Biosynthesis of the luteinizing hormone releasing hormone (LH-RH) in the rat hypothalamus.

The biosynthesis of LH-RH was followed and evaluated in the hypothalamus of intact and castrated female rats after the infusion into the 3rd cerebral ventricle of L-3H-Glycine and its incorporation into the synthetized hormone. Incorporation of 3H-Gly into the LH--RH molecule that means biosynthesis of this hormone was found 30 min after the infusion of labeled amino acid. The incorporation rate in castrated animals was 2 times higher than in intact ones. Estradiol-17 beta only slightly depressed the LH--RH biosynthesis rate in castrated animals. Pretreatment with cycloheximide or puromycin decreased biosynthesis rate of the hormone by 50%. On the basis of cycloheximide and puromycin action it is suggested that the ribosomes are involved in the biosynthesis of LH--RH.


Prostaglandin-induced diarrhoea treated with loperamide or diphenoxylate. A double-blind study.

Loperamide was compared double-blind with diphenoxylate and a placebo in 59 women with diarrhoea due to prostaglandin administration for mid-trimester abortion. Treatment was started with the intake of two capsules two hours before the first intramuscular injection of 15(S-)15 methyl prostaglandin F2alpha and was then adapted individually, i.e. one capsule after each unformed stool, with a maximum of ten per 24 hours. Both antidiarrhoeals were significantly more effective than the placebo in preventing diarrhoea, and loperamide was found to be more active than diphenoxylate. The course of abortion, BP and vital signs, or prostaglandin side-effects other than diarrhoea were not affected by either antidiarrhoeal, nor could any adverse experience be specifically attributed to them.


Plasma renin, plasma aldosterone and exchangeable sodium in normotensive and hypertensive kidney transplant recipients with and without transplant renal artery stenosis.

Blood pressure (BP), plasma renin concentration (PRC), plasma aldosterone concentration (PAC) and exchangeable sodium (ES) were studied in 19 kidney recipients on different fixed levels of sodium intake after successful kidney transplantation. The following groups of kidney recipients were investigated: group 1: 7 normotensives, group 2:7 hypertensives without transplant renal artery stenosis (TRAS), group 3:5 hypertensives with angiographically verified TRAS. Hypertension in the recipients without TRAS (group 2) was characterized by a positive correlation between BP and ES and a normal response of PRC and PAC to a fixed low (10 mEQ/day) and high (150 mEq/day) sodium intake. In contrast, hypertension in the recipients with TRAS (group 3) was characterized by a normal or varyingly increased PRC on a liberal sodium intake and a reduced response of PRC to sodium restriction, whereas PAC did not differ from the other groups of recipients. In one recipient in group 3 who underwent surgical correction for TRAS, PRC and PAC decreased before operation during sodium restriction, but BP remained high until after operation, when it normalized simultaneously with a decrease in ES. The results indicate that sodium retention is involved in the pathogenesis of posttransplant hypertension and suggest that an increased activity of the renin--angiotensin system is counterbalanced by an accumulation of sodium in TRAS.


Hemodynamic effect of long--term treatment with pindolol in essential hypertension with special reference to the resistance and capacitance vessels of the forearm.

Ten patients with essential hypertension have been studied at rest, during and after exercise following oral treatment for on an average 16 months with a beta-adrenoreceptor blocking agent, pindolol. The study was a direct continuation of an earlier, performed after 2 months' treatment. The hypotensive effect of pindolol was highly significant after 2 as well as 16 months of treatment. Heart rate was similarly lowered at 2 and 16 months, while carciac output, which was significantly lower during exercise after 2 months, had increased to the pretreatment level after 16 months. Peripheral vascular resistance, which was not affected after 2 months, had decreased significantly during and after exercise in the long-term study. A comparison between the hemodynamic situations after 2 and 16 months thus suggests that while a decrease in cardiac output is an early mechanism in the lowering of BP, changes in systemic vascular resistance seem to be more important after long-term treatment with pindolol.


Coarctation of the aorta. The world's longest follow-up.

A 32-year follow-up of the first coarctations of the aorta ever operated upon in the world has shown a systolic blood pressure below 155 mmHg in 12 of 18 patients and a diastolic blood pressure below 95 mm Hg in 15 of 18 patients. No gradient over the anastomosis was noted in 13 of 18 patients when measured by a cuff and in 5 of 12 patients when measured by catheterization. If the diameter of the anastomosis was 75% of that of that of the aortic arch, only a very small or no resting gradient was found. If there was no gradient at rest, there was usually only an insignificant or no gradient during exercise. A small gradient at rest was always higher during exercise, depending on the degree of work load, length of narrowed segment and aneurysm at the suture line. There was an incidence of 44% aortic valvular disease and of 20% degenerative changes in caput femoris. The anastomosis had grown with the patient.


The toxicity of ethanol. A tentative risk evaluation.

A substantial knowledge has been collected on the dose-dependent toxic effects of ethanol. Whereas ethanol probably is the chemical substance exerting most toxic effects in many populations, a quantitative estimate of the upper limit of long term safe consumption from a toxicological and public health standpoint has not earlier been performed. It may be summarized that the toxic range of ethanol consumption is 35-200 g per day. Based on the available data we would propose an acceptable daily intake (ADI) for ethanol of 7 g per day. The practical consequences are discussed.


Alcohol withdrawal syndromes in the human: comparison with animal models.

Alcohol withdrawal syndromes in humans lie on a continuum of increasing severity, from the acute hangover to delirium tremens. Early mild reactions consist primarily of hyperexcitability phenomena such as tremor, insomnia, hyperreflexia and hyperventilation. In more severe degree, the same process gives rise to hallucinations and seizures. These early reactions are mimicked closely by alcohol withdrawal signs in experimental animals. Late reactions in humans are characterized by marked sympathetic nervous system overactivity, profound disorientation and hallucinations. Analogous reactions have not yet been observed clearly in other species. The problem may be one of finding appropriate techniques for detecting such changes, rather than a true species difference in their occurrence.


Alterations of macromolecule biosynthesis after chronic administration of opiates and ethanol.

The literature concerning the effects of opiates, alcohol and barbiturates on RNA and protein metabolism is reviewed. Recent findings from this laboratory suggest that chronic morphine treatment increases the template activity of chromatin from oligodendroglial nuclei while chronic ethanol treatment decreases this activity. In addition, chronic morphine treatment stimulates protein synthesis in cell free systems and may increase the synthesis of discrete synaptic membrane proteins. Results from other laboratories suggest a general decrease in macromolecule biosynthesis with long term ethanol consumption. These results are discussed in terms of the possible roles of protein synthesis in the effects of chronic opiate and ethanol administration.


Anhydride intermediates in catalysis by pepsin: is pepsin an enzyme with two active sites?

By the use of sulfite ester substrates together with hydroxylamine as a highly reactive trapping agent, we have been able to obtain strong evidence for the intermediacy of enzyme-bound anhydride species in the pepsin-catalyzed hydrolysis of these substrates. From our observations that in the trapping experiments hydroxamate functions are introduced at the beta-carboxylates of Asp-32, Asp-215 and at least one additional Asp residue, it appears that several reactive carboxylate species can function as nucleophiles against sulfite esters, leading to the formation of anhydride species. Because the location of the hydroxamate incorporated into pepsin other than at the Asp-32 and Asp-215 residues is unknown, it remains conceivable that, at least for the action of pepsin on sulfite substrates, there are two distinct active site regions. If the possibility is considered that peptides possessing common amino-terminal residues but different acyl residues may bind productively in different fashions so that in some cases the beta-carboxylate of Asp-32 acts as the attacking nucleophile while in others the beta-carboxylate of Asp-215 acts in this way (as has been observed for sulfites), much of the confusion in the literature concerning the reactions of pepsin with peptidase may be explained.


New data on pepsin mechanism and specificity.

New data on the specificity and mechanism of action of porcine pepsin are presented, including statistical analysis of protein cleavage by the enzyme, kinetics of synthetic substrates, enzyme inhibition and activation, kinetics of transpeptidation reaction, and 180 exchange studies. From these data it was concluded that pepsin has an extended active site being able to accomodate specifically five amino acid residues of the substrate. The orientation of the substrate molecule relative to the ethanol binding loci in pepsin crystals has been determined. Pepsin mechanism includes "amino-enzyme" formation which chemically is not an amide, formed by the enzyme carboxyl with the amino fragment of the substrate.


Pepstatin inhibition mechanism.

Pepstatin is a low molecular weight, potent inhibitor specific for acid proteases with a Ki value of about 10(-10)M for pepsin. The chemical structure of pepstatin is essentially a hexapeptide which contains two residues of an unusual amino acid, 4-amino-3-hydroxy-6-methylheptanoic acid (statine). The complete structure of pepstatin is isovaleryl-L-valyl-L-valyl-statyl-L-alanyl-statine. To study its mode of inhibition, we prepared several derivatives and measured their kinetics of inhibition. Both N-acetyl-statine and N-acetyl-alanyl-statine are competitive inhibitors for pepsin with Ki values of 1.2 x 10(-4)M and 5.65 x 10(-6)M, respectively. The Ki value for N-acetyl-valyl-statine is 4.8 x 10(-6)M. These statyl derivatives, therefore, are very strong inhibitors. The Ki value for N-acetyl-statine is 600-fold smaller than that of its structural analog N-acetyl-leucine. The derivative which contains two statyl residues in a tetrapeptide exhibits inhibitory properties which approach those of pepstatin itself. Other acid proteases, human pepsin, human gastricsin, renin, cathepsin D, the acid protease from R. chinensis and bovine chymosin, also are inhibited by pepstatin and its derivatives. We suggest that the statyl residue is responsible for the unusual inhibitory capability of pepstatin and that statine is an analog of the previously proposed transition state for catalysis by pepsin and other acid proteases.


Chemical modification of a pepsin inhibitor from the activation peptides of pepsinogen.

The peptide comprising the first 16 amino acids of porcine pepsinogen, prepared from the activation mixture, has been modified by guanidination of its three lysine residues to form homoarginine residues. The modified peptide is a better pepsin inhibitor than is the native peptide; for 50% inhibition of the milk-clotting action of pepsin at pH 5.3, the molar ratio of peptide to pepsin required is 9 for the native inhibitor and only 2 for the guanidinated inhibitor. Stepwise removal by Edman degradation of the amino-terminal Leu-Fal-Homoarg residues from the guanidinated inhibitor decreased the activity slightly at the first step and markedly at the second and third steps. Thus, all of the amino-terminal sequence except the leucine residue is necessary for full activity.


X-ray analysis and circular dichroism of the acid protease from Endothia parasitica and chymosin.

The structure of an acid proteinase from Endothia parasitica has been solved by x-ray diffraction using multiple isomorphous replacement. A 3 A resolution map was interpreted in terms of a bilobal structure with a long 25 A cleft. The secondary structure is mostly distorted beta-sheet. The circular dichroism was measured and model curves for different secondary structures were fitted by least squares indicating a large component of beta-structure. The structure was seen to be homologous with that of the acid proteinase from R. Chinensis and hence with pepsin and chymosin. A rotation function against diffraction data from chymosin crystals confirm confirm this and suggested an approach to the solution of this structure.


Penicillopepsin: 2.8 A structure, active site conformation and mechanistic implications.

The crystal structure of penicillopepsin, an extracellular acid protease isolated from the mold Penicillium janthinellum, has been determined at 2.8 A resolution by the method of multiple isomorphous replacement. The resulting electron density map computed from the native structure factor amplitudes and MIR phases has an overall mean figure of merit of 0.90. The molecule is decidedly nonspherical, with the majority of residues in beta-structure. There is an 18-stranded mixed beta-sheet which forms the structural core in the region of the active site. This site, identified by the covalent binding of two EPNP molecules to Asp-32 and Asp-215, is located in a deep groove which divides the molecule into two approximately equal lobes. Both aspartic acid residues in the active site are in intimate contact with one another and the carboxyl group of Asp-32 makes two other important hydrogen-bonded contacts: one with Ser-35 and the other with the main chain peptide bond between Thr-216 and Gly-217. A proposed mechanism for acid protease catalysis is similar in many aspects to that proposed for carboxypeptidase A. The electrophilic component which polarizes the substrate carbonyl bond in the acid proteases is the proton shared between the beta-carboxyl groups of Asp-32 and Asp-215. The beta-carboxyl group of Asp-32 removes a proton from a water molecule bound between this side chain and the substrate; the resultant OH- attacks the carbonyl carbon atom of the substrate molecule. The phenolic -OH group of Tyr-75 donates its proton to the amide nitrogen of the scissile bond of the substrate.


Use of precordial ST-segment mapping.

Serial precordial ST-segment ECG mapping with a grid consisting of 49 recording marks made on the anterior thorax of patients with acute anterior transmural myocardial infarction has been applied in the study of usefulness of this technique. It has been found that a pattern of variable devolution of the magnitude of ST-segment elevations is seen in uncomplicated myocardial infarction. Extension of the infarct has been characterized by re-elevation of ST-segments. Beneficial therapeutic interventions have resulted in reduction of the magnitude of ST-segment elevation. However, the technique cannot be applied in patients with inferior transmural myocardial infarction or in patients with functioning pacemakers, bundle branch blocks, or pericarditis. The significance of adherence to strict guidelines in performing ST-segment mapping and the analysis of mapping data in the light of the total clinical picture at the time of recordings is emphasized.


Diet and cerebral malaria: the effect of famine and refeeding.

In an outbreak of Plasmodium falciparum malaria following refeeding after famine cerebral malaria was restricted to children eating grain. Nomad children consuming a predominantly milk diet were free of this complication despite an equivalent incidence of uncomplicated malaria. Freedom of nomads from cerebral complications may be due to inhibition by the milk diet of rapid division of the parasite combined with delayed recovery after famine of T cell function.


An improved technic for examining urinary casts and a review of their significance.

Casts represent an important, diagnostic component of urinary sediment, and may signal renal parenchymal disease in asymptomatic individuals. Accurate, precise identification of certain casts may be difficult due to poor visualization by current technics. Casts from freshly voided urine specimens, cytocentrifuged and stained by the Papanicolaou method, can be visualized optimally from permanent slide preparations. The genesis of these casts and their diagnostic potential related to renal disease and acute renal allograft rejection are discussed.


A reliable test for differentiation and presumptive identification of certain clinically significant anaerobes.

A modification of the slide catalase test was evaluated to determine its reliability for the presumptive identification of certain anaerobic gram-negative and gram-positive organisms isolated from clinical specimens. A total of 650 fresh isolates was evaluated. Growth from a trypticase blood agar plate or Schaedler's agar with laked blood was transferred to a slide and a drop of 15% H2O2 with Tween 80 added. Veillonella alcalescens, Proprionibacterium species, Peptococcus species, and Bacteroides fragilis, B. thetaiotaomicron, B. distasonis, B. ovatus, and B. vulgatus were positive by this method. Comparative slide and tube catalase tests were performed with the above-mentioned bacteroides species by growing each isolate on trypticase soy agar, Brucella agar, brain-heart infusion agar, each with and without added hemin, and on Schaedler's agar. Four solutions of H2O2 were used, 3 and 15%, and 3 and 15% with Tween 80. The addition of Tween 80 to H2O2 increased the sensitivity of the reaction with both slide and tube methods. The 15% H2O2 with Tween 80 consistently gave the most rapid and persistent positive reaction. A slide catalase test in combination with a Gram stain should be performed on each anaerobic isolate; this would significantly decrease the time required for presumptive identification of many anaerobic organisms.


Evaluation of a multitest system for identification of saccharolytic pseudomonads.

The API-20 Enteric Strip has been proposed to have the capacity to differentiate the nonfermentative gram-negative bacilli. This multitest strip serves as the basis of an evolving system, which first provided a Register, then a Selector, and more recently a computer Index. Twenty-three strains of Pseudomonas aeruginosa and P. putida, 21 of P. fluorescens, 27 of P. maltophilia, and 33 of P. cepacia were investigated by duplicate test runs to determine reproducibility. The results were then evaluated at each of the three stages to determine accuracy of identification and the effect of the system evolution on the identification rate. Seventy-one of the 127 pseudomonads gave reproducible results in the multitest strips. Approximately half of them were correctly grouped or speciated by the Register, whereas 80 to 83% were similarly identified by both the Selector and Index. Of the clinically important pseudomonads, 61 to 65% of P. aeruginosa and 93% of P. maltophilia strains were correctly speciated; neither P. putida nor P. fluorescens strains were speciated, although most were correctly grouped. P. cepacia was speciated by the Index with only 55 to 58% accuracy. Although the present stage of the evolving system offers improvement over the Register, further modifications are needed to eliminate identification problems and to increase speciation.


A method for the use of immunofluorescence on paraffin-embedded tissues.

Immunofluorescence is increasingly used for the visualization of antigens and antibodies in various tissues. The commonly used frozen sections present several disadvantages, which can be avoided by the present adaptation of paraffin-embedded sections for immunofluorescence. In this method, Bouin's solution achieves fast, deep fixation which preserves well the capacity of antigens to react with specific FITC-labeled antibodies. The method gives superior resolution of morphology, lower nonspecific fluorescent background, and permanent sections suitable for indefinite storage and retrospective studies. It has been successfully applied thus far to the study of immunofluorescence of lymphoid, thyroid, renal, pulmonary, and intestinal tissues.


In vivo leukemic transformation: cytogenetic evidence of in vivo leukemic transformation of engrafted marrow cells.

A 4-year-old girl with acute myeloblastic leukemia was treated with 50 mg/kg cyclophosphamide daily for 4 days before being given 1.7 X 10(8) bone marrow cells/kg from her HL-A identical, MLC nonreactive, cytogenetically normal brother. The patient died 92 weeks after the marrow graft. Postmortem examination showed increased myeloblasts and promyelocytes. Cytogenetic studies before transplantation showed that all sex determination metaphases had an XX pattern, and 41% of the hyperdiploid metaphases had an additional 19-20(F) chromosome. At autopsy all hyperdiploid metaphases with XY pattern and 43% of the hyperdiploid metaphases with an XX pattern had an additional F chromosome. Occasional metaphases with 47, XX, + F or 47, XY, + F were seen during the follow-up studies. These findings indicated that an acute leukemia had developed in the XY cell line of this artifically induced sex chimeric child. This suggests that a leukemic stimulus other than that proposed to be induced by total-body irradiation existed in this patient and transformed the engrafted cells.


Pharmacy-assisted burn unit skin bank program.

Assistance by pharmacy services in the development and production of a sterile fluid for the preservation of homograft skin after "harvesting" from cadavers is described. Discussion includes the need for skin banking; sterile skin bank fluid formulation, production, storage use; physiological effects of homograft skin; indications for homograft usage; and acceptable cadaver donors.


Cervical-vaginal flora of immunosuppressed renal transplant patients.

The purpose of this investigation was to determine the endocervical microflora present in 25 renal allograft recipients hwo were receiving therapeutic dosages of azathioprine or cyclophosphamide and prednisone. The aerobic flora was similar to that found in other populations. However, these immunosuppressed patients had more different anaerobic species per culture than were found in most other populations. This was reflected in the more frequent isolation of many species of anaerobic bacteria, especially the anaerobic gram-negative rods. The clinician should be aware of these differences since they may be significant in regard to gynecologic or obstetric postoperative infectious morbidity in women using immunosuppressive medications.


Content of luteinizing hormone-releasing factor in the human placenta.

Immunoreactive luteinizing hormone-releasing factor (LRF) was quantitated in the human placenta. It was found that the total placental content as well as the content per milligram of placental tissue varied with the stages of gestation. The fetal sex did not affect the LRF production. These studies establish that the placenta contains large amounts of LRF, immunologically identical to hypothalamic LRF.


A two-year trial of intraocular lenses at the Wilmer Institute.

Using the Binkhorst four-loop intraocular lens, we began a trial of intraocular lens implantation in 1975. We compared the operative and postoperative complications and the visual results of 100 implant cases during a two-year period to those of 100 age-matched aphakic control cases. Although the additional steps of lens implantation resulted in more operative and postoperative complications in the intraocular lens group, the visual results were good and were the same for both groups at an average follow-up of 12 months. Because the long-term follow-up results of implant cases are unknown, we recommend a conservative approach to selection of patients for intraocular lens implantation.


Bilateral central lipid infiltrates of the cornea.

A 55-year-old woman developed a skin rash and lipid deposition centrally in previously normal corneas. Despite a family history of coronary artery disease, no serum lipid abnormality was detected. Lipid droplets and granules were deposited throughout the corneal epithelium and stroma. Histochemical stains were positive only for phosopholipid and galactolipid. After a keratoplasty, deposition of similar lipid material recurred in the graft. An inflammatory process and increased corneosceleral limbal vascular permeability may have accounted for the unusual corneal findings in this patient.


Bimanual bipolar diathermy for treatment of bleeding from the anterior chamber angle.

We used a modified bimanual bipolar diathermy technique to treat bleeding vessels in the anterior chamber angle in two patients. We attached one lead of a Mentor Wet Field coagulator to an instrument positioned in the anterior chamber angle at the bleeding site, and attached the second lead to a needle positioned externally at the corneoscleral limbus in the same meridian. Diathermy current passed between the instrument tips to coagulate the bleeding vessels.


Results of intraocular lens implant surgery. The third Binkhorst medal lecture.

I compared an early series of 162 consecutive Copeland intraocular lens implants with a later series of 650 consecutive Binkhorst implants. Of the eyes with Copeland implants, 76.5% achieved 6/12 (20/40) or better visual acuity compared to 89.8% in the Binkhorst series. There was a striking difference in the incidence of clinically significant cystoid macular edema (less than 6/12 [20/40], visual acuity); 7.4% in the Copeland series and 1.4% in the Binkhorst series. I studied the Binkhorst series for visual acuity, causes of less than 6/12 (20/40) visual acuity, operative vitreous problems, additional surgery, secondary membranes, dislocations, and retinal detachment. A fluorescein angiographic study of 190 Binkhorst implants and 113 aphakic controls was done. There was a comparable incidence of cystoid macular edema in both groups at four, eight, and 16 to 24 months postoperatively. Extracapsular Binkhorst implants showed a lower incidence than intracapsular Binkhorst implants.


Dermis-fat graft as a movable implant within the muscle cone.

A 31-year-old woman had an extruding ocular implant in her right orbit. After surgically removing the implant, we transferred an autogenous dermis-fat graft from the hip region to the freshly prepared socket. The graft was sutured to the conjunctiva, and a conformer was placed in the socket. Eight weeks postoperatively, the dermis-fat graft was covered with conjunctival epithelium and a prosthesis was fitted successfully. No evidence of infection has occurred. This technique of using composite dermis-fat grafts in enophthalmos avoids recurrent extrusions and corrects the cosmetic problems produced by migrating or extruding implants.


Relation of visual acuity to illumination, contrast, and distance in the partially sighted.

Visual acuity (minimum target size for threshold visibility) was measured as a function of luminance, contrast, and distance in experiments using 16 partially sighted persons. The results indicate large individual differences in dependence of visual acuity on both luminance and contrast. Visual acuity often failed to change systematically with variations in the testing distance; the effects of contrast and luminence on visual acuity also frequently failed to show any systematic dependence on viewing distance. The relation of acuity in the partially sighted to medical diagnosis is discussed along with some practical implications.


Lateral displacement as a response cue in the Titmus Stereo test.

Forty-nine subjects (ages 8-55) were tested with the circles and animals of the Tigmus Stereo test while wearing Polarid filters at axis 135 deg before both eyes so that the right eye's target was presented to both eyes. This procedure removed retinal image disparity as a cue to depth and left lateral displacement as the primary cue to obtain correct responses on the test. The subjects' scores on the circle test were much higher than expected by chance guessing. Different instructions to the subjects did not influence this result. Scores on the animal test were similar to those expected by chance. The subjects used lateral displacement as a response cue on the circle test but not on the animal test. Procedures for improving the validity of the Titmus Stereo test are described.


The effects of wear, acid etching, and bond removal on human enamel.

A method of marking human enamel so that reduction in enamel thickness by etching, bonding, and wear could be measured to within a range of -2.5 to +3.5 microns for the impression accuracy and to within a range of -1.5 to +3.8 microns for the measurement error, was devised and used to measure the effects of the above factors on enamel. For five unetched surfaces studied in vivo, the 85-day loss of enamel averaged 1.6 microns. For twenty teeth etched and studied in vivo, the etch removed 9.9 microns of enamel and the subsequent loss over 85 days exceeded normal wear by 3.0 microns. The etch produces microporosities up to 50 microns in depth; therefore, the remaining 40 to 45 microns must be filled rather than worn smooth. For twelve teeth subjected to etching, bonding, bracket removal, and "clean up," enamel removed averaged 55.6 microns or approximately the entire thickness of the etch. The surface immediately following the "clean up" and 2 months after "clean up" were clinically and microscopically comparable to an untouched enamel surface.


The effects of indomethacin on the generalized shwartzman reaction.

The antiflammatory drug indomethacin, an inhibitor of prostaglandin synthesis, prevents the generalized Shwartzman reaction produced in rabbits by two intravenous injections of bacterial endotoxin. Indomethacin has this effect if given before the first but not the second injection of endotoxin. Measurements of circulating white blood cells, platelets, partial thromboplastin time, prothrombin time, fibrinogen, plasminogen, and soluble fibrin were made at several times after either the first or second injection of endotoxin treated and nontreated rabbits. Four hours after the first injection of endotoxin, leukopenia and thrombocytopenia were somewhat greater in treated rabbits and the prolongation of the activated partial thromboplastin time was shortened. Twenty-one hours after injection of endotoxin, leukocytosis and elevation of plasma fibrinogen were not as great in treated animals. Four hours following the second injection of endotoxin a decrease in fibrinogen, prolongation of the prothrombin time, and the elaboration of soluble fibrin were consistently found in rabbits with the generalized Shwartzman reaction. In treated rabbits, none of these changes occurred. Indomethacin prevents the generalized Shwartzman reaction by preventing the development of the prepared state in this endotoxin model.


The immunohistopathology of glomerular antigens. II. The glomerular basement membrane, actomyosin, and fibroblast surface antigens in normal, diseased, and transplanted human kidneys.

Immunofluorescent studies have demonstrated that actomyosin (AMY) is present in the mesangium in a restrictive pattern, whereas fibroblast surface antigen (FSA) has a more extensive mesangial distribution. Antibody to glomerular basement membrane (GBM) is localized to the GBM. One hundred ninety-six tissue samples, including 17 from normal subjects, 94 from patients with primary renal diseases, and 85 from transplanted kidneys, were examined for changes in distribution of AMY, FSA, and GBM antigens. The distribution of AMY and FSA in the mesangium is markedly increased in width in patients with diabetic nephropathy, and the GBM is thickened. AMY and FSA are mildly increased in patients with glomerulonephritis and GBM is normal. Patients with membranoproliferative glomerulonephritis (MPGN) show a loss of all glomerular antigens. Increased mesangial AMY was found in 12 of 37 transplanted kidneys in diabetic patients vs 4 of 33 nondiabetics 0 to 4 years after transplantation (P < 0.025). This difference is more notable at 2 to 4 years, with 5 of 9 diabetics showing increased AMY vs 0 of 6 nondiabetic patients (P < 0.0005). In MPGN, 5 of 8 tissues showed decreased mesangial AMY vs 3 of 36 diabetic patients (P < 0.0005) and 1 of 32 patients with other glomerulopathies (P < 0.0005). GBM thickening is not associated with specific pretransplant diseases. In transplanted kidneys, the pattern of FSA is dissociated from that of AMY: over half of all patients have increased FSA, even when AMY is normal. Whether this unique finding in transplanted kidneys reflects an increase in the synthesis of FSA by mesangial cells or the failure to clear this (circulating) antigen from the mesangial matrix is unknown.


Structural and functional heterogeneity of mammalian nephrons.

Since the anatomical descriptions of Bowman showing differences between nephrons originating in the superficial and deep cortex, the concept of heterogeneity has been extended from identification of dissimilarities between nephrons to recognition of inhomogeneity within major portions of individual nephrons. We are now aware of functional correlates for the anatomical differences between nephrons, between analogous parts of different nephrons, and between the three portions of the proximal tubule and the three or more parts of the distal tubule. The implications of all of these differences for major renal processes, such as isosmotic fluid transport, salt balance, hypertension, urinary acidification, and the concentration or urine are now being defined. It seems likely that new conceptual and technical approaches, especially electron probe microanalysis, will add appreciably to defining the role of heterogeneity in these and other processes. Despite the increasing complexity of nephron heterogeneity, it is recommended that our basic nomenclature be retained and that new findings be incorporated into the schema set forth by Karl Peter. It would be very helpful if reports of investigations on single nephrons or segments of nephrons were to include diagrams delineating the structures on which the work was performed.


Effects of decreasing lung compliance with oleic acid on the cardiovascular response to PEEP.

In 12 anesthetized mongrel dogs on a constant volume ventilator, the response of the cardiovascular system to increasing positive end-expiratory pressure (PEEP) was examined before and after inducing acute lung injury with oleic acid. As PEEP was raised to approximately 16 mmHg, lung volume increased by approximately 900 ml before oleic acid and only 350 ml after. Pleural pressure increased by the same amount, indicating that both lung and chest wall compliance decreased with oleic acid. Right atrial pressure, the back pressure to venous return, also increased by the same amount. Although cardiac output at PEEP = 0 was lower after oleic acid, the relative decrements produced by increasing PEEP were the same as before oleic acid.


The seroepidemiology of malaria in Middle America. IV. Passage of malaria antibodies from mothers to infants.

In an area of El Salvador moderately endemic for malaria, use of the indirect fluorescent antibody test (IFA) showed that 44% of the infants born to mothers who had IFA responses to Plasmodium vivax of 1:20 or higher during the latter part of their pregnancy had positive IFA responses of 1:10 or higher to this antigen. No serum from an infant was positive in the absence of some level of malarial response in the mother.


Evaluation of the indirect immunofluorescence and complement fixation tests for the serodiagnosis of schistosomiasis.

Sera from patients with a variety of infections were used to compare the sensitivity and specificity of the complement fixation (CF) and the indirect immunofluorescence (IIF) tests for schistosomiasis. Adult antigens were used in both tests. The sensitivities of the IIF and CF tests were 95% and 69%, respectively; the specificities were 98% and 100%, respectively. There was no statistical difference between the number of positive reactors among those individuals with no detectable helminth infection and those infected with helminths other than schistosomes. Infected people native to endemic areas had lower reactivity in both tests than did infected U.S. citizens who resided in endemic areas for only a few years. We concluded that the IIF test with adult antigen was more sensitive than and as specific as the CF test; therefore, the IIF test is the procedure of choice for routine diagnostic serology of schistosomiasis.


Management of subclavian and innominate artery injuries.

Subclavian and innominate arterial injuries are life-threatening and require aggressive treatment. Physical findings, chest x-ray examinations, and a high index of suspicion led to expoloration in seventeen of twenty-two patients in this series, but the selective use of arteriography is helpful. Primary repair was accomplished in nineteen of the twenty-two patients. Wide proximal exposure proved to be accompanied by little morbidity with the reward of increasing survival to 95.5 per cent.


Vascular access for chronic hemodialysis: polytetrafluoroethylene (PTFE) versus bovine heterograft.

Between May 1975 and March 1977, 193 bovine heterografts and 184 polytetrafluoroethylene (PTFE) grafts (Impragrafts) have been placed for hemodialysis access. A comparison of these materials demonstrates that Impragrafts have significantly fewer late thromboses, increased resistance to infection, and comparable longevity, and they are easier to repair.


[New PEEP device--application of PEEP and CPAP during manually operated ventilation (author's transl)].

A new PEEP device has been developed for use with manually operated resuscitators. The PEEP valve can be combined with adult resuscitators as well as with neonatal resuscitators (40 g). The PEEP can be varied between 0 and +10 cm H2O. With this new PEEP device it is now possible to apply PEEP during manually operated artificial ventilation, e.g. during transportation etc.


Serum cholinesterase in tetanus.

This paper describes the correlation between serum cholinesterase levels and the severity and course of tetanus in a young patient. The diagnostic and prognostic value and significance of this enzyme as well as the therapeutic value of cholinesterase-restoring agents in tetanus are discussed.


A control-free ventilator alarm.

An alarm for use with positive-pressure lung ventilators is described. The device gives audible warning if the pressure in the patient circuit fails either to exceed or to fall below 15 cmH2O within a period of 20 seconds or if the batteries are running low. No external controls are provided and the alarm is activated when a probe connected to the breathing circuit is inserted into the alarm. The probe whistles if incorrectly connected during intermittent positive pressure ventilation. Battery life in clinical practice is longer than 6 months.


[Easy alteration of the PEEP-system to CPAP by using exclusively original bird parts (author's transl)].

In various situations breathing with positive-end expiratory pressure (PEEP) and spontaneous respiration with continously positive airway pressure (CPAP) is of advantage to the patient. Not all intensive care units are equipped with the modern apparatus that makes possible alternative application of PEEP and CPAP. We have developed a system using a BIRD Mark 7 or 8 that allows alteration of PEEP to CPAP by only few manipulations. As a safety measure we exclusively apply original parts of the same firm (BIRD). The system allows exact adjustment and controllable application of a continuous positive airway pressure, exact proportion of oxygen in the inspired gas, moistening of the in spired air and nebulization of medicaments. If the patient should show inadequate ventitation after a certain times then artificial respiration with the PEEP system is quickly possible with only a few manipulations.


Clover's portable regulating ether inhaler (1877). A notable one hundredth anniversary.

The 100th anniversary of the first description of the 'portable regulating ether-inhaler' by Joseph T. Clover (1825-1882) is recalled. The importance of this piece of apparatus in the development of British anaesthesia is considered and the techniques of its use are outlined. Clover's personal portable inhaler is described and illustrated.


[Morphological methods for estimation of the vitality of cartilage and bone tissue (author's transl)].

For estimation of the vitality of bone probes before transplantation it is possible to evidence the succinic dehydrogenase in native slides, which were made on a special microtome. For experience it is possible, too, to show the vitality of cartilage after injection of 35S (as Na-sulphate) with autoradiographic methods.


Frederic Hewitt lecture 1977.  Anaesthesia as a career.

The contribution of Frederic Hewitt (1855-1916) to the development of the specialty of anaesthesia is acknowledged and his reasons for becoming an anaesthetist explored. Three hundred and forty-nine replies to a questionnaire on professional philosophy, status and training sent to 676 anaesthetists who joined the Association of Anaesthetists of Great Britain and Ireland during the years 1972-1975 are assessed. The factors which influence a medical practitioner to take up anaesthesia and find satisfaction in its practice are explored in the light of these replies and suggestions are made with regard to the future of the specialty.


[Ultrahistochemical evidence of Ca2+-ions with the aid of freeze-substituted slide technique (author's transl)].

This ultrahistochemical method is based on the precipitation of free Ca2+-ions in biological material with the free oxalic acid. The precipitation reaction will be made during the freeze-substitution. The efficience of this method is 99%.


Membrane alterations during cornification of mammalian squamous epithelia: a freeze-fracture, tracer, and thin-section study.

Tight junctions (zonulae occludentes) create a pericellular barrier to the diffusion of large molecules in non-keratinizing mammalian epithelia. However, in cornifying epithelia such as the epidermis, the importance of tight-junctional elements versus secreted intercellular lipid for barrier function is uncertain. In an attempt to resolve this question, we compared membrane structure in the stratum granulosum and stratum corneum of epidermis, esophagus, and vagina of newborn and adult humans and mice under both normal and various experimental conditions. We incubated pieces of epidermis in organ culture and infused tissues with lanthanum or horseradish peroxidase in vivo and in vitro. All were processed for electron microscopy of freeze-fracture replicas or thin sections. Lanthanum seeped outward to the stratum granulosum in all tissues examined--further apical migration was halted by lamellar-body contents in skin. A similar pattern of intercellular lamellar lipid deposition and membrane structure occurred in all epithelia studied. Freeze-fracture replicas of these obstructive regions revealed occasional, incomplete junctional strands (particularly in moist epithelia) and abundant lamellar material, but complete zonulae occludentes were never encountered. A possible relationship between moisture and tight junction formation was further suggested by organ culture experiments during which brief incubations stimulated an increase in the number of junctional strands and diminished numbers of lamellar bodies. We conclude that, in the epithelia studied, the deposition of secreted lamellar body contents forms the barrier to water-soluble tracer loss: tight-junctional elements are either absent or too fragmentary to constitute an effective barrier.


Etomidate in a new solvent. A clinical evaluation.

The introduction of polyethylene glycol as a solvent for etomidate appears to markedly reduce the incidence of pain on injection while maintaining the previously demonstrated advantageous features of cardiovascular stability and rapid recovery.


Comparison of real and simulated acupuncture and isoproterenol in methacholine-induced asthma.

In a double-blind (patient and evaluator), crossover study effects of real acupuncture, simulated acupuncture, nebulized isoproterenol, nebulized saline and no treatment in reversing methacholine-induced bronchospasm were compared in 12 asthmatics (ages 16 to 64). Saline and simulated acupuncture did not result in any significant improvement in specific airway conductance (SGaw), thoracic gas volume (Vtg) or forced expiratory flow rates compared with no treatment following methacholine-induced bronchospasm. Isoproterenol and real acupuncture were both followed by increases in SGaw and flow rates and decreases in Vtg which were significantly different from the changes observed following no treatment, saline or simulated acupuncture, although isoproterenol produced greater improvement than real acupuncture, although isoproterenol produced greater improvement than real acupuncture. These findings suggest that stimulation of specific acupuncture loci reduces methacholine-induced bronchospasm and hyperinflation to an extent greater than can be attributed to placebo phenomena.


Fenoterol: clinical trial of a new long acting bronchodilator.

The bronchodilator and side effects of fenoterol and isoproterenol were evaluated in 19 asthmatic adults in a double-blind study. The study demonstrated that fenoterol has an onset of action which is just as rapid as isoproterenol and a duration of action that is markedly superior. Side effects were minimal.


Double-blind one-year clinical study of fenoterol metered dose inhaler: preliminary results of a cooperative study.

As part of a controlled multi-center study 44 chronic asthmatics were treated for one year with either fenoterol (0.4 mg t.i.d. or q.i.d.) or isoproterenol (0.15 mg t.i.d. or q.i.d.) by metered dose inhaler. According to spirometric tests, fenoterol significantly improved pulmonary function until the end; isoproterenol became less effective after six months. Periodic global evaluations also gave no evidence of tolerance developing to femoterol. Side effects remained within acceptable limits.


Actin like filaments in the peritubular cells of human testis chemical extraction and binding with heavy meromyosin.

Two types of the cytoplasmic filaments are found in human peritubular cells; thin filaments (50-80 A) and 100 A filaments. The thin filaments are numerous and tightly packed in cytoplasma of peripheral cell processes, and form bundles. These bundles are arranged in parallel with the long axis of the cells. Dense areas are occasionally seen among the filaments, or underneath the cell membrane to which the thin filaments seem to be anchored. The 100 A filaments are generally located around the perinuclear region or in the middle region of cytoplasma. The thin filaments are not altered after incubation with Hasselbach-Schneider's solution. These filaments, however, disappear in cytoplasma when extracted with 0.6 M KI solution. And also, the thin filaments form chracteristic arrowhead complexes, when incubated with HMM, while these complexes are never found, when incubated with HMM plus ATP. The 100 A filaments do not react to HMM. Thus it is suggested that the thin filaments are actin or actin like and that a contractile system exists in human peritubular cells, which may be involved in transport of nonmotile sperm or permeability of the seminiferous walls.


Comparison of albuterol and isoproterenol aerosols in bronchial asthma.

Albuterol and isoproterenol aerosols were compared with placebo in a double-blind manner in 18 patients with bronchial asthma. Both drugs elicited significant improvement in flow rates and vital capacity. Duration of action was longer with albuterol than with isoproterenol. Neither was associated with significant increases in heart rate or blood pressure.


Prolonged immunotherapy with alum-precipitated pyridine ragweed extracts-a clinical and immunological study.

In 18 ragweed hay fever patients who received injections of alum-precipitated pyridine (Allpyral) ragweed extracts in maintenance doses of between 6000 and 8000 P.N.U. at intervals of between two and four months over a two-year period, the prolonged interval did not seem to influence either the clinical response or the tendency to reaction, or result in significant change in immunological tolerance as determined by antibody studies, which included fluorescent antibody assays, as well as hemagglutination and RAST technics.


Biochemical characteristics of enterotoxigenic and nonenterotoxigenic Escherichia coli isolated from calves with diarrhea.

Eighteen isolates of enterotoxigenic Escherichia coli (ETEC) and 15 isolates of nonenterotoxigenic E coli (NETEC) obtained from calves with diarrheal disease were characterized biochemically. Of 64 biochemical tests employed, none allowed making differentiation of ETEC from NETEC. Eleven tests were used to separate ETEC isolates into 1 of 5 biotypes, although the ability to ferment dulcitol, salicin, sucrose, and sorbose gave sufficient information to identify the 5 biotypes of ETEC. The biotype data were confirmed upon testing 159 additional isolates of ETEC of bovine origin. All isolates of ETEC studied belong to serogroups O9:K35, O101:K30, O8:K85, O20:K? O8:K25, and O101:K28. The ETEC in different serogroups were also different biotypically, with the exception that isolates in serogroups O101:K28 and O101:K30 were of the same biotype. The K99 antigen was detected in 172 of the 177 isolates of ETEC and in 1 of 15 isolates of NETEC. Marked biochemical differences were not found between K99 + and K99- isolates of E coli.


Bactericidal activity of standard bovine serum against coliform bacteria isolated from udders and the environment of dairy cows.

Coliform organisms were isolated from bedding, udders of cows exhibiting acute or chronic mastitis, and milk of cows tested for udder pathogens. The bactericidal activity of standard bovine serum was tested on 362 isolates, of which 2.4% were killed at a serum dilution of less than 1:5; 2.7% were killed at a dilution of 1.5; 3.0% were killed at a dilution of 1:12.5; and 4.4% were sensitive to a dilution of 1:25. Organisms isolated from mastitic udders were not killed by serum. Sensitivity to agglutination in 1:500 solution of acriflavine was tested on 157 isolates, and only 54 had any degree of agglutination. Of these 54, only 4 organisms had any susceptibility to killing by serum. Results suggest that most organisms in the environment of the cow are resistant to serum, few serum-sensitive coliforms cause mastitis, and agglutination in acriflavine (indicating organisms in the rough phase) does not correlate with sensitibity to serum.


Skin testing, fecal culture, and lymphocyte immunostimulation in cattle inoculated with Mycobacterium paratuberculosis.

Fourteen calves at 21 days of age were experimentally inoculated with 100 mg (wet weight) of Mycobacterium paratuberculosis. Three calves were inoculated orally, 4 intravenously, and 7 subcutaneously. Lymphocyte immunostimulation, fecal culture, and intradermal tuberculin skin testing were done between 112 to 150 days following exposure. Lymphocyte immunostimulation test results, conducted at 112 days after inoculation, showed all animals positive to Mycobacterium avium purified protein derivative. Fecal culture results, taken at 120 days after inoculation, showed that 2 of 3 animals inoculated intravenously were positive, whereas only 2 of 7 inoculated subcutaneously were positive (8 of 14 total were positive). Intradermal skin testing results at 150 days with M avium purified protein derivative showed 13 of the 14 calves were positive. Calves were examined at necropsy 153 days after inoculation, and M paratuberculosis was isolated from tissues of each of the 14 calves.


In vitro stimulation of bovine peripheral blood lymphocytes: suppression of phytomitogen and specific antigen lymphocyte responses by aflatoxin.

The effects of aflatoxin B1 on responses of the peripheral blood lymphocytes (PBL) of 2 normal animals to phytohemagglutinin, concanavalin-A, and pokeweed mitogen and of the PBL of 2 Mycobacterium bovis-infected animals to phytohemagglutinin and purified protein derivative of M bovis (PPD) were studied. Aflatoxin concentrations of greater than or equal to 10 microgram/ml significantly suppressed the lymphocyte response of normal animals to the phytomitogens. Lymphocyte response of M bovis-infected animals to specific antigen PPD was significantly suppressed at aflatoxin concentration of 0.5 microgram/ml. Fifty- to 100-fold higher concentrations of aflatoxin were required to produce 50% suppression of lymphocyte response to phytomitogens, as compared with that produced to PPD.


Immunization of mice after airborne infection with various strains of BCG.

The growth of 6 strains of bacillus Calmette-Guérin (BCG) in the lungs of mice was compared after direct implantation into those organs. Bacilli of the Connaught, Pasteur, Phipps, and Tice strains multiplied appreciably in the lungs and disseminated into the spleen In contrast, BCG Birkhaug and Glaxo strains did not replicate in the lungs or spread to the spleen. The immunizing ability of 3 of these strains was examined in more detail. Aerosol infection with BCG Glaxo, Pasteur, or Phipps strains produced resistance to subsequent pulmonary challenge with Mycobacterium tuberculosis RIRv. Such immunity was significantly greater in mice immunized with the Pasteur and Phipps strains and was not attributable to nonspecific resistance. Spleen cells from mice immunized with these 3 strains of BCG conferred similar degrees of immunity to intravenous challenge with M. tuberculosis on syngenic recipients. It was concluded that growth of BCG in the lungs influenced the degree of local immunity but not the degree of systemic immunity.


Chronic experimental interstitial pneumonitis in the rabbit.

The effects on the lungs of chronic aerosol and intravenous antigen challenges in preimmunized and control rabbits were studied. Soluble and particulate antigens included ovalbumin, keyhole limpet hemocyanin, antigen-adsorbed latex particles, glutaraldehyde cross-linked ovalbumin, and killed bacille Calmette-Guérin (BCG). Despite the development of acute alveolitis in sensitized animals, chronic aerosol challenge with both soluble and particulate antigens failed to produce chronic interstitial lung disease. Chronic intravenous challenge with killed BCG, but not other particulate antigens, resulted in a progressive interstitial pneumonitis, with evidence of fibrogenesis in animals that had been presensitized to tuberculin by toepad injection of complete Freund's adjuvant. Adaptive alveolar clearance mechanisms thus appear to protect rabbits from chronically inhaled antigen. Pulmonary circulatory clearance of BCG, however, results in an interstitial pneumonitis that is dependent on previous sensitization.


Cyanoacrylate sealing of pancreatic biopsy sites in dogs.

The ability of ethyl cyanocrylate monomer adhesive in preventing leaks following pancreatic surgery dogs was evaluated. Seventeen of 18 dogs in the control group had evidence of pancreatic leak following biopsy. There was no evidence of leak in 17 of 18 dogs on which the adhesive was used to seal the cut surface of the pancreas. Similar successful use of ethyl cyanoacrylate in patients would provide a safe method of taking a specimen from a mass for biopsy in the pancreas.


Pancuronium bromide.

Pancuronium bromide is a nondepolarizing muscle relaxant approved to induce skeletal muscle relaxation during anesthesia and to facilitate the management of patients undergoing mechanical ventilation. The use of pancuronium bromide during surgery led to the appreciation that it has advantages over drugs previously used for muscle relaxation. Patients in whom pancuronium bromide is of value are (1) hypoxemic patients resisting mechanical ventilation and so cardiovascularly unstable that use of sedatives is precluded, (2) patients with bronchospasm unresponsive to conventional therapy, (3) patients with severe tetanus or poisoning where muscle spasm prohibits adequate ventilation, (4) patients with status epilepticus unable to maintain their own ventilation, (5) shivering patients in whom metabolic demands for oxygen should be reduced, and (6) patients requiring tracheal intubation in whom succinylcholine administration is contraindicated. Without concomitant sedation, use of pancuronium bromide is associated with psychological risks. Other risks are undetected ventilator disconnection, tachyarrythmias, prolonged paralysis and drug interactions.


UCLA Conference. Monocytes and macrophages: functions and diseases.

The mononuclear phagocyte complex is a widespread system of cells originating in the bone marrow monoblast and promonocyte, passing through the intermediate monocyte stage in the blood, and culminating in the tissue macrophages of the lung, liver, spleen, and pleural and peritoneal spaces. The cells are prominently phagocytic and have a well-developed lysosomal system. They function in host defense reactions against micro-organisms, in interactions with lymphoid cells in immunity, in disposal of cell debris, and possible in the regulation of granulopoiesis. Monocytes and the alveolar macrophage are the most accessible cells of this system for study. Several diseases of mononuclear phagocytes have been identified and characterized. These include microbicidal defects associated with increased susceptibility to infection, enzyme defects leading to storage diseases, and neoplastic diseases in which both cell proliferation and biologically active cell products contribute to the clinical disorder.


Hormonal therapy of breast cancer: new approaches and concepts.

The most useful new hormonal therapy against estrogen receptor-containing metastatic breast cancer is the development of antiestrogenic agents such as nafoxidine and tamoxifen. Both of these drugs possess antitumor activity comparable to that of other additive hormonal agents, and they are better tolerated for lack of any serious toxicity. The clinical usefulness of antiprolactin drugs in breast cancer is at present limited. Adrenal suppression using aminoglutethimide has been shown to induce useful remissions. We discuss the implications of new treatment modalities for the future management of disseminated breast cancer.


Small airways of the lung. The importance of understanding and assessing the function of pulmonary bronchioles.

Recent findings have emphasized the importance of the bronchiole to the function of the lung. The surface of the bronchiole differs from that of the alveolus. Rather than being covered by a thin coat of phospholipid, the surface is covered with cilia that are surrounded by a low-viscosity fluid. This permits the removal of foreign particles. Surface forces are important to the function of the bronchiole. The diameter of the bronchiole is a function of the volume of the lung. When the lung is partially collapsed, the bronchiole acts as a capillary tube and is readily obstructed by fluid. In chronic bronchitis, obstruction is related to narrowing by fibrosis and inflammation, alteration in the secretion, and loss of traction on the walls. Obstruction of the bronchiole by fluid in edema of the lung contributes to hypoxemia. Positive end expiratory pressure may prevent obstruction by increasing the bronchiolar diameter.


[Psychological approach to Céline's obscenity].

The aim of the psycho-analytical approach the author attempts is the obscene character of Céline's dependent of the writer's whole personality. The obscenity of the celinian language proceeds from several causes. It can be explained by the lucid and the phallic-narcistical features of Céline's personality in relation with psycho-sociological factors. Obscenity is lecherous and sullen in regard to women and virulent towards men: it may then be interpreted as a mean of struggle against the anxiety of death. It is also used to translate the celinian contempt of the human being.


[Transmissive drug resistance and virulence of "epidemic" strains of S. typhimurium].

A total of 59 "epidemic" strains of S. typhimurium and 52 cultures isolated from the cases with sporadic diseases were studied with respect to the nature of their resistance to 10 antibiotics and virulence for albino mice under conditions of subcutaneous and oral inoculation. The virulence of the cultures isolated from the cases with sporadic diseases was higher in the strains sensitive to antibiotics. The "epidemic" strains were characterized by the lowest virulence for the mice and resistance to 8-10 antibiotics simultaneously with the transmissive nature of resistance to 1-5 drugs. The transmissive nature of resistance to antibiotics and its spectrum may serve an additional epidemiological marker of the strains.


[Use of tablet forms of monomycin in children with acute dysentery].

The clinical picture of acute dysentery caused mainly by Shigella sonnei was studied in 160 children: 50 children were treated with monomycin tablets and for the treatment of 110 children monomycin in the form of amorphous powder in bottles was used. The treatment was carried out in accordance with the official instructions. Coincidence of the recovery time in the both groups was registered. When the patients were treated with monomycin tablets, 5 and 15-34 per cent of the antibiotic a daily dose was excreted with the urine and excrements respectively. It was concluded that monomycin in the from of tablets was more convenient in the treatment of children.


[Study of the composition and elaboration of a catalytic method for purifying the gaseous waste from neomycin and monomycin production].

Composition of the waste gases in the production of neomycin and monomycin at the stages of fermentation, coagulation and filtration was studied. It was found that the main components of the waste gases in the production of neomycin and monomycin were carbon dioxide (0.15-6.0 mg/1), moisture (22-34 mg/1) and organic substances (0.5-4.2 mg/1) calculated for carbon dioxide. These substances have a specific unpleasant odour. A procedure for purification of the waste gases in the production of neomycin and monomycin by catalytic oxidation was developed.


[State of the blood coagulating system in the treatment of puerperal infections using semisynthetic penicillins and cephaloridine].

The effect of some semi-synthetic penicillins, such as methicillin and oxacillin and cephalosporings, such as cephaloridin on the condition of the blood coagulation system in 85 patients with postnatal mastitis and endomyometritis was studied. It was shown that the above antibiotics had no significant effect on the parameters of the blood coagulating system. A decrease in the fibrinogen level was found in the mastitis patients treated with semi-synthetic penicillins and cephaloridin. An increase in the prothrombins index in the patients treated with methicillin oxacillin was shown. The use of the semi-synthetic penicillins and cephaloridin for the therapy of the puerpera with endomyometritis resulted in prolongation of the recalcification period. A decrease in the fibrinolytic activity most pronounced in therapy with cephaloridin was also found. Therefore, the above changes in the blood coagulating system of the puerpera with postnatal infections subjected to short-term treatment courses were insignificant and required no special correction.


Characterization of the E. coli K12 strain AB1157 as impaired in guanine/xanthine metabolism.

The widely used E. coli K12 strain AB1157 is impaired in guanine (xnathine) metabolism. Mutants blocked in purine biosynthesis before the stage of inosine monophosphate synthesis do not grow on external guanine or xanthine. The genetic nature of the Gua/Xan lesion is a deletion in the chromosome that covers the proA gene. The lesion causes reduced uptake of guanine.


Microbial metabolic activity in soil as measured by dehydrogenase determinations.

The dehydrogenase technique for measuring the metabolic activity of microorganisms in soil was modified to use a 6-h, 37 degrees C incubation with either glucose of yeast extract as the electron-donating substrate. The rate of formazan production remained constant during this time interval, and cellular multiplication apparently did not occur. The technique was used to follow changes in the overall metabolic activities of microorganisms in soil undergoing incubation with a limiting concentration of added nutrient. The sequence of events was similar to that obtained by using the Warburg respirometer to measure O2 consumption. However, the major peaks of activity occurred earlier with the respirometer. This possibly is due to the lack of atmospheric CO2 during the O2 consumption measurements.


Enhancement of isoleucine hydroxamate-mediated growth inhibition and improvement of isoleucine-producing strains of Serratia marcescens.

Growth inhibition by isoleucine hydroxamate in Serratia marcescens was significantly enhanced by adding valine plus leucine and by using glycerol as the carbon source. Isoleucine hydroxamate-resistant mutants were isolated under conditions in which growth inhibition was enhanced. One of the mutants, strain GIHVLr2179, lacked both feedback inhibition and repression of threonine deaminase. An alpha-aminobutyric acid-resistant mutant derived from strain GIHVLr2179, strain GIHVLAr2795, produced 12 mg of isoleucine per ml in the medium containing glucose and urea as carbon and nitrogen sources (a twofold increase over prior reports). This strain had increased activities of threonine deaminase, acetohydroxy acid synthase, aspartokinase, and homoserine dehydrogenase.


Temperature effects on bacterial movement.

Details are presented for the construction of a simple precision temperature-controlled chamber for investigating bacterial motile behavior. Independent of original incubation temperature, all species of motile bacteria observed showed a five- to sevenfold increase in average translational velocity (micrometers per second) as the environment temperature was incremented over the range from 10 to 50 degrees C. Temperature jumps downward produced transient tumbling or reciprocal behavior responses, depending on the mode of flagellar distribution, in all species examined. Upward temperature jumps induced accelerated velocities without tumbling or reversal. A partial capacity adaptation to temperature was noted, in that the greatest average translational velocity at any given observation temperature occurred when the organisms were grown at temperatures less than the optimum.


Performance characteristics of a new photometer with a moving filter tape for luminescence assay.

The performance characteristics of a new photometer that incorporated a reaction system consisting of a movable filtration tape have been studied for use with the firefly luciferase assay for adenosine 5'-triphosphate. Precision, linearity, and sensitivity are given for measuring a graded series of constant-light emitters, concentrations of adenosine 5'-triphosphate, and washed bacterial cells. Precision ranged from 1 to 10% coefficient of variation. The coefficient of correlation was 0.9985 for 7 X 10(8) to 7 X 10(3) bacteria per ml; however, the accuracy decreased at the low levels. The sample processing time was 2 min for a 1-ml sample. This instrument shows potential for many applications in quantitating small numbers of organisms, e.g., pollution, water monitoring, and clinical infection detection.


Isolation of Yersinia enterocolitica from well water and growth in distilled water.

Yersinia enterocolitica was recovered from well water during a large water-borne outbreak of gastrointestinal illness. Isolates were predominantly Nilehn biotype 1, of which 57% were serologically nontypable. Isolation and enumeration of these Y. enterocolitica strains were made on M-Endo broth. Laboratory studies were conducted on selected isolates to establish the growth of Y. enterocolitica in distilled water and the competitive growth of this organism in various enteric media. Growth was obtained in sterile distilled water without added nutrients at 4, 25, and 37 degrees C. M-Endo medium gave equal or better recovery of Y. enterocolitica in competitive growth studies than did other commonly used enteric media using the membrane filter technique and incubating at 35 degrees C. All well water isolates were confirmed biochemically at 25 and 35 degrees C and serotyped, and antibiotic susceptibility tests were performed.


Macromolecule synthesis of Escherichia coli BB at a lower or transient growth state.

Macromolecule synthesis in Escherichia coli BB at lower growth rates was investigated. The results indicate that a deviation in ribonucleic acid (RNA) content per cell at a lower growth rate from the exponential relationship to a specific growth rate is entirely attributable to the presence of nonviable cells, in which the RNA content is lower than in viable cells. Based on this fact, a mathematical expression of macromolecule contents versus specific growth rate was devised. Moreover, continuous changes in macromolecule content during unbalanced growth from late-logarithmic phase to stationary phase were measured. Although growth rates changed continuously, the data on deoxyribonucleic acid (DNA) or RNA content versus the specific growth rate calculated from the increments in cell number satisfactorily fitted the exponential lines obtained under balanced growth at a higher growth rate. However, no such relationship was observed in the plot of DNA or RNA content versus the specific growth rate calculated from the increments in optical density.


Occurrence of Aspergillus fumigatus during composting of sewage sludge.

Aspergillus fumigatus, a medically important fungal opportunist and respiratory allergen, was isolated from woodchips and sewage sludge used in the production of compost at the U.S. Department of Agriculture's composting research facility in Beltsville, Md. It was also regularly isolated as a dominant fungus during forced aeration composting and after 30 days in an unaerated stationary curing pile; in both cases, the fungus was found in pile zones with temperatures less than 60 degrees C. Compost stored outdoors in stationary unaerated piles from 1 to 4 months after screening out of woodchips contained easily detectable amounts of A. fumigatus in the exterior pile zones (0- to 25-cm depths). Semiquantitative studies of the airspora at the composting site revealed that A. fumigatus constituted 75% of the total viable mycoflora captured. At locations 320 m to 8 km from the compost site, the fungus constituted only 2% of the total viable mycoflora in the air. Of 21 samples of commercially available potting soil, one had levels of A. fumigatus nearly equivalent to those of 1-month-old storage compost; 15 others had lower but detectable levels.


Beneficial effects of catalase or pyruvate in a most-probable-number technique for the detection of Staphylococcus aureus.

The effects of the addition of catalase (EC 1.11.1.6) or pyruvate on the enumeration of Staphylococcus aureus in Trypticase soy broth with 10% NaCl were examined using a most-probable-number technique. Addition of catalase or pyruvate to the broth increased enumeration of all heat-stressed S. aureus strains tested. Increases were also observed with nonstressed cells. Catalase and pyruvate were similarly effective when added to Trypticase soy broth-10% NaCl in enumerating staphylococci naturally present in low-temperature-rendered ground-beef samples.


Comparison between two methods of assaying relative microbial activity in marine environments.

Two methods for determining relative microbial activity in the marine environment were compared. In one method, a single concentration of a labeled substrate was used to calculate rates of substrate utilization; in the other, multiple concentrations of the same substrate (heterotrophic activity method) were used to calculate maximum potential substrate utilization rates. These studies were made on 232 seawater and 79 sediment samples taken from a variety of marine environments. The highest correlations between these two methods were seen in the sediment samples tested. The lowest correlation coerfficient seen in the sediment samples was 0.90, and the highest was 0.98. In seawater samples (six studies), the lowest correlation coefficient was 0.77 and the highest was 0.95. The correlation between these two methods was also substrate concentration dependent. Higher correlation coefficients were observed when higher substrate concentrations were used. Under certain conditions, these two methods appear to be comparable for estimating relative levels of microbial activity in the marine environment.


Double-stranded ribonucleic acid in viruses of Penicillium citrinum.

The nucleic acid content of two viral populations in a strain of Penicillium citrinum is shown to be double-stranded ribonucleic acid, resolved through polyacrylamide gel electrophoresis into 10 size groups ranging from 1.17 to 3.98 megadaltons.


Cryogenic gamma irradiation of prototype pork and chicken and antagonistic effect between Clostridium botulinum types A and B.

Inoculated, irradiated pork (2,300 cans) and chicken (2,000 cans) pack studies were performed to establish the 12D dose for these foods. Each can was inoculated with a mixture of 10(6) spores of each of 10 strains of Clostridium botulinum (five type A and five type B), or a total of 10(7) spores. The cans received a series of increasing doses of gamma rays (60Co) at -30 +/- 10 degrees C; they were incubated for 6 months at 30 +/- 2 degrees C and examined for swelling, toxicity, and recoverable botulinal cells. The highest rate of swelling for both foods occurred within the first week of incubation, and maximum swelling was observed within 4 to 5 weeks. The minimal experimental sterilizing dose (ESD) based on flat, nontoxic sterile cans was 3.0 less than ESD less than or equal to 3.2 Mrad for pork and 4.0 less than ESD less than or equal to 4.2 Mrad for chicken. An analysis of the partial spoilage data by extreme-value statistics indicated with 90% confidence that the rate of spore death in the two foods was not a normal distribution, but appeared to favor a shifted exponential function. Based on the latter distribution, and assuming one most resistant strain in the mixture of 10 used, the 12D dose computed to 4.37 Mrad, with a shoulder of 0.11 Mrad, for pork and to 4.27 Mrad, with a shoulder of 0.51 Mrad, for chicken. An assumption that there were two or more most resistant strains in the inoculum progressively lowered the 12D dose. There was an apparent antagonism between the irradiated type A and B viable strains in the two foods. Cans with type B cells and toxin predominated over cans with type A cells and toxin, but cans with a mixture of type A and B toxins predominated over cans with a mixture of Type A and B cells. At the highest sublethal doses, only type A cells survived in pork, but in chicken there was a least one type B strain that was at least as resistant as type A strains.


Viability of Rhizobium bacteroids.

Bacteroids prepared from nodules of soybean and bean were tested for viability. Contrary to the prevailing view that bacteroids are nonviable, it was found that bacteroids averaged 90% viability, irrespective of Rhizobium strain, nodule age, or nodule environment.


Pemphigus foliaceus associated with absence of intercellular antigens in lower layers of epidermis.

A patient with pemphigus foliaceus was found to lack normal intercellular (IC) antigens in the lower layers of the epidermis. This was evidenced by the inability of her own IC antibodies, or of those from other patients with pemphigus vulgaris, to bind to the IC substance in the lower layers of her epidermis; whereas these same antibodies reacted to IC antigens in all layers of normal allogeneic skin and monkey and guinea pig esophagus. Lack of IC antigens in the lower layers of the epidermis may account for the subcorneal location of bullae in some patients with pemphigus foliaceus.


Topical use of caffeine with hydrocortisone in the treatment of atopic dermatitis.

In a double-blind study, topically applied caffeine 30%-hydrocortisone 0.5% in hydrophilic ointment was compared to betamethasone valerate 0.1% cream and to hydrocortisone 0.5% in hydrophilic ointment. Eighty-three patients were evaluated over a three-week period for pruritus, erythema, scaling, lichenification, excoriation, oozing, and global impression. The betamethasone and caffeine-hydrocortisone groups performed significantly better than the hydrocortisone group on three of the seven scales: lichenification, excoriation, and global impression. Also, the betamethasone group differed significantly from the hydrocortisone group on six of the seven scales, but did not differ significantly from the caffeine-hydrocortisone group on any scale. It is suggested that caffeine is effective because it elevates local levels of cyclic adenosine-3',5'-monophosphate by inhibiting phosphodiesterase.


A mechanobullous disease of the newborn. Bart's syndrome.

A patient had a unique mechanobullous disease (Bart's syndrome). The characteristic congenital localized skin defects, trauma-induced erosions, and nail deformities are present. The inheritance pattern appears to be autosomal dominant but, as in this report, isolated cases have been recognized. In a review of the other mechanobullous diseases, Bart's syndrome appears to present a distinctive clinical picture and course and has a favorable prognosis. The progressive spontaneous improvement emphasizes the importance of early recognition and conservative treatment.


Comparison between microscopical examination of unstained deposits of urine and quantitative culture.

Side-room examination of fresh samples of urine was compared with the results of surface viable bacterial counts. Examination of centrifuged deposits of urine for bacterial content was shown to compare very well with subsequent culture results. 87% of infected urines were detected, and only 6% of noninfected urines were wrongly identified. Evaluation of the uncentrifuged samples was less easy. There was poor agreement between the naked eye appearance, the presence of protein, and the pus cell count and the ultimate laboratory bacterial count. Microscopy of urinary sediments after centrifuging is recommended to assist in the rapid diagnosis of urinary tract infections particularly in young children.


Immunopathogenesis of Libman-Sacks endocarditis. Assessment by light and immunofluorescent microscopy in two patients.

The possible contribution of immunological mechanisms in the development of Libman-Sacks endocarditis was studied in 2 patients with systemic lupus erythematosus who underwent aortic valve replacement. Sections of verrucous lesions, stained with haematoxylin and eosin, showed three apparently distinct zones: an outer exudative zone of fibrin, nuclear debris, and haematoxylin-stained bodies; a middle organizing zone of proliferating capillaries and fibroblasts; and an inner zone of neovascularization which showed distinct, thin-walled junctional vessels. The striking finding was the apparently selective deposition of immunoglobulins and complement identified by direct immunofluorescence, within the walls of the small junctional vessels of the zone of neovascularization. We suggest that the observed immune deposits are immune complexes and that circulating immune complexes may play a critical role in the growth and proliferation of the verrucous lesion.


Immune reactants in cryoproteins. Relationship to complement activation.

Cryoproteins were isolated from the serum of 5 patients with essential cryoglobulinaemia 5 patients with rheumatoid arthritis, and 2 patients with Sjøgren's syndrome. These cryoprecipitates contained IgG, IgM, and IgA as well as complement proteins C1q, C4, C3, and factor B. The cryoprecipitates were analysed further for content of antibody and antigen, and were tested for their ability to activate complement. In the cryoprecipitates of 2 patients with Sjøgren's syndrome, nuclear antigen and antinuclear antibody characteristic of an immunological specificity found in Sjøgren's syndrome were shown. The cryoprecipitates of 6 other patients contained rheumatoid factor and antibody to a lymphocyte nuclear antigen. The solubilized cryoprecipitates were tested by in vitro assays for their ability to activate complement by the classical or alternative pathways. All 12 cryoprecipitates activated the classical pathway. 9 of the 12 cryoprecipitates also activated the alternative complement pathway under conditions which did not involve activation of C1 and C4. These studies show that a high percentage of cryoprecipitates consist at least in part of immune reactants. We discuss the relationship of these findings to pathogenetic mechanisms in disease.


Autotransplantation of pancreatic fragments to the portal vein and spleen of totally pancreatectomized dogs: a comparative evaluation.

Forty-nine dogs were made diabetic by total pancreatectomy. Fifteen untreated pancreatectomized animals survived a mean (+/-S.E.) of 7.0 +/- 1.1 days with a mean (+/-S.E.) plasma glucose level of 402 +/- 26 mg/100 ml before death. The pancreata of 32 dogs were distended with cold (4 degrees ) Hanks' solution, minced, digested with collagenase (600 U/ml tissue) for 15-25 minutes, and autotransplanted either into the splenic artery (three dogs), directly into the splenic pulp (21 dogs), or into the portal vein (ten dogs). Tissue infusion into the splenic artery resulted in infarction and persistent hyperglycemia. Direct implantation into the splenic pulp of tissue digested for 15, 20 and 25 minutes resulted in permanent normoglycemia (fasting plasma glucose < 150 mg/100 ml) in 7 of 8, 7 of 7, and 6 of 6 dogs respectively. Glucose tolerance test mean (+/-S.E.) K values (% decline of plasma glucose concentration/minute) in these groups two weeks after transplantation were 1.20 +/- 0.20%, 1.60 +/- 0.25 and 0.70 0.08% respectively, indicating that 20 minutes digestion was best for intrasplenic transplantation. Tissue prepared in the optimal manner (20 minutes digestion) and embolized into the liver resulted in normoglycemia in three of eight dogs, and a mean (+/-S.E.) K value of 0.77 +/- 0.10%. Both dogs receiving tissue dispersed for 25 minutes into the portal vein remained hyperglycemic. In the dogs subjected to intraportal transplantation, portal pressure rose from a mean (+/-S.E.) of 6.5 +/- 0.6 cm H(2)O before to 21.9 +/- 2.2 cm H(2)O immediately after tissue embolization, but declined to 6.5 +/- 1.0 cm H(2)O by ten weeks in animals becoming normoglycemic. We conclude that in dogs direct implantation of pancreatic tissue into the splenic pulp is superior to embolization into the portal vein or splenic artery because the splenic circulation is not compromized, portal hypertension is obviated, and glucose metabolism is best controlled as judged by glucose tolerance test K values.


In vivo and in vitro studies of chloroquine-resistant malaria in Thailand.

Fourteen patients infected with falciparum malaria admitted to the Hospital for Tropical Diseases in Bangkok, Faculty of Tropical Medicine, Mahidol University, were studied. In vivo and in vitro methods were used to compare the effects of chloroquine on Plasmodium falciparum. The results showed that RI in vivo corresponded to samples containing chloroquine base 2.5-3.5 millimicromoles per ml of blood in vitro and RII in vivo corresponded to samples with chloroquine base of 4.0 millimicromoles per ml of blood.


The chemotherapy of rodent malaria, XXVII. Studies on mefloquine (WR 142,490).

Mefloquine (WR 142,490) is a potent blood schizontocide active against drug-sensitive and drug-resistant lines of Plasmodium berghei. The ED50 and ED90 against the P. berghei N strain in albino mice are 1.5 and 3.8 mg/kg respectively. The highly chloroquine-resistant RC line is less sensitive and mefloquine is not fully effective at the maximum tolerated dose in the '4-day test'. Mefloquine has a similar mode of action to quinine both in vitro and (as demonstrated by the morphological changes it induces in P. berghei) in vivo, but is some 100 times more potent. Unlike quinine and WR 122,455 it appears not to interact with DNA. It has no causal prophylactic effect. Mixtures of mefloquine with pyrimethamine, sulphaphenazole or primaquine have an additive effect.


Studies on parasitic crisis in malaria: I. Signs of impending crisis in Plasmodium berghei infections of the white rat.

White rats infected with Plasmodiam berghei were observed throughout the course of infection for indicators of impending crisis (penultimate stage). Two ratios, percentage young compact forms:percentage trophozoites and percentage reticulocytes:percentage parasitaemia, were reliable markers of the penultimate period and impending crisis. When the percentage young compact form:percentage trophozoite ratio exceeded 1.0 and was coincident with an increase of uninfected reticulocytes in the circulation (as given by a percentage reticulocyte:percentage parasitaemia ratio greater than 1.0) the parasitaemic decline of crisis consistently occurred 24-48 hours later.


Combined Collis-Nissen reconstruction of the esophagogastric junction.

Recent reports have indicated that combined Collis-Belsey reconstruction of the esophagogastric junction fails to control reflux in 30 to 46% of patients undergoing the procedure. The major factor thought to be responsible for this result is the limited Belsey fundoplication possible after construction of the gastroplasty tube. This report describes our technique of combining the Collis gastroplasty with a 360-degree Nissen type fundoplication. The radiographic and manometric characteristics of the distal esophageal high-pressure zone produced by the Collis-Nissen operation are discussed.


Interrupted aortic arch complex: successful total correction in the neonate.

Two neonates subjected to definitive repair of interrupted aortic arch complex during the first week of life are presented. Results correlated well with preoperative status. Our definition of complete correction, including direct aortic anastomosis, is discussed along with the surgical strategy employed for successful repair of this otherwise dismal anomaly.


Aspergillus fumigatus epidural abscess in a renal transplant recipient.

An epidural abscess caused by Aspergillus fumigatus occurred in a recipient of a cadaveric, renal allograft. The patient had persistent back pain and a peripheral neuropathy that involved the lower extremities. Signs of spinal cord compression evolved. No definite portal of entry was found. Diagnosis was made by histologic examination and culture of a biopsy specimen. Therapy, consisting of aggressive surgical debridement, intravenous amphotericin B, and oral flucytosine was unsuccessful in eradicating the organism. At postmortem examination, Aspergillus was identified at the abscess site. To our knowledge, aspergillosis presenting as an epidural abscess in the immunosuppressed, renal transplant recipient has not previously been reported and should be considered in the differential diagnosis of back pain and peripheral neuropathy in such a patient.


Ticrynafen: a novel uricosuric antihypertensive natriuretic agent.

Interest in new diuretics with less side effects has led to the synthesis of ticrynafen, an uricosuric diuretic. This agent was compared with hydrochlorothiazide in a crossover design study involving 12 hypertensive men. Both agents significantly decreased mean arterial pressure from 8% to 18% in eight of the 12 patients. In addition to reducing body weight, these diuretics induced reversible changes in BUN and carbon dioxide content (increased) and plasma concentration of potassium and chloride ions (decreased). The most important change in renal function was a 2.5-fold increase in fractional urate clearance by ticrynafen associated with reduction of serum uric acid by 62%. Thus, ticrynafen is a promising therapeutic agent in hypertension, adding a unique uricosuric effect that should improve patient compliance.


Listeria cerebritis: relapse of infection in renal transplant patients.

In 3 cases of Listeria cerebritis, two of the patients had relapse with cerebritis after antimicrobial therapy for acute Listeria septicemia or meningitis. Each had received ten to 14 days of intravenous penicillin. Relapse occurred with fever and sudden focal cerebral dysfunction. Brain scans showed focal uptake; arteriograms and computerized tomography were normal. Cerebrospinal fluids were nondiagnostic; blood cultures yielded Listeria in two patients. Penicillin treatment for six weeks produced rapid clinical responses that were complete in one and minimal residual in two. Progress brain scans were normal. A relapse rate of 35% is reported in transplant patients with Listeria meningitis and/or bacteremia who are treated for less than three weeks; to our knowledge, cerebritis in such patients has not been reported previously. High-dose penicillin or ampicillin therapy for four to six weeks is recommended for Listeria infections in this select group.


Cellular content of the Krebs cycle keto acids in yeasts grown on different nitrogen sources, including hydroxylamine.

The cellular pool of Krebs cycle keto acids was followed as a function of growth in three yeasts. The keto acids were analyzed as silylated methoximes by quantitative gas chromatography with capillary glass columns. The 2-oxoglutaric acid content was strikingly high in the hydroxylamine (HA)-tolerant, HA-utilizing Endomycopsis lipolytica when compared to that in the nitrate-utilizing yeast Cryptococcus albidus and Saccharomyces cerevisiae, requiring fully reduced nitrogen for growth. The content of E. lipolytica increased throughout the log phase to maxima of about 200-250 microgram per g dry weight in HA and ammonia media. These amounts are 20-25 times greater than those attained in the two other yeasts. The cellular content of pyruvic acid was at a maximum early in the log phase, amounting to 50-70 microgram per g dry weight for all yeasts. The oxalacetic acid content never exceeded 9 microgram per g dry weight in any of the yeasts. Oximeformation, for which keto acid production is a prerequisite, is discussed as part of the HA-tolerance.


Physostigmine in mania.

Seven men and one woman with primary affective disorder, mania, were given a slow intravenous infusion of physostigmine salicylate. In six patients, mood and thought content changed from mania toward depression as evaluated by either a visual analog mood scale or the Pettersen scale. Two other patients, who were the only predominantly irritable manics in the study, demonstrated little change in their hostility, although one became somewhat depressed. These findings are consistent with earlier reports of suppression of manic symptoms after physostigmine infusion in some but not all patients with mania. The pharmacologic mechanism of physostigmine reversal of manic symptoms may be the direct result of increased cholinergic activity or a result of the effect of increased cholinergic activity on other brain neurotransmitters.


Open circulation in the human spleen, Dissection scanning electron microscopy of conductive-stained tissue and observation of resin vascular casts.

Human spleen specimens conductive-stained by the tannin-osmium method were microdissected under the scanning electron microscope and it was revealed that arteries open through one or two end-pores (3-4 mu in diameter) into the reticular cell meshes in the Billroth cord and in the perifollicular area. The endothelial cells lining the arterial terminal portion, which may be swollen into a saccular space, are perforated intracellularly. Dumb-bell shaped erythrocytes are seen passing through these side-pores (1-2 mu in diameter). The termination of arteries not in sinuses but in the cordal reticulum was also confirmed by scanning electron microscopy of blood vascular casts of methacrylate resin. These findings evidence that the "open" theory is valid in the human spleen.


Induction of lymphokines by tilorone.

Serum obtained 16 hr after p.o. application of tilorone [2, 7-bis/2-diethylaminoethoxy/-fluoren-9-one dihydrochloride] to ABD2F1 mice demonstrated both interferon and migration inhibitory (MIF) activity. Kinetic studies showed a close correspondence between interferon and MIF serum levels. The physiochemical characteristics of tilorone-induced MIF (heat and pH lability, molecular size) are compared with those of MIF generated in in vitro lymphocyte cultures. The findings are discussed in relation to production of lymphocytogenic lymphokines.


Xeroderma pigmentosum: recent studies on the DNA repair defects.

Xeroderma pigmentosum is a recessive autosomal disease of humans that is characterized by a high prevalence of skin cancers. Results of studies on cells from such patients indicate a defect in the repair of DNA damage associated with exposure to ultraviolet radiation. Since this observation was reported, a large amount of information on this disease has accumulated in the literature.


Diagnostic electron microscopy of head and neck tumors.

One hundred sixty-one neoplasms from the region of the head and neck were studied by electron microscopy to define (1) subcellular structures important of essential to diagnosis, and (2) the application and/or limitations of fresh, formaldehyde-fixed, and paraffin-blocked tissues for diagnostic use. It was concluded that electron microscopical identification of specific cytoplasmic structures was helpful in the diagnosis of head and neck neoplasms, especially those that were equivocal at the light microscopical level. Although electron microscopy could permit a more accurate classification of neoplasms in many cases, it was of little value in separating benign from malignant lesions. It was also concluded that formaldehyde-fixed tissue was a reliable source of material for these studies. Paraffin-embedded tissue was much more limited.


Neurotransmitters in spinal cord injury.

The authors report the distribution of acetylcholinesterase activity and catecholamine fluorescence in the intact and completely transected rat spinal cord. The catecholamine terminals were scarce in the posterior horn and abundant in the intermediale and anterior horn regions. In the thoracic region, intense amine fluorescence was seen in the intermediolateral cell column. Spinal transection resulted in the enhancement of fluorescence above the lesion and disappearance below the lesion within seven days. The cholinesterase activity in the controls was found mostly in the anterior horn region and the tip of the posterior horn. Following transection, there was no significant change in the distribution of this enzyme. These changes correlated with the appearance of spasticity.


[Body proportions in sculpture and painting. An anthropometric and historical essay (author's transl)].

Taking anthropometric mean values of the European population as a standard, we examined some proportions in representative sculptural and pictorial works of art. We established that the classical antique sculptures and those of Michelangelo and his school conform very closely to the European norm. Mid-Italian wooden crucifixes of the fourteenth and fifteenth centuries and early medieval European paintings of the Corpus Christi, on the other hand, display quite different proportions: exaggerated length of forearms, or torsos that are stunted in relationship to the legs. Proportions similar to these can be found in the art of the New Kingdom of the Egyptians, reflecting the physique of the Nubian population. We discussed the extent to which an artistic proportion is conditioned by style, imitation, racial aesthetic ideals, or anatomy of the ambient population.


Colorectal complications of renal allograft transplantation.

The occurrence of perforated sigmoid diverticulitis in a renal transplant recipient stimulated a review of colorectal complications in renal allograft recipients. One hundred twenty-five renal transplantations were performed in 113 patients between January 1968 and December 1975. Six patients (5%) were identified as having colorectal complications and five of these patients died as a direct result. Chart analysis of these 113 transplant recipients identified 55 patients as having undergone colonic evaluation (contrast enema, postmortem examination), with seven of these 55 (13%) found to have diverticulosis and major colonic complications eventually developing in four of these seven. Since the mortality from the complications of colorectal diseases in immunosuppressed patients is so prohibitive, in patients with diverticulosis and a previous history suggestive of diverticulitis, consideration should be given to exclusion from transplantation or elective segmental colectomy prior to transplantation.


Listeria infection in transplant patients. Five cases and a review of the literature.

We report five cases of Listeria monocytogenes infection in renal transplant patients at the University of Minnesota and compare them to 15 additional patients reported on in the United States literature. All patients were noted to have fever, malaise, and nonspecific symptoms of infection. There were no consistent diagnostic laboratory findings except for positive bacteriologic studies. Successful treatment consisted of intravenous penicillin G potassium in most cases (ampicillin sodium was required in two patients). Mortality was low, with only one patient of the 20 (and no Minnesota patients) dying of listeriosis. The time interval from transplant to infection was definitively longer in the Minnesota patients; this may be due to the routine use of sulfisoxazole following renal transplantation. Listeria infection, though mild itself, may herald other infectious processes in the immunoincompetent host.


[Estimation of the molecular weight of the matrix protein of insect baculovirus inclusion bodies (author's transl)].

The proteinaceous matrix of 23 insect Baculovirus inclusions consists of a single polypeptide of molecular weight varying from 25,100 to 31,360 daltons depending upon the virus and in correlation wwith taxonomic position of the host.