Membrane structural specialization of the toad urinary bladder revealed by the freeze-fracture technique. III. Location, structure and vasopressin dependence of intramembrane particle arrays.

Examination of the toad urinary bladder by freeze-fracture electron microscopy reveals intramembrane particle arrays at a number of membrane sites. An array in which particles are aggregated into closely apposed parallel rows is found in the granular cell luminal membrane of dehydrated toads fixed in situ. These aggregates are structurally indistinguishable from those previously associated with vasopressin exposure in vitro. Aggregates are not found in granular cell luminal membrane in the case of hydrated toads fixed in situ. However, structurally similar arrays are found at low frequency in the membrane of cytoplasmic vacuoles in granular cells and in the plasma membrane of basal cells in both hydrated and dehydrated toads. Aggregates are also present at these sites in control and vasopressin-treated bladders from in vitro experiments. Particle arrays characteristic of gap junctions, desmosomes and hemidesmosomes also occur in the plasma membrane of basal cells. In addition, distinctive square arrays of particles exist in the plasma membrane of the bladder's mesothelium. Although a variety of intramembrane particle arrays exist in the toad urinary bladder, only the occurrence of organized particle aggregates in the luminal membrane of granular cells appears to be associated with vasopressin exposure.


Evidence for a transcellular component to the transepithelial sodium efflux in toad skin.

The transepithelial efflux of sodium, from the inner to the outer surface was measured across the isolated toad skin, mostly after abolition of the electrochemical gradient. The effects on this efflux of several agents and manipulations were studied in order to make a distinction between the paracellular component and a hypothetical transcellular one. Amiloride decreased the transepithelial efflux, while ouabain and cyanide increased it. From the known mode of action of those agents, it was inferred that part of the efflux occurred across the cell. Removal of sodium from the external solution interfered apparently with both components of the transepithelial efflux, while the action of external hypertonicity seemed to be restricted to the paracellular shunt pathway. Access of sodium from the internal solution to the active transport pool is thus suggested, with consequent increase in metabolic cost of transport. Yet, compared with the net influx, the amounts involved are very small; consequently, they escape detection by oxygen consumption measurements.


Vasopressin-like effects of psychotropic drugs in amphibian epithelia.

Amphibian epithelia have been used as models for studying the effects of psychotropic drugs on membrane transport. Several of these agents added to the internal or to the external media, at concentrations greater than 10(-3) M, had inhibitory, "ouabain-like" effects on Na transport. In contrast, stimulatory, "vasopressin-like" effects were seen at lower concentrations. The stimulation was additive to that of oxytocin if the drug was present in the external solution but nonadditive if in the internal solution. On water transport, harmala alkaloids had a vasopressinomimetic action in toad skin, while inhibition was seen with Li and amitriptyline. To account for these multiple effects, it is hypothesized that psychotropic drugs act on the following cell targets: the Na pump, the cyclic nucleotide system, microtubules, and membrane calcium sites at the outer barrier of the epithelium. Direct, biochemical evidence is needed to substantiate this hypothesis.


Direct visualization of epithelial morphology in the living amphibian urinary bladder.

Differential interference-contrast microscopy has been applied to the study of amphibian urinary bladders, in vitro. It is demonstrated that well-resolved images can be obtained with little loss of tissue viability. Direct observations have been made on the structure of microvilli, the distribution of mitochondria in the mitochondria-rich cells, and the patency of lateral intercellular spaces. It is noted that the effective viscosity of cytoplasm is very high--that it is apparently a gel in which there is no Brownian movement of organelles. The frequency, shape, and pattern of distribution of granular and mitochondria-rich cells is determined for the commonly studied varieties of Bufo marinus. Bladders from Colombian toads contain more and larger mitochondria-rich cells than do those of the Dominican variety. There is no specific arrangement of cell-cell contacts to suggest a structural basis for cooperativeness of action. Finally, a longitudinal study of osmotically-induced changes in the structure of the "tight" or "limiting" junctions establishes the validity of previous findings by electron microscopy.


Biochemical response of squirrel monkeys to ozone.

Biochemical studies were performed on blood and lung tissue of squirrel monkeys (Saimiri sciureus) following acute exposure to 0.75 ppm ozone (O3) for 4 h/d for 4 consecutive days. One group of animals was sacrificed at the end of the last exposure day and another group was sacrificed 4 d later after the last exposure. Evidence was sought for oxidation-induced changes known to occur in rodents when high levels of O3 are inhaled. A significant increase in red blood cell membrane fragility was observed, as well as significant decreases in red blood cell glutathione and erythrocyte acetylcholinesterase; however, the red blood cell enzymes, lactic acid dehydrogenase (LDH), and glucose-6-phosphate dehydrogenase (G6PDH) were not changed significantly. Lung tissue analysis showed that lipid peroxidation was markedly increased and tissue vitamin E levels were significantly decreased. The tissue enzymes G6PDH, glutathione reductase, and LDH significantly increased in activity. No significant changes were seen in either superoxide dismutase or malic acid dehydrogenase. The results of this experiment indicate that O3, or reaction products resulting from O3-tissue interaction in the lung, pass the air-blood barrier and are capable of producing biochemical changes in blood as well as in lung tissue.


Early detection of childhood hearing impairment - problems and possible solutions.

The identification of infants with profound hearing loss is a complex task, and one that is beset with problems. This paper discusses some of these problems and points out a few of the ways by which, hopefully, they are coming closer to solution. The first problem results from the nature of the beast, which seems to have so many social, medical, educational, and political implications. There are also some problems with the high risk register and with screening for hearing loss; but probably the most disturbing are the conflicts that arise between professionals when their aims, objectives, and methods don't quite match. Current progress in the linking up of high risk and screening methodologies is discussed, as well as ways in which existing health care systems can be utilized in deafness detection.


Concentrations of circulating steroids in normal prepubertal and adult male and female humans, chimpanzees, rhesus monkeys, rats, mice, and hamsters: a literature survey.

Radioimmunoassay (RIA) data on concentrations of circulating steroids in normal prepubertal and adult male and female humans, chimpanzees, rhesus monkeys, rats, mice, and hamsters have been collated from the literature. Few reports include data for both sexes, for age groups, or for more than one species. In selecting references for inclusion in the tables, efforts were made to choose data only from RIA procedures that were adequately validated. A number of similarities can be found by reviewing the tables. Levels of estradiol appear somewhat similar for humans, chimpanzees, and rhesus monkeys of both sexes. Among the notable differences are the levels of estradiol and progesterone in primates and rodents, the apparently high level of aldosterone in mice, and the patterns of progesterone secretion in mice and rats. All values in the tables have been converted to picograms for easy comparison between steroids and species. Data for humans are fairly complete, but there is a significant lack of information for several other species.


Effect of ethanol on the retention of americium-241 in the baboon liver.

The oral administration of ethyl alcohol enhanced the excretion of 241Am from the liver of a baboon by 2.5 times that of a control animal. After ethanol administration, increases in the total content of 241Am excreted in feces were accompanied by corresponding increases in fecal volumes, although administration of nonalcoholic cathartics would not be expected to produce a similar effect. The effectiveness of ethanol as a decorporating agent may result from its ability to mobilize intracellularly bound 241Am from the liver, thereby making the nuclide more available for metabolic secretory mechanisms occurring via liver-bile-fecal route.


Effects of NO2 on the response of baboon alveolar macrophages to migration inhibitory factor.

Pulmonary alveolar macrophages (PAM) were obtained by lavage from baboons exposed for 6 mo to 2 ppm NO2 for 8 h/d, 5 d/wk, and the response of these cells to autologous migration inhibitory factor (MIF) was determined. PAM from two of three antigen-sensitized, NO2-exposed animals failed to respond to MIF derived from antigen-stimulated autologous lymphocytes. Similarly, PAM from three of the four NO2-exposed animals had diminished responsiveness to MIF obtained by phytohemagglutinin stimulation of their own lymphocytes. The altered responsiveness resulted from an effect on the macrophages and not on the lymphocytes used to prepare the MIF, as shown by the normal blastogenic responsiveness of the lymphocytes and the normal activity of the MIF thus produced on guinea pig peritoneal macrophages. These results demonstrate that inhalation of 2 ppm NO2 may have important subtle effects on pulmonary cells, which may result in altered immune capabilities within the lung.


Relationship of Bacillus subtilis DNA polymerase III to bacteriophage PBS2-induced DNA polymerase and to the replication of uracil-containing DNA.

In vivo studies of PBS2 phage replication in a temperature-sensitive Bacillus subtilis DNA polymerase III (Pol III) mutant and a temperature-resistant revertant of this mutant have suggested the possible involvement of Pol III in PBS2 DNA synthesis. Previous results with 6-(p-hydroxyphenylazo)-uracil (HPUra), a specific inhibitor of Pol III and DNA replication in uninfected cells, suggest that Pol III is not involved in phage DNA replication, due to its resistance to this drug. Experiments were designed to examine possible explanations for this apparent contradiction. First, assays of the host Pol III and the phage-induced DNA polymerase activities in extracts indicated that a labile Pol III did not result in a labile phage-induced enzyme, suggesting that this new polymerase is not a modified HPUra-resistant form of Pol III. Indeed the purified phage-induced enzyme was resistant to the active, reduced form of HPUra under all assay conditions tested. Since in vitro Pol III was capable of replicating the uracil-containing DNA found in this phage, the sensitivity of the purified enzyme to reduced HPUra was examined using phage DNA as template-primer and dUTP as substrate; these new substrates did not affect the sensitivity of the host enzyme to the drug.


DNA of Bacillus subtilis bacteriophage SPP1: physical mapping and localization of the origin of replication.

The genome of Bacillus subtilis bacteriophage SPP1, a linear, 28.5-megadalton DNA duplex, was mapped by analysis with the restriction endonucleases endo R.Sal I, Sma I, Xba I, Bgl I, Bgl II, and EcoRI. The SPP1 genome, like that of the Salmonella typhimurium phage, P22, was found to be a terminally repetitious, circularly permuted molecule. 6-(p-Hydroxyphenylazo)uracil, a selective, reversible inhibitor of SPP1 DNA synthesis, was exploited to synchronize the initiation of genome replication and to selectively label the site of its initiation with radioactive thymidine. Restriction endonuclease analysis of the distribution of the label located the origin of replicative synthesis at an area approximately 0.2 genome length from one molecular terminus.


Characterization of a variant of human adenovirus type 2 which multiples efficiently in simian cells.

In a previous report (Klessig, J. Virol. 21:1243--1246, 1977), the isolation of a variant (H2hr400) of adenovirus serotype 2 (Ad2) that overcomes the block to multiplication of wild-type Ad2 in simian cells was described. H2hr400 replicates efficiently on both human and simian cells, resulting in virus yields that are comparable to those found when wild-type Ad2 infects permissive, human cells. An extensive comparison of the genome of H2hr400 with that of its parent by restriction endonuclease, electron microscopic, and hybridization analyses failed to detect any differences and excludes the possibility that simian virus 40 sequences, which in certain Ad2-simian virus 40 hybrid viruses (e.g., Ad2+ND1) allow adenovirus to multiply efficiently in simian cells, are present in H2hr400. In contrast to Ad2, H2hr400 can fully express its late genes in both simian and human cells. The mutation has been mapped by a modified marker rescue technique to the segment of the viral genome located between coordinates 59 and 80.


Neurofibromatous ureteral obstruction relieved by sigmoid conduit cystoplasty.

Neurofibromatosis is a neural disease of hereditary nature affecting both sexes of all races. Visceral and central nervous system involvement can cause serious interference with normal function of affected structures. Under these circumstances, lifelong observation and individualized treatment of the patient are essential to proper management. This report is an account of nearly 2 decades of conservative management of neurofibromatosis of the pelvis in a young woman. Progressive, bilateral ureteral obstruction developed but normal function of the urinary tract has been maintained for the last 10 years with a sigmoid conduit cystoplasty. It is anticipated that continued progression of the disease will require cutaneous transfer of the sigmoid conduit. Also, a colostomy might become necessary because of recent evidence of rectal obstruction noted on computed tomography.


Chromium deficiency during total parenteral nutrition.

Chromium is required for maintenance of normal glucose tolerance. After complete bowel resection and five months of total parenteral nutrition, severe glucose intolerance, weight loss, and a metabolic encephalopathy-like confusional state developed in a patient. Serum chromium levels were at the lowest normal level. Supplementation of 150 microgram of chromium per day reversed the glucose intolerance, reduced insulin requirements, and resulted in weight gain and the disappearance of encephalopathy. The low levels of chromium and response to chromium supplementation suggest that chromium deficiency can arise in long-term total parenteral nutrition.


Protein-sparing therapy during pneumococcal infection in rhesus monkeys.

A model was developed in the rhesus monkey to determine if the marked wasting of body proteins associated with sepsis could be prevented by an intravenous supply of various nutritional substrates. All monkeys were given a basic infusion of 0.5 gm of amino acid nitrogen/kg body weight via an indwelling catheter in the jugular vein. Three groups were given diets with no added calories, 85 calories/kg from dextrose or 85 calories from lipid. In each group, six monkeys were inoculated with 3 x 10(8) Streptococcus pneumoniae and four with heatkilled organisms. In the monkeys infused with the amino acids alone, pneumococcal sepsis resulted in a fourfold increase in loss of body proteins compared with calorie-restricted controls. Addition of 85 calories/kg/day of either dextrose or lipid reduced body wasting associated with infectious disease. The calories from lipid were utilized bythe septic host as a source of energy, with a slightly reduced efficiency when compared with the isocaloric infusion of dextrose. The nitrogen sparing of the fat emulsion could not be accounted for by its glycerol content. Therefore, the septic monkey seemed to utilize fatty acids as an energy substrate. It appears that the carbohydrate calories tend to favor the synthesis of peripheral proteins (associated mainly with skeletal muscle), while lipid calories favor synthesis of visceral proteins such as plasma albumin and acute-phase proteins.


Protein-sparing in cystectomy patients.

Forty-four patients undergoing radical cystectomy and urinary diversion for invasive bladder cancer were studied prospectively in order to evaluate the substitution of crystalline amino acids (A3W) for dextrose (D5W) in their postoperative fluid management. Nutritional assessment revealed 17 (39%) patients to be malnourished prior to operation; the postoperative complication rate in Group I (D5W) was 33% vs 17% in Group II (A3W). Nitrogen losses in both groups were low, secondary to the large amounts of albumin used postoperatively; however, more exogenous albumin was needed after operation to maintain serum albumin levels in Group I compared with Group II (77.5 +/- 3.1 gm vs 65 +/- 5.2gm). Cell-mediated immunity, determined by reactivity to a battery of recall antigens, revealed that 56% (5) of Group I patients were able to maintain their skin test reactivity throughout the postoperative course compared with 94% (17) in Group II. Four nutritionally depleted patients in Group I required conversion to a forced feeding regimen (IVH), while none of those in Group II required a change in nutritional regimen. Invasive bladder cancer represents a major injury, and preoperative x-ray therapy along with surgical extirpation is associated with considerable nutritional depletion. Early nutritional support in the management of these patients is mandatory, and where hypocaloric feeding regimens are appropriate, the use of A3W in place of D5W solutions would appear to be indicated.


Titration of tetanus antitoxin by passive hemagglutination. II. Serological characteristics of antitoxin production in rabbits and monkeys.

1) Production of tetanus antitoxin in rabbits and monkeys was followed by passive hemagglutination (HA) and toxin-neutralization (TN) tests. The HA activity was observed in both IgM and IgG in both animal species. 2) In rabbits, IgM antitoxin was detected as early as in 7 days, reached the maximum titer in 10--14 days, and disappeared in 3 weeks after the primary immunization. Antitoxin of IgG class was detected in 10 days, and increased gradually. The ratio of HA/TN titers ("serum ratio") was high at an early stage of primary immunization and approached the unity in 3--4 weeks. Unlike the case of guinea pigs, IgM was found to contribute greatly to this high level of ratio. Besides, most rabbits produced IgG antitoxin of high ratios at early stages of immunization. 3) The immune response of monkeys showed a pattern very similar to that of rabbits except a few days' delay in the time course of antitoxin titers. No IgG antitoxin with a high serum ratio was demonstrated. Therefore, the high serum ratio of early sera could be accounted for mainly by IgM. 4) In response to the secondary immunization, no IgM antitoxin was detected in either animal species. 5) No definite correlation between serum ratio and avidity in terms of "dilution ratio" was demonstrated. However, both the dilution ratio and serum ratio were high at an early stage of immunization and gradually decreased, though the magnitudes of the ratios were variable depending on individual animals.


Breeding of cynomolgus monkeys through successive generations by indoor cage system.

Vital statistics on the breeding through successive generations were presented for the cynomolgus monkey colony of NIH, Tokyo. The results of this retrospective survey clearly demonstrated the third (F2) and the fourth (F3) generations could be bred and reared successfully by the indoor caged-breeding system in which either individual timed-mating or group mating procedure was adopted. Several important and difficult problems involved in the production of successive generations of the cynomolgus monkey by our breeding system were discussed from the standpoint of laboratory animal science.


[Clinical aspects of deprivation amblyopia (author's transl)].

Experiments in animal models revealed that unilateral lidclosure, artificial esotropia or anisometropia cause amblyopia comparable to that occuring in humans and produces morphological and functional anomalies in the visual centers. Form vision deprivation and abnormal binocular interaction have been identified as amblyopiogenic factors. The age of susceptibility for amblyopia in humams needs better definition. Uncontrolled occlusion in infants must be avoided and congenital or traumatic cataracts occuring in infancy should be operated upon as early as possible and the aphakic eye(s) optically corrected without delay to prevent deprivation amblyopia.


[Trifluorothymidin-prophylaxis of dendritic keratitis in steroid-treated herpetic keratouveitis (author's transl)].

In a randomized double-blind study trifluorothymidine was tested for its ability to prevent dendritic keratitis at a dose of 5 drops daily in patients with steroid-treated herpetic keratouveitis. The corneal epithelium of all 56 patients in the study was free of viral foci prior to initiation of therapy. In the placebo- "protected" group, 6 of 28 patients developed virologically confirmed dendritic keratitis while they were under steroids, whereas all 28 trifluorothymidine-protected patients showed uneventful courses of their steroid regimes. No clinically relevant side-effects of trifluorothymidine prophylaxis were observed in this study.


[Vital staining of the endothelium of preserved corneae with Trypan Blue (author's transl)].

As a development of Capella's and Kaufman's procedure we examined on four series each with 20 pig corneae the four antifreezing solutions described by the authors singly with regard to their protective effect against freezing. After thawing at +60 degrees within 50 seconds and rehydration with 25% Serum albumin (in the fourth series 10 corneae were rehydrated with polyvinylpyrrolidone) the endothelium was stained with Trypan blue. Microphotographs were made of the endothelial surface, stained nuclei counted and the results were analysed statistically and compared one with other. Hence we could show that with increasing concentration of the antifreeze solution the vitality of the cornea increases.


[Cherry red spot without secure evidence of sphingolipidosis (author's transl)].

The occurence of bilateral cherry red spot without neurological disorders is a rare event. The reported case is a girl aged 14 years, whose only complaint was slight deterioration of vision. No secure enzymatic defects was found on examination of leucocytes. Though the cherry red spot is hardly to be explained in another way than by storage in optic ganglion cells. Static perimetry revealed a paracentral depression of contrast sensitivity.


The incidence, pathogenesis and treatment of helminth infections in rhesus monkeys (Macaca mulatta).

In a survey of 259 newly-imported rhesus monkeys, 5 species of nematode parasites were commonly found. Of these 5 species, Oesophagostomum spp. and Strongyloides fulleborni were implicated in the deaths of 3 monkeys. 5 other nematode species, 2 cestode species and 1 trematode species were also found; their pathogenicity is discussed. The results of treatment of parasitic infections with 6 different drugs is reported. Thiabendazole at an initial dose of 100 or 133 mg/kg and repeated at 50 mg/kg was found to be the most effective treatment against Oesophagostomum spp.


Trends in the use of nonhuman primates in biomedical programmes.

Recent surveys of the use of primates in biomedical laboratories indicate that the demand, especially for imported animals, is declining. Reasons for this trend are not clear, although restrictions on export by countries of origin undoubtedly have a significant effect. More precise survey techniques and terminology would aid comparisons and help to identify the factors involved in changes in demand.


Variations in the blood clotting time and lipid patterns of the Nigerian monkey, Cercopithecus aethiops tantalus, during captivity.

The blood clotting time and serum lipid values of newly-captured Nigerian monkeys were determined during the period of adaptation. Large fluctuations in serum free and total cholesterol and phospholipid values were observed throughout the 12-week period of investigation. The variations in blood clotting time were not significant (p greater than 0.05). These wide variations in lipid values suggest the need for caution in interpreting data from newly-captured subhuman primates.


Polycation-induced dislocation of slit diaphragms and formation of cell junctions in rat kidney glomeruli: the effects of low temperature, divalent cations, colchicine, and cytochalasin B.

Neutralization of negatively charged groups in the glomerular capillary wall by polycations causes extensive loss of podocyte footplates, formation of tight and gap junctions, and dislocation of slit diaphragms within a few minutes (M. W. Seiler, M. A. Venkatachalam, and R. S. Cotran: Science 189:390, 1975). This study attempts to elucidate further the development of podocyte abnormalities by quantitating the effects of inhibitors of microfilaments, microtubules, and cellular metabolism. The decrease in the number of footplates per micrometer of basement membrane caused by the polycationic chemical protamine sulfate (PS) was determined after in situ perfusion of the left kidney of rats. An approximate 50 per cent amelioration of this effect of PS was observed when in addition to perfusion with PS: (1) perfusion was performed in the cold (6 degrees C.); (2) the perfusate contained cytochalasin B; (3) the perfusate lacked Ca2+; and (4) the perfusate contained ethylenediaminetetraacetic acid. In contrast, colchicine did not affect PS-induced footplate loss. It was concluded that the PS-induced footplate retraction observed in scanning micrographs, is partially an active process involving podocyte actin filaments. Intact microtubuli are obviously not necessary. Formation of tight and gap junctions between foot processes and dislocation of slit diaphragms were not influenced by any of the inhibitory conditions listed above.


School nursing services--some current justifications and cost-benefit implications.

A variety of justifications for maintenance of adequate school nursing services within the school health program, especially in view of current health problems prevalent among school-age children in this nation, is described. In this process, the main emphasis of the article is centered on the cost-benefit implications of school nursing.


Autoregulation of cerebral blood flow during alcohol infusion.

Vascular changes, in the absence of respiratory complications, were observed in monkeys and dogs after infusion of 20% ethanol solutions.


The economic returns to employment-based alcoholism programs: a methodology.

A model for the estimation of the economic returns to a firm's investment in an occupational-based alcoholism rehabilitation program is described.


Age dependent reaction of mouse thymus cells with autologous and syngeneic erythrocytes.

The age dependent events influencing the rosette forming capacity of Balb/c thymus and spleen cells against autologous or syngeneic erythrocytes were examined. A large number of autologous and syngeneic rosette forming cells (RFC) were observed in normal Balb/c mice in vitro. RFC were significantly greater in the thymus than in the spleen. The rosette forming T-cells (T-RFC) have the following characteristics: newborn Balb/c thymus has T-cells which react syngeneic erythrocytes from older donors. The T-RFC showed broad cross-reactivity with erythrocytes from other mouse strains but low reactivity with human or sheep erythrocytes. The auto and syngeneic T-RFC could be enhanced by non-specific serum proteins (FCS or BSA) or EDTA but was effectively inhibited by normal mouse serum. T-RFC resided in the cortisone sensitive population. The data indicate that the development of autologous and syngeneic rosette formation of thymus cells is dependent on the age of the erythrocyte donor. The age dependent change on the erythrocyte surface occurred relatively early in the life of the animal. The results also imply that certain subpopulations of thymus lymphocytes are capable of recognizing possible surface antigenic changes of the erythrocytes.


Serological evidence for the alteration of enolase during aging.

Pure enolase isolated from young and old Turbatrix aceti has been compared using immunologic techniques. Antiserum prepared to "young" and "old" enolase, respectively, will completely precipitate either enzyme. However, antiserum prepared to "young" enolase reacts more efficiency with "young" than with "old" than with "old" enzyme and vice versa. A third form of enolase (inactive enolase) is found in homogenates of old organisms. This material yields a pattern of identity with "young" enolase and partial identity with "old" enolase. It also gives rise to specific antibodies which do not react with "young" or "old" enolase. The material appears to accumulate with age. The results indicate a close structural relationship between "young", "old" and inactive enolase.


[Results of replantations, organizational and financial problems (author's transl)].

After 363 replantations of fingers, thumbs, and hands with 87.9% successful revascularizations, conditions for optimal results and reasons for failure are discussed in terms of surgical management, organization, and costs. Several case studies document the importance of preoperative handling, the time span between accident and treatment, and the postoperative control of thrombosis. Finally, microsurgery is regarded as a first step toward a future routine technique in reconstructive surgery.


[Hyperthyroidism: diagnosis (author's transl)].

In hyperthyroidism we differentiate two main forms: (1) hyperthyroidism due to Basedow's (Graves') disease, always characterized by endocrine eye signs, frequently with goiter; (2) hyperthyroidism due to nodular goiter or to Plummers' disease, without endocrine exophthalmos. The clinical diagnosis includes typical complaints (e.g., weight loss, heat intolerance, sweating) and findings (e.g., tachycardia, tremor, soft-warm skin). The technical diagnosis includes in vivo (scintigraphy, RI-uptake, X-ray examination) and in vitro (T3-RIA, T4-assay, TRH response to TRH) tests.


[The seat belt: effect on the consequences of traffic accidents (author's transl)].

At the present time, more than 90% of the motor vehicles in the Federal Republic of Germany are equipped with seat belts. On the average, however, only one out of two drivers uses his belt. It has been established that the seat belt, considering the present rate of use, annually protects about 1700 car occupants from fatality and about 30,000 from injuries (resulting in economic savings of approx. DM 1.8 X 10(9)). If all car occupants were to observe seat-belt regulations, this gain in safety might be doubled. Experience of other countries indicates that the introduction of the fine would result in much better compliance with the regulation than has been observed thus far.


[Indications and possibilities for parenteral nutrition (author's transl)].

Parenteral nutrition is a basic therapy. It is necessary to have a preoperative definition of the nutritional condition and metabolism of the surgical patient. All disturbances such as catabolism and hypoproteinemia must be analyzed and treated. Patients in good general condition who need parenteral nutrition for more than two days receive a "basic nutrition" with 0.8-1.0 g amino acids and 4-5 mg carbohydrates/kg body weight/day, which may be given via peripheral veins. A "total parenteral nutrition" is always indicated if the patient is in a marked catabolic condition pre-operatively, or if it is anticipated from the extent of the operation procedure that parenteral replacement must continue beyond four days.


[Practical management of parenteral nutrition (author's transl)].

Three different plans of parenteral nutrition are available: (1) postoperative water and electrolyte substitution; (2) basic parenteral nutrion; (3) total parenteral nutrition. The decision for one of these plans depends on the duration of necessary parenteral support and on the patient's situation. ad 1: solution with electrolytes, 40 ml/kg body weight/day ad 2: solution with electrolytes, amino acids (25 g/day) and carbohydrates (125 g/day) in a 75 kg patient ad 3: solution with electrolytes, amino acids (1 g/kg body weight/day) and carbohydrates (5 g/kg body weight/day).


[Special questions in connection with the energy supply in extensive burns (author's transl)].

There is no other trauma that gives such a high increase in resting metabolic rate as an extensive burn. Treatment in a very warm, dry environment minimizes body heat loss by radiation, convection, and conduction. Covering the burned wounds with homograft or heterograft skin reduces the evaporative loss. Despite these treatments, the burn patients needed at least 3000 kcal (12 MJ) per day to be in energy balance. Carbohydrates, crystalline amino acid solution, Vamin, and Intralipid were infused; 345 patients with burns over 20% have been treated with good results.


[Complications of caval catherization (author's transl)].

The following approaches to the caval vein are applicable: Vena saphena, basilica, subclavia, and jugularis. Based on collective studies from the literature and our own experience, the puncture of the internal jugular vein is recommended. The approach via the veins of the lower extremities should no longer be used in adult. Many complications--independent of the approach--are caused by the catheter model applied or by poor application technique or care. A model of our own was developed presenting siliconized polyethylene and a removable needle. As compared to PVC, the rate of inflammation and thrombosis was significantly decreased.


Symptoms, findings, and methods of diagnosis in patients with acoustic neuroma.

The records of 225 patients with surgically documented acoustic neuromas seen at the Mayo Clinic between 1966 and 1976 were studied. Included in this group were 4 patients who had von Recklinghausen's disease with bilateral ear involvement, 7 patients with recurrence of acoustic neuroma, and 8 patients who were referred because of recurrent acoustic neuroma. Symptoms, clinical findings, and results of audiologic, vestibular, and roentgenographic studies were analyzed. Nine patients had a history of sudden onset of hearing loss, and 11 had a history of vertigo. A correlation between the size of the lesion and the symptoms, physical findings, and roentgenographic accuracy was made in an attempt to gain further knowledge of the natural course of the pathologic processes involved.


Reduced chromium retention in patients with hemochromatosis, a possible basis of hemochromatotic diabetes.

Chromium (III) has recently been shown to be an essential trace mineral in rats, being required for normal function of insulin in controlling glucose metabolism. Chromium is transported in the body bound to transferrin, where it binds competitively with iron. Hemochromatosis is an iron storage disease in humans characterized by highly saturated transferrin levels and sometimes by diabetes. We postulated that the diabetes may be due to exclusion of chromium by iron at metabolic binding sites. 51Cr(III) was administered i.v. to 5 normal males, 6 patients with hemochromatosis prior to therapeutic removal of iron, and 5 patients with varying levels of iron loading. The retention of 51Cr was measured with a whole-body counter for 8 mo and blood levels were measured for 40--80 days. Analysis of the whole-body retention curves revealed 3 exponential components with T1/2s of .56 days, 12.7 days, and 192 days; the blood curves had 4 components with T1/2s of 13 min; 6.3 hr, 1.9 days, and 8.3 days. The T1/2s were not significantly different between the normals and patients. The coefficients of these components however, were significantly lower for the long T1/2 components in the iron-loaded patients, demonstrating reduced retention of 51Cr as postulated. Whether this reduced retention of chromium is causally related to diabetes in hemochromatosis and whether abnormal chromium metabolism is involved in endogenous diabetes, thus, becomes an important question for future study.


The chemical composition of the lipopolysaccharide from Pseudomonas aeruginosa strain PAO and a spontaneously derived rough mutant.

The chemical composition of the lipopolysaccharide (LPS) of the smooth strain Pseudomonas aeruginosa PAO 307 and a spontaneously derived rough mutant, obtained by selection for resistance to the LPS-specific phage E79, are compared. The rough LPS was shown to contain lipid A, heptose, 2-keto 3-deoxyoctonic acid, galactosamine, alanine and phosphate but lacked glucose, rhamnose and fucosamine which were important constituents, on a weight basis, of the smooth LPS. These results, and chromatographic analysis of the polysaccharide fraction indicate that the rough strain lacked side chain material and was defective in its inner core region. The chemical date obtained were consistent with a core in the PAO strain similar to that of strain NCTC 1999, enhancing the evidence for a common core polysaccharide in the LPS of P. aeruginosa strains.


Bacterial attack on phenolic ethers. Purification and characterization of the components of the meta O-dealkylase of Pseudomonas fluorescens Tp.

The meta O-dealkylase of Pseudomonas fluorescens Tp has been resolved into two protein components, neither of which is a cytochrome. The substrate binding terminal oxidase has been purified and shown to be a non-haem iron protein of approximate molecular weight 118,000, consisting of two seemingly identical subunits, each of molecular weight 55,000. Binding of substrate by the terminal oxidase has been established by difference spectroscopy. The amino acid composition of the protein has also been determined. The NADH-dependent reductase of the system has been partly purified and appears to have a molecular weight of 80,000. The similarity between this and other bacterial O-dealkylases is discussed.


Immunological relations of proteins from four salmonellae sharing an "O" factor 8.

The proteins from S. virginia, with the sole 8 "O" factor, precipitated against homologous and related heterologous sera by a conspicuous, homogenous line of serological identity, with proteins from: S. newport (6.8), S. blockley (6.8), S. emek (8.20). The proteins, however, were not involved in the bacterial agglutinations since the absorptions, which removed the common precipitins from the sera, did not modify the homologous agglutinations. The results with anti-S. newport and anti-S. blockley sera sharing identical "O" factors while displaying different immunochemical compositions as well as the strong immunochemical relations found between S. virginia and S. newport belonging to the different subgroups C2 and C3 underline the non-relatedness of agglutinins and precipitins.


Long term fixation for histological studies.

It was found that a glutaraldehyde-formalin-phosphate buffered fixative could preserve retinal tissue for light microscopy, even if the tissue remained in the fixative for a month. Retinal tissue that previously was difficult and expensive to procure could now be obtained.


Consequences of ileal dysfunction: an approach to management.

Fourteen patients with ileal dysfunction due to resection or bypass were encountered over an 18-month period. Symptoms had been present for a mean period of 1.8 years. Diarrhoea was a universal symptom, and varied from mild to incapacitating. Weight loss, due in part to malabsorption and in part to the patients' fear of eating, occurred in 10 of 14 patients. The chief metabolic abnormalities were steatorrhoea and hypokalaemia. Vitamin B12 deficiency, folate deficiency, anaemia, hypoalbuminaemia, hypocalcaemia, hypomagnesaemia, hyperoxaluria, and an abnormal prothrombin ratio were less frequently seen. Treatment with cholestyramine and/or long-chain fat restriction effectively reduced diarrhoea in every case, and this was supplemented by replacement of specific deficiencies. There was little added benefit from non-specific antidiarrhoeal agents. It was found that the major symptoms of ileal dysfunction are readily treated, but that attention should also be given to a number of nutritional deficiencies.


Relationship between mutant amidases of Pseudomonas aeruginosa and hydroxyurea as an inhibitor.

Hydroxyurea inhibited growth of Pseudomonas aeruginosa strain AI 3 on media containing either acetanilide (N-phenyl acetamide) or acetamide as sole carbon sources. Mutants resistant to hydroxyurea inhibition of growth on acetanilide (OUCH strains) and acetamide (AmOUCH strains) displayed altered growth properties on various amide media compared with the parent strain AI3. AI3 amidase, which catalyses the initial step in the metabolism of acetanilide and acetamide, was inhibited by hydroxyurea in a time-dependent reaction that was slowly reversible at pH 7.2. Compared with AI3 amidase, amidases from the OUCH mutants were much less sensitive to inhibition by hydroxyurea and showed altered substrate specificities and pH/activity profiles; amidases from the AmOUCH mutants were more sensitive to hydroxyurea inhibition but showed increased activity towards acetamide. Association of resistance to hydroxyurea inhibition with a mutation in the amidase structural gene of strain OUCH 4 was confirmed by transduction.


Argon/propane ionization-chamber dosimetry for mixed x-ray/neutron fields.

The photoneutrons produced by high-energy x-ray machines can diffuse through the mazes usually employed at the treatment-room entrance and readily penetrate the lead-lined doors used for x-ray shielding. The measurement of these neutrons in the presence of x-rays and the determination of dose equivalent poses a problem for which there is currently no standard method of solution. In order to separate x-ray dose from neutron dose, the author employed an ionization chamber alternately filled with argon or propane. The response characteristics of this chamber to x-ray and neutrons are described. Quality factors were determined from a calculated neutron spectrum. As a result of these measurements, a 10-in. polyethylene door was added to the entranceway of a 25-MV linear accelerator.


Improvement of linear accelerator depth-dose curves.

A semiempirical analytic description of the accelerator depth-dose curve is described along with its physical explanation. The results of Monte Carlo calculations are presented and compared with experimental data to test this model. Calculations were made for different atomic number (Z) materials used as x-ray targets and flatteners, with the results showing that medium-Z materials are the logical choice. It is demonstrated empirically that Dmax is a simple function of the average energy (E) of the x-ray spectrum. The variation of E with Z of the target and flattener is demonstrated. As a practical example, Monte Carlo calculations and experimental data for old and new Clinac 35 accelerators are presented.


SPP1 DNA replicative forms: growth of phage SPP1 in Bacillus subtilis mutants temperature-sensitive in DNA synthesis.

The development of bacteriophages SPP1 and phi 29 has been studied in several B. sutilis mutants defective in host DNA replication, under non permissive conditions. Several gene products, involved in the synthesis of host DNA, are required for phi 29 replication, while SPP1 seems to require only the host DNA polymerase III. In addition both phages are unable to grow in a dna A mutant (ribonucleotide reductase). Taking advantage of the fact that SPP1 DNA is actively replicated in several dna mutants at non-permissive temperature, we have studied the structure of the replicative intermediates of this phage in the absence of interfering host DNA synthesis. Fast sedimenting forms of SPP1 DNA can be isolated from phage infected cells and evidence of covalently joined concatemers has been obtained, suggesting the presence of terminally repeated sequences.


A review of the reliability of chamber factors used clinically in the United States (1968--1976).

One of the principal concerns of a physicist responsible for calibrating megavoltage radiotherapy equipment is the validity and stability of the 60Co exposure correction factor assigned to his ionization-chamber and electrometer system. It is the practice of the AAPM Radiological Physics Center (RPC) to perform an intercomparison between the RPC chamber and electrometer system and the chamber and electrometer in use at each of the various institutions visited by the RPC. The results of 202 such intercomparisons are reviewed to determine (1) the consistency in the assignment of exposure correction factors by a calibrating agency with itself and with other calibrating agencies, and (2) the dependence of the reliability of the exposure correction factors upon the type of field instrument and the time since calibration.


An analysis of discrepancies encountered by the AAPM radiological physics center.

The AAPM Radiological Physics Center has reviewed 188 institutions and has evaluated such parameters as coincidence of radiation field and light field, timer error (end effect), beam flatness and symmetry, transmission through blocking trays, wedges and compensators, and central-axis depth-dose data. In previous papers these data had been presented in combination as they resulted in discrepancies in tumor dose. The individual sources of discrepancies were listed only as frequency and maximum deviation. A detailed analysis is now presented which may help define criteria of recommended practice.


Chromosomal location of genes participating in the degradation of purines in Pseudomonas aeruginosa.

Genetic mapping of the genes (puu) that encode the enzymes catalysing degradation of purines in Pseudomonas aeruginosa strain PAO has been carried out. Mutants that are deficient in adenine deaminase (puuA), guanine deaminase (puuB), xanthine dehydrogenase (puuC), uricase (puuD), allantoinase (puuE), and/or allantoicase (puuF) were isolated and used for the genetic study. Conjugation by FP5 factor and generalized transduction by phage G101 gave the following map locations of these six genes on the chromosome: hisI--puuB--hisII; trpA,B--puuA--ilv202; met9011--catA1--tyu--nar9011--(puuC, puuD, puuE)--puuF. A close linkage among the puuC, puuD and puuE was demonstrated by the transduction.


Enzymatic fragmentation of tetanus toxin. Identification and characterization of an atoxic, immunogenic fragment.

Purified filtrate tetanus toxin was subjected to limited digestion with papain and the resulting fragments were separated by gel exclusion chromatography and characterized. One atoxic fragment was shown to react with antiserum against tetanus toxoid and was capable of inducing antibodies in rabbits that neutralized native tetanus toxin, The fragment had an estimated molecular weight of 56,000 by SDS polyacrylamide gel electrophoresis and 62,000 by sedimentation equilibrium. In the presence of a reducing agent, the fragment yielded two components with approximatec molecular weights of 23,000 and 32,000. Thus, it appears that the atoxic, immunogenic fragment is composed of two peptides joined by at least one disulfide bond. The fragment was examined by circular dichroism and data analysis indicated the presence of considerable beta-structure, but little, if any, alpha-helicity. This is significantly different from the estimates for filtrate toxin. 29% alpha-helicity and 23% beta-structure. Above 250 nm, the circular dichroic spectrum of the fragment was also distinct from that of intact toxin.


[Modern internal therapy of skin diseases (author's transl)].

Modern internal therapy of skin diseases is based on a knowledge of pharmacology and biochemical pharmacology. The importance of the cytochrome P 450 system and its changes during treatment are referred to. Standard treatment in dermatology is not discussed but the literature is mentioned here. Treatment with glucocorticosteroids and non-steroidal anti-inflammatory substances are discussed in detail. The treatment of porphyria cutanea tarda with chloroquine shows good success. The results of carotinoid therapy of erythropoietic protoporphyria and non-porphyrin induced photodermatoses are debated.


[How much of classical topical therapy is still current today? (author's transl)].

Classical topical therapy has been largely displaced by the development of up-to-date drugs and advances in the galenic field. Serious objections have even been leveled against some older drugs and others are no longer current in spite of their good efficacy (e.g. dyes) because less discriminatory drugs can be substituted for them. The fundamental principles of classical topical therapy are still as valid as ever (inherent action of the base). However, many of the active principles of the prechemotherapeutic era have meanwhile been superseded as for example boric acid, mercury, desquamative pastes, sulfur among others. In contrast to this, topical applications such as dithranol, salicylic acid, coal tar and a few others still belong to the permanent stock of dermatological topical therapy.


[Inclusion of clinical-dermatological therapy into general practice? (author's transl)].

The ever increasing expenditures in health service urgently call for a critical revision of the therapy habitually practiced so far. This also includes the complete utilization of ambulatory therapeutic approaches. Moreover, after many years of clinical practice, the dermatologist in general practice should not forego the manifold therapeutic methods in which he had been trained and by the application of which he has gained particular experience. The dermatologist's small office consisting of a desk and couch must be a matter of the past once and for all. It is just the dermatologist who has the opportunity to try many forms of clinical treatment in general practice.


[Boutonneuse fever in tourists as a model for clinical diagnosis of rickettsioses (author's transl)].

Case histories of boutonneuse fever are described in order to exemplify major characteristics of most rickettsioses: recent travel history, feverish illness with severe headache, skin eruptions and histological findings. Up-to-date informations concerning the epidemiologic situation of typhus, scrub typhus and Rocky Mountain spotted fever are given. The characteristics of Q fever and the possibility of rickettsial laboratory infections are pointed out.


Study of MFD in Bacillus subtilis.

The frequency of UV-induced extragenic suppressor reversions to leucine independence in B. subtilis carrying a leu8 mutation decreased when irradiated cells were temporarily incubated in medium deprived of nitrogen sources. This mutation frequency decline (MFD) was inhibited by acriflavine and was poorly expressed in a uvr1 mutant. Consequently, MFD may be considered as the manifestation of an anti-mutagenic activity of excision repair. MFD was decelerated and even vanished in cells subjected to prolonged starvation of nitrogen sources before irradiation. MFD was accelerated in bacteria that were first irradiated and incubated in nutritional medium for at least 30 min. The stimulation of MFD by UV exposure was observed only in the uvr+ strain and depended on protein synthesis after irradiation. It is assumed that different rates of MFD in cells of various pre-radiation histories reflect different levels of the excision-repair activity inherent in these cells.


Determination of the minimal inhibitory concentration of amphotericin B and miconazole for 21 strains of Aspergillus.

The susceptibility of 21 strains of Aspergillus (11 of A. fumigatus, 8 of A, niger, and 2 of A. flavus) isolated from human pathologic specimens to Amphotericin B and Miconazole has been comparatively studied. Determination of the minimal inhibitory concentration of both drugs in a liquid medium showed a noticeably variability for the different strains. The values obtained for Amphotericin B varied between 0.25 microgram/ml (2 strains) and 1.25 microgram/ml (5 strains) after 48 hours, and between 1,25 microgram/ml (1 strain) and 50 microgram/ml (1 strain) after 10 days. For Miconazole the results varied between 0.1 microgram/ml (1 strain) and 25 microgram/ml (1 strain) after 48 hours of incubation, and between 0.5 microgram/ml (5 strains) and greater than 100 microgram/ml after 10 days. The variability of these results indicates the usefulness of carrying our in vitro sensitivity studies whenever it is possible.


[Candidiasis and obstructive intestinal tumor in a captive baboon 'Papio papio' (Desm.)].

Report of a case of candidiasis of the digestive tract associated to an obstructive epithelial tumor, with great invasive ability, in a captive Baboon, Papio papio (Desm.). Included is a discussion of the incidence of some intestinal disturbances involving candidiasis of subhuman Primates.


Identification of inhibitory and stimulatory control of prolactin secretion in the rhesus monkey.

In the unanesthetized, ovariectomized rhesus monkey, gonadotropin secretion is episodic while prolactin (Prl) release is relatively constant. Under pentobarbital anesthesia, however, Prl secretion also becomes pulsatile in synchrony with the discharges of LH. This finding suggests that the anesthesia has unmasked normally inhibited Prl releasing stimuli which are driven by the circhoral 'clock' that also times the discharges of GnRH.


Effects of centrally acting drugs on serum prolactin levels in rhesus monkeys.

Prolactin (Prl) responses to anesthetics, stress of immobilization, and agents that block adrenergic receptors were determined in 13 female rhesus monkeys. The local anesthetic (lidocaine HCl) had no effect, but the general anesthetics (ketamine HCl and sodium pentobarbital) significantly increased serum Prl levels in intact animals. There was no indication of a pentobarbital-induced inhibition of Prl secretion as reported for other species. A combination of halothane anesthesia and immobilization for 30 or 60 min produced significantly greater increases in Prl levels than immobilization alone for similar periods of time. Prl responses to blockers of adrenergic receptors varied in chair-adapted ovariectomized monkeys. The increase in serum Prl concentrations produced by the beta-receptor blocker propranolol was less marked than that induced by the alpha-receptor blockers phentolamine and phenoxybenzamine. Prl elevations of the highest magnitude and longest duration were produced by haloperidol, which blocks both adrenergic and dopaminergic receptors. Pretreatment of these animals with estradiol-17beta had no effect on Prl responses to phentolamine and haloperidol. These results indicate involvement of an adrenergic neurotransmitter system in the control of Prl secretion in primates.


The annual Pap test: a dubious policy success.

The annual Pap test became a recommended standard for American women without ever having been subjected to controlled trials to estimate its efficacy and effectiveness. After more than 30 years of routine use, the Pap test fails to meet most of the generally accepted criteria for a mass screening program. The policy persists, however, because the nation's ideology supports the maximum utilization of new technologies; and special interest groups have promoted the test as the major weapon in the "War on Cancer." With some exceptions, this is a questionable allocation of public and private health resources.


Anatomical localization of corneal afferent cells in the trigeminal ganglion.

Corneal afferent cells were identified in the trigeminal ganglion in the cat and monkey by the method of retrograde axonal transport of horseradish peroxidase. The corneal cells were found only in the ophthalmic portion of the ganglion and were scattered randomly within that division. These data are compatible with clinical and other experimental descriptions of the organization of the trigeminal ganglion and sensory root.


[Diverticula of the esophagus. Etiopathogenetic aspects and principles of surgical treatment].

On the basis of the new knowledges recently acquired with the manometry on the esophageal physiology, the Authors first consider both etiologic and pathologic problems then emphasize the essential principles for correct surgical treatment of esophageal diverticula. With this purpose is confirmed the importance of careful and systematic preoperative study of esophageal pressure. In this way the etiologic role of functional disorders is cleared and a correct surgical treatment, particularly as regards the indication of extramucosal esophagomyotomy, can be performed. Nevertheless the diverticulectomy, performed alone or combined with myotomy, still maintains its role in the treatment of large-size diverticular pouches.


[Preoperative renutrition in patients with esophageal stenosis].

50 patients suffering from dysphagia and oesophageal stenosis were treated in the period 1975-77. Of these 31 had renutrition of longer than two weeks and are the subject of the present study. Three nutrition systems were employed: 1) total parenteral feeding (7 patients), 2) feeding by naso-gastric tube or gastric fistula (15 patients), 3) feeding per os with semiliquid foods (9 patients). The patients were suffering from benign cicatricial stenosis (5), tumours of the cardia (7), tumours of the oesophagus (19). Short-term survival, weight behaviour and the course of certain blood parameters (Hb, GR, cholesterol, albumin, total proteins) are reported. --in benign cicatricial stenosis and tumours of the cardia, a normal protein-caloric amount (2000-3500 KCal., 80-120 g/24 h of proteins) is sufficient to obtain weight increase and stabilization of blood examinations. The administration route is unimportant; --in malignant stenosis, 4000-6000 KCal. and 100-130 g of protein/24 h must be provided to obtain the same result. In patients treated with total parenteral nutrition the weight loss persists. The reason for this behaviour is not known; it is likely that enzymatic blocks exist in substrate utilization; --further study is needed to improve results obtained and to clarify the reasons for such behaviour.


Chlamydia trachomatis cervicitis in gynecologic outpatients.

Symptoms suggestive of a lower genital tract infection (LGTI) are common complaints in women who consult gynecologists. Sexually transmitted microorganisms, such as Chlamydia trachomatis. Neisseria gonorrhoeae, and Trichomonas vaginalis, are responsible for a substantial proportion of LGTI. This study was performed to establish the frequency of LGTI caused by C trachomatis in women attending a gynecologic outpatient clinic. Of 170 women with LGTI, 32.9% harbored one or more of these organisms: C trachomatis was found in 19.3%, N gonorrhoeae in 4.7%, and T vaginalis in 25.9%. The results of the isolation studies were correlated with clinical signs and symptoms. In women under 25 years of age, chlamydial cervicitis was found significantly more often in users of oral contraceptives than in nonusers. In women not taking such drugs, cervical erosion was found more often in Chlamydia-positive than  Chlamydia-negative women. Since clinical examination failed to reveal any characteristic signs in cases of chlamydial infection, it was not possible to distinguish a chlamydial from a gonococcal infection. This study also reports the successful treatment of 15 women affected by chlamydial cervicitis with doxycycline or trimethoprim sulphamethoxazole.


Intraoperative radiation of the paraaortic nodes in cancer of the uterine cervix.

Intraoperative electron beam irradiation is being used for the therapeutic and prophylactic treatment of the paraaortic nodes in cancer of the uterine cervix. A Varian 18 meV accelerator is employed at an electron energy setting of 6--18 meV. Special aluminum and lucite collimators allow visualization of treatment area and keep the uninvolved small bowel out of the treatment beam. A one-time dose of 2000 rads is delivered in 4 minutes. The procedure presents no special surgical problems, is well tolerated, and appears as a promising supplement in cases where abdominal exploration for surgical staging of cervical carcinoma is carried out.


Pituitary and ovarian function in women with congenitally absent uterus.

Pituitary-ovarian function was studied in 2 women with congenital absence of the uterus and the vagina. Daily serum levels of luteinizing hormone (LH), follicle stimulating hormone (FSH), prolactin, estradiol-17beta, and progesterone were measured by radioimmunoassay for 1 month. Gonadotropins and ovarian steroids showed normal cyclic variations in both patients. Prolactin was persistently elevated in one of them, who also demonstrated 2 abnormally high testosterone values among 6 determinations. The pituitary gland was stimulated by intravenous leasing hormone (LRH-TRY). Gonadotropin and prolactin responses to LRH-TRH were normal. The lifelong absence of the uterus does not alter the function of the pituitary-ovarian axis. The relation of hyperprolactinemia to this syndrome must be ascertained in a greater number of patients.


[Artificial gastrointestinal tract in gastrointestinal neoplasms].

From 1970 to 1977 an artificial gut was used in 1350 patients suffering from gastrointestinal cancer. This type of prolonged intestinal assistance was recognized to be an important adjuvant in anticancer therapy with indications prior to, during and following the traditional course of treatment. Prolonged intestinal assistance makes it possible to reestablish or maintain a biological and clinical status in patients who must undergo aggressive anticancer therapy. The indications for its use are multiplying. In 54% of the cases parenteral nutrition is associated with therapy of the curative type and this percentage is continuously increasing.


Alcohol and hamster buccal pouch carcinogenesis.

Alcohol was shown to enhance the carcinogenic effect of DMBA applied to hamster buccal pouch. DMBA animals given alcohol developed dysplastic leukoplakic lesions and epidermoid carcinomas 2 weeks ahead of water-drinking control animals. The tumors also grew to larger size, were more invasive, and were more anaplastic histologically. Forty young adult Syrian hamsters were divided into four groups (alcohol-DMBA, DMBA control, untreated control, and alcohol control) and were killed after 10, 12, and 14 weeks of DMBA applications three times weekly. Alcohol was given as a 10 percent solution instead of drinking water.


Short-term tissue reactions to enclosed glutaraldehyde-fixed tissue.

Polyethylene tubes closed at both ends and with four perforations in the sidewalls were filled with glutaraldehyde-fixed isologous tissue and implanted subcutaneously in rats. The cell reaction during the first 12 days in the tissues adjacent to the tubes was histologically examined. The reaction was compared to the reaction around tubes implanted empty. The examination showed a severe inflammatory reaction with probably immunologic aspects in the tissues adjacent to the filled tubes. The reaction around the empty tubes was slight and transient.


Cancellous bone marrow grafts in irradiated dog and monkey mandibles.

A pilot study was conducted to investigate the osteogenic potential of autogenous cancellous marrow grafts placed in irradiated tissue. Five dogs and three monkeys received either 4,100 or 6,520 rads of cobalt-60 irradiation during a 5- or 8-week period. Postirradiation discontinuity mandibular defects were created surgically and restored with autogenous cancellous bone marrow grafts held in position by a titanium mesh basket. Bony union occurred in all the mandibles. Intraoral ulceration was common in the dogs, and extraoral wound dehiscence was found in the monkeys. Hematopoietic marrow was present in the graft sites of both species 6 months to 1 year after surgery.


Glanzmann's thrombasthenia. Report of two oral surgical cases using a new microfibrillar collagen preparation and EACA for hemostasis.

Glanzmann's thromboasthenia is a rare congenital platelet disorder characterized by a prolonged bleeding time, a qualitative platelet defect, and severe hemorrhagic episodes. Patients with this disorder have been managed by administration of blood and blood components (most recently, platelet-rich plasma and platelet concentrates) to control hemorrhage resulting from trauma or surgical procedures. The two case reports presented here illustrate the use of a local hemostatic agent (microfibrillar bovine collagen, Avitene) and a systemic fibrinolytic inhibitor (epsilon aminocaproic acid, Amicar) to control postoperative hemorrhage secondary to elective extraction of teeth. The clinical results demonstrate excellent postoperative hemostasis and support recent in vitro observation of platelet adherence to the collagen preparation. This provides an alternate therapeutic modality in the management of patients with Glanzmann's disease and possibly other disorders of platelet function.


Blurred vision: problems of auditing elective surgery, as seen in an audit of lens extraction for cataract.

Failure to limit the topic can complicate the audit process by producing too many variations and data not relevant to all patients in the study. Because assessment of the need for lens extraction is subjective, formulating justification criteria is difficult; objective evidence that the patient actually needed the surgery may be lacking. Outpatient records showing the results of surgery, ie, whether a patient's vision has been improved, are usually not available to the audit committee. Consequently, the patient's true outcome after surgery cannot be properly evaluated unless specific follow-up criteria are developed and outpatient records are available to the audit committee. An ideal audit of lens extraction for cataract might combine outpatient records noting results of preoperative workup, the hospital chart, and the clinic record of postoperative care and results. Only with all pertinent information can a complete assessment of the quality of care be made. Because audits rely heavily on the use of data from inpatient records, other methodologies may be more appropriate for review of elective procedures. Audit committees should consider this possibility and beware.


Sight on social work: the social worker's involvement with the patient undergoing cataract surgery.

A commintment to the concept of total patient care requires consideration of the social and emotional, as well as the physical, problems of the patient. Assessing the quality of the social work service--including adequate attention to problem evaluation, social treatment, and outcome--can help to assure that patients will return to as high a level of social functioning as possible.


Six flaws revealed: how to make your audit/MCE studies more meaningful.

A study that lacks a definite design lacks direction and is defeated before it starts. Careful study design, however, is not the only indication of a successful audit. Approaching variation analysis in a positive rather than punitive manner enhances the committee's ability to recognize important findings and discover imaginative uses for audit data. When problems in care are revealed through evaluation activities, the committee must make recommendations that are appropriate to the causes of the problem and that can be readily implemented. An audit committee that discharges these responsibilities will produce a study that should surely yield informative data. The committee's ultimate goal--improved patient care--can not be far behind.


Our surgical approach towards the treatment of urethrocele and urethral fistula.

A new technique, described in the text, has been elaborated inspired by that of Monseur (1968) for urethral techniques. It has been performed with success in three paraplegics and in one incomplete tetraparesis. The plastic reconstruction of the diseased part of the urethra after excision of the stenosis and a fistula or diverticula by rotation and fixation to the subcavernal groove creates, in fact, an enlarged neo-urethra rendering the recurrence of the primary lesion practically impossible. This technique, first applied to spinal cord injuries, has been extended with permanent success to other lesions, such as tuberculosis stenosis and malformations.


The para-articular ossifications in our paraplegics and tetraplegics: a survey of 704 patients.

The X-ray examination of 704 spinal cord injured patients have showed that in 20 per cent of the cases para-articular ossifications were present most frequently in the hips. They were less frequently found in non-traumatic and incomplete cases. No other clear relationship was found.


Rickets as a complication of intravenous hyperalimentation in infants.

Fifteen newborn infants developed roentgenographic evidence of rickets while on long-term intravenous hyperalimentation. In each instance, the initial diagnosis of rickets was suggested on the chest roentgenogram, where characteristic cupped and frayed upper humeral metaphyses were noted; subsequent knee and wrist roentgenograms substantiated these findings. Factors which may have predisposed to the development of rickets include inadequate doses of vitamin D, prematurity and a rapid change in body weight during hyperalimentation therapy.


Spondylo-epiphyseal dysplasia with ocular changes: report of two "new" variants in two different families.

Two families with "new" types of spondyloepiphyseal dysplasias are reported. The disease(s) are characterised by spinal changes, capital femoral epiphyseal involvement and minor changes in the first family and shortening of the hands and feet in the second.


Phasic registration of venous diameter changes in-situ with the induction angiometer.

The method of induction angiometry has been used for observation of active and passive venous vasomotion, without surgical exposure of the blood vessel. The diameter sensor is a resilient loop introduced into the vasculature through a fine No. 5 French (1 mm i.d.) angiographic catheter or a needle of comparable internal diameter. An extracorporeal a. c. magnet induces an electromotive force (e.m.f.) in the loop which acts as the secondary of a transformer, the electromagnet being the primary. Pulsations in the blood vessel diameter vary the loop area and with it the induced e.m.f. thus providing a linear measure of relative changes in vascular diameter. Changes in the order of 2 micra in a venous diameter of 5 mm can be resolved in-situ. Examples are given of registration of phasic venous diameter changes at the frequencies of the heart beat, respiration and Mayer waves. Pharmacological tests illustrate the ability to detect venous vasomotion in response to a dose below 0.1 microgram/kg of nitroglycerin in dogs.


The flow resistance of the spiral artery and the related intervillous space in the rhesus monkey placenta.

Uteroplacental arteries of 4 rhesus monkeys were cannulated at their myometrical portions and perfused with dextran solutions and blood. Pressure-flow curves were obtained for the spiral artery and the related intervillous space, i.e. for the functional cotyledonary unit of the haemochorial villous placenta. For a flow of 3 ml.min-1, which is probably the normal rate of flow through the spiral artery, the pressure at the entry of the spiral artery was found to be 13--18 mm Hg (1.7--2.4kPa) during uterine relaxation (uterine diastole). There was a direct proportional relationship between the spiral artery flow and the pressure difference between the spiral artery and the amniotic fluid; the pressure difference per flow (the resistance of the cotyledonary unit) was found to be 1--3 mm Hg . ml-1 . min (8--24kPa . ml-1 . s). It is concluded that the spiral artery and the related intervillous space do not offer a limiting resistance to maternal blood flow in the absence of uterine contractions.


[Zinc in digestive diseases (author's transl)].

The present review is concerned by the main features of zinc metabolism (requirements, intestinal absorption, tissue distribution, excretion). The relationships between zinc variations and gut pathology are discussed with respect to the following points: criteria for the diagnostic of zinc deficiency, pathophysiological mechanisms, clinical consequences, therapeutic implications. Evidence for zinc malabsorption is present in Acrodermatitis enteropathica and in chronic zinc deficiency observed in Middle-East. During last decade zinc deficiency has been frequently reported in total parenteral feeding. Alterations in plasma zinc concentrations have been described in coeliac disease and inflammatory bowel disease but a true deficiency remains to be established in this pathological states.


[The value of potassium phosphate supplements in the treatment of diabetic ketoacidosis. Effects upon 2.3-diphosphoglycerate and tissue oxygenation (author's transl)].

Amongst 8 diabetics with severe ketoacidosis and treated identically, 4 received intravenous supplements of potassium phosphate (25 mmol PO4/I) for 24 hours. This resulted in blood 2.3-diphosphoglycerate and in vivo P50 levels which were invariably higher than in the control subjects and a fall in lactate/pyruvate ratio. These results reflect improved tissue oxygenation.


Hematologic toxicity of drugs used in cardiovascular disease.

Many diuretic, antiarrhythmic, and antihypertensive drugs have potential hematologic toxicity. Any patient with cardiovascular disease receiving long-term drug therapy or massive doses of a drug should be watched carefully for early detection of hemolysis, thrombocytopenia, neutropenia, or other toxic effects.


Mutations altering the cellular localization of the phage lambda receptor, an Escherichia coli outer membrane protein.

Two mutant strains of Escherichia coli have been isolated in which the cellular location of an outer membrane protein, the phage lambda receptor (the lamB gene product), is altered. These mutations were initially selected in a strain containing a lamB-lacZ fusion. In the parent strain the protein coded for by the hybrid gene is located, at least in part, in the outer membrane. In the mutants it is located in the cytoplasm. The mutations responsible for the alteration of cellular location lie very early in the lamB gene, in a region corresponding to the NH2-terminus of the lambda receptor protein. One of these mutations is a small deletion internal to the lamB gene. When this mutation is present in an otherwise wild-type lamB gene, the protein produced is of lower molecular weight than normal receptor. The other mutation behaves as a point mutation; when it is present in an otherwise normal lamB gene, reversion can be demonstrated. The molecular weight of this mutant protein, which is located in the cytoplasm, is larger than that of the wild-type gene product by approximately 2000. It is suggested that these two mutations are in the portion of the lamB gene coding for a signal sequence and thereby block export of the protein.


Dose-dependent preferential binding of polycyclic aromatic hydrocarbons to reiterated DNA of murine skin cells in culture.

The distribution of active metabolites of polycyclic aromatic hydrocarbons bound to reiterated or unique regions of murine DNA has been studied by a DNA-DNA renaturation technique. Murine skin cells were exposed to different doses of radioactive polycyclic aromatic hydrocarbons for 24 hr; then the hydrocarbon-labeled DNA was isolated, fragmented, and denatured. Renaturation kinetics and thermal stabilities of DNA-DNA duplexes were studied. At high carcinogen doses, polycyclic aromatic hydrocarbon adducts seem to be distributed equally among the DNA of all reiteration frequencies. At low carcinogen doses, however, a dose-dependent preferential binding to reiterated DNA sequences occurs. An inverse linear relationship appears to exist between the enrichment of hydrocarbon adducts in reiterated DNA sequences and the logarithm of the amount of total hydrocarbon bound to DNA.


Isolation and characterization of ColE1-derived plasmid copy-number mutant.

The plasmid pBGP120 is a ColE1 derivative that contains elements of the Escherichia coli lac operon and the Tn3 transposon. We have selected and isolated a copy-number mutant of pBGP120. In exponentially growing cultures, the copy-number mutant, pOP1, represents approximately 30% of total intracellular DNA compared to about 5% for pBGP120. Plasmid-encoded beta-galactosidase monomer can represent 50% of newly synthesized protein in cells carrying pOP1. pOP1 is structurally unstable in certain genetic backgrounds and under certain growth conditions, breaking down to a smaller sized plasmid that retains the DNA overproducer phenotype and the Tn3 transposon. The smaller overproducer plasmid, pOP1delta6, is generated by a continuous deletion of sequences located between one end of the Tn3 transposon and a site about 630 nucleotides from the EcoRI site in the beta-galactosidase structural gene of pOP1. pOP1delta6 retains the ColE1 origin of replication but has lost the lac promotor and operator and most of the beta-galactosidase structural gene. pOP1delta6 exists at approximately 210 copies per chromosome in exponentially growing cells.


A gene adjacent to satellite DNA in Drosophila melanogaster.

Several copies of a sequence adjacent to 1.688 g/cm3 satellite DNA in the Drosophila melanogaster genome have been isolated by molecular cloning. This sequence, called the Dm142 gene, is homologous to a 1.6-kilobase RNA found in both D. melanogaster embryos and tissue culture cells. One cloned DNA segment includes two copies of the Dm142 gene and 1.688 g/cm3 satellite DNA sequences, which are located between and flanking both gene copies. The Dm142 gene is repeated many times in the D. melanogaster genome, and some copies are not flanked by 1,688 g/cm3 satellite DNA.


Interaction of secreted nascent chains with surrounding membrane in Bacillus subtilis.

To determine the length of secreted nascent polypeptide chain that is surrounded by membrane, we digested labeled nascent chains protruding from protoplasts of Bacillus subtilis with Pronase and isolated the residual ribosome-attached chains from the membrane-polysome fraction. Gel chromatography revealed a sharp major peak that had been protected by membrane plus bound ribosomes. The ribosomes themselves protected half as great a length. Because no free chain between the ribosome and the membrane was detected by Pronase treatment, the difference between the two protected lengths should measure the length protected by the membrane. More accurate measurements of these lengths, obtained by dansylation of the exposed NH2 terminus of the isolated fragments, yielded a difference of 21 amino acids. This value corresponds to an extended chain of 75 A, which is approximately the thickness of the bacterial cell membrane. We earlier presented evidence that bacterial ribosomes are attached to membrane solely by their secreted chain. The present results further show that after loss of the extracellular segment of the chain its attachment persists, at 37 degrees as well as 0 degrees C. These findings suggest that the chain does not slip through a passive membrane but is actively held within a channel.


Chicken ovalbumin is synthesized and secreted by Escherichia coli.

By recombinant DNA methods, the chicken ovalbumin structural gene has been fused to Escherichia coli lac transcriptional and translational control regions. When a plasmid containing the hybrid gene was introduced into E. coli, a protein identified as ovalbumin by immunoreactivity and sodium dodecyl sulfate/polyacrylamide gel electrophoresis was synthesized. The chicken ovalbumin made in bacteria was full length (43,000 daltons) and constituted 1.5% of the cellular protein. In addition, the microbially synthesized ovalbumin was secreted through the cell membrane into the periplasmic space of E. coli. The ability of the E. coli secretory apparatus to recognize chicken ovalbumin, which is normally synthesized and secreted in hen oviducts, suggests that common features exist in the secretion-recognition mechanisms found in these two organisms. The bacterial synthesis of significant amounts of chicken ovalbumin demonstrates that the E. coli cellular machinery may be utilized to synthesize a higher eukaryotic protein which is relatively stable in the bacterial intracellular environment.


Thiostrepton-resistant mutants exhibit relaxed synthesis of RNA.

Spontaneous mutants of Bacillus subtilis resistant to thiostrepton (TSP) exhibit relaxed synthesis of RNA when starved for required amino acids. Intact cells of tsp mutants cannot synthesize the regulatory nucleotides, ppGpp and pppGpp, after amino acid deprivation. Because ribosomes isolated from spontaneous revertants to thiostrepton sensitivity and from wild-type stringent strains can synthesize (p)ppGpp whereas ribosomes isolated from tsp strains cannot synthesize these regulatory nucleotides in the presence of stringent factor, it appears that the lesion is expressed at the level of the ribosome. Genetic mapping, via three-factor transformational crosses, has shown that tsp is closely linked to rif, in the order cysA14, tsp, rif-I, strA. The phenotype of the tsp mutants indicates that they are of the relC type. Their map position indicates that they are different from a previously described B subtilis rel mutation. Ribosomes from the latter strain can synthesize (p)ppGpp in cell-free extracts.


Variable and constant regions are separated in the 10-kbase transcription unit coding for immunoglobulin kappa light chains.

UV transcription mapping with recombinant DNA probes containing immunoglobulin kappa light chain mRNA sequences has been used to determine the size of the transcription unit coding for kappa light chain m RNA and to establish the arrangement of variable and constant regions in this transcription unit. In relation to ribosomal RNA standards, the transcription of kappa light chain constant region sequences into nuclear RNA exhibits a UV target size of 9.6 kbases (kb). The kappa light chain variable region exhibits a UV target size of 7.6 kb indicating that it is separated by approximately 2.0 kb from the constant region in the kappa light chain transcription unit. The size of the primary transcript (i.e., the direct, unprocessed RNA product of transcription) predicted from the constant region target size concurs with our previous pulse-labeling results which showed that the largest presumptive nuclear RNA precursor to kappa light chain mRNA is approximately 10 kb. In addition, the UV target size of cytoplasmic kappa mRNA is indistinguishable from the target size of constant region sequences in nuclear RNA. These results suggest that the kappa light chain transcription unit is copied directly into a 10-kb nuclear RNA precursor in which the kappa variable and constant regions are separated by approximately 2 kb. Accordingly, it is proposed that the joining of immunoglobulin kappa light chain variable and constant regions occurs in the post-transcriptional processing of this large nuclear RNA precursor into kappa light chain mRNA.


beta-Galactosidase is induced by hormone in Drosophila melanogaster cell cultures.

Drosophila melanogaster cell lines Kc and Ca and clones FC and RF6, cultured in vitro, have no detectable beta-galactosidase (beta-galactoside galactohydrolase, EC 3.2.1.23) activity (as measured by hydrolysis of o-nitrophenyl-beta-D-galoctoside). Ecdysterone, a hormonal steroid of critical importance in insect physiology, clearly induces beta-galactosidase activity in D. melanogaster cells cultured in vitro. Induction occurs in cell lines or clones known to be sensitive to ecdysterone (K, Ca, and Fc) and does not occur in clones known to be resistant to the hormone (RF6). Some properties of the hormone-induced beta-galactosidase activity were studied. The Km for o-nitrophenyl galactoside is 0.35 mM and the Ki for lactose is 12 mM (similar to those of Escherichia coli beta-galactosidase); the activity can be recovered after sodium dodecyl sulfate treatment; the enzyme is a tetramer (Mr of the monomer is 64,000).


Mechanism of dexamethasone inhibition of plasminogen activator in rat hepatoma cells.

Glucocorticoids rapidly and completely inhibit intracellular plasminogen activator activity in rat hepatoma cells, as assayed by the solubilization of 125I-labeled fibrin. Experiments in which extracts of dexamethasone-treated cells are mixed with extracts of control cells demonstrate an inhibitor of protease activity. Plasminogen activator is found primarily in the particulate fraction of cell lysates, whereas the inhibitor is localized in the soluble fraction. Variant cells have been isolated previously that are fully resistant to the dexamethoasone inhibition of plasminogen activator activity. These variants have no demonstrable inhibitor activity, whereas plasminogen activator in these cells is fully sensitive to inhibitor from wild-type cells. Thus, the basis for hormone resistance appears to be the failure of dexamethasone to induce an inhibitor.


Unusual resistance to ionizing radiation of the viruses of kuru, Creutzfeldt-Jakob disease, and scrapie.

The titers of several preparations of kuru. Creutzfeldt-Jacob disease, and scrapie viruses were reduced by only 1/10th or less by high doses of gamma radiation of 50 kGy and by only 1/10th-1/1000th or less for 200 kGy. This unusual radiation resistance of the two human viruses further links them with the scrapie virus and suggests that the genetic information of all three viruses is considerably smaller than that of any other known viruses of mammals.


Self-administration of an enkephalin analog by rhesus monkey.

Intravenous injections of a synthetic enkephalin analog, FK-33-824 were found to maintain operant responding under second-order schedule control (FR 4[VR 16:S]) in five, morphine-dependent rhesus monkeys. All monkeys self-administered enkephalin in amounts equivalent to morphine at comparable doses per injection. Each of five doses of enkephalin (0.5, 0.25, 0.125, 0.05 and 0.01 mg/kg/inj) were substituted for morphine during 10 consecutive sessions over a 56 hr period. No monkey developed opiate withdrawal signs during enkephalin substitution except at the lowest enkephalin dose (0.01 mg/kg/inj). Although the number of enkephalin injections self-administered increased as the dose per injection progressively decreased, there was a significant linear decrease (p less than 0.05) in mg/kg/enkephalin per session at doses of 0.25 mg/kg/inj and below. Reductions in morphine dose per injection, over a range of 0.5 to 0.125 mg/kg/inj produced comparable increases in number of injections per session, but no significant changes in morphine intake. The number of food pellets earned on a second order FR 4 (VR 16:S) schedule decreased during enkephalin substitution. These decreases were significant at the highest doses of enkephalin (0.5 to 0.125 mg/kg/inj). These data attest to the reinforcing characteristics of an enkephalin analog in rhesus monkey and suggest that natural polypeptides may contribute to the reinforcing properties of opiate drugs.


Cocaine reinforced progressive ratio performance in the rhesus monkey.

A series of experiments were conducted to determine the effectiveness of a progressive ratio (PR) procedure in measuring the relative reinforcing efficacy of several intravenous doses of cocaine. In Experiment 1, utilizing much smaller increases in the ratio requirement than previously reported, the animals generally displayed increases in breaking point with increases in the cocaine unit dose up to 0.4 mg/kg/inj. The highest dose studied (0.8 mg/kg/inj.) engendered breaking points lower than the 0.4 mg/kg dose but higher than the remaining lower doses. Experiment 2 was conducted utilizing the same reinforcement schedule as in Experiment 1 but with liquid Tang as the reward. The results demonstrated that this procedure would function to discriminate reinforcing strength with a more traditional reward. Experiment 3 examined a more expedient procedure to see if results similar to those seen in Experiment 1 could be obtained in a shorter period of time. However, the shorter procedure engendered excessive intrasubject variability, suggesting that some intermediate level of baseline experience between the 5-7 days used in Experiment 1 and the 50 reinforced responses used in Experiment 3 would be necessary to obtain consistent breaking point-unit dose functions.


Behavioral effects of D-Ala2-beta-endorphin in squirrel monkeys.

The effects of D-Ala2-beta-endorphin administered either intravenously (IV) or intracisternally (IC) in squirrel monkeys were tested using a number of behavioral measures: general activity, eating, social behavior, aggression/distress, analgesia, and startle/escape. There were 10 groups (N = 5) consisting of 4 dose levels administered IC (0.4, 40, 400 microgram/kg) and 6 dose levels injected IV (0, 4, 40, 80, 400, 800 microgram/kg). Every monkey was tested with all tasks on each of 5 identical repeated trials, one pre-injection baseline trial and 4 post-injection trials. After IC administration, the 2 largest doses exerted toxic effects, which were partially reversed with naloxone, producing in 2 cases muscular rigidity and profound sedation. The smaller 4 microgram/kg dose produced significant decreases in activity over trials but increased reactivity to noxious stimulation after the initial post-injection trial. With IV injection reliable changes in activity and approach to food were found. The results demonstrate significant behavioral effects of an endorphin analog in the squirrel monkeys after both central and peripheral injection.


A method for measurement of platelet regeneration in man.

Platelet suspensions obtained at different time intervals following a single dose of oral aspirin were incubated with [1-(14)C]-arachidonic acid and the amount of [1-(14)C]thromboxane B2 formed was determined by a double isotope technique. Since aspirin is an irreversible inhibitor of platelet cyclooxygenase and since circulating platelets do not synthesize cyclooxygenase the rate of reappearance of active cyclooxygenase determined in this way was a measure of the rate of regeneration of functioning platelets. In two subjects the regeneration half-times were 4.2 and 4.8 days.


[An economical modification of radial immunodiffusion for the determination of immunoglobulins in the cerebrospinal fluid].

In a total of fifty cerebrospinal fluids, such immunoglobulins as IgG, IgA, and IgM were quantitatively determined in a parallel manner on LC partigen plates and on slides (SEVAC set of means of testing). The comparability of the two methods of test proved excellent with good precision. The sensitivity of IgA determination on slides was made higher, the measurability of all precipitates was improved, and the economic advantage increased by cutting the cost of one determination fifteen times.


Stimulus properties of thyrotropin-releasing hormone.

Male Sprague-Dawley rats were trained in a two-lever operant discrimination task using 20 mg/kg thyrotropin-releasing hormone (TRH) and saline as cues. Following completion of 40 daily training sessions, 22 of 25 subjects demonstrated a high level of discriminative responding based on the TRH and saline cues. An evaluation of the time course of TRH indicated that the stimulus properties peak between 5 and 15 min and dissipate substantially by 55--65 min. During additional testing, rats showed dose-dependent generalization between the training treatments (20 mg/kg TRH and saline) and novel doses of TRH (1, 5, 10, and 40 MG/KG). However, animals failed to show generalization between the training drug (20 mg/kg TRH) and d-amphetamine sulfate (0.8, 1.6, or 2.4 mg/kg); likewise, animals trained to discriminate d-amphetamine (0.8 or 1.6 mg/kg) from saline failed to show generalization between d-amphetamine and TRH (10, 20, OR 30 MG/KG). Microgram quanitites of TRH (2.5--25 microgram administered into either the lateral or third ventricle elicited dose-dependent generalization to the training drug (TRH 20 mg/kg, i.p.), suggesting a CNS mechanism of action for this effect of TRH.


Behavioural effects of amphetamine in a small primate: relative potencies of the d- and l-isomers.

Acute administration of d-amphetamine (up to 8 mg/kg) or l-amphetamine (up to 12 mg/kg) in the marmoset results in a dose-dependent increase in small head movements (checking), an almost total suppression of activities including eating, grooming, playing, and social interaction, but little change in the amount of movement. Severe stereotypy is seen at high doses of both isomers. The d-isomer has approximately twice the potency of the l-isomer in increasing checking behaviour.


A putative multipartite model of haloperidol interaction in apomorphine-disturbed behavior of the dog.

The interaction between various doses of apomorphine and haloperidol on intracranial self-stimulation in the dog was studied using a pradigm in which reinforcing brain-stimulation was controlled by a discriminative auditory stimulus. Reinforced lever-pressing was decreased by low doses of apomorphine and completely suppressed by stereotypogenic doses. At various doses of apomorphine, low doses of haloperidol either increased response inhibition by enhancing stereotypy, or increased lever pressing by reducing stereotypy while concomitantly increasing the number of nonreinforced responses. Intermediate to relatively high doses of haloperidol antagonized stereotypy and the response inhibition produced by apomorphine. High doses of haloperidol antagonized stereotypy but also suppressed self-stimulation. Thus, haloperidol is not only able to restore performance capability, but also disturbed reinforcing and discriminative stimulus control.


Lithium prevention of amphetamine-induced 'manic' excitement and of reserpine-induced 'depression' in mice: possible role of 2-phenylethylamine.

Repeated treatment of mice with lithium chloride (45 mg/kg, i.p., daily for 8 days) reduced the jumping, fighting, stereotypies, and hyperactivity induced by d-amphetamine (5 mg/kg, i.p.). Lithium also reduced the hypoactivity observed 1--3 h after reserpine (0.75 mg/kg, i.p.). In biochemical studies we found that 8-day treatment with lithium markedly reduced (to 45% of control) the recovery from brain of labelled 2-phenylethylamine (PEA) following i.p. injection of labelled  L-phenylalanine, while decreasing recovery from brain of labelled PEA following its i.p. injection of 63% of control. In saline-treated mice, d-amphetamine appeared to increase PEA synthesis and to accelerate its disposition, whereas reserpine enhanced PEA synthesis and reduced disposition; all of these effects were antagonized by lithium pretreatments. Since PEA appears to be one of the most powerful behavioral stimulants among endogenous neuroamines, and because its deaminated metabolites are behavioral depressants, such antagonism of brain PEA metabolism may significantly contribute to the prophylactic action of lithium against both manic and depressive behavior.


The effect of antidepressant drugs on plasma kynurenine in depressed patients.

The concentration of kynurenine in plasma from depressed patients and control subjects has been measured using a sensitive and specific method. The levels of kynurenine in the plasma of depressed patients and controls are not significantly different and are not influenced by age or sex. The severity of affective disturbance was not related to plasma kynurenine levels in depressed patients. Clinical outcome could not be accurately predicted by measurement of plasma kynurenine levels. Amitriptyline did not significantly increase plasma kynurenine concentration in vivo, whereas lithium and mianserin did have a significant effect. These results are discussed with reference to known abnormalities of tryptophan metabolism in depressive illness and in particular to the 5-hydroxytryptamine uptake characteristics of blood platelets in depressive patients.


Influence of polyphloretin phosphate on the central effects of prostaglandin E2 and F2alpha in rats.

The possibility that polyphloretin phosphate (PPP) antagonizes the central effects elicited by prostaglandin (PG) E2 and F2alpha was investigated. PPP was administered i.c.v. to male Wistar rats (10 or 25 microgram) 10 or 30 min before i.c.v. injection of PGF2 or PGF2alpha (1 or 10 microgram). The duration of several component of behavior, the degree of irritability, and the rectal temperature of rats were measured; the levels of noradrenaline, dopamine, 5-hydroxytryptamine, and 5-hydroxyindoleacetic acid were measured spectrophoto-fluorometrically in discrete brain areas. PPP antagonized temperature and behaviroal changes induced in rats by PGF2alpha, but not those induced by PGE2. The magnitude of antagonism depended on the dose of PPP and on the time of the pretreatment before PGF2alpha administration. Changes in the level of biogenic amines in discrete brain areas evoked by PGs were not affected by PPP. We found that PPP antagonizes the central effects of PGF2alpha but not those of PGE2, and that changes of biogenic amines in discrete brain areas elicited by PGs are not specific.


Involvement of norepinephrine in startle arousal after acute and chronic d-amphetamine administration.

Treatment with d-amphetamine produced a dose-dependent increase in startle amplitude in response to a buzzer. This increase appeared to be a reflection of a sensitization effect, i.e., enhanced responsivity as a function of repeated stimulus presentations. Treatment with alpha-methyl-p-tyrosine, which reduced whole brain concentrations of dopamine (DA) and norepinephrine (NE), or treatment with FLA-63, which reduced only NE, antagonized the effects of d-amphetamine on the startle reflex, suggesting a role of NE in this behavior. Startle amplitude was also reduced following chronic d-amphetamine treatment. The effect of d-amphetamine on startle was found to be independent of changes in drug-induced locomotor excitation. The data of the present investigation, together with earlier reports, suggests that tolerance occurs to those behaviors that involve a noradrenergic component.