATP content of mitochondria.


Selected sulfhydryl inhibitors capable of inducing immunity against cancer in mice. Selected sulfhydryl inhibitors show greater toxicity to some animal and human cancers than to normal cells, both clinically and in drug sensitivity tests. Such selected SH inhibitors can induce immunity against cancer in mice, unlike other commonly used antitumor agents. Scanning electron micrographs of the surface of Ehrlich ascites cancer cells treated with the sulfhydryl inhibitors show blunting to absence of microvilli and modification of the surface texture of the cancer cells.


HLA system and testicular germinative tumours. In 62 patients with testicular germinative tumours and 301 healthy unrelated subjects, 23 HLA antigens of A and B loci were tested. In the group of 40 seminomas the incidence of HLA-Bw35 antigen and in 22 patients with non-seminomas (embryonal carcinomas, teratocarcinoma and mixed forms) the frequency of HLA-A 10 antigen were significantly higher (27.50 vs. 14.28% in the controls, p greater than 0.025; 36.36 vs. 15.28%, p less than 0.025). After correction by multiplying p by the number of typed antigens there was no statistically significant result any more. The causes of dubious results of the studies about the association between HLA and malignancies are discussed.


Mode of spread of thyroid cancer.

Mode of spread of thyroid cancer. Metastatic dissemination of differentiated cancer was studied in a personal group with the following results. Invasion of cancer to adjacent structures can be encountered even in children with typical increase with age. The lymphatic spread to regional lymph nodes is typical of papillary cancers and in young patients. The same type of spread without the age-dependent decrease can also be proved, with lower incidence, in follicular cancers. Pulmonary metastases are frequently the only type of distant metastases and may originate from previous spread to lymph nodes. The isolated bone metastases a;e probably brought about through the vertebral venous system. Patients having multiple bone metastases or both bone and lung lesions are probably the only typical examples of metastasizing through the systemic blood flow. As the above types of distant metastases carry different prognosis they should also be recognized by the TNM system.


Intralesional immune therapy: methanol extraction residue of BCG or purified protein derivative. 6 patients with cutaneous malignant melanoma and multiple secondary cutaneous lesions were treated with intralesional methanol extraction residue of bacillus Calmette Guerin (MER-BCG). Separate lesions were injected with purified protein derivatives (PPD) in 5 of the study patients. 5 of the 6 MER-BCG injection lesions developed marked inflammation clinically. Excisional biopsy 7-14 days later demonstrated complete dissolution of tumor in 2 patients and was accompanied by infiltration with acute and chronic inflammatory cells; 3 lesions revealed necrosis with residual tumor, and in 1 patient there was no apparent host response. Clinical tumor regression was not observed with PPD applied intralesionally, although histopathologic analysis revealed a granulomatous inflammatory response in 3 of 5 patients. No patient demonstrated regression of uninjected cutaneous lesions (4 evaluable patients) or visceral lesions (2 patients). The critical determinants of tumor regression are the size, site and depth of the lesion in relationship to the cutaneous surface. The mechanism of tumor eradication may be related to 'innocent bystander' necrosis secondary to nonspecific inflammation rather than immunologically mediated via host sensitization.


Correlation between tumour size, metastatic spread and galactosyl transferase activity in cyclophosphamide-treated mice bearing the Lewis lung carcinoma. Galactosyl transferase activity was measured in tumour and normal tissues of mice receiving cyclophosphamide treatment for Lewis lung carcinoma. Animals which responded to cyclophosphamide therapy had significantly smaller tumours with fewer metastases than the untreated mice. The level of galactosyl transferase was significantly reduced in the tumours which were inhibited by the cyclophosphamide treatment.


[Nuclear structures in the telotrophic ovarioles of nocturnal ground beetles (Tenebrionidae, Polyphaga). II. The oocyte nucleus of Blaps lethifera and Gnaptor spinimanus. Light optical data]. Changes in the nuclear structures and their participation in RNA synthesis in the growing oocytes were followed in two species of beetles Blaps lethifera and Gnaptor spinimanus. In the oocytes of both the species, the chromosomes join into the karyosphere following the short-term lampbrush stage. A large capsule appears around the karayosphere which consists of the fibrous substance, granules and karyosphere nucleoli. The latter form in the karyosphere and contain RNP but they are not true nucleoli since they do not include 3H-uridine. RNA synthesis on the chromosomes, active at the lampbrush stage, falls markedly following their joining into the karyosphere. The oocyte nuclei of these beetles are, thus, characterized by the absence of RNA synthesizing nucleolar system and, as compared with the trophocytes, by the low level of RNA synthesis on the chromosomes.


[Nuclear structures in the telotrophic ovarioles of nocturnal ground beetles (Tenebrionidae, Polyphaga). III. The oocyte nucleus. Electron microscopic data]. The fine structural organization of nuclei was studied in the growing oocytes of Blaps lethifera, B. mortisaga and Gnaptor spinimanus. In the beginning of diplotene the nuclei contain primary fibrillar nucleoli and numerous electron dense globules dispersed all over the nucleus; the loose chromosome material (lampbrush chromosomes) is distributed all over the nucleus. With the oocyte growth the chromosomes are spiralized and join into the karyosphere. A capsule of fibrous material forms around the karyosphere. The karyosphere nucleoli appear on the chromosomes and, then, move to the capsule region and outside its limits, to the nuclear envelope. They are fibrillar and non-active with respect to RNA synthesis. The fibrous material of the capsule is represented by strands which consist of bundles of cross-striated filaments. These latter contact directly with the chromosomes in the karyosphere and with the surface of the karyosphere nucleoli. The fibrillar-granular bodies are distributed along the strands in the capsule; they contain both RNA and DNA. The nature of extrachromosomal DNA in the karyosphere capsule and its participation in the formation of the capsule material are discussed. A suggestion is put forward on the similarity of the capsule strands with the modified central elements of synaptinemal complex.


[Characteristics of oogenesis in the chick. I. The extrafollicular period in the development of the oocytes]. The early stages of oogenesis in the chick were studied by means of light cytochemistry and autoradiography. The oocytes devoided of follicular epithelium are located in the ovarian cortex in groups of 8, 16 or 32 cells. Within the bounds of the group they develop synchronously until the beginning of formation of the follicular epithelium around each oocyte. By 15 days of postembryonic development all oocytes in the ovarian cortex enter the diplotene stage of meiotic prophase. The formation of follicles is completed by 22 days. The morphological descriptions are given for the oocyte nuclei at the preleptotene, leptotene, zygotene, pachytene and early diplotene stages of meiotic prophase. The nucleolus appears at the early diplotene stage and is characterized by extremely weak synthetic activity. It is specially stressed that the nucleolus forms not in alloocytes and that the population of germ cells in the chick ovary is heterogenous by this character. The beginning of RNA synthesis in the oocyte nucleus is timed to the early diplotene stage. The data are obtained on DNA synthesis in the nuclei of preleptotene and leptotene oocytes not related to the amplification of ribosomal genes.


[Cell proliferation and migration in the roof of the mesencephalon (tectum) in Xenopus laevis tadpoles and adult frogs normally and in brain injury. II. Cell proliferation and differentiation of the tectum in frogs]. The proliferation and directions of cell differentiation in tectum opticum were studied in the young frogs under the conditions of normal development and upon brain trauma by means of 3H-thymidine autoradiography. The same types of cells were shown to be able of proliferation in both the cases: cells of the ventricle zone and glioblasts (gliocytes) in all other tectum layers. A study of directions of the tectum proliferating cells' differentiation in the frogs has shown that the proliferating cells differentiate mainly in the ependyme tanicytes in the ventricle layer 1 and gliocytes in the other tectum layers. The trauma did not change the direction of proliferating cells' differentiation towards the formation of neurons. The complete regeneration is observed in the tectum layer 1 only.


[Protein functional groups of the ova in the roach and carp-bream of varying degrees of maturity]. The Black Sea roach and carp-bream eggs of different degree of maturity differ from each other by the content of SH-, S--S-groups of proteins and non-protein low molecular weight thiol compounds. Definite differences were found in the optical density of soluble proteins and degree of ionization of their side groups.


[3H-thymidine incorporation into the macrophages in the process of eye regeneration in adult tritons]. Changes in the number of labelled macrophages in the regenerating eye cavity of the adult common newts were studied within 2 to 12 days following the injection of 3H-thymidine and removal of retina and lens from the eyes. A small number of labelled macrophages was found in the eye cavity (0,2--5.9%) at all regeneration stages under study upon the pulse 3H-thymidine incorporation. Their number rapidly increased and attained by the end of observation (12 days) 73%. These results suggest that mainly mature non-dividing forms of macrophages which completed the mitotic cycle S-phase in the places of their active reproduction migrate in the eye cavity. The sharp increase of the number of labelled macrophages in the eye cavity is determined by the migration of those macrophages the precursors of which were labelled as a result of both the pulse 3H-thymidine incorporation and reutilization of the labelled precursors of DNA synthesis. New portions of labelled macrophages migrate in the eye cavity within 2 to 4 days.


[Heat resistance of the eggs of a mulberry silkworm strain adapted to a subtropical climate]. The heat stability of the eggs of a polyvoltine strain of Bombyx mori occurring in the conditions of hot climate was studied. No marked differences between this strain and the moderate climate strains were found in the level of heat stability and the character of its age changes. The mechanisms of heat stability upon the diapause-less egg development are discussed.


[Functional state of the thyroid gland in the postnatal period in mink of different genotypes]. The thyroid gland functional state was studied by means of 131J-triiodothyronine in minks of two genotypes. The thyroid activity in the standard (dark brown) minks increased from the 3--4th month of postnatal ontogenesis (July--August) and decreased gradually by the 6th month (november). Similar changes in the thyroid activity were found in the Hedlung (white) minks as well. Their thyroid activity was, however, markedly higher on the 3rd month than in the standard minks.


Peripheral iridectomy via a corneal section: a follow-up study. A method of performing peripheral iridectomy through a corneal incision is described. Of the fifty patients reviewed, there were no immediate postoperative complications. In the follow-up period the incidence of lens opacities associated with visual loss was 16% and 21% in the prophylactic and therapeutic groups respectively. The percentage of posterior synechiae in the prophylactic group was 16%. Ninety-three percent of patients had a visual acuity of 6/12 or better at the end of the follow-up period. When compared with the results of previous surveys, the method is as safe as the ab externo approach. The technique avoids bleeding and leaves the bulbar conjunctiva undamaged and available for any subsequent drainage procedure.


Coated Vicryl (polyglactin 910) suture in extraocular muscle surgery. A newly available coated Vicryl (Polyglactin 910) suture was evaluated in laboratory and clinical trials for use in extraocular muscle surgery. The suture retains the increased strength and low antigenicity of uncoated Vicryl suture, while providing easier passage through tissue and improved tying characteristics. The improved handling properties result from the coating which produces a smoother suture surface.


Complications of 10-0 nylon sutures.

Complications of 10-0 nylon sutures. Three cases are presented which document the finding that 10-0 monofilament nylon suture may cut through corneal tissue after a coup or contrecoup injury to a recently operated eye. The authors speculate that a larger gauge suture does not have the tendency to cut through recently operated corneal tissue as easily as 10-0 monifilament nylon. The authors recommend the use of a larger gauge suture in closing corneal incisions in persons whom the surgeon feels are at a greater postoperative traumatic risk.


Praeger micro irrigating hook for intraocular lens implantation. A new micro blunt irrigating hook is introduced for utilization in intraocular lens implant  surgery. It is simple, inexpensive, and requires no previous experience. It allows for adequate reposition of the superior loop of any type of lens along with the recovery of the proximal loop of a McCannel suture. Finally, it allows the most inexperienced operator to center a lens ideally in a totally deep chamber, avoiding the vicissitudes of either perforation of the posterior capsule, anterior hyloid, or damage to the delicate endothelium.


Praeger irrigating micro intraocular scissors. The Praeger Irrigating Micro Mini Irrigating Scissors is a valuable instrument particularly in phacoemulsification with or without intraoucular lens implantation and when used with microscopy. Secondary procedures such as a posterior capsulotomy may be safely carried out on very dense posterior capsules either beneath a pseudophakosis or following extracapsular cataract extraction. Inferior sphincterotomies through the superior incision and resection of anterior capsule through a 3.0-mm incision during the course of phacoemulsification can be easily accomplished without fear of perforation to the posterior capsule or damage to the overlying corneal endothelium. Additional intraocular manipulations such as direct observation and resection of a McCannel suture in the lower 6 o'clock meridian can be accomplished under direct visualization without excessive traction on the suture.


Excretion of vanilmandelic acid in the urine of retinoblastoma patients. The idea of determining the urinary excretion of vanilmandelic acid (VMA) in children with retinoblastoma derives from the fact that elevated amounts of VMA were found in children with neurogenic tumours and especially neuroblastoma. The method of VMA analysis and the results are discussed. In view of the fact that in only 5 out of our 12 patients an elevated urinary VMA excretion was found, we cannot recommend this determination as a routine diagnostic procedure. However, further research in this direction is necessary.


Malignant epithelioma of the ciliary body. A rare case of malignant epithelioma of the ciliary body (verified histologically) is described. Some difficulties of clinical diagnosis are mentioned as well as the general properties of this kind of tumor, which mostly requires an anatomical investigation for recognition. As a special feature of this kind of tumor the precocious consecutive cataract is mentioned; this arises in cases of melanomas of the ciliary body considerably later in the course of malignant growth.


Effects of urea treatment in malignancies of the conjunctiva and cornea. A series of 9 patients with extensive squamous cell carcinomas of the conjunctiva, affecting also the cornea in 5 of them, were treated with local applications of urea. 8 out of these patients were cured. In 1 patient with a concomitant extensive conjunctivitis, the treatment was ineffective. Urea treatment is very simple and without any complications, apart from a transient opacity of the cornea. Recurrences are easily and effectively retreated as in 1 of 2 of our cases. But if the eyeball has been destroyed, as in the second case, retreatment is impossible. At least 5 out of the treated patients would have had an enucleation of the globe or an exenteration of the orbit without the urea treatment.


[Clinical experiences with timolol eye drops]. Three groups of chronic simple glaucoma (group I: newly adjusted patients; group II: previously satisfactorily pressure-regulated patients; group III: previously notsatisfactorily pressure-regulated patients) received treatment with Timolol eye drops for 4 months. In 34 eyes the intra-ocular pressure could be lowered below 22 mm Hg by Timolol alone, whereas 10 eyes additionally had to be treated with 1% epinephrine. The higher the initial pressure effect, the more pronounced the pressure-lowering properties of Timolol became. Especially in the first 2 weeks, less in the following 14 weeks, Timolol showed a loss in effectiveness. The application of Timolol instead of carbonic anhydrase inhibitors with acute angle-closure glaucoma and secondary glaucoma was successful. Timolol eye drops were tolerated very well. There were no local or systemic side effects.


Retinal function after surgical treatment of detachment. 1--8 years after successful surgery, for retinal detachment 47 patients (48 eyes) were included in the study. By using Goldmann's static perimetry macular and retinal periphery sensitivities were determined (in 2 meridians) as compared with the healthy eye. It was established that the changes in static perimetry run a course parallel to the disturbances in the perception of the Haidinger phenomenon and poor performance at the Amsler tests. The longer the period of macular detachment was, the greater were the changes in its sensitivity curve despite good visual acuity. A distinct lowering in sensitivity occurs also outside the macula, all over the area in which retinal detachment had occurred.


[Echographic differential diagnosis of leukokorie in childhood]. After the description of the most important differential diagnoses of leukocoria in childhood, their ultrasonographical findings in both A- and B-mode are discussed. Ultrasound proofs to be a useful aid in the evaluation of leukocoria.


Change in oscillatory potential by thioridazine. Toxic effects on the retina by oral administration of thioridazine was investigated by electroretinography (ERG) using male Wistar rats. An obvious reduction followed by a disappearance in the O2 component of the oscillatory potentials of the ERG was seen in a dose-dependent manner. The minimum dosage given to produce the above change was 3 mg/kg/day for 7 days' administration. This change seemed to be permanent, whereas a and b waves as well as other oscillatory potentials, e.g., O1, O3, were normal throughout the experiment. The significance of the data is discussed.


Diffuse malignant ring melanoma of the iris and ciliary body. 2 cases of diffuse malignant ring melanoma of the anterior uvea are presented. A correct clinical diagnosis led to enucleation in case 1, while in case 2, the eye was enucleated 2 years after anti-glaucomatous surgery.


Polymers produced by heating an amino acid mixture in sea water enriched with transition elements. A mixture of eighteen protein amino acids was heated in sea water medium enriched with transition metal ions. Small granules were obtained as precipitates. Both dialyzable polymers and undialyzable polymers were obtained from the supernatant. Dialyzable polymers yielded mainly Glu, Asp, Ser, and Thr on hydrolysis; undialyzable polymers (C, 29.45; H, 3.87; N, 4.87; and ash, 31.5 wt%) yielded Thr, Asp, Glu, Gly, Leu, Ser, Lys, Pro, His, Phe, and a few unidentified ninhydrin positive peaks after acid hydrolysis. Five wt% of the undialyzable polymers con-ist of acid-hydrolyzable protein amino acids.


Mirror symmetry breaking in biochemical evolution. The problem of origination of molecular asymmetry in biochemical evolution is discussed. The theoretical analysis shows that chiral purity of biomolecules has the biological significance for self-reproduction of organisms. The models of spontaneous symmetry-breaking in molecular systems are given. The aspects of various stages of biochemical evolution associated with the development of chiral polarization are analysed.


On the physical origin of biological handedness. In the racemic conglomerate crystallization of over 1,000 samples of D,L-sodium-ammonium tartrate the effect of 32P beta irradiation on the weight, optical activity, and crystallite size was measured. Both weight and optical activity showed a statistical dependence on the intensity of beta irradiation. The crystallite size is also affected by the presence of 32P. Asymmetric crystals are suggested to have been potential mediators between asymmetric parity violating forces and molecular asymmetry so that stereo-selective prebiotic chemical reactions involving crystals need not be considered 'chance' processes. No measurable difference in the energy content of optical isomers was found. An upper limit for the direct contribution of weak interactions to electromagnetic ones has been calculated. The mechanism of stereoselective crystal seeding by beta particles is discussed.


Solar-driven chemical energy source for a Martian biota. Microorganisms deep in the Martian soil could derive energy indirectly from the sun via chemical reactions involving atmospheric products of the solar ultraviolet flux. The Viking discovery of a chemically uniform regolith which, though poor in organics, is rich in sulfur-containing compounds suggests reaction sequences in which sulfur is recycled through reduced and oxidized states by biologically catalyzed reactions with photochemically-produced atmospheric constituents. One candidate reaction, reduction of soil ssufate minerals by molecular hydrogen, is already exploited on earth by bacteria of the ubiquitous and tenacious Desulfovibrio genus.


Some comments on interpretations of Viking biological experiments. Data from Viking experiments are analyzed from a biological viewpoint. The lack of organic matter in Martian soil could be due to the specificity of regions with optimal landing conditions. All data of labeled release experiments may be explained by assuming the existence of psychrophilic organisms, cultivated at temperatures above optimal ones, and other factors of a biological origin. The biological interpretation does not contradict the results of other life search experiments.


[Change in the content of inorganic ions in the hemolymph of freshwater mollusks infected with trematode parthenitae]. Changes in the concentration of ions of sodium, potassium, calcium and chlorine in the haemolymph of Lymnaea stagnalis and Planorbis corneus were studied during their infection with sporocysts and rediae of trematodes. Statistically reliable disturbances in the ion balance caused by the infection were established.


Two new species of Lepeophtheirus (Copepoda: Caligidae) parasitic on fishes from southern California waters. Two new species of Lepeophtheirus are described and illustrated based on a collection from the Orange County sewer outfall, California. They are: L. remiopsis sp.nov. from the branchial cavities and external body surfaces of Parophrys vetulus Girard, Hippoglossina stomata Eigenmann & Eigenmann, Pleuronichthys verticalis (Jordan & Gilbert), Chitonotus pugetensis (Steindachner), and Porichthys notatus (Girard); and L. rotundipes sp.nov. from the external body surfaces and occasionally the gill cavities of Scorpaena guttata (Girard) and Citharichthys stigmaeus Jordan & Gilbert.


[Phosphoenolpyruvate carboxykinase in Calicophoron erschowi (Trematoda: Paramphistomidae)]. The trematode Calicophoron erschowi possesses high active phosphoenolpyruvate carboxykinase. Enzyme activity is concentrated in the cytoplasm. The enzyme has the optimum pH 6.0 and is active in the presence of ions Mn++ and inosine diphosphate. Alanine does not affect its activity. Sulphide oxinide in concentration 1.4-10(-6) M inhibits the activity up to 93%. Some kinetic characteristics are presented.


Bovine trypanosomiasis: the red cell kinetics of ndama and Zebu cattle infected with Trypanosoma congolense. The responses of susceptible Ndama and Zebu cattle to needle challenge with Trypanosoma congolense were followed using parasitological, haematological and radio-isotopic methods and compared with those of corresponding uninfected animals. In both breeds, infection became patent at the same time but peak parasitaemias were significantly lower, were attained later and were of short duration in the Ndama. All infected animals became anaemic, the severity of which correlated with the level and duration of parasitaemia. However, even when parasites could no longer be detected in the blood, packed cell volumes showed little tendency to recover. The anaemia was due to increased intravascular red cell destruction and was more pronounced in the Zebu. Haemodilution was not a feature. Increased red cell syntheisis occurred in infected animals of both breeds but particularly in the Zebu; this accounted for the capacity to maintain packed cell volume levels following the initial drop associated with parasitaemia. However, in most cases red cell synthesis was less than expected from the degree of anaemia, suggesting impairment of bone marrow function. Measurement of red cell iron utilization indicated that this was due to effective from re-utilization from degraded red cells arising from reticulo-endothelial blockade. It is concluded that the anaemia in this disease and its underlying processes are broadly in line with the number of parasites in the blood and that the superior resistance of the Ndama cattle lies in their ability to control parasitaemia rather than their capacity to mount a more efficient erythropoietic response.


[Fleas of small mammals in northern Amur Province and their distribution by biotopes (Aphaniptera)]. In June-September of 1975 on the southern slope of the Stanovoy ridge, in the region of construction of the Baikal-Amur main line 2014 small mammals of 14 species were examined, on which 1499 fleas of 13 species were collected. Most species of fleas are widely distributed throughout the territory. Ceratophyllus penicilliger, C. advenarius, Catallagia dacencoi, C. ioffi are mass species, Ceratophyllus calcarifer, C. indages, Leptopsylla ostsibirica, Doratopsylla birulai, Rhadinopsylla pseudodahurica are common species. Ceratophyllus taiganus, Amphipsylla marikovskii, Neopsylla acanthina and Tarsopsylla octodecimdentata are rather rare.


Lysosomes and tegument pathology in the chemotherapy of schistosomiasis with 1,7-bis(p-aminophenoxy)heptane (153C51). One therapeutic oral dose (400 mg/kg) of 153C51 administered to infested mice caused pathological changes in the dorsal region of the tegument of male Schistosoma mansoni during the period 3--24 h after treatment. These changes occurred prior to the 'hepatic shift'. At the ultrastructural level they consisted of a gradual accumulation in the tegument epidermis of numerous membranous inclusions with the characteristics of residual lysosomes and changes in the localization of acid phosphatase, a lysosomal enzyme. It seemed likely that these changes were due to inhibition or exhaustion of enzyme in the epidermis, followed by re-synthesis of enzyme in the cell bodies and its export to the epidermis. The elimination of hydrolytic activity from lysosomes in the epidermis would explain the accumulation of residual lysosomes. Drug-treated parasites retained their disguise of host red blood cell ghost antigens as shown by indirect fluorescent antibody-labelling and, therefore, it seemed unlikely that immunological factors could be important in producing the tegument pathology.


[Gamasid ticks of small mammals in the Charskaya Basin (Gamasoidea)]. Zooparasitological investigation of small mammals (17 species) was carried out in one of the regions of construction of the Baikal-Amur main line, Charskaya hollow. 8475 gamasid mites belonging to 8 families and represented by 25 species were collected. In addition, in the nests of the northern redbacked vole and root vole there were found gamasid mites belonging to 6 families. The mass species, Haemogamasus ambulans Thorell and Hirstionyssus isabellinus Oud., were recorded from all landscape zones, of the territory under investigation.


Synthesis of macromolecules by the epithelial surfaces of Schistosoma mansoni: an autoradiographic study. The use of tritiated leucine as a marker for protein synthesis and of tritiated glucosamine as a marker for polysaccharide/glycoprotein synthesis, is described. Adult worms were pulse-labelled by incubation in medium containing the substrate. Labelled worms were then incubated in chase medium, without labelled substrate, for varying lengths of time before fixation. The distribution of label which had been incorporated into macromolecules in the worm tissues, was examined by light and electron microscope autoradiography. It was estimated that the tegument and tegument cell bodies were the source of 67--80%, and the gut epithelium of 20--30%, of exportable leucine-containing protein. Conversely, the gut epithelium was the source of 72%, and the tegument cells 28%, of exportable glucosamine-containing polysaccharide. The specific activity of labelled protein reached a peak in the tegument cytoplasm after 1.5 h of chase incubation. Half of the labelled protein was secreted into the worm's environment by 3 h of chase incubation. The half-life of secretory protein in gut cells appears to be around 2 h. Labelled protein disappears from the gut lumen relatively rapidly but labelled polysaccharide remains in the lumen at high specific activity for at least 24 h. The major carbohydrate labelled may be the glycocalyx on the luminal surface of the gut epithelial cells. The results suggest that the bulk of worm secretions have a rapid turnover with a half-life of a few hours. Against this background of rapid mass secretion a slower process of membrane turnover would be difficult to detect and quantitatively small.


Different levels of immunity to Schistosoma mansoni in the mouse: the role of variant cercariae. Very variable levels of immunity to a second infection with Schistosoma mansoni were recorded in 7 strains of mice, 12--15 weeks following a small primary infection. When 2 or more strains of mice were assayed at the same time, less variation occurred within the experiment than between different experiments. This evidence suggested variation between pools of cercariae as the main cause of variability in immunity. In direct experiments in one strain of mouse, 2 different pools of cercariae stimulated widely different levels of immunity to the same challenge. Conversely, challenge infections drawn from different pools showed different susceptibility to immunity stimulated by the same primary infection. Individual clones of cercariae, from snails infected with single miracidia, showed a high level of susceptibility to immunity stimulated by a small bisexual infection, or were not susceptible at all. Antigenic polymorphism is the most likely explanation for the differences observed between clones of cercariae. However, indirect immunofluorescence showed the presence of at least 1 common antigen on the surface of schistosomula derived from different clones of cercariae and clone-specific antigens have not been detected.


[Structural characteristics of the cuticule of the phytonematode, Aporcelaimellus obtusicaudatus in mechanical injury]. The fine structure of the cuticle of A. obtusicaudatus (Dorylaimidae) during the turgor unbalance was studied. Mechanical injury causes the delamination of the cuticle and reveals the tonofibrillary interrelations between its structures. The cortex and basal layer were found to possess the highest tensile strength. The peculiarities of the structures destruction dynamics depending on the removal from the perforation place were recognized.


The effect of the expulsion phase of Trichinella spiralis on Hymenolepis diminuta infection in rats. The effect of the intestinal changes brought about by the expulsion of Trichinella spiralis in rats was studied in relation to the growth and survival of a concurrent infection with Hymenolepis diminuta, a cestode not normally rejected by the rat in low-level infections. Growth of H. diminuta was stunted in rats given T. spiralis just before, or after, infection with H. diminuta, the stunting being more pronounced when the cestode was given closer to the period of inflammation. There was no loss of the cestode from dual-infected rats and no evidence for destrobilation was found. Lower T. spiralis burdens had a correspondingly weaker effect on growth of H. diminuta, and stunting was abolished by administration of the anti-inflammatory drug cortisone acetate. It is concluded that the stunting of H. diminuta is probably due to the non-specific inflammatory component of the rat's response to T. spiralis infection.


Experimental infections with Cooperia oncophora (Railliet, 1918) in calves. Results of single infections with two graded dose levels of larvae. Two experiments were carried out in which calves reared parasite-free were infected with a single dose of 3rd-stage larvae of Cooperia oncophora. In the first experiment the calves received 20 000 or 200 000 infective larvae and they were autopsied 28 or 56 days after the infection. In the second experiment the doses were the same but the animals were killed 14, 84 or 140 days after infection. If a dose of 20 000 was given, clinical signs were never observed, while at a dose level of 200 000 the weight gain was less on 56 and 84 days after the infection compared with the low-infected groups or the control animals. After 170 days the differences in weight gain were compensated. Faecal egg output was higher in the 200 000 groups only in the first period of patency, thereafter the calves in the 20 000 groups produced more. No obvious differences between the two infection levels were observed with regard to the haematological data. In the low-infected groups worm counts were only slightly lower when the results after 28 days were compared with those after 56 days. Also, the worm numbers after 14 days were almost equal to those after 84 days, while at 140 days 1 animal still had the same number, the other one had lost its worm burden. In the high-infected groups the worm loss was much quicker. After 28 days a great part of the population had already been lost. Obviously, at the 200 000 level the reaction of the host against the parasite was much stronger. Adult worms were expelled at a higher rate than early 4th-larval stages. In the first experiment worm measurements revealed differences between the length of females, males and spicules of males, these being significantly longer in the low-infected groups. Analysis of the distribution of worms over the small intestine showed that in the low-infected groups worms were mainly restricted to the first 6 metres. In the high-infected groups the worm population was distributed more evenly over the whole small intestine.


The uptake in vitro of dyes, monosaccharides and amino acids by the filarial worm Brugia pahangi. The uptake in vitro of various substances by Brugia pahangi was investigated using infective larvae obtained from Aedes aegypti and worms removed from Meriones unguiculatus at 2, 3, 10, 20 and 90 days post-infection. Worms incubated in growth medium 199 containing 1% Trypan blue possessed demonstrable dye in the oral orifice, the anterior oesophageal lumen and the external openings of the vulva and the cloaca or anus but the dye was not found in the gut lumen even after incubation for 24 h. No uptake of ferritin particles into the intestine of the worms was found and no fluorescence could be demonstrated in the gut lumen of worms incubated in medium containing 50% (v/v) fluorescein isothiocyanate-conjugated calf serum for up to 24 h. Trypan blue uptake by the gut of Aspiculuris tetraptera was clearly observed after incubation for several hours. The uptake of D-glucose and L-leucine by B. pahangi was demonstrated using autoradiographic and scintillation counting techniques and incorporation into worm tissues was detected. Glucose was found to be readily incorporated in the apical, glycogen-rich areas of the myocytes of worms of all ages studied and in the uterine epithelium of the adult female. In contrast, a lower incorporation of D-glucose was found in the eggs, embryos and vas deferens and especially in the gut. The incorporation of L-leucine occurred throughout the tissue of the worms during a 30 min incubation. Labelling was also located over the surface of the cuticle of the worms, when incubated for a period of 15 to 60 min in L-[H]leucine. Scintillation counting techniques demonstrated that there was no uptake of 14C-labelled L-glucose or sucrose by B. pahangi. The data presented on the uptake in vitro of nutrients or other compounds by infective larvae and adult stages of B. pahangi did not demonstrate an intestinal route of uptake but indicated that the transcuticular route of uptake may be employed.


[Seasonal dynamics of the development and reproduction of parthenogenetic generations of Xiphidiocercaria sp. VII Odening 1962 (Trematoda: Plagiorchiidae) in the mollusk, Coretus corneus]. Intensity of reproduction of parthenogenetic generations of Xiphidiocercaria sp. VII Odening 1962 was shown to exhibit a seasonal dependence. Comparative studies of generative and somatic cell nuclei size, amount of divisional cells, quantity of cercariae and embryos were conducted in summer and winter.


In vitro variation of glycogen content in three sheep nematodes. In vitro variation of glycogen content under aerobic conditions was measured on fresh weight basis in 3 sheep nematodes inhabiting different niches; Haemonchus contortus, Oesophagostomum columbianum and Trichuris ovis. The parasites were saparated into species and then sexes and starved for varying periods of time up to 24 h in glucose-free physiological saline. The differences between females and males and among the species with respect to glycogen content and its rate of change with time are discussed.


Serum factor in cystic fibrosis: correlation with clinical parameters. The relationship between the activity of the cystic fibrosis serum ciliary dyskinesia factor, detected by the rabbit tracheal bioassay, and clinical status of the patient has been investigated in children, 1-24 years old, with cystic fibrosis. No significant correlation was found between the amount of serum factor activity and age, clinical status assessed by the Schwachman score, pulmonary function (vital capacity, functional residual capacity, total lung capacity, residual volume, maximum breathing capacity, maximal midinspiratory flow, and maximal midexpiratory flow) or blood gas levels (pCO2, pO2). The activity showed no significant relationship to serum galactosyltransferase activity in children with cystic fibrosis.


Plasma renin activity related to sodium balance, renal function and urinary vasopressin in the newborn infant. Plasma renin activity was determined in 25 healthy, full-term, newborn infants aged 1 day to 9 weeks. High values were found, the mean level at 1-2 days of life (24.8 +/- 8.4 ng/ml/hr, SE) being significantly higher than the mean levels at 7-9 days (5.8 +/- 1.5) and at 4-9 weeks (8.1 +/- 1.3) (P less than 0.05). No correlation was found between plasma renin activity and systolic blood pressure, hematocrit, creatinine clearance, serum sodium, or serum potassium. Plasma renin activity (log values) was inversely correlated with sodium intake (r = -0.58) or with urinary sodium (r = -0.44), and positively with urinary osmolality (r = 0.67). The correlations reached higher coefficients if only infants aged less than or equal to 9 days were considered. In addition, vasopressin was measured by radioimmunoassay in the urine. The daily excretion was lower in newborn infants (9.4 +/- 1.6 ng/m2/day, SE, at 1-2 days of postnatal life) than in healthy children (37.1 +/- 5.6), and was significantly correlated with creatinine clearance (r = 0.69), but not with urinary osmolality.


Human propionyl CoA carboxylase: some properties of the partially purified enzyme in fibroblasts from controls and patients with propionic acidemia. We report some properties of propionyl CoA carboxylase (PCC) partially purified from cultured human fibroblasts obtained from controls and several patients with propionic acidemia. A series of steps (Triton X-100 treatment, high speed centrifugation, ammonium sulfate precipitation, and density gradient centrifugation) led to 100- to 300-fold purification of control enzyme. Control PCC had a molecular weight of nearly 700,000, contained biotin, demonstrated a pH optinum at 8.0-8.5, was activated by potassium, and followed Michaelis-Menten kinetics for each of its substrates. It was distinguished from acetyl CoA carboxylase immunologically as well as by differential purification. Each of seven lines from patients with propionic acidemia had clearly detectable PCC activity which was less than 5% of that in control lines. Although yields were poor and purification less extensive than in control lines, mutant PCC was enriched 2- to 40-fold by the same procedures employed for the control enzyme. Mutant enzyme had a pH optimum, ionic requirements, and substrate Km's similar to those of control PCC, but was distinctly more labile to both cold and heat. These findings suggest that the markedly reduced activity of PCC in these patients results from a mutation in the PCC structural gene locus or loci which leads to the synthesis of altered enzyme protein molecules.


Altered intracellular calcium in fibroblasts from patients with cystic fibrosis and heterozygotes. The importance of intracellular calcium (Ca) in secretion and transmembrane ion movement led us to study Ca in cells from patients with cystic fibrosis (CF) which is a lethal genetic exocrinopathy. Skin fibroblasts from patients with CF, obligate heterozygotes (HZ), and age- and sex-matched controls (C) were used in matched pair experiments measuring 45Ca exchange into and efflux from the cells over time. CF cell lines and HZ cell lines exhibit increased 45Ca exchange when compared with their respective controls (P less than 0.005). The magnitude of this difference (approximately 30%) is not reduced when cells are washed with lanthanum chloride after the exchange period. This difference is likely attributable to an altered capacity of one or more of the intracellular Ca sequestering organelles. Further evidence for this explanation was seen in 45Ca efflux experiments in which CF cells retained a higher percent of their initial 0-time 45Ca than did C cells late in the efflux period (P less than 0.05). The finding of an altered Ca pool size in both CF and particularly HZ cells suggests that altered Ca metabolism is related to the basic gene defect in CF.


Utilization of liposomes for correction of the metabolic and bactericidal deficiencies in chronic granulomatous disease. IgG-coated liposomes containing glucose oxidase (GO) in order to provide a means of generating H2O2 were prepared. Leukocytes from patients with chronic granulomatous disease (CGD) which are lacking a means of generating H2O2, ingested the IgG-coated liposomes and metabolic oxidative deficiencies of glucose-1-14C oxidation and iodination were normalized. Both of these activities have been shown to depend upon the availability of H2O2 within polymorphonuclear leukocytes. Improvement in the capacity to kill Staphylococcus aureus by chronic granulomatous disease leukocytes were observed under similar conditions. Thus, it is possible to restore the oxidative metabolic capacities to CGD leukocytes by the introduction of glucose oxidase containing liposomes to these cells.


Small intestinal mucosal fatty acid uptake and esterification in infants and children. Oleic acid uptake and esterification in intact intestinal mucosa were studied in 14 infants and children with chronic non-specific diarrhea, but histologically normal small intestinal mucosal biopsies, using an in vitro technique. The uptake rate was 5.876 +/- 1.942 nmol fatty acid/mg Nigrogen/minute and the esterification rate was 4.060 +/- 1.010 nmol fatty acid/mg Nitrogen/minute, comparable to previous adult esterification studies. No effect of age on either esterification or uptake was present. Mucosal injury resulted in significant reductions in esterification (p less than 0.001) and uptake (p less than 0.05) compared to controls. Bile acid deficiencies led to reductions in mucosal esterification (p less than 0.05) but not uptake.


Bidirectional placental transfer of glucose and its turnover in fetal and maternal sheep. Glucose biokinetics were assessed simultaneously in the pregnant ewe and its fetus by a primed constant infusion of 2-3H glucose and U-14C glucose. Late in gestation fetal glucose turnover was 27.3 +/- 3.7 mg/min; expressed in terms of fetal weight this is 6 to 10 mg/kg/min. In the fed state the results indicated that all of the fetal glucose turnover was derived from the mother via placental transfer and there was no evidence that the fetus was capable of glucose production. Maternal glucose turnover was 145.6 +/- 9.3 mg/min (2.8 mg/kg/min). There was a significant amount of glucose (16.3 +/- 2.3 mg/min) transferred from the fetus to the mother. This feto-maternal transfer of glucose accounted for 11% of the maternal glucose turnover and approximately 50% of the total glucose coming to the fetus from the mother. This study provides the first in vivo simultaneous quantification of the bidirectional glucose transfer across the placenta.


Changes in lymphocyte sub-populations in the blood of healthy and sick newborn infants. Normal values for the percentages of lymphocytes carrying surface membrane-bound immunoglobulin, or rosetting with sheep erythrocytes, ox erythrocytes coated with rabbit immunoglobulin G, or ox erythrocytes coated with rabbit immunoglobulin M and reacted with human serum partially de-complemented with zymozan, have been estimated for populations from human umbilical cord blood and the peripheral blood of babies aged one week and one month. These samples have been compared with values obtained from normal adult volunteers and eighteen newborn infants, measured during and after a suspected infective episode. The dynamic change in those lymphocytes from normal infants staining for both IgM and IgD is shown, demonstrating that the number of circulating cells of this typeapproaches adult levels by the age of one month. Falls in the levels of all three types of rosetting lymphocyte were demonstrated over the same period. A drop in the number of lymphocytes forming sheep erythrocyte rosettes, and particularly those binding C3b-coated ox erythrocytes, in those babies suspected of infection showed a correlation with acute septicaemia or viraemia.


Postnatal development of renin-angiotensin-aldosterone system, RAAS, in relation to electrolyte balance in premature infants. In an attempt to provide information about the role of RAAS in development of late hyponatremia in low-birthweight neonates, simultaneous measurement of plasma renin activity, (PRA), plasma aldosterone concentration (PA), and urinary aldosterone excretion (UAE) was made using RIA methods along with determination of Na and K balance weekly up to the 6th week of life. Seven healthy male infants with mean birthweight of 1580 g, range: 1160-1850 g, and mean gestational age of 31 weeks, range: 30-32 weeks, were selected for the study. Due to the increased urinary Na loss, negative Na balance developed in the first 2 weeks followed positive balance thereafter. PRA, PA, and UAE increased tremendously from the initially high values of 18.2 +/- 4.1 ng/ml/hr, 1.7 +/- 0.5 ng/ml, and 2.6 +/- 0.4 microgram/day, mean and SEM, to their maximum of 78.6 +/- 18.1 ng/ml/hr, p less than 0.01, 6.8 +/- 3.7 ng/ml, p less than 0.05, and 26.4 +/- 2.9 microgram/dayp less than 0.01, in the 3rd week, respectively. Later on, gradual declines occurred, however, PRA, PA, and UAE remained highly elevated even at the 6th week with values of 45.5 +/- 15 ng/ml/hr, 1.6 +/- 0.5 ng/ml, and 14.5 +/- 1.4 microgram/day, respectively. It is suggested that late hyponatremia of premature infants is due to tubular unresponsiveness to aldosterone and not to inadequate response of RAAS to stimulation.


In vivo evaluation of monopolar intravascular PO2 electrodes. Ten intravascular electrodes were evaluated on ten rabbits. The mean stabilized time of 118 +/- 52 min was excessively long for clinical use. The in vitro cal factor was not reproducible nor accurate. The differences between the PO2 values measured by the electrode and those obtained from intermittent blood samples were within +/- 10 mm Hg during the first 12 hr using the in vivo calibration after electrode stabilization. After 12 hr, the electrode PO2 values using the in vitro cal factor or based upon the in vivo calibration were increased significantly indicating a possible membrane rupture. This occured more rapidly in the animal experiments than in the in vitro studies using a tonometer, suggesting that continuous flow and pressure changes inside of the aorta contribute greatly to mechanical breakage of the membrane. Histologic evaluation indicated the electrode catheter system was thrombogenic at the level of the electrode tip and this thrombogenicity was primarily related to intimal injury caused by the electrode tip movement as a result of flow and pressure changes inside the aorta.


Increased heparin binding in cystic fibrosis: a reflection of altered glycoprotein biosynthesis? Some of the serum proteins which bind to heparin and contribute to the pH 5.57 "heparin binding capacity" of human serum are glycoproteins; those from cystic fibrosis serum were found to be 27% higher in fucose (methylpentose) content, 27% lower in sialic acid content, and 31% lower in hexose content when compared to heparin-precipitated serum glycoproteins from normal control subjects. Hexosamine content of the heparin-precipitated serum glycoproteins was the same. Results of this preliminary investigation indicate that altered carbohydrate composition in serum glycoproteins may affect significantly their heparin binding capacity.


Abnormal copper metabolism in Menke's steely-hair syndrome. Copper (Cu) metabolism was selectively studied in seven infants with Menke's steely-hair syndrome (SHS). A daily oral regimen of CuSO4 (584 microgram Cu/kg) and L-histidine (100 mg/kg) in three infants produced an increase in serum Cu concentrations ranging from 33-95% of normal, but without the formation of ceruloplasmin. Cohn serum protein fractionation after oral Cu/L-histidine loading showed a disproportionate accumulation of Cu in the albumin fraction (V). The electron spin resonance spectrum of fraction V showed a heightened signal for the SHS patients, suggesting that an increased concentration of a radical Cu species is present after oral loading. The Sephadex G-150 chromatographic profile of serum fraction V in SHS did not differ significantly from controls. These results suggest that, in SHS, Cu absorbed in the presence of L-histidine is in an abnormal complex involving albumin, which does not allow for holoceruloplasmin biosynthesis. Cu and ceruloplasmin concentrations in the cord blood specimen of an infant who went on to develop SHS were normal, a finding which may account for the transient period of seemingly normal development after birth in SHS patients. An almost 6-fold difference in mean Cu concentration was observed in SHS fibroblasts compared to controls. Fibroblast Cu concentration was elevated in one to two possible maternal heterozygotes, a finding which may permit diagnosis of the carrier state for some SHS heterozygotes.


The effect of hemoglobin F-Chesapeake (alpha 2 92 Arg. leads to Leu gamma 2) on fetal oxygen affinity and erythropoiesis. A carrier of hemoglobin Chesapeake, born of a normal mother, had a cord-blood hematocrit of 60%. The oxygen affinity of his blood was increased. Hemoglobin F-Chesapeake (alpha 2 Ches gamma 2), partially purified from the infant's blood, had oxygen affinity greater than that of hemoglobin A, but less than that of the adult form of the abnormal hemoglobin (alpha 2 Ches beta 2). These findings suggest that the conformation of that part of the gamma chain which contacts the site of amino acid substitution in Hb F-Chesapeake is similar to the analogous region of hemoglobin F. They also support the hypothesis that regulation of erythropoiesis in late fetal life is similar to that of the adult, and is under fetal control.


Developmental aspects of renal beta-amino acid transport I. Ontogeny of taurine reabsorption and accumulation in rat renal cortex. Newborn Sprague-Dawley rat pups were found to have reduced net tubular reclamation of the beta-amino acid taurine in vivo. The reabsorption of this compound increased between the 2nd and 4th week of life and the excreted taurine fell despite a rise in glomerular filtration rate indicative of increased transport with maturation. Kidney cortex in vivo accumulated taurine from plasma against a large chemical gradient. Newborn cortex slices in vitro accumulated taurine to higher levels at steady state at less than 0.4 mM, but uptake was less efficient at higher taurine concentrations. Further metabolism of taurine by cortex slices was not found at any age. Accumulation in adult and newborn cortex was greatest at 10-15 mEa/liter K in the external medium. Slices from younger animals had slightly higher pH optima for uptake and temperature elevation increases uptake more in neonatal than in adult kidney.


Immediate and late ventillatory response to high and low O2 in preterm infants and adult subjects. The differences in the immediate (30 sec or 1 min) and late (5 min) ventilatory response to high and low O2 have not been quantitated in preterm infants and adult subjects using the same methods. It was thought that these differences might explain the paradoxical ventilatory response to CO2 at various O2 concentrations in preterm infants (12). Thus, 9 preterm infants and 10 adult subjects were given 21% O2 to breathe and then 100 or 15% O2 for 5 min each. Adults also breathed 15% O2 before 100% O2 or 12% O2 in order to make their resting arterial PO2 more comparable to those of infants breathing 21% O2. The ventilatory response to 100% O2 was the same in preterm infants and adult subjects, but the late response to 15% O2 remained paradoxical, ventilation decreasing at 5 min by 18% in infants and increasing by 19% in adults. The authors conclude: 1) the traditional concept of the ventilatory response to 100% O2 being different in infants and adult subjects is false; 2) the notion that the response to low O2 is paradoxical in infants is correct; and 3) the data do not explain why the response to CO2 under various background concentrations of O2 in infants is the reverse of that in adult subjects, but the depressed ventilatory response to hypoxia in infants may justify, at least in part, their flatter response to CO2 during low O2 breathing.


Inhibition of the glycine cleavage system by branched-chain amino acid metabolites. The effects of 18 normally occurring and 11 patalogical metabolites of the branched-chain amino acids on the glycine cleavage system were investigated on intact rat liver mitochondria. It was demonstrated, that 2-oxo-isovaleric acid, 2-methyl-butyric acid, and isobutyric acid significantly inhibited the glycine cleavage system in intact mitochondria. Further studies on the solubilized glycine cleavage system demonstrated that the inhibitory effect was due to 2-methyl-butyryl-CoA (linear noncompetitive inhibition, ki: 0.1--0.15 mM) and isobutyryl-CoA (S-hyperbolic, I-linear noncompetitive inhibition, ki: 0.2--0.3 mM). Both 2-methyl-butyric acid and isobutyric acid exhibited less inhibition (2-methyl-butyric acid: competitive inhibition, ki: 5.5 mM, isobutyric acid: competitive inhibition, ki: 16 mM), while 2-oxo-isovaleric acid was without inhibitory effect, and probably affects intact mitochondria through transformation to isobutyryl-CoA. It is suggested that the inhibitory action of 2-methyl-butyryl-CoA and isobutyryl-CoA may explain the hyperglycinemia seen in propionyl-CoA carboxylase deficiency, methyl-malonyl-CoA mutase deficiency and beta-ketothiolase deficiency.


Cardiopulmonary changes in the crying neonate. To determine hemodynamic effects of crying, 12 newborn infants recovering from the respiratory distress syndrome (RDS) were studied. When crying, the range of inspiratory esophageal pressure was -18.8 to -32.5 cm H2O and the range of espiratory pressure was +6.2 to 34.4 cm H2O. The esophageal pressure remained positive for a mean value of 66% of the respiratory cycle. There was a mean significant increase in heart rate of 19 beats/min. The systolic and diastolic blood pressures increased significantly at the beginning of strain to 115 and 135% of the respective control values. There was a progressive decrease in systolic and diastolic pressures during the period of strain and the systolic pressures reached values significantly less than control. With the decrease in systolic and diastolic pressures, there were pronounced reductions in pulse pressures. Three infants reached pulse pressure values less than 1% of control when cries were sustained for nine cardiac cycles. There was a significant mean decrease in arterial oxygen tension (PaO2) of 16.8 mm Hg. There were no changes in arterial carbon dioxide tension (PaCO2), pH, or base excess.


Pulmonary function studies of conjoined thoracopagus twins. Lung functions were measured on 13-day-old conjoined thoracopagus twins. Mean values for tidal volume and minute ventilation were 14.8 ml and 1102 ml/min for twin A and 12.8 ml and 963 ml/min for twin B. Functional residual capacities (FRC) were 35 ml/kg and 39 ml/kg for twins A and B, respectively. Pulmonary compliance and flow resistance for twin A were 2.8 ml/cm H2O and 75 cm H2O/liter.sec-1 with 45% of the total work used to overcome elastic resistance. Although values for resistance and work of breathing are within the normal range for studies reported elsewhere, these results tend to be elevated and probably reflect an abnormal state.


Abnormal pyruvate and alpha-ketoglutarate dehydrogenase complexes in a patient with lactic acidemia. Activities of pyruvate decarboxylase (PDC), alpha-ketoglutarate decarboxylase (KGDC) and both the pyruvate and alpha-ketoglutarate dehydrogenase complexes (PDH complex and KGDH complex) were measured, and kinetic properties of PDC were studied in fibroblasts derived from normal individuals and from a 2-yr-old girl with congenital lactic acidemia and severe retardation of growth and development. The activities of PDC, KGDC, PDH complex, and KGDH complex in the patient were 1.12 +/- 0.12, 2.33 +/- 0.42, 9.00 +/- 0.50, and 16.46 +/- 1.57 and in controls 3.10 +/- 0.16, 5.36 +/- 0.56, 24.13 +/- 1.61 and 44.95 +/- 3.72 nmole/mg protein/hr. The optimum pH (6.0) and Michaelis constants (Km) for pyruvate of PDC (1.0-1.6 X 10(-5) M) were similar in fibroblasts of the patient and controls. PDC activity was more sensitive to denaturation by heat in the fibroblasts of the patient than those from controls, while heat denaturation curves of KGDC were similar in the patient and control. Higher concentrations of thiamine pyrophosphate (TPP) were required to protect PDC from heat denaturation in the patient. TPP was more easily removed from PDC in the patient than in the control by washing the fibroblasts with alkaline buffer. These results suggest that the PDC enzyme of the patient is in an altered molecular form, to which TPP is loosely bound. This particular constellation of abnormalities has not previously been reported in patients with lactic acidemia.


Pulmonary vasodilator action of tolazoline. The pulmonary vasodilator action of tolazoline in newborn lambs was shown to be mediated via histamine receptors. Maximal changes in pulmonary vascular resistance, deltaPVR, were calculated as percents of the base line value, %deltaPVR. The mean %deltaPVR after tolazoline, 1 mg/kg, was -25 +/- 4% for eight lambs. Four lambs then received the histamine H1 receptor antagonist, diphenhydramine, and the mean %deltaPVR due to tolazoline was -12 +/- 4%. Four lambs received the H2 receptor antagonist, metiamide, and the mean %delta PVR due to tolazoline was -18 +/- 5%. After both H1 and H2 antagonists, the mean %deltaPVR due to tolazoline was +6 +/- 8%. Therefore, both histamine H1 and H2 receptors were involved in the vasodilator response to tolazoline.


Quantitative noninvasive method to measure cerebral blood flow in newborn infants. We measured cerebral blood flow (CBF) in 32 healthy neonates by venous occlusion plethysmography. Mean CBF was 63 ml/min/100 gm which compared favorably with invasive methods used in older children and adult subjects. We suggest that this is a useful method to quantify CBF in neonates. It may be valuable in assessing sequential changes occurring during asphyxia, intracranial hemorrhage, or during administration of various gas mixtures and drugs such as theophylline.


Fatal Haemophilus influenzae endocarditis diagnosed by echocardiography in an infant. A 1-year-old boy was admitted to the hospital with Haemophilus influenzae meningitis. On the second hospital day a heart murmur heard on admission seemed louder. No signs of congestive heart failure were present. An echocardiogram demonstrated a persistent echo-dense mass behind the anterior leaflet of the mitral valve. A presumptive diagnosis of endocarditis was made. After ten days of antibiotic treatment the child was considerably improved. Treatment was continued for endocarditis. Over the next several days the infant's condition deteriorated. On the 16th hospital day he died. Autopsy examination showed a large vegetation attached to the posterior mitral valve leaflet. Bacterial endocarditis caused by H influenzae is uncommon at any age and rare in children. Echocardiography provided a definitive diagnosis early in the hospital course of this patient.


Risk factors associated with failure to receive vaccinations. A major purpose of a state-wide survey to document the vaccination status of 1,003 2-year-old children was to identify factors associated with failure to receive the recommended vaccinations. With a basic series of immunization defined as three doses of diphtheria-tetanus-pertussis (DTP), three oral polio vaccine (OPV), one measles, and one rubella, 72.5% of the children had completed the series. When the completed series was redefined to include a fourth DTP and mumps vaccine the rate of completion dropped to 40.8%. However, 59.1% of the children who had not completed this optimal series could be brought up-to-date with a single visit to their provider of medical care. Demographic variables independently associated with completion of the basic series were increased paternal education (P less than .001), increased maternal education (P less than .02), smaller family size (P less than .01) and higher socioeconomic status, as determined by census tract or rural town of residence (P less than .02). Race was not found to be a factor associated with vaccination rates when socioeconomic status was controlled. Patients who received their vaccinations from private physicians had a better vaccination rate than those who attended health department clinics. This difference persisted even when socioeconomic status was controlled by residence (P less than .02). The simultaneous comparison of parental education and family size demonstrated that a child having one parent with less than 12 years education or having at least three siblings has a fourfold greater risk of failure to complete his immunization than children whose parents are both college graduates. By using paternal and maternal education level and family size as screening variables, children at high risk for failure to complete their immunizations could be identified prospectively and made the target of intervention programs to improve compliance.


Experimental pneumothorax detected by thermography. After induction of pneumothorax in rabbits, thermograms showed decreased heat emission from the involved side. These observations suggest that noninvasive monitors of thoracic wall temperatures might be useful for early detection of air-leak phenomenon in high-risk neonates.


Refractory hypoglycemia associated with a malpositioned umbilical artery catheter. An infant with unexplained hypoglycemia who responded poorly to medical management had the tip of his umbilical artery catheter positioned near the major arteries supplying the pancreas. Catheter repositioning resulted in immediate normoglycemia. A "reactive" response to the direct infusion of glucose is postulated on the basis of the clinical response and a decrease in serum insulin/blood glucose ratio.


The effect of head position and angle of tracheal bifurcation on bronchus catheterization in the intubated neonate. The effect of head position and angle of tracheal bifurcation on bronchus catheterization was studied in newborn infants. Frequency of bronchus catheterization following appropriate head positioning was evaluated radiographically after passage of a No. 5 French feeding tube in eight intubated neonates within 30 minutes post mortem. Positioning the infants head to the right in preparation for a suctioning procedure may facilitate but not assure catheterization of the left main stem bronchus (LMSB). Positioning the infant's head straight or rotating to the left appears to be equally effective in catheterization of the right main stem bronchus (RMSB). The predominance of RMSB catheterization in infants with their head in the straight position may be explained by the different angles of mainstem bronchi divergence which we determined using radiographs. The angles of divergence of the LMSB and the RMSB from the trachea averaged 44.4 degrees and 24.1 degrees, respectively.


Vitamin E and neonatal bilirubinemia.

Vitamin E and neonatal bilirubinemia. A study was designed to determine the effect of vitamin E on bilirubinemia in the preterm infant. Twenty infants with birth weight between 1,000 and 1,500 gm and 20 infants with birth weights between 1,501 and 2,000 gm were studied. Half the infants in each birth weight group received vitamin E administered intramuscularly in a total dose of 50 mg/kg during days 1 to 3 of life; the remaining infants served as controls. The administration of vitamin E produced significantly increased plasma tocopherol concentrations and normal hydrogen peroxide hemolysis tests by the end of the first week of life. Infants with birthweights less than or equal to 1500 gm who received vitamin E demonstrated a significant decrease in serum bilirubin on day 3 of life (6.5 +/- 2.2 vs 8.8 +/- 2.2 mg/dl) as well as a significant decrease in peak serum bilirubin during the first week of life (8.3 +/- 2.2 vs 10.6 +/- 2.6 mg/dl). The duration of phototherapy also was significantly less in the vitamin E-supplemented group (48 +/- 18 vs 107 +/- 31 hours). These differences were less pronounced in infants with birth weights more than 1,500 gm.


Nonimmune hydrops fetalis: report of 22 cases including three siblings. Twenty-two cases of nonimmune hydrops fetalis (NIHF) seen over a three-year period are described. Eight cases were associated with major congenital anomalies, seven cases with minor anomalies or other disease entities, and seven idiopathic cases. The overall mortality rate was 50%, greatest in those cases complicated by major anomalies. The clinical problems commonly encountered in management of these patients are reviewed, and include prenatal detection, perinatal asphyxia, disseminated intravascular coagulopathy, fluid and electrolyte imbalance, and respiratory difficulty. A review of the literature for those entities found in association with NIHF is also included. The case studies of three consecutive siblings with NIHF born to the same parents are briefly analyzed.


Folic acid supplementation in low birth weight infants. Low birth weight infants (246) entered a trial to folic acid supplementation from 3 weeks to 12 months of age. The folic acid group had significantly higher mean hemoglobin levels at 6 and 9 months of age but the differences were only about 0.5 gm/dl, there was no significant difference in hematocrit, and in both groups of infants the mean hemoglobin levels were higher than those of normal birth weight infants. The differences in hemoglobin, although statistically significant, are of uncertain clinical significance. Median red cell folate levels remained within the normal adult range in both groups of infants. A minority of infants in the untreated group had low red cell folate levels but this was usually temporary, corrected by dietary folate, and not associated with low hemoglobin. Weight gain was not affected by folic acid supplementation. The infants in this trial were fed with a milk preparation containing 3.5 microgram/100 ml of folic acid which is a similar concentration to that of human milk and we recommend that the folate content of milks fed to low birth weight infants should not fall below this level. We do not have sufficient grounds to recommend routine folic acid supplements for all low birth weight infants throughout the first year of life but there is a possibility that their folate intake may sometimes be suboptimal.


Hyperammonemia associated with perinatal asphyxia. Twelve infants with severe perinatal asphyxia were found to have elevated blood ammonia levels (302 to 960 microgram/100 ml). In the seven survivors, hyperammonemia was associated with CNS irritability, hyperthermia, hypertension, and wide neonatal heart rate oscillations. Follow-up examinations revealed severe neurologic dysfunction in five of seven infants. CNS depression, hyperthermia, hypertension, and a nonreactive, fixed heart rate characterized the infants that died. These findings suggest a clinical entity secondary to perinatal asphyxia whose signs and symptoms may be related to hyperammonemia.


Neurologic abnormalities in near miss for sudden infant death syndrome infants. As part of the Sudden Death Research Project at Stanford University School of Medicine, we have performed systematic neurologic examination of 41 near miss infants, 7 normal siblings of babies who died a sudden infant death, and 21 normal control infants. Many infants were examined longitudinally until 2 years of age. We found that near miss infants under 3 months of age had consistent abnormalities of muscle tone, particularly shoulder hypotonia. These abnormalities disappeared with maturation, but only 60% of older infants who had suffered near miss episodes of neurologically and developmentally normal. In addition, only one of the seven apparently normal siblings had an entirely normal neurologic examination when first seen. Thus, infants who present with near miss episodes may have an underlying central nervous system abnormality or may acquire some abnormality as a result of the episode.


MMPI characteristics associated with cerebral palsy and dystonia musculorum deformans. The origins of dystonia musculorum deformans are now considered to be organic. However, misdiagnosis of dystonia as a functional psychiatric disorder--usually conversion reaction--has persisted. The present study describes personality traits as measured by the Minnesota Multiphasic Personality Inventory in 30 persons with dystonia and in a control group of 37 persons with cerebral palsy. The data, examined by diagnosis, level of disability, and sex, showed no differences for diagnostic groups or levels of disability. Males scored in the direction of greater psychopathology than did females. The male dystonics showed the highest elevations of MMPI scales of all the groups. Although only one person with dystonia musculorum deformans and none with cerebral palsy produced the profile usually associated with conversion reaction, 36% of all profiles showed two scales above a T score of 70. This finding suggested that young adults with a physically disabling disease may be at higher risk for developing maladaptive personality traits.


Relationship between anxiety and performance in scuba diving. The present research examined the relationship between the anxiety levels of 62 beginning Scuba diving students and standardized performance tests from the Y.M.C.A. training program. Results suggested that there was no relationship between anxiety and performance on relatively simple tasks, while there was a relationship between anxiety and performance on the more complex diving maneuvers.


Longitudinal study of cognitive abilities and academic achievement. Assessment was made of the effectiveness of a battery of cognitive tests administered in kindergarten in the prediction of sixth grade achievement in reading comprehension, spelling, language usage, and arithmetic. Cognitive abilities included several factors of intelligence, visual perception and visual sequential memory, visual-motor integration, and auditory perception and auditory sequential memory. Measures of prior learning were also included. Subjects were 58 children in a suburban public school district. A criterion for predictive utility for correlation coefficients was established, and simple correlation coefficients for various kindergarten measures and sixth grade achievement ranged from the criterion of .35 to .69. In partial correlations with the effects of ability to understand ideas expressed in words removed, correlation coefficients for various cognitive measures and achievement tests ranged from the criterion of .35 to .63. Combinations of kindergarten measures having optimal multiple correlations with later school achievement generally approached or exceeded .70. These findings are discussed and suggestions are made for further research.


Discrimination of infants' cry-signals.

Discrimination of infants' cry-signals. A technique for clustering infants' cry-signals on the basis of perceptually discriminable acoustic characteristics is reported. A cry-sequence containing all pairwise combinations of 24 signals was constructed. These signals have been used previously in cry-recognition studies (e.g., Wasz-Hockert, et al., 1968) and consist of six each of pain, hunger, pleasure, and birth. 20 musically competent subjects were tested individually and instructed to compare each cry with the one immediately preceding it in the sequence. Forced-choice "similarity" scores were summed for every pair of cries. These "similarity scores" were data for both a manual and a computerized clustering method. There was absolute agreement between these two methods, and the clusters of cry-signals correspond very closely to the four original cry groups. This seems a valid technique for examining the acoustic similarity of infants' cry-signals.


ITPA interchannel differences.

ITPA interchannel differences. The extent to which auditory and visual channel part-score means differ typically was studied by reference to the performance of 962 average children in the normative sample of the Illinois Test of Psycholinguistic Abilities. A standard error of measurement difference of 1.87 scaled score points was obtained, such indicating comparatively little difference in the mean performance of average children on the two communication channels of this test. Differences between means of auditory and visual channels greater than 3.09 or 4.36 scaled score points are presented as statistically significant at the 5 or 1 percent level of confidence, respectively. Significant part-score differences suggest atypical performance in the channel with the lesser mean scaled score and may indicate the presence of a disability among behaviors assessed by subtests within that channel.


Kinesthetic augmentation and reduction in adult females. The Petrie Block Test was used to measure kinesthetic after-effect in a sample of 60 normal adult female subjects. In addition to the establishment of normative data for this sample, several procedural questions raised by other investigators were addressed. It was determined that the use of ascending trials produced more accurate baseline measures than the alternate use of ascending and descending trials. Also, order of test presentation affected baseline measures. Since a rather large proportion of this sample was comprised of stimulus-governed individuals, some factors related to their particular perceptual style were examined.


Effects of clinical dosage levels of methylphenidate on two-flash thresholds and perceptual motor performance in hyperactive children. Three groups (ns = 10) of children (normals, hyperactives, hyperactives on medication) were administered eight perceptual-motor tasks. The normal controls were significantly superior in performance in comparison with the hyperactives taken off methylphenidate on three tasks but only superior on one task (Digit Symbol) when compared to hyperactives on methylphenidate. The hyperactives on medication were also significantly superior to the hyperactives not on medication on the Digit Symbol task.


Aesthetic dimensions and picture memory: a structural re-analysis. The data of Franken and Davis (1975) on the prediction of memory for pictures from aesthetic ratings were re-analyzed, employing smallest space analysis to explore the structural aspects of memory and the aesthetic dimensions. The major results of this re-analysis identified one relatively pervasive dimension, distinctiveness, which encompassed most of the memorial and aesthetic variables.


Beliefs and anticipated situations influencing intentions to use drugs. Unique differences between usage segments in beliefs, perceptions, and anticipated situational influences regarding the salient dimensions underlying motivations to use marijuana are described. An extended model of behavioral intention is used for examining and explaining motivations to use marijuana in an attempt to replicate and extend recent research on drugs. Respondents' opinions concerning the interventing influences of external situations on the intentions-behavior relationship are also addressed. Implications for public policymakers concerned with drug-related social issues are also provided.