Binding of imipramine to plasma protein and to brain tissue: relationship to CSF tricyclic levels in man.

The possible clinical significance of the plasma protein binding of tricyclic antidepressants has been evaluated using imipramine (IMI), a typical tricyclic. Using equilibrium dialysis, the in vitro binding of IMI to plasma was compared to that of brain tissue. Cerebrospinal fluid (CSF) IMI was used as an independent measure of 'free' drug in the central nervous system. Intrinsic metabolic clearances were calculated on the basis of steady-state plasma IMI concentrations. There were three significant results: (1) variations in plasma binding are not great; (2) plasma protein binding does not limit the entry of IMI into the CSF; (3) variations in metabolism (intrinsic clearance) account for almost all variations in CSF concentrations of drug. It is concluded that measurement of free tricyclic antidepressant is not indicated in studies of clinical efficacy.


Circadian variations in the effect of alpha-methyl-p-tyrosine on avoidance learning.

Circadian variations in alpha-methyl-p-tyrosine's (alpha MT) disruption of active avoidance acquisition were studied, alpha MT administered between 11.0 and 13.00 h, 17.00 and 19.00 h and 23.00 and 01.00 h impaired learning, but alpha MT administered between 05.00 and 07.00 h did not impair learning. The time of alpha MT ineffectiveness corresponds with the reported circadian peak in brain catecholamines, suggesting that the circadian susceptibility rhythm of alpha MT depends upon circadian fluctuations of brain catecholamines.


Gamma-ray spectrometry of humans at the University of Utah.

A human total-body counter was designed and built with two 20 X 10 cm NaI (Tl) crystals suspended over an "isoresponse surface" upon which the subject reclines. This surface is curved from head to knee and from left to right, so that a gamma-ray emitting object is detected with equal efficiency when placed anywhere upon it. The positioner and detectors are housed in a low background enclosure constructed of steel 31 cm thick with a graded inner lining of lead + cadmium + copper. Calibration of the system was accomplished by administering trace amounts of various radionuclides to 48 human subjects of various sizes, ranging in age from 4--80 years. Counting rates per retained muCi at 0.53, 0.66, 1.53, and 2.75 MeV (83Rb, 137Cs, 42K, and 24Na) were determined as a function of body size and were compared with counting rates per muCi of corresponding emitters centered in a polyethylene cylinder of radius 10.3 cm. Limits of detection, corresponding to three times the standard deviation of a 50 min background, were 170 nCi 90Sr (via Bremsstrahlung X-rays), 0.78 nCi 131I, 0.48 nCi 83Rb, 0.52 nCi 137 Cs, 4.9 nCi 40K (or 5.8 g of natural potassium) and 1.7 nCi 222Rn.


Incidence of cataracts in rhesus monkeys treated with whole-body irradiation.

The incidence of cataract formation was investigated in rhesus monkeys exposed to different doses of whole-body irradiation. Application of 850-900 rad (8.5-9 Gy) caused cataracts in 17% of the monkeys within 3 years after treatment; after 10 to 15 years, incidence increased to 100%. "Young" lenses showed a significantly lower incidence than "adult" lenses, although no differences in the stage of cataractogenesis could be demonstrated. Sex differences did not play a role in incidence and severity of cataracts. Lower doses (400 rad or 4 Gy) did not cause cataracts. In view of the close similarity between monkeys and humans, these results indicate that a single dose of 850-900 rad, sometimes employed in the treatment of acute myeloid leukemia in children, carries a strong risk of cataract development.


A technique for scatter dose calculation.

The intent of this article is twofold: to gain a basic understanding of radiotherapy dosimetric techniques that separate primary radiation dose from tissue scatter dose, and to introduce the use of a polar grid to simplify manual calculation of scatter dose in irregularly blocked fields. This technique requires the introduction of a new term, 'scatter-pixel,' which is defined in terms of more familiar expressions. Finally, the polar grid technique is evaluated against measured data for various cases of blocking and contour fall-off.


Inactivation of slow reacting substance of anaphylaxis (SRS-A) by lipoxidase.

Lipoxidase (E.C.1.13.1.13) inactivates rat SRS-A. The inactivation is time, temperature, and concentration-dependent. Linoleic acid and eicosatetraynoic acid inhibit the enzymatic deactivation of the mediator. It is concluded that SRS-A is a genuine substrate for lipoxidase and contains a cis, cis-1, 4-pentadiene structure. It is suggested that lipoxidase could play a major role in tissue removal of the mediator during hypersensitivity reactions.


[The clinical, radiological and epidemiological aspects of duodenal diverticula (author's transl)].

Ninety-five cases of duodenal divertigestive apparatus. The epidemiological, clinical and radiological features of this form are discussed with particular reference to its complications and associated diseases. The indications for surgery are examined and several cases are presented, along with their radiographical pictures.


Immunologic and morphologic effects of cryosurgery of the monkey (macaque) prostate.

A reduction in size of the Macaque prostate following single and multiple in situ freezings was accompanied by histologic alterations, which occurred predominately in the caudal lobe and were characterized by what appeared to be specific periacinar foci of lymphocytic infiltrates. These lymphocytes were observed to infiltrate onto acinar epithelial cells, resulting in their subsequent separation from the basal lamina and epithelial destruction. Other histologic alterations were in consonance with studies of the prostate following cryosurgery by others. Circulating antibodies specific for prostate were present in only one of the seven animals at the time at which these histologic observations were made. These observations suggest the possible development of a cellular immunologic response following cryosurgery of the prostate. The relevancy of these observations to those obtained following cryoprostatectomy in man and other species is considered. Pending confirmation, they may be of potential significance in providing an explanation of reported cases of eradication of human prostatic carcinomas following cryotherapy.


Protective effect of ketotifen and disodium cromoglycate against bronchoconstriction induced by aspirin, benzoic acid or tartrazine in intolerant asthmatics.

Oral challenge tests with acetylsalicylic acid, tartrazine or benzoic acid were performed in 7 intolerant asthmatic patients after a 3-day treatment with either orally taken ketotifen (1 mg twice daily) or inhaled disodium cromoglycate (20 mg four times daily) at random. Protection was noted with ketotifen in 5, with DSCG in 3 patients. On the evaluation of the mean percentage of the maximum decline in the forced expiratory volume in 1 sec (FEV1) only ketotifen afforded significant protection statistically (p less than 0.05). All the intolerant asthmatics studies showed, as an immunological abnormity, a slight, but significant decrease of the C1-inhibitor levels. Moreover, in three out of these the alpha 1-antitrypsin serum values were under the lower normal range.


[Temporal post-traumatic epilepsy: corticographic and ultrastructural study of a case].

A case of post-traumatic temporal epilepsy, submitted to a temporal lobectomy, is reported. During surgery, electrocorticography was carried out in order to differentiate epileptic areas from normal tissue. The ultrastructural study of nervous tissue removed from both normal and epileptogenic areas showed diffuse and aspecific process of neuronal alterations without a correlation to the electrographic epileptic areas. The importance of trauma in the evolution of these alterations is discussed.


[Epilepsy and pregnancy: preliminary studies].

The study concerns 17 clinical cases of epilepsy during the progress of 32 pregnancies. It is reported the frequency variations of epileptic fits, the eventual pharmacological adjustments and also some parameters of influence on the newborn. The result are briefly argued.


[Proteolytic enzymes in multiple sclerosis].

The paper is a review of the literature on the role of proteolytic enzymes in the human and experimental demyelinating diseases.


Use of a macrophage cytotoxicity system to show macrophage activation by Listeria monocytogenes cell wall fraction.

Experiments were conducted to determine whether a partially purified listeria cell wall fraction could stimulate macrophages to high levels of activation. To detect activation of macrophages, a macrophage-mediated cytotoxicity system were established. The data demonstrate that listeria cell wall components are capable of activating thioglycollate-induced adherent peritoneal exudate cells to be cytotoxic for 51Cr-labelled target tumour cells, and that the listeria fraction is as effective as bacterial lipopolysaccharide in inducing cytotoxicity. The listeria fraction can also induce peritoneal exudate cells from congenitally thymusless nude mice to become cytotoxic, suggesting that mature T cells are not required. Furthermore, thioglycollate-induced adherent peritoneal exudate cells from mice hyperimmunized to live Listeria organisms are already stimulated to be cytotoxic for tumour cells, and do not need to be activated in vitro. Additional data are presented which characterize the system. These data demonstrate that a critical concentration of adherent peritoneal cells is required for in vitro activation. Moreover, only peritoneal cells induced with aged batches of thioglycollate, and not uniduced peritoneal cells or those induced with fresh thioglycollate or with protease peptone can be activated in vitro to kill tumour cells. Evidence is presented which suggests that the cytotoxic cell is a macrophage.


The immune response to the alpha 1-6 epitope of dextran is determined by a gene linked to the IgCH locus.

There is a marked strain variability in the immune response against the alpha 1-6 epitope of dextran B512. Responsiveness was independent of the H-2 genotype of the strains but completely determined by the IgCH allotypes of the strains. Thus, IgCHb and IgCHj allotypes characteristic of C57BL and CBA strains, respectively, determined high responsiveness, whereas strains possessing all other allotypes studied were low responders. Backcross analysis indicated that a gene(s) determined responsiveness and that this gene was linked to allotypes of the IgCH locus. F1 hybrids between high and low responder strains always gave a response, but the number of plaque-forming cells was approximately half of that obtained in the high responder strains.


Efficient conjugation of rabbit Fab' with beta-D-galactosidase from Escherichia coli.

An efficient procedure for the conjugation of rabbit Fab' with beta-D-galactosidase from Escherichia coli using N,N-o-phenylenedimaleimide is described. Thiol groups of Fab' were stabilized by the presence of ethylenediaminetetraacetate, and malemide groups were shown to be stable at pH 5 at 4 degrees C. The stability of thiol and maleimide groups enabled an efficient introduction of maleimide groups into Fab' and the average number of maleimide groups introduced into Fab' was 0.76 (range 0.73-0.79; n = 10) per molecule. As a result, 43.4% (range 41.3-46.9%; n = 6) of Fab' used could be conjugated with most of beta-D-galactosidase used. The average number of Fab' molecules conjugated per enzyme molecule was calculated to be 4.2 (range 4.0-4.6; n = 6). Both the enzyme and antibody activities were well preserved in the conjugate. There was no self-coupling of Fab', although the enzyme was polymerized to some extent during the conjugation reaction. The enzyme activity and cross-link in the conjugate was stable at pH 6.0-7.0 at 4 degrees C for at least 3 months.


Formation of carcinogenic N-nitroso compounds in corn-bread inoculated with fungi.

DMNA, DENA and MBNA are formed in corn-bread which has been inoculated with the most common species of fungi found in foodstuffs of Lin Xian County, Henan Province, such as F. moniliforme, A. flavus and others, and then, added with small amount of NaNO2 after a few days of incubation. These carcinogenic N-nitroso compounds can induce cancer of the liver or/and esophagus in experimental animals. Results of the present study show the capability of some fungi to produce chemical carcinogens as well as mycotoxins in contaminated food, and thus, open a new field of research in cancer etiology.


A new N-nitroso compound, N-3-methylbutyl-N-1-methylacetonylnitrosamine, in corn-bread inoculated with fungi.

A new N--nitroso compound, N--1--methylacetonyl--N--3--methylbutylnitrosamine (MAMBNA) is found in corn-bread inoculated with the common fungi, such as Fusarium moniliforme, Geotrichun candidum, Aspergillus terreus or A. flavipes, encountered in food of Lin Xian County, Henan Province. The preliminary identification of this compound with TLC has been confirmed by GC-MS analysis. Furthermore, we have synthesized the MAMBNA and the chemical analysis shows that it is identical with the MAMBNA isolated from the corn-bread extract. In addition to the MAMBNA, dimethylnitrosamine, diethylnitrosamine and methylbenzylnitrosamine are formed also in the fungus-inoculated corn-bread after 8-day incubation and an addition of a small amount of sodium nitrite. The presence of precursor compounds for the formation of nitrosamine in the mouldy maize flour and their significance in respect to the etiology of esophageal cancer in high-risk areas have been discussed.


Temperature dependence of ADH-induced water flow and intramembranous particle aggregates in toad bladder.

Antidiuretic hormone (ADH)-induced luminal intramembranous particle aggregates and hormonally stimulated water flow in toad urinary bladder are reduced simultaneously with a reduction in temperature. When water movement is factored by the aggregation response, the apparent activation energy for this process decreases from 12.1 +/- 1.6 to 3.0 +/- 2.3 kilocalories per mole. The data are consistent with the view that the particle aggregates contain sites for transmembrane water movement and that these sites behave as pores.


Cognitive deficit caused by regional depletion of dopamine in prefrontal cortex of rhesus monkey.

Depletion of dopamine in a circumscribed area of association cortex in rhesus monkeys produces an impairment in spatial delayed alternation performance nearly as severe as that caused by surgical ablation of the same area. This behavioral deficit can be pharmacologically reversed with dopamine agonists such as L-dopa and apomorphine. These data provide direct evidence that dopamine plays an important role in a specific cortical function.


Basic principles of ROC analysis.

The limitations of diagnostic "accuracy" as a measure of decision performance require introduction of the concepts of the "sensitivity" and "specificity" of a diagnostic test. These measures and the related indices, "true positive fraction" and "false positive fraction," are more meaningful than "accuracy," yet do not provide a unique description of diagnostic performance because they depend on the arbitrary selection of a decision threshold. The receiver operating characteristic (ROC) curve is shown to be a simple yet complete empirical description of this decision threshold effect, indicating all possible combinations of the relative frequencies of the various kinds of correct and incorrect decisions. Practical experimental techniques for measuring ROC curves are described, and the issues of case selection and curve-fitting are discussed briefly. Possible generalizations of conventional ROC analysis to account for decision performance in complex diagnostic tasks are indicated. ROC analysis is shown to be related in a direct and natural way to cost/benefit analysis of diagnostic decision making. The concepts of "average diagnostic cost" and "average net benefit" are developed and used to identify the optimal compromise among various kinds of diagnostic error. Finally, the way in which ROC analysis can be employed to optimize diagnostic strategies is suggested.


General problems in medical decision making with comments on ROC analysis.

Medical decision-making studies continue to focus on two questions: How do physicians make decisions? How should physicians make decisions? Researchers pursuing the first question emphasize human cognitive processes and the programming of symbol systems to model observed human behavior. Those researchers concentrating on the second question assume that there is a standard of performance against which the physician's decisions can be judged, and to help the physician improve his performance, an array of tools is proposed. These tools include decision trees, Bayesian analysis, decision matrices, receiver operating characteristics (ROC) analysis, and cost-benefit considerations including utility measures. Medical decision-making questions must be answered in an ethical context where ethics and decision analysis are interviewed.


Efficacy...what's that??

We need to develop techniques for measuring the usefulness of medical services. If resources are limited, and we cannot do all the diagnostic tests we would like to do, we must be able to select those that are most useful. To do this we need to known how to weigh benefits against risks and how to measure the worth of a given outcome. This article discusses efficacy, in diagnosis, management, and outcome. Diagnostic efficacy of a test is measured by its ability to change the probability of disease (pre- versus post-test likelihood). Management efficacy is a measure of how the test changes patient management. Outcome efficacy, which may take years to evaluate, is the ultimate yardstick of usefulness. Even though there are many problems in estimating the likelihood of a disease (subjectivity, varying terminology, etc.), physicians can make reasonably close estimates, as shown by the American College of Radiology's Efficacy Study, which analyzed the diagnostic process in 9000 cases. Efficacy studies may be a mixed blessing, however, as they may result in overly strict criteria and sweeping economic changes. They may be ignored because of the difficulty in following the "perfect" protocol for a given clinical situation, and it remains to be shown that they themselves are efficacious. Nevertheless, we are finally coming to grips with the question of how useful our tests are in patient management.


Rationale for the use of bone scans in selected metastatic and primary bone tumors.

Since the introduction of bone scans in 1951, there have been many studies comparing biologic and physical characteristics of new bone-imaging agents and the results of scintigraphy and radiology in large numbers of patients. Relatively speaking, there have been fewer studies detailing the health benefits and financial cost associated with the use of skeletal scintigraphy. This review concerns these aspects in patients with malignancies of various sites and stages. About 2% of patients with stage I or II breast cancer have bone metastases at the time they first present, whereas nearly 28% of patients with stage III disease have bone metastases. A large percentage of patients with initially negative scans develop bone metastases during the first 3--4 yr; many of them develop them within the first 12--18 mo after initial diagnosis. For patients with lung cancer, the use of bone scans in staging their disease is somewhat controversial. Several studies indicate that the yield of positive bone scans may range from as low as 2% to as high as 35%. Data on the use of bone scans in staging prostatic cancer initially are similar to those in patients with breast cancer, that is, yields of 7% in patients with stage I or II disease and a yield of about 20% with stage III disease. Children with osteosarcoma or Ewing's sarcoma rarely have bone disease distant from the site of their primary bone lesion at presentation. However, a large percentage of them (30%--40% or so) develop bone metastases during the follow-up period. As in the case with patients with breast cancer, about half of these bone metastases are evident by 12--18 mo.


Recurrent streptococcal endocarditis.

A woman is described who suffered from multiple episodes of Streptococcus viridans endocarditis over a decade. The possible mechanisms for recurrence are discussed and the past literature on recurrent endocarditis is reviewed. In addition, the patient developed fever and eosinophilia in response to penicillin V, while tolerating penicillin G without incident.


Exceptionally high arterial oxygen tension in diabetic ketoacidosis.

We recently managed a patient with diabetic ketoacidosis who had an exceptionally high arterial oxygen tension of 144 mm Hg while breathing room air. This was higher than the calculated alveolar oxygen tension and suggested the impossible situation of an uphill diffusion gradient. We were surprised to find this is a relatively common phenomenon (occurring in 25% of a retrospective study of similar patients). There are a number of probable mechanisms responsible for this observation, all of which reflect the severe metabolic aberration occurring in these patients.


Spondylitis caused by Brucella abortus.

A case of severe chronic spondylitis of the lumbar spine caused by Brucella abortus is presented. Infection was probably associated with ingestion of raw cow's milk. A technetium bone scan provided evidence of activity as early as two years before the radiographic abnormalities were evident. Although rarely seen in brucellosis, a large left psoas abscess formed. After extensive resection and debridement of all necrotic tissue, along with prolonged use of oral doxycycline, the patient recovered completely. The clinical, laboratory, therapeutic, and pathogenic aspects of Brucella spondylitis are discussed.


[The influence of endogenous insulin and glucagon on the free fatty acids in the circulating blood plasma].

The effect of increased endogenous plasma insulin and glucagon concentrations on the free fatty acid (FFA) levels in the circulating blood was investigated in sheep, 2 baboons and 1 vervet monkey. Elevation of the plasma insulin level was obtained by vagal stimulation or intravenous glucose administration and vagal stimulation, whereas increased glucagon levels were induced by sympathetic stimulation, increased plasma insulin levels, with simultaneous increased plasma glucose concentrations (in our experiments with sheep), produced a pronounced lowering of the FFA levels. From this observation a lipogenetic function could be ascribed to insulin. However, in the primate experiments, increased plasma insulin without concomitant glucose administration caused an elevation of FFA levels, and would indicate a lipolytic rather than a lipogenetic action of insulin. Increased glucagon levels, as produced by sympathetic stimulation, did not alter the FFA concentrations significantly. It thus appears that glucagon has no lipolytic effect, as claimed by previous investigators. In our experiment on the vervet monkey, sympathetic stimulation, with increased plasma glucagon, even caused a decrease in FFA levels.


Neurofibromatosis and hypertension. A case report.

The case of a 12-year-old boy with neurofibromatosis, kyphoscoliosis, and hypertension is reported. The association of neuroflibromatosis and kryphoscoliosis is well known. There are no reports on the association of neurofibromatosis and hypertension in the orthopaedic literature. The cause was found to be intrarenal vascular abnormalities which are characteristic of neurofibromatosis. Other possible causes of hypertension in this disease are discussed. This patient was successfully treated by a partial nephrectomy.


The importance of different calorie sources in the intravenous nutrition of infants and children.

The intravenous infusion of amino acid and carbohydrate solutions is a well-established technique for nutritional support of the pediatric surgical patient. By using peripheral veins for total parenteral nutrition (TPN), weight gain can be achieved and the complications of central venous catheters avoided. Over a 2-year period, 45 patients from 1 day to 16 years of age received peripheral TPN in which fat provided a major portion of the daily calories. Treatment periods ranged from 5 to 74 days. Each patient received 125 cc/kg/day, with 30% of the calories derived from a fat emulsion and the remainder from a 12% glucose-2% amino acid solution. All 29 patients under 1 year of age gained weight, averaging 18 gm/day. These infants received an average of 98.8 calories/kg/day, with 31 calories provided by fat. In this group, the mean nonprotein calorie to nitrogen ratio (CNR) was 285 calories/gm, ranging from 239 to 343. Fat calorie and carbohydrate CNRs were determined and no correlation to weight gain could be found for either calorie source. The few complications related to this technique included three episodes of phlebitis, two small skin sloughs, two subcutaneous abscesses, and two episodes of jaundice. Normal weight gain can be achieved in infants after operation by employing peripherally infused, intravenous fat as a major calorie source. Furthermore, regardless of calorie source, a CNR of 285 calories/gm allows normal growth and weight gain in these critically ill neonates.


Unusual muscle abnormalities associated with thalidomide treatment in a rhesus monkey: a case report.

Unusual musculotendinous abnormalities were observed in the forelimbs of a rhesus monkey treated prenatally with thalidomide (10 mg/kg maternal body weight, gestation days 33, 34, and 35). Although the hindlimbs exhibited malformations typical of thalidomide dysmelia, the forelimbs appeared relatively normal externally. However, dissection revealed totally anomalous insertions of preaxial muscles of both forearms. Extensor muscles inserted on flexor surfaces even though normal sites of insertion were present and unoccupied. Radiographs revealed only minor ossification deficiencies in the carpus and distal radius. These observations suggest that thalidomide, given at the appropriate time, can disrupt condensation and splitting of pre-muscle masses without greatly disturbing condensation of corresponding preskeletal elements. These types of musculoskeletal relationships are unusual findings in congenital malformations of the limbs and have not been widely associated with thalidomide teratogenesis.


[Periosteal new bone formation in the horse induced by trauma. (author's transl)].

The radiological interpretation of periosteal new bone formation in the horse induced by trauma is described and illustrated by some casereports. The better the margins of the new bone can be defined the lesser the activity. The greater the density of the new bone, the longer the duration of time since injury.


Effect of alternating magnetic fields (60--100 gauss, 60 Hz) on Tetrahymena pyriformis.

Tetrahymena pyriformis and neuroblastoma cells were studied following exposure to low intensity low frequency alternating magnetic fields. Tetrahymena showed cytomorphologic changes, with delayed and reduced cell division concurrent with increased oxygen uptake. The resulting dead cells appeared intact, as compared with dissolution characteristic of the control group. In contrast, magnetically exposed actively growing neuroblastoma cells showed no growth alterations in vitro, but were affected when exposed in vivo.


[Polychlorinated biphenyl intoxication and nutrition. I. Effect of dietary variations on PCB storage in the rat (author's transl)].

Rats were fed three dietary variations containing 100 ppm of Phenoclor DP6 (a commercial PCB mixture) for 30 days. Compared to the normal diet, rats on high fat (20%, and low protein (3,5%) diets had a same curve of PCB storage in liver and carcase fat. However the DP6 in whole body (as per cent of ingested dose) was lower in rats receiving unbalanced diets. Intestinal absorption of DP6 was unaffected by higher-fat diet ingestion.


Effect of blockade of the reticuloendothelial system on the carbaryl toxicity in the rat.

The time dependence of the level of blood cholinesterase was determined in rats with the reticulo-endothelial system (RES) inhibited with colloidal carbon and in control rats after i.v. administration of 2 does of carbaryl: 0.75 mg and 1.50 mg/100 g body wt. Pretreatment with colloidal carbon had no effect on the blood cholinesterase activity when compared with the controls. Carbaryl rapidly inhibits cholinesterase; the time of "reactivation" of this enzyme increases with the administered dose. However, when the RES is inhibited with colloidal carbon, "reactivation" of cholinesterase is significantly slowed down, to a varying degree, depending on the dose of carbaryl. Our results bring to light a relationship between the inhibition of the RES and the toxicity of carbaryl, inhibition increasing the anticholinesterase effect of the insecticide.


[Results from radiotherapy of cancer of the vallecula or of the base of the tongue obtained in 171 patients between 1950 and 1976 (author's transl)].

The results of radiotherapy in 171 patients with cancer of the base of the tongue or vallecula from the period between 1950 and 1976 are reported. 19% of all patients were cured (5 years no evidence of disease). There is no difference of the cure rate between conventional kilovoltage and highvoltage irradiation. In early cases, there can be achieved a cure rate of about 60% by irradiation with 1900 to 2000 ret without an unacceptable rate of complications. In the majority of the patients, however, there is a moderate or advanced stage of the tumour at the time of the diagnosis. In the moderately advanced stages, the cure rate is between 20 and 50%, whereas only a small percentage of the patients with advanced tumours (T3 or N2 + N3) can be cured by radiotherapy. In order to achieve significantly higher cure rates in this cancer, further development of radiotherapy is decisive, especially perhaps radiotherapy with fast neutrons and development of agents which modify the radiation effects selectively in normal or in cancer cells.


A study of leptospirosis among animals in Barbados W.I.

Microscopic agglutination tests performed during 1971 and 1972 on Barbadian livestock showed positive serological reactions for leptospirosis as follows: cattle 51%, pigs 13%, sheep 18%, horses 64% and goats 19%. The serogroup Autumnalis predominated in all but horses in which the reactions to the Pyrogenes group appeared slightly higher. After the isolation of a strain of Leptospira serotype fort-bragg (Barbadian strain No. 119) of the Autumnalis serogroup in 1973, and its subsequent inclusion in our test battery of leptospiral antigens, high percentages of cattle, dogs, mongooses and man showed sero-positive reactions against the strain. Attention is called to the wide dissemination of the fort-bragg serotype on the island and to the role of rodents and the mongoose in its spread. 74 clinically affected Barbadian cattle from three herds were studied during 1975-76; 60 (81%) were serologically positive and nine different serogroups were represented. Predominant sero-positive reactions to Hebdomadis, Autumnalis, Ballum and Pyrogenes antigens were recorded. The highest titres were against Autumnalis, Hebdomadis and Pomona. Hebdomadis and Pomona serogroup antibodies may be due to many importations of cattle with those infections into Barbados.


Chagas's Disease in the Amazon Basin: 1. Trypanosoma cruzi infections in silvatic mammals, triatomine bugs and man in the State of Pará, north Brazil.

A total of 1,197 wild animals from Pará State north Brazil, were examined for haematozoa. Trypanosoma cruzi-like parasites were found in 13 different species, and were particularly common in a variety of marsupials (Didelphidae), porcupines (Coendou spp.), armadillos (Dasypus novemcinctus) and coatimundis(Nasua nasua). Three human infections are reported, making a total of seven autochthonous cases of Chagas's disease from Pará since the first were described in 1969. A serological survey of 5,319 inhabitants from the Belém suburbs revealed 14 positive reactions with immunofluorescent antibody titres greater than 1:64, and 15 equivocal reactions at 1:16. No evidence was found of silvatic species of triatomine bugs (Hemiptera: Reduviidae) colonizing houses, but occasional infected specimens of Panstrongylus geniculatus and Rhodnius pictipes were found in suburban houses, near the forest. Human infection is considered to be silvatic in origin. Chagas's disease could become endemic in the Amazon Basin if silvatic triatomine bugs were able to adapt to a domestic habitat: the real danger, however, is in the possible importation of already domiciliated vector-species along the newly opened highways, from other endemic regions of Brazil. Other Trypanosoma species were recorded in a variety of wild animals. Haemogregarines were found in some marsupials and rodents, and piroplasms in marsupials and a single armadillo.


Domiciliary biting frequency and blood ingestion of the Chagas's disease vector Rhodnius prolixus Ståhl (Hemiptera: Reduviidae), in Venezuela.

Demolition of a rural house in the State of Cojedes, Venezuela, provided a collection of 7.934 Rhodnius prolixus of which a random sample of 1,415 was weighed within 48 hours. The field weights, coupled with laboratory information of weight loss (in %) with time, average blood ingestion and meal size sufficient to promote moulting, were used to estimate biting rate under domiciliary conditions. The results show that in this particularly highly infested house, the R. prolixus population bites, on the average, at a rate of 58 times/person/day, draining blood at a rate of about 100 cm3/person/month; this meant a total of 1.2 litres/month from the 11 people inhabiting the house. It was found that the more advanced R. prolixus is in its development, the more aggressive it is in securing its meal: 15, 25, 30, 59 and 77% of fed insects of instar 1 through 5, respectively, were able to achieve moulting with only one meal. Applying the estimated biting rate to R. prolixus collections of other 13 demolished houses, with more typical insect population densities, an average biting rate of 9 bites/person/day was obtained; this value was, however, extremely variable, ranging from 0.2 bites/person/day (once every five days) to 33 bites/person/day.


Anti-Rh39--a "new" specificity Rh system antibody.

Two examples of an autoantibody that defines a hitherto unrecognized Rh system antigen are described. Both were produced by C-negative individuals and ostensibly resembled anti-C in specificity. However, adsorption studies showed that the antigen that the autoantibodies define is present on all red blood cells with a "normal" Rh phenotype and on D--/D-- and Dc--/Dc--samples. The antigen detected is not present on Rhnull red blood cells. Serologic studies have shown that the new antibody, that has been named anti-Rh39, has a different specificity from those that define the antigens C, Ce(rhi), G, Hro, Hr, CG, LW, Rh:29, Rh:34 and U. A possible relationship between auto-anti-Rh39 and allo-anti-C, in terms of the immune response, is discussed.


The immunoglobulin structure of human anti-M agglutinins.

Fifty examples of human anti-M agglutinins were subjected to reductive cleavage using both 2-mercaptoethanol (2-ME) and dithiothreitol (DTT). Thirty-nine (78%) were resistant to inactivation by sulphydryl compounds indicating IgG composition. This was confirmed by column chromatography. The remaining eleven sera were sensitive to reduction cleavage. There was no obvious association of immunoglobulin composition of the antibody with previous immune exposure to the M antigen. These results confirm observations in the literature that anti-M agglutinins are an exception to the generally expected correlation of saline agglutinating activity with IgM structure.


The flotation method for detection of tubercle bacilli in sputum smears.

Both the flotation smear examination and culture techniques yielded results for detection of tubercle bacilli which were superior to either direct smear examination or to examination of smear from liquefied or liquefied-centrifuged sputum specimens.


Tuberculin hypersensitivity following BCG vaccination in Brisbane school children.

Seven hundred and fifty Brisbane school children were tuberculin tested, in paired groups, with purified protein derivatives of Mycobacterium tuberculosis, bovis, BCG and avium. Reaction to avian PPD were stronger than to any of the others used. This finding may be of some importance in interpreting the variation in protection afforded by BCG vaccination.


Hydroxylamine sensitivity and salt tolerance in screening and identifying mycobacteria.

Hydroxylamine sensitivity offered no advantage over p-nitrobenzoic acid in distinguishing between tubercle bacilli and other (opportunist and non-significant) mycobacteria. It was of limited use in identification procedures. Salt tolerance assisted in the identification of strains which may be Mycobacterium triviale and M. chelonei var borstelense.


Intrascrotal rhabdomyosarcoma.

Rhabdomyosarcoma is the most frequent spermatic cord tumor of infants, children, and young adults, but also occurs as a primary tumor in the testis, epididumis, and testicular tunics. In the last fifteen years, 7 patients with intrascrotal rhabdomyosarcoma were treated at our institution, and an additional 155 cases were found on review of the English literature. On the basis of these 162 cases, incidence and survival statistics were calculated with particular attention to employed forms of therapy. An over-all survival of greater than 73 per cent should be obtainable with proper utilization of surgery, radiation therapy, and combination chemotherapy.


Photocoagulation of the fovea.

The visual outcome, histopathology, and electrodiagnostic tests of a man with a malignant melanoma of the choroid who received foveal argon laser photocoagulation prior to enucleatiion are described. The low intensity foveal burn destroyed only the outer retinal layers and spared the inner retina. Vision was reduced to 20/50 immediately, but recovered to 20/30 after one day. The visually-evoked-potential (VEP) was altered in both amplitude and waveform by the small foveal burn. A patient with solar retinopathy and permanent visual loss demonstrated only waveform changes on VEP testing. Monkeys with mild experimental foveal burns demonstrated outer layer retinal damage and waveform changes on VEP testing. The retinal energy density threshold for argon laser photocoagulation of the fovea is lower than 0.13 joules/mm.2.


[Method for immobilization of enzymic preparations catalyzing the splitting of low-molecular substrates].

A new method is suggested for immobilizing enzymes, catalyzing the splitting of low-molecular substrates. It consists in applying the layer of the enzymic preparation with a filler and a stabilizer onto the inert carrier by the rolling-up method in the dredging box and the subsequent coating of particles with a semipermeable film. The efficiency of the mentioned method is examined in two enzymic preparations: beta-galactosidase and beta-fructofuranosidase. Its advantages are discussed, the main of which are the simplicity of technology possibilities of using the enzymes technical preparations, maximal preservation of native properties.


[Biosynthesis of rat skin collagen under amino acid imbalance].

Protein differing from the normal one by the content of S-S-bonds and by the amount of the carbohydrate component was found in the acid-soluble fraction of skin collagen in rats which were fed the protein-free diet and the protein-free diet with the glycine loading for 3 and 14 days and tryptophan for 1, 2 and 3 days. The result testifies to the fact that under extremal states in the animal skin there occurs the synthesis of collagen the structure of which differs from that in the normal animal skin.


Retinal oxygenation via the choroidal circulation.

The possibility of supplying normal amounts of oxygen to the inner layers of the retina by diffusion from the choroid in the presence of retinal arterial obstruction was studied in cats and rhesus monkeys. While the animals were under general anesthesia, an oxygen electrode was placed in the vitreous cavity immediately adjacent to the retina, and a retinal artery blocker probe was used to occlude various segments of the retina blood supply. The inspired oxygen concentration was alternated between 20% and 100%. The choroidal circulation was intermittently occluded by elevating the intraocular pressure. In all animals it was possible to return the oxygen tension of the innermost retina to normal concentrations or above while the retinal arterial circulation alone was occluded, by having the animal breathe 100% oxygen at one atmosphere pressure. This could not be done when the intraocular pressure was elevated to 85 mm Hg, occluding the choroidal as well as the retinal circulation. The electroretinogram and the visually evoked response were recorded in cats while the retinal circulation was occluded and the inspired oxygen concentration changed from 20% to 100% at one atmosphere pressure. The electroretinogram and the visually evoked response were extinguished by occluding the retinal circulation while the animal was breathing 20% oxygen, and these responses were returned to normal by changing to a 100% inspired oxygen concentration.


Altered myocardial function and collagen in diabetic rhesus monkeys on atherogenic diet.

We have demonstrated that in rhesus monkeys, 18 months of diabetes alters the end-diastolic pressure, end-diastolic volume relations without hypertrophy. Accumulation of collagen in the myocardial interstitium was the apparent basis for abnormal left ventricular performance. Neither collagen concentration nor left ventricular performance were signigicantly affected by dietary lipid composition. These myocardial abnormalities occurred at a stage when coronary atherosclerosis was limited. However, the relative influence of coronary atherosclerosis and myocardial alterations during more prolonged lipid feeding remains to be determined.


The half-life of bovine (incomplete) antibodies to Brucella abortus.

The half-life of bovine immunoglobulins was established in a group of 60 calves suckled on non-infected dams immunised with antigens to Brucella abortus. The half-life of the "incomplete antibody" as determined by the anti-bovine globulin test was 20.9 days. Up to 45 days, the mean half-life of antibodies in the calves was 17.1 days; from 46 to 99 days it was 21.1 days and for periods exceeding 100 days it was 24.4 days. In 39 calves born of and suckled on infected dams the mean half-life of antibodies was 22.4 days. Up to 100 days the figure was 19.5 days; over 100 days it was 22.8 days. There was no significant difference in the mean half-life of antibody between calves from infected and non-infected dams. In both cases the antibodies appear to be catabolised at a progressively slower rate.


[Diagnosis and therapy of acute leukemia in adults].

Apart from the most essential aspects of the diagnosis and differential diagnosis of acute leukaemias concerning the early diagnosis of leukaemias the author deals with the so-called praeleukaemia. On the basis of a survey of international literature the modern polychemotherapy and its successes are characterized as well as the necessary supportive haemotherapy) are dealt with. Despite the improved frequency of remissions the survival time of acute leukaemias could only little be prolonged, that of the first remission could not be prolonged. Perhaps it is possible by an in future improved immunotherapy and by allogenic transplantation of the bone-marrow after supralethal total body irradiation to set new measures in the treatment of acute leukaemias.


[Emergency endoscopy in acute upper gastrointestinal hemorrhage: Does the effectiveness justify the effort?].

On the basis of a common care of patients with acute upper gastrointestinal haemorrhage by internists, surgeons, and anaesthetists lasting several years advantages and disadvantages of emergency endoscopy are analysed from the standpoint of effectivity. High diagnostic ability, help in the decision concerning operative or conservative activity, the influence of the operative-tactic approach and the furthering influence on the close cooperation of the specialities are to be emphasized. Criteria of effectivity, such as mortality rates, duration of the stay in the hospital and frequency of relapsing haemorrhages underlie many factors of influence. They express results of therapy, to which emergency endoscopy may at present contribute only limitedly. The basic decision to medical activity -- active striving for a rapid, exact diagnosis or waiting when the diagnosis is uncertain -- does not inessentially influence the standpoint in the controversy about the emergency endoscopy.


[Clinical diagnosis and course of arteriosclerosis obliterans].

The great diagnostic importance of the clinical heart and circulation state as well as of the simple clinical functional tests in comparison to the apparative bloody and unbloody diagnostics is emphasized. Concerning the course the unfavourable prognosis is elaborated on the basis of the survival rates and the appearance of cardiovascular complications. The role of the essential prognostic influence factors, such as age of manifestation, concomitant diseases and long-term therapy is proved by instances. It is referred to the favourable effect of the prolonged treatment with anticoagulants on the prognosis quoad vitam and to the retardation of the cardiovascular progressing. The long-term dispensary care is generally recommended.


[The effect of various steroid hormones on the course of pseudomonas infections in 3rd grade burns].

The effect of hydrocortisone, aldosterone, and estrogen on the course of pseudomonas infection after third-degree burns was examined in animal experiments. The effect of the drugs is represented by different lethality rates. Hydrolytic hydrocortisone reduced the average survival time as well as aldosterone. Estrogen, however, had no statistically ascertained effect on lethality.


Thyroid function in chronic liver disease.

There is a recent hypothesis that thyroxine (T4), secreted by the thyroid gland under physiological conditions, is mono-deiodinated in extrathyroidal sites to form the more active 3, 3', 5-tri-iodothyronine (T3) before exerting biological activity at target tissue level. Futhermore, circumstantial evidence suggests that the liver is an important site for the extra-thyroidal conversion of T4 to T3. Thyoid hormone pathophysiology in liver disease is therefore of interest. Patients with hepatic cirrhosis have normal or raised plasma T4 concentration and markedly reduced plasma T3 concentration. Free hormone measurement reflect this pattern and three is kinetic and other evidence to support the concept that extra-thyroidal conversion of T4 to T3 is reduced in patients with liver dysfunction. Comparable finding have however been reported in patients with other non-hepatic chronic systemic diseases but, unlike in hepatic cirrhosis, serum thyrotropin (TSH) is not increased. Increased serum TSH is found in hepatic cirrhois and is often accompanied by an abnormal TSH response to thyrotropin-releasing hormone (TRH) suggesting, in addition, disordered hypothalamic-pituitary control of thyroid function in these patients. Thyroid physiology is clearly markedly disturbed in hepatic cirrhosis but no single hypothesis adequately accounts for all the observed abnormalities. The recent finding of increased plasma 3, 3', 5-tri-iodothyronine (reverse t3; rT3) concentration in hepatic cirrhosis may ulimately clarify our understanding.


Thyroid status in fifty patients with alcoholic cirrhosis.

Because the liver is of considerable importance in metabolism of thyroid hormones, plasma levels of thyroxine (T4), triiodotyronine (T3) with their unbound fractions (FT4 and FT3), reverse T3 (rT3)--an inactive isomer of T3-tyrotropin (TSH) and TSH response to thyrotropin releasing hormone (TRH; 250 micrograms i.V.) were determined by radioimmunoassays in 50 clinically euthyroid patients with alcoholic cirrhosis. T4 mean concentration (7.3 micrograms/dl) did not differ from normal values but T3 was decreased (101 vs 154 ng/dl; p less than 0.001) and was correlated with the degree of liver damage appreciated by a clinico-biological index. FT4 was elevated in patients (17.1 vs 13.1 pg/ml; p less than 0.02) although FT3 was slightly decreased (3.4 vs 4.5 pg/ml; p less than 0.10) with an increased FT4: FT3 ratio (7.0 vs 3.0; p less than 0.02). rT3 was elevated (592 vs 206 ng/100 ml; p less than 0.001) and correlated with FT4/FT3: rT3/T3 ratio (p less than 0.01) and with the severity of the cirrhosis. Basal TSH levels (3.3 microU/ml) and TSH responsiveness to TRH was normal though very scattered, and independant from T3 and T4 values. It may be concluded that: 1. euthyroidy in cirrhosis assessed by a normal responsiveness to TRH, results from a compensatory increase in FT4. 2. The low T3 and FT3 levels may proceed from an impairment of peripheral T4 in to T3 conversion with a deviation pathway towards rT3. 3. T3 and rT3 levels provide valuable index of the severity of the cirrhosis.


Isolation of late complement components by affinity chromatography: I. Purification of the human complement component C9 and production of a C9-defective human serum.

A new procedure for the isolation of the human complement component C9 is described. This procedure offers the possibility to prepare functionally pure C9 in a one-step procedure with a high recovery of 10-22% of the biological activity. The 125iodinated C9 had a molecular weight of 78,000 daltons and was only contaminated in traces with other proteins. Further purification by absorption with an "anti-impurity" column lead to a C9 preparation which behaved as a homogenous single polypeptide chain in SDS polyacrylamide gel electrophoresis after reduction with mercaptoethanol. It formed a single bell-shaped precipitate in crossed immunoelectrophoresis with antibodies against human serum in the gel of the second dimension. The recovery of the biological activity after the second purification step was in the order of 6-10%. Both preparative steps could be performed within a few hours 450 microgram C9 protein were isolated from 135 ml human serum. A human serum completely defective in C9 was prepared by the extensive absorption of a smaller volume of human serum proteins with the anti-C9 column.


A method for the preparation of solidified colloidal sulphur media.

The chemical reaction between tetrathionate and sulphide produces colloidal sulphur and thiosulphate. This reaction can be employed to prepare agar media containing thiosulphate and finely divided colloidal sulphur particles.


[Toxins and enzymes of several species of Bacillus, especially of the B. cereus-thuringiensis group (author's transl)].

In the examined strains the production of following toxins or enzymes was determined by bioassay or by semiquantitative and routine diagnostical tests: delta-endotoxin, alpha-exotoxin, beta-exotoxin hemolysin, phospholipase C, proteinase. The production of delta-endotoxin (= a parasporal crystal toxic for several insects) is the only character in that B. thuringiensis differs from B. cereus. Other biochemical features as production of so-called alpha-exotoxin (= soluble toxic protein), hemolysin, phospholipase or proteinase are common in both species. Strains of B. megaterium may produce proteinase, but no phospholipase, hemolysin or alpha-exotoxin. The identity of the alpha-exotoxin of the B. cereus-thuringiensis group with any of the exoenzymes studied here could not be confirmed. At present, this toxin is only demonstrable by bioassay. Formation of beta-exotoxin (= soluble toxic nucleotide) is restricted to special strains of the B. cereus-thuringiensis group. -- All strains of B. megaterium tested do not produce any of the toxins quoted; they have found to be apathogenic under the experimental conditions. As the so-called "egg yolk clearing factor" is produced by all strains of B. megaterium (in contrast to strains of the B. cereus-thuringiensis group) it does not represent a factor of pathogenicity and therefore the term "gamma-exotoxin" is unfounded. -- Not too much attention should be paid in connection with taxonomic studies to the ability or non-ability of strains of bacteria to produce a special toxin.


[Effect of successive electric stimulation of different brain regions on delayed spatial choice in monkeys].

The effect of paired successive electrical stimulation of the prefrontal cortex, hippocampus, caudate nucleus head and mediodorsal nucleus of thalamus on the delayed spatial choice was studied in two rhesus monkeys. During the first second of delay one structure was stimulated, during its last second--another one. It was found that some combinations of paired successive stimulation interfere with the precision of solving the experimental problem by animals. The obtained results are discussed with regard to the complex temporal dynamics of brain structures interactions during short-term memorizing.


[Diagnostics and therapy of the carcinoma of the prostate (author's transl)].

By well organized preventive examinations early tumour stages can be recognized. The diagnosis of prostatic cancer has to be secured by biopsy. The primary reliability of aspiration biopsies (cytology) was 94% compared with punch biopsies (histology) amounting to 73%. Indications and results of aspiration biopsies, radiological and nuclear medical techniques in diagnosing prostatic cancer are described. The combined anti-androgenic hormonal therapy (infusions of cytonal, subcapsular orchiectomy, permanent administration of oestrogen) is considered to be the unchanged basis of treatment. Comparative cytologic investigations in therapy indicate that high-voltage treatment connected with hormonal therapy seems to be superior to exclusive hormonal treatment. Observations after additional therapy by a radionuclid (89-Strontium) for affecting metastases are encouraging. Indications of a therapy by cytostatica in progressive prostatic cancer are explained.


[Ability of birds of the Corvidae family to operate by the empirical dimensions of figures].

The reasoning ability was investigated in 29 Corvidae birds. The experimental task consisted in finding a hidden bait, the task being based on the fact that volumetric bait could be hidden in a volumetric geometrical figure only and not in a flat one. Thus it was possible to value the bird's ability to operate the empirical dimensions of objects. It was found that although the structure of bird brain is basically different from that of mammals, Corvidae surpass carnivorous mammals (dogs and cats) in solving this problem, their ability to operate the dimensions of objects being developped almost as well as that of monkeys.


[Interaction between the hippocampus and posterior hypothalamus in actualization of the orienting reflex].

Unit activity of the dorsal hippocampus in response to electrical stimulation of the posterior hypothalamus was recorded in 3--3.5 months old alert rabbits in chronic and acute experiments. Electrical stimulation of the sties of the posterior hypothalamus which had produced orienting behavior in preliminary tests, led to the appearance in the majority of cells at all hippocampal levels of tonic inhibitory and activational reactions with a long-term after-effect. With increased frequency of the stimulating current there was an increase in the number of responding elements and in the reactivity of neurones. The conditioning stimulation of the posterior hypothalamus increased the pronouncement and duration of hippocampal unit responses to sound stimuli. It is concluded that functional manifestations of the afferentation, ascending from the posterior hypothalamus to the hippocampus during the development of orienting reaction, are determined by a nonspecific character of its influences on the neurones of the dorsal hippocampus.


[Interrelationship of toxin formation with proteolytic enzyme synthesis in the process of cultivating diptheria microorganisms].

For the first time the synthesis of proteolytic enzymes by Corynebacterium diphtheriae has been shown to precede the process of toxin formation. The process of controlling the proteolytic activity of enzymes seems to be a suitable basis for the evaluation of toxin formation in mathematically planned experiments with strictly controlled tasks.


[Evaluation of the immunogenicity of meningococcal vaccines in experiments on mice].

The immunogenicity of 2 meningococcal vaccines, multicomponent vaccine produced at the Mechnikov Research Institute for Vaccines and Sera in Moscow and polysaccharide vaccine obtained from Merck Sharp & Dohme (USA), was evaluated on experimental meningococcal sepsis in mice, produced by the injection of meningococcal culture in mucin suspension. The protective effect of these 2 vaccines, expressed in terms of ED50, was 0.28 +/- 0.12 for the multicomponent vaccine and 0.25 +/- 0.24 for the polysaccharide vaccine; the challenge dose used in the test was 10 LD50 of the culture. The multicomponent vaccine gave the maximum immunological effect in a dose of 8 micrograms, while higher or lower doses induced a lesser increase in antibody titer and thus gave lower protection to mice against infection.


[Telemetric electroencephalographic and stereoelectroencephalographic studies in the topical diagnosis of an epileptic focus].

Telemetrical recordings of the EEG and stereoelectroencephalographic (SEEG) studies of patients with generalized epilepsy demonstrated a high informativeness of these techniques. The existence of focal changes in the routine EEG recording require an obligatory control by telemetrical EEG studies. An absence of focal changes in the EEG and teleEEG recording may serve as an indication for teleSEEG studies with the use of durative deep electrodoes. In patients with generalized seizures a trigger focus in the frontal or temporal lobe may be found quite frequently.


[Clinico-electroencephalographic analysis of wakeful epilepsy and sleep epilepsy].

Some results of a clinico-physiological analysis of epileptic patients with a different diurnal distribution of generalized convulsive seizures in the sleep-vigilance cycle are reported. It is demonstrated that in vigilant epilepsy there is an intensification of L-rhythms in the EEG recordings in the different functional states of vigilance, combined with a prevalence of delta-sleep in the sleep structure. In sleep epilepsy there is a predominance of the 2nd sleep stage in the sleep structure, besides an EEG desynchronization in the state of vigilance. These results indicate some differences in the activity of nonspecific (synchronizing and desynchronizing) structures in epilepsy with a different diurnal distribution of generilized convulsive seizures.


[Generalized epileptic seizures].

Some important questions concerning the pathogenetical mechanisms of the so-called primary-generalized epileptic seizures are discussed. Reviewing the large literary material and personal clinical experience, the author attracts attention of neurologists and psychiatrists to the necessity of very thorough and detailed anamnestic data and eventual neurological observations, in order to detect a focal onset of a generalized seizure. This is very important bor purposes of clinical practice, especially from the standpoint of indications for neurosurgical operations.


Cell wall characteristics of Pseudomonas aeruginosa and its carbenicillin-induced L-form.

L-forms of Pseudomonas aeruginosa were induced and cultured on a medium supplemented with carbenicillin. Morphological studies of the passaged variant revealed the presence of a triple-layered cell wall similar to that found in the parent species. Furthermore, the L-form was found to be more susceptible to gentamicin, kanamycin, tetracycline and colistin sulphate. Chemical analysis of the lipopolysaccharide fraction showed a difference in phosphorus content, and changes in cell wall envelope fatty acid content were also exhibited. It is suggested that these differences may influence the transport of certain antibiotics through the cell wall.


Genetic relatedness between streptomycin-producing and non-producing strains of Streptomyces griseus, studied by means of DNA-DNA hybridization.

DNA-DNA hybridization was studied in order to determine the genetic relatedness between a streptomycin-producing and a non-producing mutant of Streptomyces griseus. The latter strain of short vegetative life cycle had been developed from the streptomycin-producing strain by means of nitrogen mustard treatment. Since the two strains differ in several features, we were prompted to examine the sequence homology between their DNAs. Hybridization experiments carried out with the membrane filter method yielded 73.8% and 67.3% DNA homology values, respectively. The results indicate that there is a significant, but not very close, relatedness between the DNA sequences that corresponds to the similarities and differences observed between the phenotypes of the two strains. Further aspects of established homology are also discussed.


[Preparation of hybrid antibodies with mouse IgG and ferritin specifities for the immune electron microscopic detection of cell membrane antigens].

Use of hybrid antibodies with one specifity for mouse-IgG and the other one for ferritin is particularly suitable for immune electron microscopical detection of cell surface antigens. Preparation of antibodies of such kind is described, whereby the method introduced by HMMERLING et al. is varied within some steps of preparation. These variations are discussed here. Activity of produced hybrid antibodies is demonstrated by labeling the THY 1.1. antigen on the cell surface of the thymocytes of the mouse. The advantages of utilizing the hybrid antibodies in comparison with known immune electron microscopical techniques are an excellent location of the antigens, the possibility of using distinct particles for labeling, the application of a multiple labeling, and the fact that investigations by both the transmission and the scanning electron microscope can be carried out by means of the same preparation of hybrid antibodies.


The effect of metoclopramide, TRH and L-dopa on prolactin secretion in pituitary adenoma and in "functional" galactorrhoea syndrome.

The degree of autonomy in prolactin secreting pituitary adenomas and also prolactin secretory reserve in cases with suspected functional galactorrhea syndrome was evaluated with the use of metoclopramide, TRH and L-DOPA. It was found that in patients with pituitary adenoma the basal prolactin (PRL) level often exceeded 150 micrograms/l and the response to stimulation with TRH and/or metoclopramide was markedly diminished or even nonexistent, while the response to L-DOPA was usually retained. In patients with galactorrhoea and/or amenorrhoea, with normal skull X-ray the basal PRL level was either normal or moderately raised but the response to stimulation was various; mostly it was excessive, it was sometimes normal, but in some other cases it was markedly diminished as in patients with adenoma. In the author's opinion the so-called "functional disorder" of prolactin secretion is mainly hyperresponsiveness to stimulation, whereas the basal PRL level in those cases is usually normal or only intermittently raised. In the cases with a moderate hyperprolactinaemia, especially if it appears to be constant, and the response to stimulation is diminished or none at all, we suspect a pituitary microadenoma. Finally, there are rare cases of galactorrhoea with normal basal PRL and normal response to stimulation, in which the sensitivity of the mammary PRL receptor is probably increased. We suggest therefore that the above mentioned PRL stimulation tests may help in distinguishing between tumoural and functional hyperprolactinaemia.


Prolactin-secreting pituitary adenomas: prolactin dynamics before and after transsphenoidal surgery.

Twenty women with hyperprolactinaemia secondary to a pituitary adenoma were studied before and after selective transsphenoidal removal of the tumour. Pre-operatively, thyrotrophin-releasing hormone (TRH) (200 micrograms iv) and metoclopramide (MCP) (10 mg po) did not produce a positive PRL response in the tumour patients. By contrast, 14 post-partum lactating women, who were used as controls, exhibited a positive response to MCP administration. Methergoline (4 mg po) was shown to decrease serum PRL levels in 8 normal subjects, in 6 puerperal women, and 9 of 10 tumour patients. Bromoergocriptine (CB-154, 2.5 mg po) decreased serum PRL levels in 10 tumour patients. Following transsphenoidal removal of the adenoma serum PRL levels were reduced in all patients, and returned to normal in 14 patients. Prognostics for completely normalizing PRL secretion after transsphenoidal surgery is bettery when initial serum PRL levels are below 200 ng/ml. After surgery all hyperprolactinaemic patients failed to show a positive PRL response to TRH and MCP. Nine normoprolactinaemic patients had a positive response to both stimuli while 3 patients failed to show a positive response immediately following surgery. Long-term studies, however, showed that a positive PRL response was obtained in all patients tested 8-14 months after treatment. A positive PRL response to methergoline and bromocriptine was observed post-operatively in the patients tested regardless of their basal PRL level. Data from this study indicate that surgically proven PRL-secreting adenomas are invariably associated with negative PRL responses to TRH and MCP. The normalization of the prolactin regulation after surgery points toward the intrapituitary localization of the lesion associated with PRL-secreting adenomas.


Autoradiographic study of the neonatal rat retina after labelled uridine uptake.

Labelled uridine uptake in the neonatal rat retinas was found to exhibit different patterns in the different regions. Also the affinities of different cell types to uridine uptake was observed to be different.


[Clinical trial of Trive 1000 in long-term parenteral nutrition (author's transl)].

The authors report a study of long-term parenteral nutrition with a homogeneous media (produce? Solution?) containing glucido-lipidic calories and essential amino-acids. This solution has the advantage of an easy dosage of the number of calories and of grams of nitrogen to administer; it also decreases the risks of bacterial contamination from "handicraft" mixing and excessive manipulations.


Nonspecific alkaline phosphatase activity in normal and diseased human breast.

Nonspecific alkaline phosphatase activity was identified in human normal and diseased breasts with the use of the calcium-cobalt, the lead-nitrate, and the azo-dye methods. The results varied not only with the staining method, but also with the functional status of the breast structures. In normal, dysplastic, and fibroadenomatous tissues there was a strong parallelism between myoepithelial and capillary enzyme activities. The calcium-cobalt method was the only technique which allowed staining of carcinoma cells; cancer stromal enzyme activity was evidenced only with the use of the same method. Our findings suggest that nonspecific alkaline phosphatase activity probably reflects a functional status of the labelled structures; the enzyme activity of myoepithelial cells is variable and not really specific.


[Electron microscopical and enzyme histochemical investigation of kidney and liver of the albino rat after cytostatic treatment (author's transl)].

Within 5 days following treatment with cytostatics (vincristine, vinblastine, trenimon, 5-fluorouracil) enzyme-histochemical and ultrastructural changes occurred in the kidney and liver of Wistar rats. The enzyme activities were influenzed by cytostatics in different ways. It was found that the activity of some enzymes increased whereas that of others decreased. Kidney and liver showed a different response in their enzymatic behaviour. The cytostatics used did not have the same effect. The histochemical changes following injection of cytostatics in juvenile rats do not agree with those in adult ones. The electronmicroscopic findings reveal marked morphological changes of the kidney and liver cells within the first 5 days following injection of cytostatics. From the 8th day on after administration of cytostatics neither histochemical nor ultrastructural changes as compared with the controlls were found.


[Occurrence of glycogen-deposites in acinar cells of pancreas in prediabetic sand rats (Psammomys obesus) (author's transl)].

The investigations were in 6 prediabetic and 8 normoglycemic sand rats carried out with a histochemical method (PAS-reaction). Glycogen is present in pancreatic acinar cells in various quantity. It is in the cytoplasm homogenously distributed. The PAS positive acini are near the islets of Langerhans localized, which have in their B cells also glycogen deposites. The phenomenon is by the vascularisation of the pancreas explained.


Analysis of hyaluronidase diffusion for histochemical purposes.

Observations on hyaluronidase difussion from natural and artificial objects to precipitated medium are described. The conclusions from this investigation are: (1) hyaluronidase diffusing from biological objects in a precipitated medium is an active enzyme. (2) hyaluronidase diffusion may be utilized for localization of the enzyme. (3) certain parameters of the reaction hyaluronidase--hyaluronic acid may be measured with the use of the notion "diffusion radius".


Alteration of the enucleating erythroblast glycocalyx.

Plasmalemmal differentiation of the enucleating normoblast of rabbit and rat was studied by means of cytochemical methods and freeze-etching. Staining with colloidal iron revealed about identical amounts of iron particles bound to various areas of the normoblast membrane. Cationized ferritin and ruthenium red, likewise, failed in the demonstration of significant changes of the enucleating normoblast glycocalyx. Despite these findings the topo-optical staining with toluidine blue showed the plasmalemmal envelope of the protruding normoblast nucleus moderately birefringent, clearly discriminated from the intense anisotropic staining of the future reticulocyte membrane. The ferritin-labeled snail lectin anti AHP localized a great number of binding sites at the plasmalemmal envelope of the nucleus under extrusion. That is in sharp contrast with rather low lectin binding to the future reticulocyte membrane which amounts to about 30 to 50% of the nuclear envelope label. The findings provide evidence of unmasking of bindings sites of the normoblast membrane. Apparently, the effect is due to conformational changes of the cell membrane, rather than it could be attributed to degradation of glycoproteins. Moreover, enucleation kinetics may also be related to supramolecular changes of membrane structure albeit missing evidence for the rearrangement of membrane particles.


[Further observations on the stimulation of the secondary immunological response in the Rh system].

The present paper is a continuation of studies for establishing the optimal schedule of blood-donor immunization for obtaining of plasma suitable for production of anti-RhD immunoglobulin. After 3 years of observation of 12 immunized subjects it was found that stimulation of the secondary immune response should be done with small doses (0.5-1 ml) of blood injected intravenously at long time intervals, that is 1-3 times in a year. This method leads to a high and long-term rise in the titre of antibodies exceeding in all cases the value of 1/128 in indirect antiglobulin test, that is suitable for production of the preparation Gamma anti-D 150.


Localization of the rat epidermal SH-protease inhibitor in proventricular and vaginal squamous epithelium. An immunofluorescence study.

The rat epidermal SH-protease inhibitor was localized with the indirect immunofluorescence method in the rat proventricle and vagina fixed in cold phosphate-buffered formalin. Bright fluorescence was seen in the cytoplasms of the superficial layers of these squamous epithelia only when a highly specific antiinhibitor serum was used. The fluorescence diminished when normal rabbit serum or a rabbit antiserum againts bovine serum albumin was used instead of the anti-inhibitor serum. When the anti-inhibitor serum was neutralized with the purified epidermal inhibitor, the fluorescence was again markedly weakened. The results confirm our previous observations showing that the epidermal SH-protease inhibitor also occurs in other squamous epithelia, especially in the cytoplasms of the cells in their upper layers.


Localization of the rat epidermal SH-protease inhibitor in the proventricular squamous epithelium using the peroxidase-antiperoxidase (PAP) method.

The rat epidermal SH-protease inhibitor was localized by the PAP method in the squamous epithelium of rat proventricle. Brown accumulation due to the peroxidase reaction was seen in the superficial and middle layers of squamous epithelia. The localization of the inhibitor in squamous epithelium is the same as we have demonstrated with immunofluorescence staining.


[Contribution on standardisation of the colloidal iron binding reaction (author's transl)].

The iron binding reaction provides inconstant results with respect to the number of electron dense particles bound to cell surfaces if acetic acid has been used for the production of the colloid and for washing procedures in the course of iron binding. In the present paper it is shown that the dilution of colloidal iron hydroxide by adding acetic acid changes the size distribution of the colloidal particles, resulting in a marked decrease of iron binding. For that reason, a standard method is proposed in which hydrochloric acid is used instead of acetic acid. By this modification more reproducible results are gained with regard to the above mentioned quantitative aspects.


[Fluorescence histochemical investigations on the distribution of GABA in the hippocampus of rat (author's transl)].

1. In the hippocampal region of the rat brain GABA was demonstrated with a modified reaction according to WOLMAN (1971). 2. In the various regions of hippocampus different intensities of GABA-fluorescence were demonstrable: A maximum of intensity being present in the area dentata and in the CA 3 region; it is very low in the CA 1 and CA 4 region. 3. The fluorescence of GABA was found to be localized around the pyramidal neurons and the dentate granule cells, respectively.


[Fluorescence histochemical investigations on the topic of GABA and dopamine in the neostriatum of the rat (author's transl)].

In the neostriatum of adult rats the distribution of Dopamine and GABA was investigated by means of fluorescence histochemical methods. There is a different mode of distribution of the transmitters in this brain region. The animals were treated with cycloserin, acting as an inhibitor of the GABA transaminase, in order to enhance the GABA content. In the neostriatum GABA containing neurons and GABA-ergic afferents could be demonstrated. GABA containing fibers are present in the whole striatum. Varicose Dopamine fibers appear as a dense fluorescent network.


Localization of non-specific esterase and acid phosphatase in human fibroblast from skeletal muscle atrophy.

The intracellular localization of non-specific esterase and acid phosphatase was investigated in human fibroblast cells from skeletal muscle atrophy. Non-specific esterase and acid phosphatase positive sites were visualized ultrastructurally in the fibroblast. Electron microscopy for the cytochemistry of these enzyme was performed in human atrophic skeletal muscle by using thiol acetate esterase method and GOMORI'S method. Lipofuscin pigment granules in fibroblast cells contain dense pigment, granular matrix and lipid droplet. Reaction products of non-specific esterase are seen in the pigment and granular matrix, and they may therefore be called residual bodies. Reaction products of acid phosphatase and non-specific esterase were found to be located in lysosomes.


Ant-egg cataract. An electron microscopic study.

The ultrastructure of the ant-egg cataractous lens has been studied. Comparison of tissue demineralized by means of EDTA with untreated tissue showed the calcium salts in the ant-eggs to be mostly crystalline. A laminar appearance of the ant-egg seen in EDTA treated material suggested an intermittent growth of the structure. In the ant-eggs, as well as in some areas separate from these, membrane limited cytoplasmic bodies could be seen in many cases, the membranes of which were partly joint and partly separated by an electron dense material. It is suggested that the calcifications seen as the ant-eggs are secondary phenomena to an abnormal metabolism, morphologically seen as membrane limited cytoplasmic bodies.


Biological indicators for the control of ethylene oxide sterilization.

A new biological indicator has been developed for  the control of ethylene oxide sterilization, particularly for large scale sterilization of disposable medical equipment. The aim has been to provide the new indicator with the same resistance to the combined effect of ethylene oxide and water vapour as the biological indicator referred to by the health authorities in Scandinavia. The reference indicator contains spores of a Danish test strain, Bacillus subtilis, in sand. The new one contains spores of a test strain used extensively for biological indicators, viz. B. subtilis var. niger (B. globigii). The spores in the new preparation are dried in pieces of cotton yarn. The two indicators were exposed to ethylene oxide and water vapour in five different series of experiments and almost the same resistance was found. In simulated routine sterilization procedures, the new indicator was placed at locations not easily accessible for the gas and water vapour, and the results reflected the blockage of diffusion. The experiments included samples of household dust. The resistance of the microorganisms in the dust was compared with that of the biological indicators. Based on these comparisons, it is concluded that the resistance of the two biological indicators to ethylene oxide is in accordance with the official Scandinavian standard for sterilized medical equipment when used in the control of sterilization of products with low microbial contamination.


[Comparative sensitivity of 4 different cell cultures in the isolation and identification of mumps virus].

Three different continuous cell lines (Am 57, Hela, Vero) and primary cell culture of human embryo kidney are compared with regard to their susceptibility for isolation of mumps virus from saliva and cerebrospinal fluid. For this purpose the Vero cell line appeared to be more suitable among the studied cell systems regarding the following reasons: it allows the highest percentage of mumps virus isolation. The cytopathic effect caused by mumps virus occurs comparatively rapidly in this cell culture. This cytopathic effect is typical enough to allow for a preliminary diagnosis of mumps virus.


Identification of renal tubular epithelial cells in urine with immunofluorescence.

Rabbits were immunized with human kidney homogenate. The rabbit sera, after absorption with human liver homogenate, showed antibody activity against human kidney, renal pelvis and urinary bladder. The sera were then absorbed with human renal pelvis and urinary bladder mucosa and subsequently showed no antibody activity against urinary bladder or renal pelvis. Immunofluorescence examinations showed fluorescing cells in kidney tubules, but not elsewhere. The finally absorbed antihuman kidney sera were used for indirect immunofluorescence examination of urinary sediments from patients with renal disease. Phase contrast microscopy was used simultaneously. Fluorescence was found in cells which in phase contrast microscopy were judged to be renal tubular cells. Fluorescing cells were often found in casts, but free cells were also seen. Immunofluorescence may thus provide a means of identifying renal tubular cells in urine.


Defective life cycle and low antibiotic production in submerged cultures of Streptomyces fradiae.

The life cycle of a Streptomyces fradiae strain producing high amounts of neomycin under industrial conditions has been investigated in liquid soybean medium where the production of antibiotic proved to be comparatively low. The changes occurring in the main macromolecular components and the enzyme activities of the mycelium during the life cycle and cytological observations proved that there was a block in the normal proecess of reproductive differentiation and a lack of exocellular alkaline phosphatase activity was found.


The influence of chronic deep brain stimulation on excitability and morphology of the stimulated tissue.

Bipolar electrical stimulations of the rostal hippocampus and of the amygdala were performed at irregular intervals in wakeful unrestrained cats via chronically implanted glass-insulated stainless steel electrodes. The excitability of the stimulated tissue remained unchanged during the whole investigation period of six months up to one and a half years, as was revealed by regularly performed comparisons of shape, latency, and amplitude of evoked potentials elicited by electrical stimulation of the rostral hippocampus and recorded within the ipsilateral mammillary body. The histological examination of the stimulated tissue revealed a fibrillary gliosis due to the trauma caused by the insertion of the electrodes, but no signs of additional tissue damage due to electrical stimulation or chronic mechanical irritation. The results indicate that it is possible to perform therapeutic stimulations of deep brain structures for long periods without inducing relevant changes in morphology or electrical responsiveness of the stimulated tissue. No kindling phenomena are to be expected, if the stimulations are performed at irregular intervals.


Evaluation of the chronic inhalation toxocity of a manganese oxide aerosol. II. Clinical observations, hematology, clinical chemistry and histopathology.

Monkeys and rats were exposed to 11.6, 112.5, or 1152 microgram Mn/m3 as an Mn3O4 aerosol twenty-four hours per day for nine months. Various serum biochemical, and hematologic evaluations were conducted on both specie. Body weight gain was accelerated in rats exposed to 1152 microgram Mn/m3. Hemoglobin concentrations were slightly elevated for both sexes and both specie exposed to 1152 microgram Mn/m3; however, the effect may not be directly related to Mn. Some evidence of hypophosphatemia was observed. No exposure related effects were demonstrated by organ weight or histopathologic observations.


Density variation in the humeral cortex of Macaca.

The purpose of this research was to describe patterns of density variation throughout the cortex of the humeral shaft in Macaca and to attempt to explain these variations in terms of the gross anatomy and mechanical function of the bone. One hundred ninety transverse sections were taken from five sites along the humeral diaphyses of 38 Macaca. The density at eight positions around each section was measured using radiographic and densitometric techniques. Analysis of variance indicated significant (p less than 0.02) differences among cross-sectional levels and positions within each level. No sexual dimorphism in density could be demonstrated, although sexual dimorphism in density has been reported for the femora of this same sample. This relationship between humerus and femur parallels that found in humans. Density increased distally in the humerus, probably due to major areas of muscle attachment. Comparison with similar data from the femur of Macaca indicated unexpected differences in density pattern which may underlie differences in the strength and mechanics of the upper and lower extremities.


The linoleic acid and trans fatty acids of margarines.

Fifty brands of margarine were analysed for cis-polyunsaturated acids by lipoxidase, for trans fatty acid by infared spectroscopy, and for fatty acid composition by gas-liquid chromatography. High concentrations of trans fatty acids tended to be associated with low concentrations of linoleic acid. Later analyses on eight of the brands, respresenting various proportions of linoleic to trans fatty acids, indicated that two of them contained still higher levels of trans fatty acids (greater than 60%) and negligible amounts of linoleic acid. It is proposed that margarine could be a vehicle for the distribution of some dietary linoleic acid and that the level of linoleic acid and the summation of the saturated plus trans fatty acids be known to ascertain nutritional characteristics.


Assessment of the efficiency of protein utilization in young squirrel and macaque monkeys.

The efficiency of protein utilization was assessed in three groups of infant squirrel monkeys fed diets containing restricted amounts of lactalbumin, casein, and soy protein isolate as the sole nitrogen source for 3-week periods. Lactalbumin was fed in similar conditions to a group of macaques for comparison. The regression of weight gain on protein intake was calculated for each dietary protein yielding an estimate of protein needs for weight maintenance and an estimate of the efficiency of utilization of protein for growth (slope X percentage protein in tissue). Mean requirements for weight maintenance of infant squirrel monkeys for lactalbumin, casein and soy protein isolate were 3.43, 3.63, and 7.96 g/kg per day and growth was accomplished with an efficiency of 27.8, 32.1, and 22.2%, respectively. In contrast, the macaques utilized lactalbumin with an efficiency of 65%, similar to that of the infant cebus monkey and adult man. The low efficiency found in young squirrel monkeys was altered neither when the habitual feeding schedule was prolonged from 16 to 24 hr per day in a group of casein-fed animals nor when sulfur amino acids were added to casein.


IgD myeloma. Report of a case with unusual clinical and immunologic features.

A case of IgD myeloma in a 48-year-old Caucasian man is reported. The unusual features of this case included the absence of osteolytic lesions by x-ray, absence of anemia, absence of monoclonal spike on serum electrophoresis, association of kappa light chains, absence of Bence Jones proteinemia and Bence Jones proteinuria, and a remarkable, temporary clinical response to therapy. Immunoelectrophoresis of whole serum yielded a pattern consistent with IgD kappa monoclonal gammopathy. Immunoelectrophoresis of a pure serum IgD preparation, previously separated by gel chromatography (Sephadex G-200), revealed definitive information about an IgD kappa monoclonal gammopathy. Immunomicroscopic examination of bonemarrow smears showed the presence of delta and kappa chains only in the cytoplasm of plasma cells.


Comparison of fetomaternal hemorrhage detection methods and Rh immune globulin usage.

A 1977 College of American Pathologists survey of hospitals has been analyzed to compare Rh immune globulin usage (RhIgG) with methods used to screen and confirm fetomaternal hemorrhage (FMH). The survey data show that there is a correlation between the rate of multiple vial usage and the confirmation method used. Laboratories using Fetaldex administered multiple vials of Rh immune globulin significantly more often than laboratories using other acid elution technics. This difference was independent of the screening methods used and was not related to the number of patients tested in laboratories giving fewer than 300 vials of Rh immune globulin per year. The incidence of fetomaternal hemorrhages of greater than 30 ml has been reported to be 0.3% by various groups using Kleihauer procedures to test large numbers of women after delivery. In 61 of 374 laboratories using Fetaldex and 15 of 253 laboratories using Kleihauer-Betke procedure more than ten times the expected number of recipients were given multiple vials.


Platelet counts in capillary blood.

Samples of venous and capillary blood were collected simultaneously from healthy adults to assess the accuracy of platelet counts in capillary blood as determined by an automated particle counter. The difference between the mean venous blood platelet count (248,300) and the mean capillary blood count (215,500) was highly significant (P less than .001). For 24% (7/29) of the subjects, the capillary blood platelet count underestimated the venous blood count by greater than or equal to 25%, with three subjects erroneously classified as thrombocytopenic. A heterogeneous group of thrombocytopenic patients showed a similar difference in mean platelet counts (venous blood: 72,500/microliter; capillary blood: 65,400/microliter; P = 0.01). In most clinical situations, capillary blood platelet counts were adequate for patient evaluation; however, when an accurate platelet count is necessary, venous blood should be used.


Closing the Rh immune globulin utilization gap.

A simple and effective system, designed to achieve 100% utilization of Rh immune globulin in a general hospital, is presented. During a one-year period, all Rh-negative women exposed to events capable of inducing Rh sensitization were identified. In every case the protection of these women was verified. Four major oversights were discovered and immediately corrected, resulting in adequate protection of all Rh-negative women at risk of Rh sensitization. The system is compared with two other successful programs currently in use. The role of the Pathology Department, as a fail-safe mechanism to close potential loopholes in a Rh prophylaxis program, is emphasized.


Pseudogonococcal ophthalmia neonatorum. Branhamella (Neisseria) catarrhalis conjunctivitis.

A culture from conjunctivitis occurring in a neonate in association with a recurrent fever yielded a nearly pure growth of Branhamella (Neisseria) catarrhalis. The conjunctivitis was not appreciated and effectively treated until a second hospitalization in the fourth week of life. Partial suppression of symptoms had followed short-term parenteral antibiotic therapy during the first admission. Resolution quickly occurred in response to instillation of sodium sulfacetamide ophthalmic solution. Although B. catarrhalis is considered a non-pathogen, the literature reviewed included a number of diverse infections, but no previous instance of conjunctivitis. The organism's close similarities to Neisseria gonorrhoeae necessitate isolation and correct biochemical differentiation. Misdiagnosis of gonococcal conjunctivitis carries obvious social, psychological and medical impact.


Cryptosporidiosis in an immunosuppressed renal-transplant recipient with IgA deficiency.

Cryptosporidia are sporozoan parasites that infect epithelial cells of the gastrointestinal tract. Infection with cryptosporidia has been found most commonly in a variety of animal species and only rarely in man. The authors report a case of an immunosuppressed renal-transplant recipient with IgA deficiency who experienced diarrhea and fever and was found to have cryptosporidia in a jejunal biopsy specimen and in air-dried smears of the specimen. By electron microscopy, trophozoite, schizont, and macrogamete forms were identified, and these forms ahd morphologic features similar to those of cryptosporidia previously found in guinea pigs. Treatment of the cryptosporidial infection in this case was with trisulfapyrimidines. The efficacy of this treatment could not be evaluated because of complications.


Zinc therapy of depressed cellular immunity in acrodermatitis enteropathica. Its correction.

A child with hypogammaglobulinemia and intractable diarrhea underwent parenteral alimentation for five months. A clinical syndrome of acrodermatitis enteropathica subsequently developed associated with a depression in thymus-dependent lymphocyte (T cell) numbers, abnormal T-cell mitogen-induced blast transformation, and anergy to skin test antigens. Plasma zinc levels were found to be abnormally low. Zinc therapy resulted in dramatic resolution of the clinical manifestations of acrodermatitis enteropathica. Cell-mediated immune function was also restored to normal, suggesting an important role for zinc and possibly other trace metals in cellular immune responses.


State of the art: total parenteral nutrition: a guide for its use.

A brief review of TPN might more clearly point out and explain some of the major areas of this protocol. The use of subclavian vein catheterization for hyperosmolar solutions is the key to TPN. The tip of the catheter resides in the superior vena cava, so solutions with a concentration of 1,500-2,200 mOsm/l. (over five times the osmolarity of serum) can be infused at a rate of 2-3 ml./min. while being diluted by a blood flow of 2-5 l./min. (a dilution factor of a thousand). The site of the catheter is in a large vein. The cutaneous entry site of the catheter is in the pectoral skin below the clavicle; site must be kept scrupulously clean and dressed sterilely. Because of potential complications, the patient should be carefully observed and monitored.


Kaufman oculocerebrofacial syndrome: case report.

The oculocerebrofacial syndrome was described from siblings of both sexes in 1971 by Kaufman. A 12-year-old child with a set of corresponding malformations is described. This would suggest that the original report did not describe a "private" syndrome.


Radioangiographic measurement of the internal diameters of the uteroplacental arteries in rhesus monkeys.

The internal diameters of successive anatomic segments of the uteroplacental arteries in Macaca mulatta were measured at 100 to 150 dyas' gestation. Although the absolute values vary widely, the proportional relationships between segments are uniform from animal to animal and from one time in gestation to another. We also observed that each of the two uterine arteries supplies a restricted portion of the placenta with little overlap, that there is predominance of one uterine artery over the other in the number of placental lobes supplied, and that two radial arteries occasionally contribute to a single spiral artery, giving rise to an anastomotic loop.


Premature onset of labor, neonatal patent ductus arteriosus, and prostaglandin synthetase antagonists--a rat model of a human problem.

Premature labor and patent ductus arteriosus are two potentially fatal hazards of the human newborn infant. Prostaglandin synthetase antagonists have thus been used to suppress early labor and to close the ductus of the neonate. Indomethacin has been most effective but not free of significant complications. Neuronal necrosis may result from numerous systemic aberrations. A controlled rat model study was therefore devised to investigate fetal neuronal necrosis in relation to maternal indomethacin dose. Dams were given various treatments of 2 mg/kg of 4 mg/kg indomethacin within the last 3 days of gestation. Liquid chromatography was used to assess serum maternal and fetal drug levels. From light microscopy of more than 200 brains it was apparent that fetal neuronal necrosis correlates with maternal dose.


Vascular anastomoses between the iris and persistent hyperplastic primary vitreous.

Prominent radial iris blood vessels created small but definite pupillary notches in five children with persistent hyperplastic primary vitreous and persistence of the tunica vasculosa lentis. Detection of these abnormal iris vessels suggested the presence of persistent hyperplastic primary vitreous and related syndromes even when the diagnosis was obscured by the presence of an opaque lens. These vessels represented early developmental arrest and may have been associated with abnormal development of the macula and optic nerve. Surgical and amblyopia therapy, therefore, may not provide useful vision, and should be undertaken with caution.


Method of production and natural history of experimental posterior penetrating eye injury in the rhesus monkey.

We developed an experimental model for a posterior penetrating eye injury that resulted in traction retinal detachment in 21 rhesus monkey eyes. The standard injury was an incision through the pars plana with vitreous prolapse and incarceration; the wound was then carefully closed with microsurgical techniques. At one to two weeks after injury, detachment of the posterior vitreous occurred and detachment of the retina occurred between seven and 11 weeks. The development of retinal detachment was related to traction on the peripheral retina over the vitreous base; and to the contraction of epiretinal membranes on the peripheral and equatorial retina. Our study supports clinical observations on the importance of blood in the vitreous in the development of vitreous traction and traction retinal detachment after a posterior penetrating injury.


Histology of wound, vitreous, and retina in experimental posterior penetrating eye injury in the rhesus monkey.

We performed a histologic study to support our clinical observations on the mechanisms responsible for traction retinal detachment after a penetrating injury in the rhesus monkey eye. The monkey eyes (40 eyes; 40 monkeys) were characterized by intraocular fibrosis with the formation of a cyclitic membrane and epiretinal and subretinal membranes. The progression to a fibrous ingrowth from the wound occurred only in eyes with blood in the vitreous. The intravitreal fibroblastic proliferation had its origin mainly from the stroma of the ciliary body and choroid at the wound but probably also from the nonpigmented ciliary epithelium. A fibroblastic response was present within the vitreous as early as four days after injury, and had progressed to form a cyclitic membrane by six weeks. Epiretinal membranes were identified as early as four weeks after injury. They were most prominent over the peripheral retina anterior to the equator. It is likely that they are derived from multiple cellular sources including the fibrous ingrowth from the wound but they were also connected to the surface of the retina by bridges of tissue indicating a glial origin. The subretinal membranes appeared to be derived from both retinal pigment epithelium cells and glial cells.