A history of nitrous oxide and oxygen anaesthesia. IVC: Henry Hill Hickman in his time.

Previous verdicts on Hickman set the scene. The genealogy of Hickman and his wife is explored, disclosing the identities of "Poor Mrs  Dudley of Shut End" and "Thomas Dudley of Kingswinford". Some previous evidence is explained by the bankruptcy of Hickman's father-in-law. The dubious means whereby Hickman qualified prematurely are examined.


Immunohistochemistry of local immunoglobulin production in nasopharyngeal carcinoma.

Immunohistochemical investigations by the immunoperoxidase method have been carried out on sections of biopsy specimens obtained from the primary tumour sites of patients with nasopharyngeal carcinoma (NPC). It was found that, in many of the sections thus examined, there was an accumulation of plasma cells, particularly of the IgA type, in the connective tissues surrounding nests of NPC cells. Similar accumulation of plasma cells in the subepithelial connective tissues was likewise observed in a case of choanal polyp. Plasma cells were rarely observed in the section of a biopsy specimen of non-neoplastic oropharyngeal mucosa. These results indicated that the nasopharynx may be a site for the local production of IgA, but the antigenic specificity of these molecules is, however, not known. The possibility that the nasopharynx is a site for the local production of antibodies to the Epstein-Barr virus (EBV)-related antigens was discussed.


Salbutamol by pressure-packed aerosol and by intermittent positive pressure ventilation in chronic obstructive bronchitis.

The forced expiratory volume in one second (FEV1) response to salbutamol administered by pressure-packed aerosol 200 microgram, and intermittent positive pressure ventilation (IPPV), 5 and 10 mg, was determined in 60 patients with chronic bronchitis with airway obstruction. The bronchodilator response to salbutamol by IPPV was greater than by pressure-packed aerosol only in patients with severe airways obstruction and little additional benefit was gained with the 10 mg dose.


Maturation linked expression of a myeloid cell surface antigen.

An antiserum raised against myelomonocytic and monocytic leukaemia cells has been used to define a cell surface antigen shared by normal and leukaemic cells of the granulocyte and monocyte cell lines. The quantitative expression of this antigen was investigated using the Fluorescence Activated Cell Sorter and was shown to correlate with the degree of morphological maturation.


A controlled trial of puncture sites for amniocentesis.

A controlled trial to determine a better site for amniocentesis was carried out over a 6-month period, involving 98 obstetric patients. The suprapubic and nuchal puncture site for amniocentesis were compared. The failure rate was found to be lower when the suprapublic site was used, and no significant difference in morbidity was found in the two groups.


A randomized controlled trial of a short course of cephaloridine in the prevention of infection after abdominal hysterectomy.

One hundred patients took part in a randomized controlled trial to test the efficacy of three 1 g doses of cephaloridine in preventing infection after abdominal hysterectomy. The first dose was given as an intravenous bolus at the commencement of surgery and the second and third as intramuscular injections 6 and 12 hours later. Given in this way, cephaloridine was found to be very effective in preventing febrile morbidity, abdominal wound infection and urinary tract infection. It was less effective in preventing pelvic wound infection and postoperative colonization of the vagina with Escherichia coli.


The importance of measuring contrast sensitivity in cases of visual disturbance.

A description is given of a practical clinical test of contrast sensitivity and of the results obtained on a normal population. An account is given of recent physiological work which illustrates the potential usefulness of the method in ophthalmology, and the clinical results obtained by the author and others are summarised.


HLA antigens in ocular cicatricial pemphigoid.

HLA antigen frequencies were studied in 20 patients with ocular cicatricial pemphigoid and 245 normal persons. HLA-B12 demonstrated an increased frequency of 45% in patients with ocular cicatricial pemphigoid which was statistically significant when compared to a frequency of 19.6% in the general population (P less than 0.02). In patients with ocular cicatricial pemphigoid the prevalance of HLA-A3 was increased to 35% when compared to 22.9% in the general population, but this was not statistically significant. The frequency of finding either HLA-A3 or B12 in patients with ocular cicatricial pemphigoid was increased to 75% in comparison with 38.8% in the general population (P less than 0.005). The present study suggests that HLA-B12 and possibly HLA-A3 are genetic markers for ocular cicatricial pemphigoid.


Structural changes of ribosome by the action of ethylene glycol.

The denaturation of ribosome and RNA by ethylene glycol (EG) has been studied in an attempt to further understand the conformation and stability of the ribosome. At high concentrations of EG, the ribosome, its subunits, and 16S RNA undergo drastic structural changes as shown by circular dichroism, ultraviolet absorption spectroscopy, and sedimentation velocity. Two separate conformational transitions were observed for the 30S subunit; one from 30 to 50% EG and another from 60 to 90% EG. This observation suggests the presence of two "domains" in the 30S subunit which differ in their stability. However, the 50S subunit undergoes a single sharp transition at 60 to 90% EG, consistent with the notion of a highly cooperative conformation. Association of the subunits stablizes part of the 30S subunit since the transition curve for the 70S ribosome does not exhibit significant change at the low EG concentration region as seen for the 30S subunit. Removal of proteins from the 30S subunit broadens the transition curve to lower EG concentrations and suggests the role of proteins in stabilizing the conformation of the 16S RNA.


Length dependence in reassociation kinetics of radioactive tracer DNA.

The reassociation kinetics have been measured for radioactive Escherichia coli DNAs (tracers) of various average single-strand lengths reassociated alone and in the presence of excess unlabeled DNA (driver) of two different average lengths. Hydroxylapatite binding was used to follow the reaction time course. The length-dependence of the rate constant determined in the tracer self-reassociation reactions is in agreement with the square-root dependence previously determined (Wetmur, J. G., & Davisond, N. (1968) J. Mol. Biol. 31, 349-370) using optical methods to follow the time course. However, for the driver-tracer reactions, where the radioactive DNA reassociates largely with DNA of a different average length, the dependence of the rate constant upon average tracer length is increased and approaches an L to the first  power dependence. In 0.18 M Na+, the variation of the rate constant for tracer reassociation with the lengths of the reassociating strands has been shown to fit the simple equation k = (9.0077).(L T 0.55 + 1/L D 0.55), where k is the observed rate constant in L mol-1 s-1 and L(T)and L(D) are the weight average tracer and driver lengths, respectively, in nucleotides. This dependence suggests that the rate of nucleation of two free strands is proportional to the sum of the reciprocals of the hydrodynamic radii of the two strands.


Lanthanide fluorescence studies of transfer RNAf(met) conformation.

The possible difference in conformation between aminoacylated and deacylated tRNA is examined using the optical and photochemical properties of the 4-thiouridine residue of E coli tRNAf(Met). No differences were seen between fMet-tRNAf(Met) and tRNAf(Met) observing the native fluorescence of 4-thiouridine, energy transfer from 4-thiouridine to the bound lanthanide ions, Tb3+ or Eu3+, or the rates of the photochemical cross-linking reaction of 4-thiourdine. While these results do not necessarily mean that there is no conformational difference between the aminoacylated and deacylated species, they do restrict the possible nature and magnitude of any conformational difference between the two species. In addition, preliminary thermal denaturation studies of tRNAf(Met), monitoring 4-thiouridine emission and energy transfer to Tb3+, indicate an unexplained melting phenomenon near 25 degrees C in the presence of Mg2+.


Chorismate mutase-prephenate dehydratase from Escherichia coli: active sites of a bifunctional enzyme.

The relationship between the active sites of the bifunctional enzyme chorismate mutase-prephenate dehydratase has been examined. Steady-state kinetic investigations of the reactions with chorismate or prephenate as substrate and studies of the overall conversion of chorismate to phenylpyruvate indicate that there are two distinct active sites. One site is responsible for the mutase activity and the other for the dehydratase activity. Studies of the overall reaction using radioactive chorismate show that prephenate, which is formed from chorismate, dissociates from the mutase site and equilibrates with the bulk medium before combining at the dehydratase site. No evidence was obtained for direct channeling of prephenate from one site to the other, or for any strong interaction between the sites.


Microviscosity changes during differentiation of neuroblastoma cells.

Microviscosity (eta) of the plasma-membrane lipid matrix was measured in exponentially growing and differentiating C1300 mouse neuroblastoma cells, attached to a glass substratum, by fluorescence polarisation of 1,6-diphenyl-1,3,5-hexatriene. Upon differentiation eta decreases progressively, reaching values below those observed in the growth phase. Treatment of the cells with dipalmitoyl phosphatidylcholine vesicles reversibly inhibits morphological differentiation. The results show that a high membrane fluidity is a prerequisite for differentiation.


The role of interoception in learned visceral control.

Research concerned with the psychology and physiology of interoceptive processes is reviewed with the purpose of evaluating theoretical formulations of learned visceral control. Basic animal research in interoception provides relevant information; however, much research dealing directly with interoception and learned control is inadequate due either to inappropriate measurement of interoceptive ability or to poor experimental design. The two primary theoretical orientations linking interoception and learned visceral control differ according to the role ascribed to external feedback; the first views feedback as an enhancement of interoceptive cues, the second as an enhancement of exteroceptive cues. These theories are discussed with regard to recent investigations of learned visceral control.


Cardiac perception and cardiac control. A review.

The evidence regarding specific cardiac perception and discrimination, and its relationship to voluntary cardiac control, is critically reviewed. Studies are considered in three sections, depending on the method used to assess cardiac perception: questionnaire assessment, discrimination procedures, and heartbeat tracking. The heartbeat tracking procedure would appear to suffer least from interpretative difficulties. Recommendations are made regarding the style of analysis used to assess heartbeat perception in such tracking tasks.


The effect of transcendental meditation on right hemispheric functioning.

This study reports two experiments investigating the effects of transcendental meditation on right hemispheric functioning. The task used in both experiments was the Seashore Tonal Memory Test. In the first experiment a non-meditator group and an experienced meditator group were run. The design involved three periods: a pretest, a meditation or rest period, and then a posttest. The results showed the experienced meditators were significantly better in both pretest and posttest performance. There were no pretest-posttest differences. The second experiment was done to replicate the first experiment and to control for possible selection bias. The design was the same as the first experiment, except that an additional group of inexperienced meditators was included. The results again showed significantly superior performance for the experienced meditators compared to the non-meditators. In addition, the experienced meditators were superior to the inexperienced meditators. There were no significant differences between the non-meditators and the inexperienced meditators. These results support the hypothesis that meditation facilitates right hemispheric functioning. Alternative explanations, such as selection bias, are also discussed.


[Topography of rRNA in ribosomes. Effect of pancreatic RNAse on small ribosomal subunits].

The treatment of E. coli 30S ribosome subunits with pancreatic RNase under certain conditions resulted in the release of rRNA (about 15%). The subunit retained as a whole structure: sedimentation coefficient was unchanged and no protein release was observed. The released RNA is a set of oligonucleotides from 1 to 9 bases, except hepta- and octanenucleotides. Base composition of this RNA fraction is similar to 16S RNA, a slight increase of purines content being due to the specificity of nuclease. Analysis of isoplit content has revealed that a spliting of long oligonucleotides in stechiometric amount from 30S subunits takes place: one nonanucleotide, one hexanucleotide and two pentanucleotides.


[Effects of non-ionogenic surface active compounds on yeast protoplasts].

The lytic effect of non-ionogenic surface active compounds (SAC), based on polyoxyethylated fatty acids and alkylphenols on the yeast protoplast cytoplasmic membranes and the extracting ability of the SAC with respect to intracellular proteins of intact yeast cells, were studied. It was shown that the lytic activity of the SAC under study depends on the overall effect of the size of their hydrophobic and hydrophylic fragments rather than on the level of the hydrophylic-lypolytic equilibrium of SAC. The absence of correlation between the lytic activity and the extracting ability of SAC is accounted for by the differences in the mechanisms of membrane degradation under the action of SAC on the protoplasts and intact cells. The data obtained support the previously made assumption that the correlation between the size of SAC mycelles and that of the cell wall pores is the limiting factor of the SAC induced protein extraction from the intact cells.


The rotorfermentor. II. Application to ethanol fermentation.

The kinetics of microbial growth and product formation are described as applied to the high cell concentration scheme of the rotorfermentor. A bench scale pilot plant was designed and built in order to demonstrate the operational feasibility of the rotorfermentor. The fermentation of glucose to ethanol by Saccharomyces cerevisiae ATCC 4126 was used. When the rotorfermentor was used with a glucose feed concentration of 104 g/liter almost 100% glucose utilization was obtained and the ethanol productivity rate was 27.3 g ethanol/liter hr which was found to be about 10 times greater than the ethanol productivity obtained from an ordinary continuous stirred tank (CST) fermentor. The ethanol experimental results obtained from the rotorfermentor and an ordinary CST fermentor were used as a basis to assess the economic feasibility of the rotorfermentor. The economics of an industrial scale ordinary CST fermentor with and without cell recycle is compared with a rotorfermentor unit for the same ethanol production throughput. For the process conditions considered in this case, calculations showed that the rotorfermentor may replace both a CST fermentor and cell centrifuge resulting in lower capital equipment costs and lower power consumption requirements.


Effect of thiol reagents on extractability of protein from yeast.

The effect of soluble thiol reagents on the extractability of protein from yeast cells was studied. The incubation of yeast cells with dithiothreitol, 2-mercaptoethanol, or monothioglycerol markedly stimulated the release of soluble carbohydrates into the medium. There was a concomitant improvement (over twofold) in the extractability of protein from the yeast cells. The thiol reagents activated the proteolytic enzymes of the yeast cells. Unless inactivated, these enzymes hydrolyze the extracted protein.


Visualization of tubulin in lymphocytes. I. Comparison of normal and chronic lymphocytic leukemia (CLL) lymphocytes.

Cell structures containing tubulin were studied in peripheral blood lymphocytes from 8 normal donors and 11 patients with CLL using specific antitubulin antibodies revealed by immunoperoxidase assay. The centriole and microtubules were clearly visible in both groups. A "nucleus-associated tubulin-containing structure" was revealed by antitubulin antibodies and was found in virtually all lymphocytes of normal subjects but in a considerably lower number of CLL lymphocytes. The nature of this structure and its relationship to other cell structures are discussed.


Cimetidine for recurrent ulcer after vagotomy or gastrectomy: a randomised controlled trial.

In a randomised controlled trial cimetidine 1 g daily for six weeks was compared with placebo in the treatment of recurrent ulcers after gastrectomy or vagotomy for duodenal ulcer. Healing, assessed endoscopically, was seen in seven out of 12 patients given cimetidine and in five out of 12 controls. Four of the controls whose ulcers did not heal were subsequently treated with cimetidine, and in two the ulcers healed after six weeks. Pain recorded by the patient and consumption of alkalis were each slightly but not significantly less in the cimetidine-treated patients. When cimetidine is to be used for recurrent ulceration probably the dosage and duration of treatment should be increased.


Beta-blockers: once or three times a day?

In a double-blind, crossover trial 16 hypertensive patients were treated, in random order, with placebo, metoprolol 300 mg in a single daily dose, or metoprolol 300 mg/day in three doses. Both therapeutic regimens produced detectable plasma metoprolol concentrations and appreciable beta-blockade, estimated from exercise tachycardia, throughout the day. Fluctuations throughout the day in plasma drug concentrations and degree of beta-blockade were insignificant on the thrice-daily regimen, but they varied considerably on the single-dose regimen. Both therapeutic regimens also significantly lowered blood pressure throughout the day. Although the thrice-daily regimen again tended to produce a stronger and less fluctuating hypotensive action, the differences in hypotensive effect between the two regimens were not statistically significant. A single-dose of 300 mg of metoprolol can therefore be recommended if the only aim is to reduce blood pressure but not if a steady degree of beta-blockade is needed.


Bromocriptine in Parkinsonism.

A review of the effects of using bromocriptine in Parkinson's disease showed that it rarely helps patients not primarily improved by levodopa. Patients who show late failure with levadopa and whose response to treatment is declining are helped by combining the two drugs. High cost and severe psychosis are the main disadvantages of bromocriptine, and, although it is not recommended for patients who are doing well on levodopa, it is the best available drug for hospital use in patients who show late failure with levodopa.


Phagocytosis and killing of bacteria and yeast by human milk cells after opsonisation in aqueous phase of milk.

Macrophages and neutrophils from human milk phagocytose and kill Staphylococcus aureus and Escherichia coli in vitro after opsonisation by the aqueous phase of milk as effectively as blood leucocytes in serum. They also phagocytose Candida albicans. The overgrowth of E coli resulting from the addition of iron to cultures of the organism in the aqueous phase of milk is not influenced by the presence of cells. We conclude that the phagocytosis and killing of bacteria by milk cells may contribute to the lower incidence of infection among breast-fed than artificially fed babies.


Organization of corticospinal neurons in the cat.

The cells of origin of the corticospinal tract of the cat were identified using the retrograde horseradish peroxidase (HRP) labeling technique. Cortical neurons labeled from the spinal cord were confined to layer V and included large Betz cells, as well as many smaller neurons of this layer. Collections of 5-10 labeled neurons concentrated in areas of 300-500 micrometer diameter were observed, suggesting a columnar-type of organization of corticospinal neurons. Injections of HRP into different spinal segments were used to determine the somatotopic distribution of corticospinal neurons. Cortical neurons projecting to the cervical spinal enlargement were found in the lateral hemisphere, with more caudal spinal levels being represented successively more medial. There appeared to be little, if any, overlap in the distributions of neurons labeled from the cervical versus the lumbosacral spinal cord. Neurons projecting to the spinal enlargements were most abundant in the primary area 4, motor cortex (MI), but substantial populations of neurons were located in each of the subfields, areas 3a, 3b, 1 and 2, of the primary somatic sensory cortex (SI), plus area 2 pre-insularis of the second somatic sensory region (SII), and area 5 of the suprasylvian gyrus. This suggested, in view of the differences in inputs and response properties of neurons in these cortical regions, that the corticospinal projections from the different areas could represent multiple, independent functions in spinal cord sensory and motor control. The soma diameters of HRP-labeled corticospinal neurons varied widely, with a distinct, large-celled (Betz-type) and a small-celled population being present in the area 4 motor cortex. The largest labeled neurons of the somatic sensory cortical areas were intermediate in size. Three types of corticospinal neurons may exist, corresponding to the giant pyramidal (Betz) cells, the largest pyramidal neurons of the somatic sensory regions, and the abundant, smaller pyramidal cells which are found throughout the sensory and motor cortical fields.


The central location of the motor neurons to the stapedius muscle in the cat.

In two cats and 10 newborn kittens, retrograde transport of horseradish peroxidase was used to locate the motor neurons of the stapedius muscle. Following injection of tracer into the muscle, labeled neurons were observed in the interface between the facial nerve nucleus and the caudal end of the lateral superior olivary nucleus. Some marked neurons were also located dorsal and ventral to the facial nucleus. The number of labelled cells varied from a low of 34 to a high of 199.


Immunohistochemical localization of choline acetyltransferase in rabbit spinal cord and cerebellum.

Guinea pig antiserum specific for purified bovine choline acetyltransferase has been shown to cross-react with rabbit enzyme. We used the peroxidase-antiperoxidase immunohistochemical method to demonstrate the localization of choline acetyltransferase in formalin-fixed and paraffin-embedded sections of rabbit spinal cord and cerebellum. In the spinal cord, in agreement with our and others' previous results using immunofluorescent techniques, choline acetyltransferase was found in the cell bodies of the ventral horn motor neurons. In the cerebellum, choline acetyltransferase was localized exclusively in the mossy fibers and the glomeruli of the cerebellar folia. The immunohistochemical findings in the cerebellum reveal the morphological detail of cholinergic axons and their terminals. The results are consistent with published biochemical data on the cerebellar distribution of choline acetyltransferase.


An epizootic of Salmonella typhimurium var. copenhagen in broilers and the use of cultured chicken interestinal flora for its control.

1. An epizootic caused by Salmonella typhimurium var. copenhagen and occurring on the farms of one company was examined with the following factors in mind: the spread of the epizootic, the infection rate of the flocks and the role of the food, hatchery and parent stock. 2. A microbiological technique was used the aim of preventing infection on the farms. 3. The method of control was not as effective the field as in the laboratory; the possible reasons for this are discussed.


DNA-sequence organization in the genome of the domestic chicken (Gallus domesticus).

The sequence organization in the DNA of chicken (Gallus domesticus) was studied using hydroxyapatite-monitored reassociation kinetics. DNA 320-nucleotides long reassociates as though it is composed of three components, i.e., a very rapidly reacting fold-back fraction, a component composed of sequences repeated an average of 640 times in the genome, and a large unique fraction representing about 80% of the genome. The sizes of the fold back and repeated components increase only moderately with large increases in fragment size, indicating that these sequences are not extensively interspersed in the genome. Even at a fragment size of 4500 nucleotides, the unique component represents 68% of the DNA. Thus, the chicken genome is not organized in the short-period (Xenopus) interspersion pattern described for a large number of other organisms; rather, the DNA-sequence organization of this vertebrate bears more resemblance to the long-period interspersion pattern of Drosophila.


Effects of intraluminal glucose on intestinal secretion induced by heat stable and heat labile Escherichia coli enterotoxin, cholera toxin and theophylline.

Glucose, l-alanine, l-aspartate, l-methionine and glycine enhanced net fluid and electrolyte absorption in acute isolated loops of the proximal jejunum of weanling swine. The effect of glucose on intestinal secretion induced by heat stable and heat labile Escherichia coli entero-toxin, cholera toxin and theophylline was examined in both the proximal and distal jejunum of weanling swine. In the proximal jejunum glucose enhanced the rate of net fluid and electrolyte absorption. This increase was accompanied by an increase in unidirectional dosium absorption. In loops exposed to either heat stable or heat labile enterotoxins, glucose significantly decreased the rate of net fluid and electrolyte secretion. The magnitude of glucose enhancement in loops exposed to heat stable and heat labile enterotoxins was similar to adjacent control loops. However, glucose enhancement did not occur in loops exposed previously to cholera toxin or concurrently to theophylline. Therefore, cholera toxin and theophylline may inhibit substrate dependent sodium absorption in the proximal jejunum. In the distal jejunum glucose enhancement did occur but the rate of enhancement was less than in the proximal jejunum. In this region glucose enhancement was not evident in loops exposed to either theophylline, heat stable, heat labile or cholera toxin.


Prediction of graft fate from cytopathology of recipient button.

We wished to know whether the fate of human corneal grafts could be predicted from the cytological study of recipient's corneal buttons removed at operation. We counted the number of different inflammatory cells in 168 full-thickness corneal buttons, and related the findings to the operative results retrospectively. If inflammatory cells, particularly polymorphonuclear cells are present in significant numbers in the corneal button the chance of a successful graft is reduced by about 20 per cent (P less than 0.05).


Acetate metabolism in Escherichia coli.

Levels of several intermediary metabolites were measured in cells grown in acetate medium in order to test the hypothesis that the glyoxylate cycle is repressed by phosphoenolpyruvate (PEP). Wild-type cells had less PEP than either isocitrate dehydrogenase - deficient cells (which had greater isocitrate lyase activity than the wild type) or isocitrate dehydrogenase - deficient, citrate synthase-deficient cells (which are poorly inducible). Thus induction of the glyoxylate cycle is more complicated than a simple function of PEP concentration. No correlation between enzyme activity and the level of oxaloacetate, pyruvate, or citrate was found either. Citrate was synthesized in citrate synthase-deficient mutants, possibly via citrate lyase.


Sequential cold-sensitive mutations in Aspergillus fumigatus.

Mutants of thermotolerant fungus Aspergillus fumigatus I-21 (ATCC 32722) unable to grow at 37 degrees C were sought. Cold-sensitive mutants were enriched from progeny spores of gamma-irradiated conidia by two or more incubations at various nonpermissive temperatures alternating with filtrations through chessecloth. The approximate minimum, optimum, and maximum growth temperatures of the parent were 12, 40, and 50 degrees C, respectively. Mutants unable to grow at 37 degrees C were not successfully isolated directly from the wild type. A mutant unable to grow at 25 degrees C was isolated and mutations further increasing the cold sensitivity by increments of 3-5 degrees C were found to occur. Mutants completely unable to grow at 37 degrees C were obtained by five sequential mutations. All mutants grew as fast as the wild-type parent at 45 degrees C and higher. Each mutant produced revertants able to grow not only at the nonpermissive temperature used for its isolation but also at lower temperatures.


Chromosomal mutants of Saccharomyces cerevisiae affecting the cell wall binding site for killer factor.

Fifty-two killer, factor-resistant, nuclear mutants were isolated from sensitive strains of yeast and assorted into three functional groups. All but one mutant owed their resistance to an alteration in the cell wall binding site for killer. In several mutant strains, an alteration at the site of killer binding was associated with a change in the susceptibility of the cell wall to degradation by glusulase. The killer-binding site could be inactivated by periodate but not by pronase treatment. The nature of the site is discussed.


Lipid composition of Escherichia coli in relation to resistance to penicillin.

Clinical isolates of Escherichia coli sensitive and resistant to penicillin were compared in lipid composition and 14C-labelled penicillin uptake, as possible factors in resistance. Except for a slight increase in the triglyceride fraction in sensitive strains there were no qualitative or quantitative differences in the classes of extractable lipids present. Gas-liquid chromatography of the phospholipid and triglyceride fatty acids of the polar and non-polar fatty acids of the bound lipids showed that the same kinds of fatty acids were present. There was an increase of myristate in the chloroform-methanol extractable lipids of highly resistant strains accompanied by a rather general decrease of other fatty acids. Gas-chromatographic analysis  of the polar-bound lipids showed an increase of the beta-hydroxydecanoic acid in the resistant strains. By studying the uptake of 14C-labelled benzylpenicillin and the crypticity of the beta-lactamase, evidence has been produced that a decreased permeability of resistant strains to penicillin cooperates with beta-lactamase to induce a high level of resistance. The altered lipid metabolism may reflect the special architectural changes in the cell wall which cause decreased permeability.


Detection of Salmonella enterotoxin using rabbit ileal loops.

The presence of an enterotoxin produced by Salmonella in broth culture has been demonstrated by using the rabbit ileal loop model. Response by the animal to enterotoxin in sterile culture supernatant fluids is enhanced when the intestinal lumen is washed with a mucolytic agent prior to the administration of toxin. Fluid secretion is untreated intestinal loops was also observed if enterotoxin was administered with a live, invasive Salmonella strain which did not evoke a secretory response. A limited survey of Salmonella isolated for clinical and food sources indicated the common occurrence of enterotoxin production, and stock cultures maintained the ability to produce the toxin. The host-adapted species which were tested varied in their ability to produce enterotoxin.


Free proline content and sensitivity to desiccation and heat during yeast sporulation and spore germination.

Ascospores of a strain of Saccharomyces cerevisiae Hansen were less sensitive to desiccation and heat than vegetative cells. Desiccation resistance was acquired earlier during sporulation and lost later during spore germination than heat resistance. As spores matured, resistance to both stresses increased. With the exception of the first few hours in sporulation medium, when proline appeared to be utilized, the intracellular free proline content increased during sporulation and decreased during spore germination. Not all the proline lost could be detected in the germination medium, indicating that some was metabolically utilized by the germinating spores. Since exogenous proline supplied to vegetative or sporulating cells before desiccation increased their survival, it is suggested that the high level of free proline in mature spores may protect against desiccation stress.


Regulation of cytoplasmic calcium: interactions between prostaglandins, prostacyclin, thromboxane A2, zinc, copper and taurine.

The regulation of cytoplasmic calcium is a key process in nerve tissue. Using a smooth muscle model we have shown that prostaglandin (PG) E2 probably regulates entry from extracellular fluid, whereas the release from intracellular stores depends on the interplay between thromboxane (TX) A2, PGEI and prostacyclin. Hormones and other agents interact with this system in the following ways: vasopressin, angiotensin and inositol mobilize arachidonic acid from membrane phospholipids and increase synthesis of PGE2 and TXA2, cortisol blocks this action. Prolactin and zinc mobilize dihomo-gamma-linolenic acid and increase synthesis of PGEI. These effects can be blocked by cortisol, lithium and taurine, three agents which on their own have no effect on basal PG production. Epileptogenic agents like penicillin and picrotoxin also stimulate PG synthesis, while diphenylhydantoin is a PG antagonist and diazepam is a TXA2 antagonist. The effects of all these agents occur at concentrations which are physiological in the case of the natural ones, and readily attained in human plasma in the case of the drgus. In view of recent evidence that calcium may be important in demyelination and considering the established role it plays in nerve conduction and synaptic transmission, we suggest that these observations may be of significance in understanding Friedreich's ataxia.


Abdominal aortic aneurysms: recent experience with 210 patients.

In the 6 1/2 years ending June 1977, 210 patients with abdominal aortic aneurysms underwent operation at Toronto Western Hospital; 160 aneurysms (76%) were unruptured and 50 (24%) were ruptured. In the patients with unruptured aneurysms the mean age was 68 years; the oldest was 91, and 12 were more than 80 years of age. The overall hospital mortality was 5.6%. Death in hospital occurred in 1 (1.2%) of the 83 asymptomatic patients, 4 (7.4%) of the 54 symptomatic patients and 4 (17.0%) of the 23 patients for whom operation was considered urgent. In the patients with ruptured aneurysms the mean age was 71 years; the oldest was 90, and five were more than 80 years of age. The overall hospital mortality was 54%. The morbidity and mortality were analysed; in particular the reasons for the markedly variable hazard of operations for the three categories of unruptured aneurysm were sought. The surgical literature is confusing because of the interchanging use of the words unruptured, elective and symptomless. The current philosophy management and technique of operation in a large cardiovascular surgery service with many trainees are presented and a plea is made for a standardized and simplified operation, always performed with three assistants helping the operating surgeon.


Grain dust and the lungs.

Grain dust is composed of a large number of materials, including various types of grain and their disintegration products, silica, fungi, insects and mites. The clinical syndromes described in relation to exposure to grain dust are chronic bronchitis, grain dust asthma, extrinsic allergic alveolitis, grain fever and silo-filler's lung. Rhinitis and conjunctivitis are also common in grain workers. While the concentration and the quality of dust influence the frequency and the type of clinical syndrome in grain workers, host factors are also important. Of the latter, smoking is the most important factor influencing the frequency of chronic bronchitis. The role of atopy and of bronchial hyperreactivity in grain dust asthma has yet to be assessed. Several well designed studies are currently being carried out in North America not only to delineate the frequency of the respiratory abnormalities, the pathogenetic mechanisms and the host factors, but also to establish a meaningful threshold limit concentration for grain dust.


Essential hypertension and pregnancy.

Approximately 1% of pregnancies are complicated by essential hypertension. During pregnancy the blood pressure often stabilizes or improves. In patients with sustained hypertension, prospective controlled studies have demonstrated enhanced fetal survival when the blood pressure was controlled with antihypertensive medication. Such medication must be chosen carefully to avoid fetal and mateerial toxicity, and diuretics and salt restriction during pregnancy should be avoided. Among patients with essential hypertension the problem accelerates late in pregnancy in 2% to 11%; the acceleration may be predicted by determination of maternal mean arterial pressures and intravascular volumes early in pregnancy. The treatment of accelerated hypertension is identical to that of severe pre-eclampsia. Fetal loss is considerable but can be lessened by careful fetal and maternal monitoring and early controlled delivery. The risks of pregnancy in most patients with essential hypertension are small, and essential hypertension is not a uniform contraindication to pregnancy.


A randomized comparative trial of adriamycin versus methotrexate in combination drug therapy.

A prospective randomized trial was conducted comparing the clinical response of 78 previously untreated patients with advanced metastatic breast cancer to a combination of cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) or to a combination of cyclophosphamide, adriamycin, and 5-fluorouracil (CAF). Sixty-two percent of the patients receiving CMF responded to treatment compared to an 82% response rate for the patients receiving CAF. Although within acceptable limits, hematologic and GI toxicity was greater with CAF. There was no significant difference in the duration of response to the two regimens. Therefore, the therapeutic difference between the two therapies is a higher initial response rate to the adriamycin containing regimen.


Comparison of methyl-CCNU and CCNU in patients with advanced forms of Hodgkin's disease, lymphosarcoma nad reticulum cell sarcoma.

In May 1972, the Cancer and Leukemia Group B initiated a randomized study comparing the effectiveness of CCNU and methyl-CCNU in patients with advanced malignant lymphomas, including Hodgkin's disease (HD), lymphosarcoma (LYS) and reticulum cell sarcoma (RCS). A single dose of 100 mg/m2 of CCNU or 150 mg/m2 of methyl-CCNU was given orally every 6 weeks. In patients with leukopenia or thrombocytopenia, due to prior treatment, this dose was reduced to 70 mg/m2 of CCNU and 100 gm/m2 of methyl-CCNU. Of 109 evaluable patients, 60 received CCNU and 49 received methyl-CCNU. Response rates (complete and partial) to CCNU and methyl-CCNU were respectively 42% (14/33) and 15% (3/20) in HD, 21% (3/14) and 21% (3/14) in LYS, 15% (2/13) and 27% (4/15) in RCS. Responses to methyl-CCNU, but not to CCNU, were seen only in patients who developed significant hematologic toxicity. Responses to both drugs were generally of short duration due to the advanced stage of the disease. Renal, hepatic or neurological toxicity was not observed. In conclusion, CCNU proved to be superior to methyl-CCNU for the treatment of advanced HD. CCNU was also observed to be of higher activity in Hodgkin's than in non-Hodgkin's lymphomas.


A quantitative approach to determining disease response during therapy using multiple biologic markers: application to carcinoma of the breast.

This analytical study was undertaken in an effort to develop a model for a quantitative approach to the evaluation of multiple biological marker levels in blood and urine as a means for determining tumor changes during treatment of patients with malignant disease. The potential biologic markers measured in patients with carcinoma of the breast consist of three urinary polyamines (putrescine, spermidine and spermine), three urinary nucleosides (pseudouridine, N2, N2-dimethylguanosine and 1-methylinosine), and plasma carcinoembryonic antigen (CEA). The distribution patterns of the seven markers measured pretreatment and five weeks after initiating therapy were examined by grouping the patients into the three categories of progression, stable, or regression based on their clinical response to treatment. In addition to the individual marker measurements, the pretreatment and posttreatment values of the ratios of the polyamine levels (spermine/putrescine, spermine/spermidine, and spermidine/putrescine) and the nucleoside levels (N2, N2-dimethylguanosine/pseudouridine, 1-methylinosine/pseudouridine, and 1-methylinosine/N2, N2-dimethylguanosine) were also evaluated. In the pretreatment measurements, CEA levels were elevated for 76% of the patients and the three nucleosides were elevated for 36% of the patients and the three nucleosides were elevated for 36% to 37% of the patients. Urinary spermidine and spermine levels were abnormal for 27% and 24%, respectively, while putrescine levels were elevated for 7% of the patients. When all 14 marker measurements and the 12 ratios of these measurements were considered, the multiple regression equation evaluated the treatment results with a multiple correlation coefficient (R = 0.891; P less than 0.100) about 2.4 times higher than with the most sensitive single marker variable, N2, N2-dimethylguanosine/pseudouridine (R = 0.377; P less than 0.05), alone. Stepwise regression analysis revealed that the minimum number of multiple marker measurements and their ratios required to achieve the maximum value of the multiple correlation coefficient (R = 0.653; p = 0.010) was fifteen. These include the pre and posttreatment measurements of CEA, spermine, N2, N2-dimethylguanosine and 1-methylinosine, as well as two ratios of the polyamines and three ratios of the nucleosides in the post-treatment of the polyamines and three ratios of the nucleosides in the post-treatment measurements. These data suggest that the utilization of regression analysis to evaluate the monitoring utility of multiple marker measurements may be of clinical value.


Demonstration of the prostatic origin of metastases: an immunohistochemical method for formalin-fixed embedded tissue.

An indirect immunohistochemical technique is described for identification of the prostatic origin of metastases in formalin fixed, paraffin or paraplast embedded material. A rabbit antiserum against the prostate specific acid phosphatase isoenzyme was developed. The method is applicable with or without previous decalcification. In 30 cases of prostatic carcinoma there was only one negative result, and in 20 cases of metastases from prostatic carcinoma positive results were obtained in every instance. All carcinomas (primary focus or metastasis) of non prostatic origin (55) stained negatively with the developed antiserum. The application and possible limitations of the method are discussed.


Cytology and colchicine sensitivity of viable cells from lymph nodes with malignant lymphoma.

Viable cell suspensions were prepared from 31 nodes diagnosed non-Hodgkin's malignant lymphoma, and from 30 non-malignant nodes. The cells were examined and counted by phase contrast microscopy. The suspensions were characterized by the percentage of large cells and by a colchicine-sensitivity index. The finding of more than 6% large cells or the finding of a sensitivity index of more than 30% was considered a positive test for a malignant lymphoma. According to these criteria there were 2 false positives in 30 reactive nodes and one false negative in 31 malignant nodes. Findings on 3 nodes diagnosed angioimmunoblastic lymphadenopathy suggested malignancy. The colchicinesensitivity index of blood lymphocytes seemed useful for monitoring lymphoma patients for leukemic involvement.


Mesonephroid (clear cell) carcinoma of the ovary and endometrium: a comparative prospective clinico-pathological study and review of literature.

Seventeen cases of mesonephroid (clear cell) primary ovarian adenocarcinoma together with 6 cases of its analogous endometrial tumor have been studied over the decade ending 1976. Eleven of the ovarian tumors and all six of the endometrial tumors formed part of a personal consecutive series of 64 primary ovarian carcinomas and 114 primary endometrial carcinomas seen during the same period, these cases being studied prospectively. The remaining 6 ovarian tumors were studied retrospectively. Aims were to reexamine evidence for considering these tumors as distinct and homogenous groups; to reexamine evidence regarding their histogenesis; to investigate the concordance between the ovarian and endometrial tumor; and to reexamine clinical, pathological, therapeutic, and survival data relevant to these tumors. Full clinical, pathological, therapeutic, and survival details are recorded. It is suggested that present evidence indicates complete compatibility between the three major current views regarding histogenesis of the ovarian tumors; that in only a small proportion of cases is there histogenic coincidence between the ovarian and endometrial lesions; and that, pending further investigation, separation of the endometrial clear cell carcinomas from other nonclear endometrial carcinomas should be on a provisional basis only. Suggestions are made for further investigations into the prognostic aspects of these tumors.


Diffuse histiocytic lymphoma involving the gastrointestinal tract.

The results of staging and treatment of 18 patients with diffuse histiocytic lymphoma involving the gastrointestinal tract are summarized. Widespread disease (Stage IV) was found in the majority (72%) of patients after rigorous staging, indicating the relative rarity of localized gastrointestinal lymphoma and the resulting need for systemic therapy in most of these patients. Chemotherapy combined with surgical resection and/or radiation therapy produced complete remissions in only 5 of 18 patients (28%). Patients failed to achieve complete remission due to 1) tumor resistance to drug therapy (46% of treatment failures), and 2) massive intestinal hemorrhage or bowel perforation secondary to tumor necrosis (38% of treatment failures). These findings indicate the need for more active chemotherapeutic regimens and for measures aimed at preventing complications such as bowel perforation or hemorrhage, possibly by combining surgical resection of bowel lesions with systemic chemotherapy.


Non-Hodgkin's lymphoma in children.

Until recently the prognosis of childhood non-Hodgkin's lymphoma has been poor. A program of combination chemotherapy and involved area radiotherapy was instituted in the Department of Pediatrics at Roswell Park Memorial Institute in 1971. Thirty-one biopsy proven untreated children entered this study. There were 4 Stage I, 9 Stage II, 6 Stage III, and 12 Stage IV. Initial site of presentation was neck and mediastinum in 16, abdomen in 12, and other sites in three. Nineteen were lymphocytic, seven histiocytic, three undifferentiated, and one was mixed. None had well differentiated or nodular histology. Chemotherapy consisted of vincristine and steroid induction along with intrathecal methotrexate followed by a maintenance phase consisting of daily oral 6-mercaptopurine, weekly oral methotrexate and monthly pulses of vincristine, cyclophosphamide and steroid. Because of initially poor results in Stage IV disease, the protocol was altered midway and high dose methotrexate on three occasions following induction was added. Twelve of 13 Stage I and II patients remain disease free. Four of 6 Stage III patients and 4 of 12 Stage IV patients remain disease free. Only 1/7 of the Stage IV patients prior to high dose methotrexate is disease free, whereas, 3/5 patients with high dose methotrexate are disease free. In total, 19/30 (63%) are disease free for a period ranging from 15+ to 63+ months with 19 patients being disease free for over one year and 12 for over two years.


Mutagenicity of aclacinomycin A and daunomycin derivatives.

An antitumor antibiotic aclacinomycin A, was nonmutagenic in a Salmonella test, but its derivative, N-demethylaclacinomycin A, was mutagenic. Similarly, 1-deoxypyrromycin, a hydrolysis product of aclacinomycin A, was nonmutagenic, but N-demethyl-1-deoxypyrromycin was mutagenic. Daunomycin was highly mutagenic, but N-methyldaunomycin showed only weak mutagenicity, and N-dimethyldaunomycin was nonmutagenic. The aglycones of aclacinomycin A and daunomycin were not mutagenic. Thus, the amino moiety of anthracycline glycosides is concluded to be essential for mutagenesis.


Combined modality therapy for stage IIIMO non-oat cell bronchogenic carcinoma.

Thirty-nine patients with stage IIIMO non-cell bronchogenic carcinoma (NOBC) were treated with combined modality therapy: radiation therapy and chemotherapy with cyclophosphamide, adriamycin, methotrexate, and procarbazine. The median survival for all patients treated was 9.6 months compared to 6.4 months for historical controls (P = 0.015). Patients who responded to the treatment program had a significantly longer survival (median, 15.2 months) compared to nonresponders and historical controls (P less than 0.005). It is concluded that combined modality therapy is moderately effective therapy in stage IIIMO NOBC.


Oral cytembena absorption and phase I--II studies.

Cytembena is a nonmyelosuppressive drug that has received phase I--II trials in this country and is presently being used as a chemotherapeutic agent in Europe. Sterile abscesses at the site of im injection and "autonomic storm" after iv bolus represent the most frequent dose-limiting toxic effects, and intermittent schedules reflect reports of prolonged plasma levels of drug. This report of excellent oral absorption and a short half-life suggests that alternative routes and schedules of administration should be evaluated. The dose-limiting toxic effects observed after frequent oral administration were transient proteinuria and increased creatinine levels.


Phase II study of cis-dichlorodiammineplatinum(II) in advanced breast cancer.

Twenty-six patients with metastatic breast cancer received cis-dichlorodiammineplatinum(II) either as a single dose of 100 mg/m2 iv every 3--4 weeks or as a continuous 5-day infusion of 20 mg/m2/day at 4-week intervals. Fourteen patients were treated with the single-dose schedule and 12 patients were treated with the continuous 5-day infusion. No significant response was observed with either dose schedule. Aside from a reduction in the frequency and severity of gastrointestinal toxicity with the continuous 5-day infusion, no real difference was seen with regard to renal and hematologic toxicity with either dose schedule.


Intermittent high-dose cyclophosphamide chemotherapy for small cell carcinoma of the lung.

Twenty-three patients with small cell carcinoma of the lung (15 with limited disease and eight with extensive disease) were randomized into one of two induction schedules of high-dose cyclophosphamide (CY), 60 mg/kg iv, given either on Days 1 and 2 or on Days 1 and 8. Following the high-dose CY, patients were treated with a sequence of three monthly courses of COMB (CY, 800 mg/m2; vincristine [Oncovin], 1.4 mg/m2; methotrexate, 20 mg/m2; and BCNU, 60 mg/m2) alternating with high-dose CY. The overall response rate to the high-dose CY was 70% with 17% being complete responses (CRs). COMB produced no additional responses. There was no significant difference in response rate with either high-dose CY schedule. There was no unexpected morbidity associated with the intensive regiment despite marked myelosuppression. The high-dose CY administered on Days 1 and 8 appeared less toxic than that given on Days 1 and 2. Laboratory studies demonstrated that small cell carcinoma cells respond to drug-induced humoral stimulation in vitro; and that tumor proliferation in vivo temporally coincides with increased serum stimulatory activity. This study demonstrates that high-dose CY is a safe and effective induction therapy for small cell carcinoma of the lung although the low CR rate obtained is disappointing.


Phase I study of maytansine using a 3-day schedule.

Maytansine, a new ansa macrolide antitumor antibiotic, was administered to 60 patients as part of a phase I study. The doses given ranged from 0.01 (starting level) to 0.9 mg/m2 for 3 days. The toxic effects encountered consisted principally of nausea, vomiting, diarrhea, and occasionally, stomatitis and alopecia. Superficial phlebitis was also encountered and occurred when the drug was diluted in a volume of less than 250 ml. Myelosuppression occurred infrequently; it was almost regularly associated with abnormal liver function tests. Antitumor activity was detected in one patient each with melanoma, breast carcinoma; and head and neck clear cell carcinoma. Further studies are indicated with this compound since it has shown evidence of activity with little or no myelosuppression.


Initial clinical trials of maytansine, an antitumor plant alkaloid.

We have conducted a phase I clinical trial of maytansine, a plant alkaloid with potent tubulin-binding activity. For evaluation of toxicity, the schedule of drug administration consisted of a single iv infusion given every 3 weeks. Dose-limiting toxicity was observed at 2 mg/m2, and was manifested as profound weakness, diarrhea, nausea, and vomiting. Symptoms persisted for 3--14 days after drug administration. No consistent myelosuppression occurred at any dose level. Responses were observed in two patients (one each with non-Hodgkin's lymphoma and ovarian cancer) who were treated on the every-3-week schedule, as well as in two patients with acute lymphocytic leukemia treated with single weekly doses. Three of the four responding patients had received extensive prior treatment with vincristine, and two were clearly resistant to vincristine.


Maytansine: a phase I study of an ansa macrolide with antitumor activity.

Maytansine has significant antitumor activity in animal model systems. The initial clinical trial of maytansine was carried out in 38 adult solid tumor patients. Five daily bolus injections were repeated at 21-day intervals. A total of 78 courses were administered over a dose range of 0.1--0.8 mg/m2/day X 5 days. Gastrointestinal toxicity was dose-related and dose-limiting at doses of greater than or equal to 0.5 mg/m2. Dose-related neurotoxicity was also observed. No drug-related myelosuppression or change in serum creatinine level was seen. Hepatic toxicity was subclinical and reversible. Of 16 patients evaluable for response, two with breast cancer had therapeutic benefit. Phase II studies of maytansine are recommended at a starting dose of 2.0--2.5 mg/m2/course repeated at 21-day intervals.


Phase II study of metronidazole therapy for advanced colorectal carcinoma.

Thirty-two patients with advanced carcinoma of the colon or rectum were given metronidazole orally at a dose of 500-1000 mg/m2 three times a day for 7 consecutive days every 6 weeks. The dose-limiting toxic effects consisted of severe nausea, vomiting, and major motor seizures. Mild peripheral neurotoxic effects were also noted. No objective responses were noted in any of the 32 patients treated. High-dose metronidazole would not seem to have any role in the treatment of advanced colorectal carcinoma and may cause serious neurotoxicity.


Action of Pseudomonas isoamylase on various branched oligo and poly-saccharides.

Pseudomonas isoamylase (EC 3.2.1.68) hydrolyzes (1 linked to 6)-alpha-D-glucosidic linkages of amylopectin, glycogen, and various branched dextrins and oligosaccharides. The detailed structural requirements for the substrate are examined qualitatively and quantitatively in this paper, in comparison with the pullulanase of Klebsiella aerogenes. As with pullulanase, Ps. isoamylase is unable to cleave D-glucosyl stubs from branched saccharides. Ps. isoamylase differs from pullulanase in the following characteristics: (1) The favored substrates for Ps. isoamylase are higher-molecular-weight polysaccharides. Most of the branched oligosaccharides examined were hydrolyzed at a lower rate, 10% or less of the rate of hydrolysis of amylopectin. (2) Maltosyl branches are hydrolyzed off by Ps. isoamylase very slowly in comparison with maltotriosyl branches. (3) Ps. isoamylase requires a minimum of three D-glucose residues in the B- or C-chain.


Immunocytological evidence for oxytocin neurons in the human fetal hypothalamus.

The use of antibodies against oxytocin or neurophysin enabled the detection by immunocytochemistry of oxytocin-neurophysin neurons in the hypothalamus in the human fetus. The perikarya of these neurons are located in the paraventricular and supraoptic nuclei. Immunoreactive neurons occure in the median eminence. The neurophysin immunoreactive neurons were more numerous than the oxytocin immunoreactive neurons. The specificity of the immunocytological reaction was controlled. The first oxytocin-neurophysin neurons are seen as early as the 14th week of gestation.


Further immunofluorescence-microscopic evidence for myosin in various peripheral nerves.

An indirect immunofluorescence microscopic technique using antibodies from rabbits against highly purified myosin from chicken gizzard was applied to various peripheral nerves (cranial nerves V. VII, X). Myosin-specific immunoreactivity was found in the axoplasm, in Schwann cells, in the perineural sheath and in vascular walls.


LH-producing cells in the ovine pituitary. An electron microscopic immunocytochemical study.

An immunocytochemical technique using the peroxidase-antiperoxidase complex (PAP) was applied to identify and characterize the LH-secreting cells in the ovine pituitary at the ultrastructural level. These cells, round or oval in shape, possessing flattened cisternae of the rough endoplasmic reticulum, contain one class of secretory granules (mean diameter 250 nm) and large dense bodies (600 to 800 nm in diameter). LH molecules and the two subunits LHalpha and LHbeta were localized on the secretory granules and on the small granules near the Golgi complex. The large dense bodies, the cisternae of the endoplasmic reticulum and the saccules of the Golgi complex showed no reaction product.


Localization of pancreatic polypeptide (PP)-like immunoreactivity in the pancreatic islets of some teleost fishes.

Immunocytochemical staining has revealed that the pancreatic islets of various teleost fishes contain a pancreatic polypeptide (PP1-like substance which cross-reacts with antibodies to mammalian and avian PP. The PP cells were frequently found at the periphery of the islets, as in mammals, and were of irregular shape.


Glucose and lactate kinetics in guinea pigs following Escherichia coli endotoxin administration.

Glucose and lactate turnovers were evaluated during the early stages (first three hours) of endotoxin-induced shock in unanesthetized male guinea pigs following the intravenous (IV) administration of 0.1 mg of Escherichia coli endotoxin. Rate of appearance (Ra), rate of disappearance (Rd), and metabolic clearance rate (MCR) of glucose and lactate were determined by the primed-constant infusion of [6-(3)H]-glucose and NA L(+)[U-14C]-lactate. Arterial glucose concentration was moderately elevated, and the Ra and Rd of glucose were increased significantly following endotoxin administration, while the slight increase in MCR was not statistically significant. Arterial lactate concentration was markedly increased and the Ra and Rd of lactate were significantly elevated. The percentage of [14C]-glucose derived from [14C]-lactate increased from 19% (control) to above 50% following endotoxin. From these data we found no evidence of impaired peripheral extraction of glucose. The increased glucose Ra and the higher percentage of [14C]-glucose being derived from [14C]-lactate suggest increased gluconeogenesis during the early stages following endotoxin administration.


Phagocytic activity of reticuloendothelial system of mice in shock-like state following administration of polysaccharide-protein complex isolated from Candida albicans.

Fever and shock are symptoms of acute disseminated candidiasis. Phagocytic activity of the reticuloendothelial system (RES), following a single administration of polysaccharide-protein complex, was studied with respect to the role of the RES in the pathophysiology of circulatory shock. The index of phagocytic activity was determined 15 or 120 minutes following IV administration of polysaccharide-protein complex (50 mg/kg) to mice, from the rates of clearance of carbon particles and of heterologous erythrocytes labeled with 51Cr. The mice were pretreated with hydrocortisone 300 mg/kg, methylprednisolone, 30 mg/kg, or saline 120 minutes before administration of the polysaccharide-protein complex. Depression of the phagocytic activity was observed following administration of polysaccharide-protein complex in both time intervals investigated. This depression could be prevented successfully by administration of both glucocorticoids studied. The fractional distribution of 86Rb was determined in other groups of identically treated mice. An increase of 86Rb uptake was found in the heart, lungs, and adrenals 15 minutes after administration of polysaccharide-protein complex. A decrease of 86Rb uptake was found in the intestines and spleen. These changes were also found in mice pretreated with glucocorticoids. A return to the normal picture of 86Rb fractional distribution was found 120 minutes after polysaccharide-protein administration. It was suggested that changes in phagocytic activity were not a result of altered hemodynamics.


The problem of valve prosthesis-patient mismatch.

Valve prostheses have played an important part in the past two decades in the management of patients with valvular heart disease. However, many of the devices used in valve replacement have introduced new clinical problems. This paper deals with some of the problems associated with valve replacement, including one not previously emphasized--valve prosthesis-patient mismatch, which may cause obstruction to ventricular outflow and/or inflow.


Hemodynamically significant primary anomalies of the coronary arteries. Angiographic aspects.

Hemodynamically significant primary anomalies of the coronary arteries are those which alter myocardial perfusion. There are four major types: coronary artery fistulae, origin of the left coronary artery from the pulmonary artery, congenital coronary stenosis or atresia, and origin of the left coronary artery from the right sinus of Valsalva, with subsequent passage of the vessel between the aorta and right ventricular infundibulum. The angiographic features of these lesions are discussed.


George Lyman Duff Memorial Lecture. Lifestyles, major risk factors, proof and public policy.

In this report major risk factors in coronary heart disease (CHD) are reviewed, with particular emphasis on the role of nutrition. International and national epidemiologic data indicate that reducing or eliminating certain risk factors (e.g., a diet high in cholesterol and saturated fats) may  reduce the risk of premature CHD. Most trends indicate that many Americans are more concerned about diet for health reasons. Preventive measures for CHD are also discussed.


Precipitating factors in respiratory allergic disease in Indonesian children.

Skin test results and IgE antibody levels measured by RAST indicate that hypersensitivity to house dust mite (D. pteronyssinus) is a major feature of asthma and allergic rhinitis in Indonesian children. Total serum IgE levels were higher in the allergic than in control children. 60% (twenty-one out of thirty-five) of the asthmatic children and 56% (five out of nine) of the children with allergic rhinitis had IgE antibodies to the helminth Ascaris lumbricoides compared with none out of four control children. A tendency was found for high IgE antibody levels to D. pteronyssinus to occur in association with low IgE antibody levels to A. lumbricoides and vice versa.


A small dose of somatostatin inhibits the pentagastrin stimulated gastric secretion of acid, pepsin and intrinsic factor in man.

The effect of a small dose of somatostatin (0.05 mg/h) on the gastric secretion of acid, pepsin and Intrinsic Factor (IF) after stepwise increases in the dose of pentagastrin was examined in six healthy volunteers. The gastric secretion of acid, pepsin and IF in response to pentagastrin was significantly reduced by a continuous infusion of somatostatin. The pattern of inhibition indicates that somatostatin is a competitive inhibitor of pentagastrin in the stimulation of gastric secretion of both acid, pepsin and IF. This finding supports the hypothesis of a direct effect of somatostatin on the exocrine secretory cells of the stomach.


Specific IgE estimations by RAST in Japanese asthmatics compared with skin, passive transfer and bronchial provocation tests.

198 asthmatics and twenty healthy persons were studied by RAST and in vivo tests with four common inhalant allergens. (a) Higher RAST classes were elicited with mite (Dermatophagoides farinae) extract and lower classes with other allergens. The agreement between positive RAST and skin or P-K tests was highest with the mite extract. RAST sensitivity was dependent on the kinds of allergens and was most sensitive to mite extract. Positive RAST was most closely related to the prick test reactions. (b) RASTs to house dust and mite extract were examined in terms of the threshold dosage of house dust and also the types of bronchial response (early, dual and late) induced by a certain amount of house dust; higher RAST classes were found in subjects with bronchial response to the dual or early type, elicited by a threshold dosage of diluted extract, while lower RAST classes were found in cases of the late-type response elicited by the threshold dosage of concentrated extract. (c) Changes in IgE antibodies to house dust and mite extract were estimated in patients with positive house dust provocation. A greater increase occurred in cases of dual or early response, a smaller increase in those with a late response. Despite discordances in skin tests and RAST between house dust and mite extracts, the increases in IgE antibodies to mite extracts as well as house dust were observed in all cases, presumably caused by an allergenic identity between the allergens.


Hypothalamic function in men with hypogonadotrophic hypogonadism.

To determine whether hypothalamic function is normal in patients with idiopathic gonadotrophin deficiency, nine men with this syndrome were studied. Water conservation after overnight dehydration, thermoregulatory response to a cold (10 degrees C) environmental stress and prolactin secretion following chlorpromazine stimulation were investigated. In response to dehydration, maximal urinary osmolality was 1058 +/- 135 mOsm/kg (mean +/- SD) and no patient showed further increase after exogenous vasopressin administration. The patients responded to the cold stimulus by vigorous shivering and maintained their core body temperatures. Basal concentrations of prolactin which were 12.7 +/- 4.6 ng/ml increased by 15 ng/ml following Thyrotrophin-releasing hormone in six of seven men tested, indicating normal pituitary reserve. Prolactin concentrations doubled in seven of eight men who received chlorpromazine. All responses were indistinguishable from those of normal men. While a diminished secretion of gonadotrophin releasing hormone by the hypothalamus remains the most plausible cause of idiopathic gonadotrophin deficiency, our data indicate that the associated functions tested are intact in men with this syndrome.


Branchial cysts, sinuses and fistulae.

Branchial cysts, sinuses and fistulae are reviewed with special reference to their origin, clinical features, pathology and treatment. The material consists of a survey of over 700 recorded cases, a series of 90 cases studied in retrospect with special reference to the pathology, and a personal experience of 42. It is suggested that a proportion of 'branchial cysts' do not arise from the branchial apparatus, but possibly may do so from epithelial inclusions in lymph nodes. It is accepted that branchial sinuses develop from the branchial apparatus, but there is little proof that such an entity as 'branchial fistula' exists.


Hereditary C2 deficiency and systemic lupus erythematosus associated with severe glomerulonephritis.

Although an unusually high incidence of immunological diseases has been described in patients with hereditary C2 deficiency, the severity of these illnesses has been relatively mild, suggesting that blocking complement activation beyond C4 may protect against significant complement-mediated inflammation. This report describes studies in a C2-deficient patient with severe systemic lupus erythematosus (SLE) and diffuse proliferative glomerulonephritis. An immunopathological study of the kidney revealed the deposition of properdin, properdin factor B, C3 and C5 in a pattern similar to immunoglobulin G deposits. Serum properdin and properdin factor B levels were low at various times during the patient's course. In vitro complement fixation studies showed C3 fixation by glomerular deposits could occur via the alternative pathway. Studies of the immune deposits in the patients' skin revealed similar results. These studies suggest that inflammation may be effectively mediated via the alternative complement pathway in the C2 deficiency-lupus syndrome.


Progress in hemodialyzers and membranes--the last 20 years.

The development of clinical dialyzers is traced over the past three decades. Beginning with the Kolff rotating device, the evolution of dialyzers has followed a path to reduce size, increase metabolite transport, and minimize blood losses. A combination of design innovations and membrane developments has been necessary to achieve the performance of current dialyzers. These include the development of thin-channel plate dialyzers, hollow-fiber membranes, and more permeable membranes. The development of better devices has been hindered by lack of complete understanding of physiological and biochemical needs for treatment of end stage renal patients. A backlog of engineering and materials information is available for future utilization when therapy needs are clarified. Future trends in membrane developments may include melt-extrudable and "non-isotropic" membranes.


Progress in hemodialysis.

Bioengineering research over the past 16 years has provided clear definition of the design parameters controlling solute transport in dialyzers and resulted in the present dialysis systems which have a broad range of solute transport and ultrafiltration properties with predictable performance. Research into the pathophysiology of uremia has further established the role of protein catabolism in pathogenesis and resulted in information indicating that endocrine metabolic, drug toxicity and immunologic pathogenetic mechanisms may also be operative in this complex syndrome. Average dialysis treatment time has decreased more than 50 percent over the last ten years, but to a considerable extent remains empirically determined. Progress in elucidation of the solute kinetic parameters controlling solute concentration during regular dialysis therapy (RDT) is reviewed and the critical role of mass balance in evaluation of this therapy is discussed. Progress in kinetic modeling to quantify RDT is reviewed, the limitations of current kinetic models are considered and anticipated requirements to develop improved model parameters outlined.


Clinical dose-response studies with guanfacine (BS 100-141), a new antihypertensive agent.

1. Blood pressure, pulse rate, salivary flow and the degree of sedation were recorded at intervals following oral administration of single doses of guanfacine, a clonidine-like agent, to hypertensive patients. 2. Between 2 and 10 h after administration of guanfacine (3 mg or 5 mg), there were dose-related decrease in lying and standing blood pressure, together with significant reductions in pulse rate and salivary flow. 3. It is concluded that guanfacine lowers blood pressure in hypertensive patients and is probably suitable for twice daily administration, but produces xerostomia and sedation.


Chronic peritoneal dialysis.

Since the introduction of the permanent peritoneal catheter, interest in chronic peritoneal dialysis is increasing. The automatic peritoneal dialysis cycler and the reverse osmosis peritoneal dialysis machine have been other development that made chronic peritoneal possible. Chronic peritoneal dialysis is indicated for the children, the elderly, those without hemodialysis access sites, those living along (for home dialysis) and the diabetics, whose retinopathy seems to progress less on peritoneal dialysis than on hemodialysis. Patients awaiting a kidney transplant can be maintained equally satisfactorily on peritoneal dialysis as on hemodialysis. Because of its simplicity almost any patient can be trained for home peritoneal dialysis, and a high incidence of rehabilitation can be achieved. A flow rate of 4 1/hr with 21 exchanges, 40 hours a week, seem to the ideal dialysis requirements. Complications of chronic peritoneal dialysis include those related to the permanent catheter such as one or two way obstruction and those related the dialysis itself. The latter can be either acute (i.e. peritonitis etc.) or chornic such as neuropathy, renal osteodystrophy, anemia etc. Integrated with hemodialysis and transplantation, peritoneal provides the nephrologists with the ability to treat his patients with the most appropriate treatment.


Para-aminosalicylic acid as a lipid-lowering agent.

The capacity of para-aminosalicylic acid (PAS) to lower initially high serum lipoprotein lipid concentrations was tested in a double-blind crossover study. Thirty patients who were on a lipid-lowering diet were treated with PAS (6 gm daily) for 4 wk. There was an average reduction of the serum triglyceride concentration of 28% (p less than 0.001) and of 12% of the serum cholesterol concentration (p less than 0.001) corresponding to a reduction of very low density lipoprotein (VLDL) triglycerides of 40% (p less than 0.001) and low density lipoprotein (LDL) cholesterol of 6% (p less than 0.05). In hypercholesterolemic patients, the LDL cholesterol reduction was 14% (p less than 0.001). In patients with hypertriglyceridemia type IV, the mean reduction of the VLDL triglyceride concentration was 47% (p less than 0.01), corresponding to a serum triglyceride reduction by 37% (p less than 0.01). In spite of the decrease of VLDL concentration, there was an unexpected reduction of the lipoprotein lipase activity in adipose tissue of 16% (p less than 0.02). The glucose tolerance and the serum insulin concentrations at fasting and after glucose injection were not changed.


Gastrointestinal blood loss after diflunisal and after aspirin: effect of ethanol.

Fecal blood loss was evaluated in normal subjects with 51Cr-labeled red cells. In a double-blind parallel study in 10 subjects, 250 mg diflunisal twice daily did not significantly increase blood loss in two consecutive treatment periods, while 750 mg acetylsalicylic acid (ASA) 4 times daily did so. In a double-blind crossover study in 2 subjects, diflunisal, 250 mg twice daily again did not significantly affect fecal blood loss during a 4-day treatment period, and there also was no significant effth diflunisal during two additional treatment days. ASA, 600 mg 4 times daily, induced an increase in blood loss and this effect was significantly enhanced by the addition of alcohol. The difference between treatments in the way they interact with alcohol was also statistically significant.


Ticrynafen and hydrochlorothiazide in hypertension.

In a double-blind study, 28 patients having mild to moderate essential hypertension were randomly assigned to a 6-week regimen of ticrynafen, hydrochlorothiazide, or placebo. Blood pressure fell after ticrynafen and hydrochlorothiazide. Serum uric acid fell strikingly with ticrynafen whereas it rose with hydrochlorothiazide. Serum potassium declined very little with ticrynafen; much less than with hydrochlorothiazide. Serum creatinine and blood urea nitrogen rose slightly more with ticrynafen than with hydrochlorothiazide. There were no clinical adverse effects to either of the medications. Ticrynafen appears to be an effective antihypertensive with a substantial hypouricemic effect.


Diagnosis and management of hypoxemia.

The following steps are necessary in the successful management of hypoxia: 1. Establish the presence of hypoxemia with measurements of arterial blood gases. 2. Search for signs of tissue hypoxia. 3. Assign a physiologic cause for hypoxemia. 4. Begin oxygen therapy by a method appropriate to underlying pathophysiologic mechanism, as outlined in Table 2. 5. Repeat arterial blood gas measurements to assure adequate reversal of hypoxemia. 6. Treat any underlying disease(s).


Adverse radiographic contrast media reactions.

There are many unanswered questions about the mechanisms and prevention of adverse reactions to RCM. Serious reactions will likely occur less often in your experience if you observe these precautions: 1. Consider that every patient is a candiate for an adverse reaction when you request the contrast study. 2. Be particularly cautious in performing the study in those with previous reactions to RMC, those who are strongly atopic, and those in whom intravenous cholangiography is planned. Look for alternative diagnostic approaches in treating these individuals. 3. If there is any likelihood of increased reactivity, inform the patient, carry out a study with intravenous infusion in place and appropriate physician observation during and after the study, consider prestudy treatment with antihistamines and/or steroids, and be prepared to institute emergency measures should the need arise.


Site-directed tumor chemotherapy.

The therapeutic effect of drugs used in cancer chemotherapy has been augmented by their complexing or chemical linking to macromolecular carriers. The role of the carrier should be to deliver the drug preferentially to the tumor site. Potential carriers are either (1) nonspecific macromolecules whose preferential activity is due to the inherently higher permeability and pinocytic activity of tumor cells, (2) lysosomotropic agents such as DNA or liposomes, or (3) the more specific agents--antitumor antibodies. Conjugates of daunomycin to antitumor antibodies, prepared either by direct binding or by binding via dextran, were shown to retain both the antibody and the drug activity. Thus they exert specific cytotoxic activity toward tumor cells that the antibodies recognize. In vivo, these complexes are more active than the free drug in prolongation of survival of mice transplanted with the tumor cells. Conjugates of daunomycin with normal immunoglobulin or with dextran also show higher therapeutic efficacy in vivo, probably due to their capacity to reduce the cytotoxicity of daunomycin and/or to the higher permeability of neoplastic cells. But under certain conditions, mainly at low drug concentrations, the drug-antibody conjugates have an advantage over all others.


Hydrocortisone valerate. Double-blind comparison with two other topical steroids.

Hydrocortisone valerate cream (0.2 percent) was evaluated in three controlled clinical trials involving a total of sixty-eight patients with atopic dermatitis. This new nonfluorinated steroid was found to be as effective as the fluorinated beta-methasone valerate cream (0.1 percent) and significantly more effective than hydrocortisone cream (0.1 percent) and the placebo cream base. All studies were double-blind, paired comparisons, utilizing application of the medications three times a day for up to four weeks or until clearing occurred.


Skin xerosis. Clinical report on the effect of a moisturizing soap bar.

Two double-blind and supervised clinical studies were conducted to determine the direct effect of a moisturizing soap bar on skin xerosis (dry skin). One study compared the moisturizing soap bar with a commercially available soap bar and used young adult subjects who resided in an area of high relative humidity. The second study compared the moisturizing soap bar with a placebo soap bar and used elderly subjects who resided in an area of low relative humidity. In both instnaces, washing twice daily with the moisturizing soap bar provided a lower level of skin flaking than the particular soap bar with which it was compared.


Multiple cytogenetic methods used to identify a new structural rearrangement of the human X chromosome.

A woman with primary amenorrhea and pure gonadal dysgenesis had two cytogenetically abnormal cell lines. The karyotype was 45,X in 56--95% of mitosis from lymphocytes and skin fibroblasts. In the remaining 5--44% of the cells there was, in addition to a normal X, a structurally abnormal X chromosome interpretable as pter leads to q21::q11 leads to pter or pter leads to q21::q13 leads to pter. The abnormal X chromosome was heterocyclic and had a normal centromere plus an extra C band in the long arm. Detailed interpretation of the structural rearrangements of this chromosome required the use of both Q-, G-, and C-banding and the BrdU-Hoechst 33258 technique.


Failure of methylprednisolone to protect acutely ischemic myocardium: a contrast with subsequent beta-adrenergic blockade in man.

Two grams of methylprednisolone was administratered to ten patients with acute myocardial infarction at an average of 13 hours from the onset of symptoms; pain in the chest was not relieved in six of the ten patients. In one hour, no significant improvement was noted in the function of the ischemic segments (examined using a multiaxis echocardiographic method) or in the S-T segments of the 12-lead electrocardiogram. Left ventricular filling pressure soon increased by an average of 4 mm Hg (P less than 0.005), without ventricular dilatation or a Frank-Starling response, suggesting a decrease (ischemic?) in myocardial compliance. Cardiac output by Swan-Ganz thermodilution later increased by 21 percent (P less than 0.01) when a decrease in peripheral vasoconstriction was evident. In contrast, small-dose beta-adrenergic blockade using 0.2 mg of pindolol intravenously after administration of methylprednisolone immediately relieved pain in the chest in all six patients. Elevation of the S-T segments was reduced by 34 percent (P less than 0.05) within 15 minutes, and the contractile function of the ischemic segments improved markedly, by 3 mm or to 34 percent of normal, from the 4 percent of normal before administration of pindolol (P less than 0.005). Hemodynamic function did not deteriorate in the eight patients with uncomplicated infarction or moderate left ventricular failure. Therapy with pindolol thus reduced clinical, electrocardiographic, and myocardial mechanical signs of acute ischemia safely, while administration of methylprednisolone had no short-term protective effect.


Bioavailability and metabolism of talampicillin.

Talampicillin is an ester of ampicillin which is readily hydrolysed on absorption to release ampicillin. It is well absorbed from the gastro-intestinal tract resulting in a greater bioavailiability of ampicillin than can be achieved with equivalent doses of ampicillin itself. Dose response studies have confirmed a direct relationship between the dose of talampicillin administered and peak serum ampicillin concentration and urinary excretion of ampicillin. Dosing of ampicillin after food has been shown to adversely affect the total bioavailability of ampicillin. This is not so after dosing with talampicillin. The bioavailability of ampicillin from a 250-mg Talpen tablet dosed after a large meal was significantly greater than that from 250 mg ampicillin dosed in the fasting state. Studies in volunteer subjects at multiples of the proposed therapeutic dose for periods of up to 28 days have indicated its acceptability, bioavailability and lack of side effects on repeated dosing. The fate of the phthalidyl moiety of talampicillin has been investigated in repeated dose studies and in a single dose studies and in a single dose study in which radiolabelled talampicillin was administered. The principal metabolite of the phthalidyl moiety in man has been shown to be 2-hydroxymethylbenzoic acid, which is identical to that in experimental animals used for toxicological investigations.


Curing of an R factor from Escherichia coli by hydroxyurea and cytosine arabinoside.

Hydroxyurea (HU) and cytosine arabinoside (Ara-C) eliminate R factor R46 from Escherichia coli strain J5-3. The highest frequency of elimination for both drugs occurred at concentrations and times that produced the lowest survivor levels. 5% of cells were antibiotic-sensitive after 5 h incubation in 5 mg/ml Ara-C, whilst 6 and 7% of the survivors had lost the R factor after 8 and 24 h incubation, respectively in 20 mg/ml HU. The number of survivors began to increase after 5 h incubation in Ara-C, probably due to the inactivation of the drug in the phosphate-buffered medium. All four antibiotic resistances (ampicillin, streptomycin, sulphonamide and tetracycline) mediated by R46 were lost simultaneously and elimination of the whole plasmid was confirmed by conjugation experiments in which the 'cured' cells was shown to be as efficient recipients of R46 as the control R- strain in crosses with E. coli strain J6-2 (R46). No covalently closed circular plasmid DNA was demonstrable in cured cell lines. R+ and R- strains had similar sensitivities to HU but J5-3 R+ was much more sensitive to Ara-C than the isogenic R- strain. It may be concluded that HU eliminates R46 actively whereas although Ara-C may produce some active elimination it acts mainly by selection of R- cells present in the culture.


Perceptions of family relationships by institutionalized and noninstitutionalized dependent children.

This paper reports research findings obtained regarding family relationships for three groups of adolescents: institutionalized, dependent children; noninstitutionalized, dependent children who are candidates for placement in institutions; and children living with their parents. It also describes a relatively novel, nonverbal, research instrument, the Family Relations Test, used to obtain the data. The conclusion is drawn that one of the major tasks of child care institutions is to restore children's self-esteem and confidence--yet it is far from certain as to whether these settings are capable of accomplishing this important task.


Immunological diagnosis of echinococcosis.

Our results with the immunofluorescence technique in the diagnosis of hydatid disease are reported. The sera of 28 patients with surgically proven hydatid disease, of 30 healthy individuals, and of 1 patient with cysticercosis were used. With a dilution of 1:100 a sensitivity of 96% was obtained in the patients affected by the disease. In the control group all but one of the sera were negative. A brief review of the immunological methods used at present for the diagnosis of echinococcosis is made. The most important problems connected with the immunodiagnosis of this disease are discussed.


Control of intracranial pressure during pediatric neurosurgery anesthesia.

Some of the important points of view of anesthesia in pediatric neurosurgery are: adequate alveolar exchange of oxygen and carbondioxide by means of artificial ventilation; stable cardiovascular function; fluid balance; monitoring, and attempts to keep intracranial pressure low. This last point is achieved by various anesthesiological procedures, e.g., hyperventilation, positive-negative pressure ventilation, rapid induction of anesthesia and choice of suitable anesthetics. Enflurane (Ethrane) increases intracranial pressure less than halothane. The new intravenous anesthetic etomidate lowers intracranial pressure in a favorable manner quite similar to thiopental (Pentothal-Sodium).


[Reconstruction following cardia resection using an interposed jejunal loop without mesenteric resection].

For reconstruction after cardial resection, we invented a method combining the cardial resection method of Nissen and the gastrectomy method of Tomoda. One peculiarity of this method is the reconstruction by means of a jejunal sling that becomes intercalated between esophagus and antrum without wide dissection of the mesentery. By this method, the esophageal passage is physiological and the frequency of esophageal regurgitation compared with esophagogastrostomy is diminished.


[Secondary amenorrhoea (author's transl)].

27 patients with secondary amenorrhoea for 6--20 months were investigated with a gonadorelin (GnRH-)test and a psychoanalytical exploration. Results, which were determined independently of each other, were then correlated. According to the gonadorelin and the gestagen test patients could be allocated to four groups: test group 1 = negative gestagen test, LH peak below 8 ng/ml, test group 2 = positive gestagen test, LH peak below 8 ng/ml, test group 3 = positive gestagen test, LH peak 8--20 ng/ml, test group 4 = positive gestagen test, LH peak 20--37 ng/ml. According to the psychoanalytical exploration two groups of patients could be differentiated. Patients of test group 1 and 2 showed psychosomatic disorders to a greater extent with pronounced associated somatic symptoms and predominantly retentive personality structures. Patients in test groups 3 and 4 showed predominantly associated mental symptoms accompanied by better insight into their own conflicts.


[Incorporation of the hospital into modern technology].

This address traces the emergence of the hospital in the 18th century as a facility for combating disease and tending to the sick. Reference is made to the reports of Tenon and Howard on hospitals in several European countries, which instead of considering the hospital as a mere architectural object make recommendations based on the numbers of beds of an institution, its usable space, the dimensions of wards, mortaility rates, etc.; the result is a new functional concept of the medical and physical organization of the hospital. The author delves into the characteristics of the hospital and medical practice in the Middle Ages, the 17th and 18th centuries, and since the middle of the 18th. He brings out the direct relationship of hospital organization to the economic regulations that emerged with mercantilism. He stresses the importance of man for social and military development on the one hand, and, on the other hand, to the application of a technology that could be described as political: the discipline. He is of the view that the introduction of disciplinary mechanisms in the confused environment of the hospital permitted its "medicalization" and the development of the medical-therapeutic hospital.


[The teaching of the integral or medico-social aspects of health: history and present situation].

This paper was presented to the Scientific Workshop on Preventive Medicine held in 1977 in commemoration of the fiftieth anniversary of the founding of the Institute of Social Medicine in San Marcos National University at Lima. The author reviews the "health-disease" concept not as an eminently medical technique but as a tool for analysis of the complex problem it implies, in the web of basic relationships of the socioeconomic structure of a country. In laying the foundation for his presentation of the subject, he analyzes the historical development of the practice of medicine and of preventive medicine in particular.


Metabolic effects of some antibilharzial drugs. Comparative study on the effect of tartar-emetic and piperazine hexahydrate on the activity of some oxidoreductase enzymes of the rat livers.

IN THIS INVESTIGATION, the effects of the examined antibilharzial agents are as follows: Bilharcid and tartar-emetic similarly affected succinate oxidation. 50% inhibition could be obtained at a concentration of 10(-3) of both drugs. Malate oxidation was differently affected by the drugs. Bilharcid and tartar-emetic at a concentration of 10(-3) M induced 50% and 70% inhibition respectively, while tartar-emetic stimulated malate oxidation if added in a concentration of 10(-5) M. Pyruvate oxidation was affected in the same manner and to the same extent as malate oxidation. Citrate oxidation was slightly inhibited by Bilharcid and tartar-emetic. 10% and 30% inhibition could be obtained if the concentration was 10(-3) M of both drugs respectively. Bilharcid had a biphasic effect on citrate oxidation. Stimulation could be observed at low concentrations (up to 10(-8) M and inhibition at higher ones (up to 10(-3) M. Piperazine hexahydrate was nearly without effect on the rate of oxidation of the four mentioned substrates.


Comparative clinicopathological and bacteriological studies in schistosomiasis mansoni.

FIFTY MALE Egyptian inpatients with active colonic mansoniasis were studied clinicopathologically, endoscopically, radiologically and bacteriologically. This was done to find out the pattern of colonic and urinary enterobacteria and serum antisalmonella agglutinins in various stages of mansoniasis. Cases are divided into three groups (A, B and C) according to the stage of their hepato-splenomegally. Their clinical presentations were dysentery, rectal bleeding, abdominal distension, anaemia, endocrinal changes and general weakness. Oesophageal varices were diagnosed in 19.8% of group C patients. Distal colonic polyps were noticed in 25% and 4% of group A and B cases respectively, while colonic ulcers were found in 20% of patients of either group. The total number of bilharzia ova per gram of fresh colonic biopsy was highest in group A and lowest in group C subjects. Mucosal and submucosal bilharzial granulation tissue formation together with mucosal hypertrophy were conspicuous among group A and B patients. Hematoxylin and eosin stain was of good diagnostic value and the rest of the stains used did not show any fungi or fibrinoid deposits.


[Psychopathological and psychopathometric findings in patients with dental prosthesis intolerance].

It is discussed whether psychological factors can be accounted responsible for the intolerance to the wearing of prostheses which can not be explained on dental grounds. Psychopathological, psychometric and psychopathometric investigations brought the following results: 1. Patients with complaints differ significantly from a control group in the variables changeable according to situation: "general somatic discomforts", disturbances of vegetative functions, and "depressive moods". This points to a constitutional predisposition to vegetative irritability and lowered threshold to frustration. 2. Less intelligent persons are less able and prepared to incorporate and accept the prosthesis. 3. Among the personality variables differences in the attributes "uncontrollability and social responsiveness" show up in sample tests. The subjects consider themselves more esteemed, popular and acknowledged. 4. In the majority of subjects the making of the tooth replacement coincided with stressful events.


[Concept and testing of the Tübingen immediate implant].

This introductory communication deals with the functional-anatomical, biophysical and neurophysiological considerations which led to the construction of an aluminium oxide immediate implant from a stepped cylindrical body. This intra-osseous implant differs in essential constructional features from the implant shapes known up to now; it endeavours to make use of the architecture of the natural gingival fibre apparatus for the placing of the mucosal cuff. Its surface was maximalised towards the bone, leaving out surface structures which could produce pressure points. The enlargement of surface compared with the root of the corresponding natural tooth amounts to 65 to 100% varying according to the shape of the implant. Descriptions are given of the concept of testing experimental implants, the physical and chemical characterisation of surfaces, animal-experimental steps, clinical tests including legal problems posed and the control system created with the view to large scale clinical trials.


[The Tübingen immediate implant in clinical studies].

95 Tuebinger immediate implants--four different types--were clinically tested. The longest time of observation was 2 1/2 years. Of the type which so far has been shown to be the best (54 implants), one was lost. The quota of losses was higher in the other types. Preservation depends on the shape of the implant head and particularly on the size  of the lacuna. Best results were achieved by the 54 implants with a lacuna radius of 100 micron. Smaller lacunae increase the failure rate.


[The sulcus fluid flow rate (SFFR) in Tübingen immediate implants made from aluminum oxide ceramics].

Determination of sulcus fluid flowrate was used to gain an insight into the peri-implantar tissue-reactive behaviour in response to Tuebinger immediate implants. The evaluation of 570 measurements on 36 implants and corresponding control teeth showed no difference between natural teeth and healthy gum and implant. Mobility influences the SFFR even in implants.