[Body composition in lean and obese persons determined by "lift balance densitometer" (author's transl)]. A new method was used to measure body density in 125 persons (divided into five groups: lean male and female; extremely obese male and female; moderately obese female). There was no correlation between body weight and total body fat in lean males, but a good correlation in lean females. Fat-free body mass correlated well with body weight in both lean groups. There was good correlation between body weight and total body fat in obese males and females. Relative weight (weight related to Broca index) correlated well with fat percentage in obese males, females, and lean women, but not in lean males. The results suggest that the Broca index of over-weight (percentage over-weight = height in cm minus 100) is a good measure of obesity in females and in extremely over-weight males, but no conclusion can be drawn about the amount of fat tissue in males who are only moderately over-weight or under-weight. In these persons fat-free body mass correlates better with body weight than "obesity tissue".


[Regeneration capacity of B-cell function in obese diabetics after weight reduction (author's transl)]. Glucose and tolbutamide-stimulated endogenous insulin secretion were measured in 12 patients with partial B-cell insufficiency (diabetes of the adult type) before and after dietary weight reduction (average reduction 6.7 kg = 8.1% of average initial weight). In three patients there was complete restoration of normal B-cell function with complete remission of the diabetes, in four there was incomplete regeneration of endogenous insulin secretion and of effective insulin reserve. In five patients with less weight reduction there was no response. The mechanism of B-cell function regeneration remains unknown. But weight reduction must be considered as causal treatment in maturity-onset diabetes associated with obesity.


[Treatment of hyperlipidaemia. A comparison of the efficacy of clofibrate and beta-pyridylcarbinol (author's transl)]. 64 patients with hyperlipidaemia, 13 of them with pure hypercholesterolaemia, were assigned to one of three pre-determined treatment regimes over a period of seven months. Two different commercial preparations of clofibrate and one preparation of beta-pyridylcarbinol were each given for two months separated by placebo periods of two weeks. All three drugs were equally effective against increased cholesterol levels. The two clofibrate preparations lowered increased triglyceride levels more reliably than beta-pyridylcarbinol.


[A comparison of different methods of measuring bleeding time (author's transl)]. Two methods of determining bleeding time (Ivy's and Duke's) were compared using a standardized method. Skin cuts were made with either a disposable scalpel or a precision plunger. Ivy's method gave results which were markedly superior to those with Duke's. It was, furthermore, shown that reproducibility of two successive determinations in the same person largely depended on the experience of the investigator. Best results were obtained using the precision plunger and automatic collection of blood. But even when these were used, there were frequent deviations of more than 20% in duplicate samples.


[Taste disorders and liver parenchymal damage after administration of thiamazole (author's transl)]. Marked, and in some cases long-lasting, taste disturbances occurred in three patients on thiamazole. In addition, all three had a rise in serum transaminases and alkaline phosphatase levels, due to associated liver parenchymal damage. Cause of these changes was the high thiamazole dosage (160 and 120 mg/d). Reduction in dosage restored normal taste sense in all three, but in two the drug had to be discontinued because of persisting high transaminase levels.


[Evaluation of diagnostic factors in chronic recurrent urinary-tract infections in children. II. Clinical symptoms (author's transl)]. 2490 investigations in 171 children with chronic recurrent urinary-tract infections seen in a specialized out-patient unit for an average of 23 months demonstrated that clinical symptoms cannot be used as indicators of pyelitis or cystitis. 43% of recurrences (n=471) were completely asymptomatic. The symptomatology depends on the age of the patient and duration of the disease. Recurrences in the late course of the disease become frequently asymptomatic. Children with predominantly asymptomatic bacteriuria show pathological X-ray findings indicative of renal parenchymatous involvement as frequently as children with predominantly symptomatic recurrences.


[Influence of antacids on plasma concentration of digoxin in man (author's transl)]. In a cross-over trial the plasma concentrations of digoxin have been studied in nine healthy subjects given oral doses of digoxin alone and simultaneoulsy with magnesium-aluminium-silicate-hydrate and dimagnesium-aluminium-trisilicate. The administration of 0.75 mg digoxin on each of 3 days and 0.375 mg on each of 2 days caused a 17 percent decrease of digoxin plasma level when given simultaneously with 1100 mg magnesium-aluminium-silicate-hydrate (n=4) and a 24 percent increase when given with 1000 mg dimagnesium-aluminium-trisilicate (n=5), respectively. The differences are not significant. The experiments suggested that antacids containing magnesium-aluminium-silicate do not impair the absorption of digoxin in man.


[Phenylketonuria: early diagnosis and mental development (author's transl)]. The relationship of early diagnosis and treatment to mental development was studied in 152 children with phenylketonuria. The average IQ at onset of the diet, if within the first two months of life, was 105 in 60 children, 70 in 28 patients if between 3 and 12 months of life, and 53 in 31 of between the thirteenth month and the end of the second year. In 33 children in whom the diagnosis had been made after the second year, diet being started this late, average IQ was 50 with correspondingly greater scatter in the severe mental deficiency range.


Limited proteolysis of tryptophanyl-tRNA synthetase from beef pancreas. Treatment of purified tryptophanyl-tRNA synthetase with either chymotrypsin, papain, subtilisin or elastase converts all the enzyme into a high-molecular-weight intermediate. This protease-resistant core molecule has the same dimeric structure as the native protein and possesses the ability to bind substrates (tryptophan, ATP and tRNATrp) but is catalytically inactive. The monomer molecular weight of the protease-treated enzyme is 39000 compared to 54000 for the intact molecule. Chemical studies indicate that proteases excise the amino-terminal part of the polypeptide chain. It has been demonstrated previously that removal of a 13000-dalton fragment from the amino-terminal region of the tryptophanyl-tRNA synthetase converts the native enzyme to another active form. Cleavage of 20 additional amino acids produces the inactive protease-resistant core.


Animal DNA-dependent RNA polymerases. Purification and molecular structure of hen-oviduct and liver class-B RNA polymerases. Hen ovidcut and liver class B RNA polymerases have been extensively purified and their molecular structure has been analysed. While only one enzyme B form (BIIb) was found in liver, three forms (BI, BIIa and BIIb) were resolved from oviduct. The molecular structures of the various class B RNA polymerase forms purified from hen oviduct and liver are identical to the corresponding forms previously purified from calf thymus and rat liver. At the present level of resolution the only difference lies in a slight difference in the charge of one subunit (SB2a) of enzyme form BIIa, when comparing the mammal and bird enzymes. It is unlikely that the absence of enzyme forms BI and BIIa in purified hen liver RNA polymerase B could be related to limited and specific proteolysis during the purification, since co-purification of oviduct and liver RNA polymerase B activities from a mixture of oviduct and liver nuclei does not affect the presence of either oviduct enzyme form BI or BIIa in the final purified mixture.


Porcine thyrotropin. The amino-acid sequence of the alpha and beta subunits. The amino acid sequences of both the alpha and beta subunits of porcine thyrotropin have been studied. Bovine thyrotropin primary structure was taken as a model for ordering the tryptic peptides of porcine thyrotropin. The amino acid sequence of the alpha subunit is identical to that of porcine luteinizing hormone, while oligosaccharide side-chains differ in composition. The primary structure of the beta subunit differs from that of bovine thyrotropin by six amino acid replacements, in positions 22, 24, 26, 36, 62 and 69, and by the absence of a methionyl residue at the carboxy terminus. Chemical evolutions of thyrotropin and luteinizing hormone are compared.


Coordinated induction and subsequent activity changes of two groups of metabolically interrelated enzymes. Light-induced synthesis of flavonoid glycosides in cell suspension cultures of Petroselinum hortense. The enzymes of the flavonoid glycoside pathway were specifically induced upon irradiation of a 10-day-old, dark-grown cell suspension culture of Petroselinum hortense Hoffm. with ultraviolet light. The curves for the activity changes of a first sequence of three enzymes (group I) revealed only small, but significant, differences. Sharp peaks in these enzyme activities were observed at about 17, 22, and 23 h after the onset of the irradiation. The apparent half-lives during the subsequent periods of decline ranged, in the same order, from about 10 to 15 and 17 h. No significant differences were found for the lag periods preceding the increases in the three enzyme activities. The possibility is discussed that the slight differences in the patterns of the light-induced activity changes are mainly due to different rates of degradation of the enzymes, suggesting an otherwise largely interpendent regulation. The patterns of the activity changes of four enzymes of the second sequence (group II) differed greatly from those observed for group I, but were again similar to one another. Thus, the two groups of enzymes appear to be regulated differently, despite their concomitant induction. A sigmoidal curve for the accumulation of the flavonoid glycosides was obtained upon the induction of the enzymes. This curve corresponded closely to that derived by integration of the curve for the activity changes of the first enzyme of group I, phenylalanine ammonia-lyase. It is concluded that this enzyme might be rate-limiting for the entire pathway.


Mechanism and stereochemistry of vinyl-group formation in haem biosynthesis. 5-Aminolaevulinate containing tritium at C-3 and C-5 was converted into haem using a preparation of anaemic chicken blood. The biosynthetic haem was degraded to ethylmethyl maleimide and haematinic acid which had relative tritium radioactivity of 0.58 and 1.0 respectively. These results indicated that in the formation of the vinyl group of haem only one of the hydrogen atoms from the beta-positions of two propionate side chains of coproporphyrinogne III was removed. Haem was also biosynthesised from [(3R)-3H1]2-oxoglutarate. The determination of relative radioactivity in ethylmethyl maleimide and haematinic acid endorsed the above conclusion and further indicated that the pro-R hydrogen atoms located at the beta-positions of the propionate side chains are retained in haem biosynthesis. In order to explore the status of hydrogen atoms located at the alpha-positions of propionate side chains haem was biosynthesised using [2RS)-3H2]succinate, [(2R)-3H1]succinate and [(2S)-3H1]succinate. Degradation of the three samples of haem into ethylmethyl maleimide and haematinic acid showed that both the vinyl groups of haem are formed through the loss of pro-S hydrogen atoms located at the beta-positions of the propionic acid side chains of coproporphyrinogen III. The results further showed that the hydrogen atoms located at the alpha-positions of the side chains are not involved in the biosynthesis of haem. Various mechanisms for the formation of vinyl groups in the biosynthesis are discussed.


Complexes of poly(adenylic acid) with complementary monomers. The interaction of a number of potentially complementary monomers with poly(A) has been investigated by equilibrium dialysis, optical rotatory dispersion and ultraviolet absorption measurements. Experiments were conducted at pH 7.0, 0.15 M Na+, where poly(A) exists as a random coil with some degree of base-stacking, and at pH 6.0, 0.15 M Na+, where poly(A) adopts the protonated double-helical acid form structure below 15 degrees C. Binding isotherms show that, at 3.5 degrees C, poly(A) forms a 1 : 1 complex with xanthine at pH 6, and a 2:1 complex at pH 7, while oxoformycin forms a 1:1 complex with poly(A) at both pH 6 and pH 7. Poly(A) forms a complex, tentatively assigned 1:1 stoichiometry, with 8-azaxanthine at pH 6, but no complexing occurs at pH 7. The complexes have been characterized by their optical rotatory dispersion and ultraviolet spectra, their thermal stabilities, and their rates of formation at low temperature. All the complexes are laevorotatory at long wavelengths (greater than 300 nm) and unplex formation at low temperature is a slow process requiring many hours for completion. The complexes of poly(A) with 3-methylxanthine have been reinvestigated and shown to undergo normal helix-coil transitions; the anomalous melting behaviour noted previously [Biopolymers, 10, 21 -- 33 (1971)] has been explained. From a comparison of optical rotatory dispersion spectra, it is concluded that the poly(A) with 3-methylxanthine have similar structures, which are quite different from the structures of the corresponding complexes with 7-methylxanthine. The structures and properties of the poly(A) - monomer complexes are discussed, and compared with those of other polynucleotide - monomer complexes. No significant interaction was observed between poly(A) and hypoxanthine, allopurinol, 6,8-dihydroxypurine, 1-methylxanthine, 9-methylxanthine, theophylline, theobromine or 3,9-dimethylxanthine.


Stereochemistry of a methyl-group rearrangement during the biosynthesis of lanosterol. 1. (3RS,6R)-[6-2H1,6-3H1,6-14C], (3RS,6S)-[6-2H1,6-3H1,6-14C] and (3RS)-[6-3H1,6-14C]mevalonolactones were synthesised from R-[2H1,3H1,2-14C], S-[2H1,3H1,2-14C] and [3h1,2-14C]acetic acids respectively. 2. Each mevalonate was converted into cholesterol by a rat liver preparation. 3. Each cholesterol specimen was converted into androsta-1,4-diene-3,17-dione by incubation with Mycobacterium phlei in the presence of 2,2'.dipyridyl. Each specimen of androsta-1,4-diene-3,17-dione was converted into androsta-1,4-dien-3-one-17-ethylene ketail. 4. The samples of androsta-1,4-dien-3-one-17-ethylene ketal were each converted chemically into oestrones in which the methyl group at C-18 is the only carbon atom that originated from C-6 in mevalonolactone. 5. The oestrone from (3RS)-[6-3H1,6-14C]mevalonolactone was oxidised chemically to acetic acid which was converted into p-bromophenacyl acetate and the 3H/14C ratio was measured. 6. There was no overall loss of tritium from the methyl group of acetic acid, as measured by determining the 3H/14C ratios of the p-bromophenacyl esters, when the synthetic and degradative procedures 1 -- 5 were tested with [3H1,2-14C]acetic acid. 7. The oestrones derived from the 6R and 6S-mevalonolactones were oxidised. The chiralities of the resulting acetates were determined by an established procedure whereby the acetates were converted into 2S-malates which were examined for loss of tritium on equilibration with fumarate hydratase. 8. The oestrone from (3RS,6R)-[6-2H1,6-3H1,6-14C]mevalonate gave acetic acid which was converted into 2S-malate that retained 68.6% of its tritium after treatment with fumarate hydratase; the configuration of this acetic acid was R. 9. The oestrone from (3RS,6S)-E16-2H1,6-3H1,6-14C]mevalonate was oxidised to acetic acid which was converted into 2S-malate that retained 31.9% of its tritium after treatment with fumarate hydratase; the configuration of this acetic acid was S. 10. There was no overall change in the configuration of a chiral methyl group between C-6 of mevalonate and C-18 of oestrone. It is cncluded that the intramolecular migration of a chiral methyl group from C-15 in 2,3-oxidosqualene to C-13 in lanosterol is stereospecific and occurs with overall retention of configuration.


Allosteric activation of the hydrolysis of specific substrates by chymotrypsin. A variety of azobenzene compounds having bis-quaternary nitrogens have been shown to accelerate the hydrolysis by chymotrypsin of certain specific substrates by an allosteric mechanism. One of the most potent, 2,2'-bis[alpha-(benzyldimethylammonium)methyl]azobenzene dibromide (2,2'-QBzl) accelerated the hydrolysis of glutaryl-L-phenylalanine p-nitroanilide 40-fold at saturating concentration. Acceleration was by increasing kcat without altering Km. The hydrolysis of acetyl-L-tyrosine p-nitroanilide and acetyl-L-tyrosine anilide was also accelerated by Q-Bzl (25-fold and 1.8-fold respectively) while the hydrolysis of hemoglobin, azocoll and a number of esters was not affected. The inactivation of chymotrypsin by diphenylcarbamyl chloride and diphenylcarbamyl fluoride was accelerated by 2,2'-Q-Bzl. Reac;ivation in the presence of NH2OH was also accelerated, but in the absence of added nucleophile (i.e. of NH20H) no increase in rate was detectable. An allosteric effector was covalently attached to chymotrypsinogen A by reaction with 2,2'-bis[alpha-(o-bromomethylbenzyldimethylammonium)methyl]azobenezene dibromide. The product, when converted to active enzyme, was about 4 times more active than chymotrypsin as a result of an increase in kcat of hydrolysis; Km was unaffected. The mechanism of the allosteric acceleration process is not known but, because for all of the substrates affected acylation of the enzyme is rate-limitimg, it is tentatively suggested that the effectors facilitate proton transfer to the leaving group by an inductive effect on the 'charge relay system'. Spectral studies indicate that the allosteric site is a portion of the enzyme with a polarity near that of water, possibly on the outside surface of the enzyme molecule.


Circular-dichroism spectra of truncated and other analogs of angiotensin II. Circular dichroism spectra on angiotensin II and analogs, and its truncated N-terminal and C-terminal peptides were determined in fluroinated alcohols under several conditions in the peptide or aromatic spectral regions. The following conclusions were suggested: (a) evidence for a beta structure for angiotensin II; (b) evidence for a folding at the N-terminal and C-terminal part of the molecule; (c) an interaction involving the C-terminal residue which decreases progressively when phenylalanine is replaced by isoleucine and then by alanine; (d) the N-terminal amino acid seems to play an important role in the overall conformation of the molecule possibly by interacting with the C-terminus, its absence in the 2 -- 8 heptapeptide giving rise to a more pronounced signal than angiotensin II; (e) in trifluoroethanol the conformation of these peptides is well defined and fits well with observed structure-activity relationships and observed binding data. There is a loss of this relationship when these solvents are diluted with water.


Topological asymmetry of phospholipid metabolism in rat erythrocyte membranes. Evidence for flip-flop of lecithin. 1. The distribution of phospholipids between inside and outside of rat erythrocyte membranes was studied by incubating the cells with phospholipase A2 from Naja naja venom and sphingomyelinase from Staphylococcus aureus. 2. Choline-containing phospholipids were found to comprise the majority of the outer layer of the membrane. 3. The incorporation of radioactive fatty acids into phospholipids occurred predominantly at the inside of the membrane. 4. Exchange of phospholipids between red cell membranes and plasma lipoproteins occurred at the outside of the membrane. 5. Indications were found for a rather slow flip-flop of lecithin across the membrane.


Studies on the role and mode of operation of the very-lysine-rich histone H1 in eukaryote chromatin. The isolation of the globular and non-globular regions of the histone H1 molecule. Digestion of calf thymus H1 histone with thrombin cleaves the molecule at the sequence -(Pro)-Lys-Lys-Ala-, corresponding to a point approximately 122 residues from the N-terminus (about 56% along the molecule). The N-terminal fragment is shown by proton nuclear magnetic resonance (NMR) to possess the globular structure of the intact histome H1 molecule, whereas the C-terminal fragment appears to possess little or no structure. The N-terminal fragment separates into two peaks on an ion-exchange column, one of which is shown to originate from a single subfraction of calf thymus histone H1 and the other to originate from the other subfractions, by detailed comparison of the NMR spectra. It thus seems that the structure of the H1 histone in solution under physiological conditions consists of a globular head with a highly basic random coil tail. It is suggested that the globular head has a specific binding site on the subunit structure of the chromosome.


Mechanism of anion transport in red blood cells: role of membrane proteins. A number of anionic chemical probes that inhibit anion permeability of red blood cells are localized in a membrane protein of about 100,000 daltons, known as band 3. The inhibitory site has been explored using a series of disulfonic stilbene compounds. It apparently contains three positive charges, probably amino groups. Two probes, pyridoxal phosphate and N-(4-azido-2-nitropheyny)-2-amino ethyl sulfonate, are transported by the anion system but can be fixed in an irreversible bond under specified conditions (reduction with NaBH4 or exposure to light, respectively). Data obtained with these compounds indicate that the inhibitory site in band 3 is the transport site itself. Band 3 protein is exposed in part on the outside of the cell but it is also hydrophobically associated with membrane lipid. A model is proposed in which the band 3 protein acts as an anion permeation channel through the lipid bilayer. Near the outer aspect of the channel an anion binding site can undergo a local conformational change allowing a one-for-one anion exchange across a diffusion barrier.


Tunable laser resonance Raman spectroscopic investigations of the transduction process in vertebrate rod cells. Tunable laser resonance Raman spectroscopy has been applied to probe (in vivo) the role of rhodopsin in transducing light energy into the chemical necessary to generate a neural response. These in vivo experiments have suggested that the Schiff base linkage through which retinal is attached to opsin in rhodopsin is protonated. Furthermore, it appears that light eventually stimulates the deprotonation of the Schiff base linkage between the Meta I and Meta II steps in the intermediate sequence which is the result of light interacting with rhodopsin. Our data suggest that this deprotonation of the Schiff base occurs on the same time scale as overall proton release and uptake by the rhodopsin molecule. It is interesting to note that this series of protonations and deprotonations also occurs within the same time scale as the neural response generation in vertebrates and the generation of a proton gradient by bacteriorhodopsin, which is used by the bacterium, Halobacterium halobium, for ATP synthesis. If these data are analyzed within the context of the in vivo resonance Raman experiments (which seem to indicate that proton release is stimulated in the disc membrane during transduction) then there is a strong suggestion that the proton will assume an important role in any working hypothesis of visual transduction. In essence it appears that protons along with ATP and calcium ions must all be essential elements in the transduction process.


Toxicology of some inorganic antihypertensive anions. Sodium nitroprusside reacts with hemoglobin in vitro and in vivo to cause the formation of cyanmethemoglobin and the liberation of excess free cyanide. The latter is responsible for the typical signs of acute cyanide poisoning in mice after lethal doses of nitroprusside. Differences in the reactivity of the red cells of various species toward nitroprusside are due to differences in the permeability of the red cell membranes to nitropruside. In vivo thiocyanate results in the formation of methemoglobin in an elevation of blood cyanide levels in mice. The latter, however, does not result in cyanide poisoning since it is bound in the biologically inert form of cyanmethemoglobin. Thus, both nitroprusside and thiocyanate generate their own antidote in mice, but an excess of cyanide is released in the case of nitroprusside whereas excess methemoglobin is generated in the case of thiocyanate. Acute poisoning with thiocyanate salts apparently involves direct excitatory effects on the central nervous system. In vitro the reaction between thiocyanate and hemoglobin proceeds only in the presence of hydrogen peroxide. Chronic administration of nitroprusside results in the elevation of blood thiocyanate levels presumably because of continuous, endogenous cyanide metabolism via rhodanese (thiosulfate sulfurtransferase). When one includes these previously unrecognized effects of nitroprusside and thiocyanate, there appears to be some correlation between the ability of a chemical to oxidize hemoglobin and its ability to activate nonadrenergic receptors for the relaxation of vascular smooth muscle.


Mechanism of protection against the delayed neurotoxic effects of organophosphorus esters. Delayed neurotoxic effects arise as a result of two distinct biochemical events: 1) inhibiton of neurotoxic esterase, and 2) 'aging' of inhibited enzyme. Protective agents undergo reaction 1 but cannot undergo 2. Reaction 2 may interfere with a normal physiological control mechanism.


Metabolism of environmental pollutants by the isolated perfused lung. An isolated perfused rabbit lung system was developed for the study of pulmonary metabolism of foreign compounds. The main features of the system include the use of autologous whole blood, constant pressure perfusion, subatmospheric ventilation, and measurement of a variety of physiological and biochemical parameters. Pulmonary metabolism of benzo(a)pyrene has been investigated with this system. In addition to the 3-hydroxy metabolite, three dihydrodiols and an unidentified polar metabolite were also found. The polar metabolite accounted for approximately 50% of all metabolites found in the five compartments of the perfusion system. Pretreatment with 3-methylcholanthrene increased total metabolism of benzo(a)pyrene and shifted the pattern of metabolites. The perfusion system for the rabbit has been extensively modified for use with rats and guinea pigs. These smaller animals are currently being used to investigate pulmonary metabolism of trichloroethylene.


Biochemical pathology of lung damage produced by chemicals. Damage to the lung may be caused by chemicals that gain access to the alveolar zone by inhalation or via the pulmonary circulation. Several agents toxic to the lung have recently been found to bind covalently to pulmonary macromolecules or to disrupt certain metabolic reactions. However, it has also been observed that extensive chemical lung injury is not necessarily preceded by a depression of pulmonary metabolic reactions. One possible explanation for this might be that biochemical changes due to cell death are often masked and/or compensated for by changes associated with lung tissue repair. Substantial cell proliferation as a response to toxic lung damage is a common phenomenon in lung pathology. This makes it necessary to develop models that permit analysis of the biochemical events triggering and accompanying cell growth in lung. We have recently examined some aspects of cell proliferation in mouse lung. Intraperitoneal injection of the antioxidant butylated hydroxytoluene (BHT) produces within 3-5 days extensive hypertrophy, hyperplasia, and general disorganization of the cellular components of the lung. Total lung weight and total DNA per lung almost double within this time and are accompanied by proportional increases in protein and lipids. RNA accumulates at a faster rate than DNA. The changes in lung composition are accompanied by dose-dependent increases in the in vivo incorporation of thymidine into DNA and of leucine into protein. The activities of several enzymes (thymidine kinase, DNA polymerase, uridine kinase, glucose-6-phosphate dehydrogenase, and 5'-nucleotidase) increase substantially after BHT. Administration of BHT to mice seems to offer a convenient tool to study cell growth in the lungs of mice.


"Second generation" prostaglandins: midtrimester pregnancy termination by intramuscular injection of a 15-methyl analog of prostaglandin F2alpha. Eighty midtrimester gravid patients were treated with prostaglandin 15(S)-15-methyl Fa alpha by repeated intramuscular injections of 250 mug at 2-hour intervals for the elective termination of pregnancy. A success rate of 97.5% was achieved, with a mean initiation-to-abortion time of 17.2 +/- 1.0 hours. Gastrointestinal side effects were prominent but no serious complications occurred. Serial serum progesterone determinations and continuous intra-amniotic pressure recording were carried out in selected cases and correlated with abortifacient activity. This method of pregnancy termination appears particularly suitable for use in the early midtrimester of gestation.


Results of ligation of internal spermatic vein in the treatment of infertility in azoospermic patients. Ten azoospermic men treated by ligation of the internal spermatic vein are reported. Treatment of two of the ten resulted in pregnancies. The advisability of thorough evaluation of the azoospermic patient is well demonstrated by the finding of one patient with Klinefelter's syndrome. In our judgement, based on this small series, azoospermia should not be considered a contraindication to surgery. Complete evaluation of the azoospermia is essential. Indeed, the varicoceles seen in patients 9 and 10 were an incidental finding and in all likelihood played no role in the azoospermia.


High deoxyribonucleic acid content of spermatozoa from infertile, oligospermic human males. A study has been carried out, by means of an indole microchemical technique, of the DNA content of spermatozoa from a group of 13 normal subjects and 13 patients affected by infertility, characterized by oligospermia with a clinical, hormonal, and testicular picture peculiar to "idiopathic spermatidic arrest." The DNA content of spermatozoa from the infertile, oligospermic patients was nearly double that of normal subjects. This finding can be explained tentatively on the basis of genetic and/or cytologic events occurring during meiosis.


Cytophilic activity in experimental immunologic orchitis in guinea pigs. Classic experimental immunologic orchitis was induced in guinea pigs by injection of homologous testis homogenate in complete Freund's adjuvant. Blood samples were obtained periodically for 45 days and the animals were hemicastrated on the 8th day after sensitization. By the 8th day, cytophilic activity was found in the serum simultaneously with several foci or orchitis. Significant levels of this activity were found until day 29, but it was absent in animals sensitized with an unrelated antigen or with complete adjuvant alone. Low and transitory levels were detected in some guinea pigs when antigen was administered with incomplete Freund's adjuvant. It is concluded that cytophilic activity is organ-specific and requires complete Freund's adjuvant. Possible implications in experimental immunologic orchitis are discussed.


Removal of sperm-bound seminal plasma components as a prerequisite to induction of the rabbit acrosome reaction. When rabbit sperm were pretreated with media of high ionic strength (380 mOsM), which had previously been shown to facilitate removal of sperm-bound seminal plasma components, and subsequently treated with follicular fluid the acrosome reaction was completed rapidly. Treatment of the sperm with follicular fluid alone yielded a greatly decreased rate of acrosome reaction completion, and treatment with the high-ionic strength medium alone caused no visible alteration to the sperm. These results suggest that removal of the sperm-bound seminal plasma components destabilizes the acrosome and prepares it to undergo the acrosome reaction. This destabilization is virtually completed after a 5-minute preincubation of the sperm in high-ionic strength media. Direct comparison of epididymal and ejaculated sperm indicated that epididymal sperm acrosomes were apparently in the same stabilized condition as ejaculated sperm. The effect of the pretreatment by high-ionic strength media could be partially mimicked by pretreatment of sperm with alpha- or beta-amylase or neuraminidase but not by beta-glucuronidase, lipase, pronase, or trypsin. Comparison of the ability of bovine follicular fluid, rabbit follicular fluid, and rabbit serum to induce the rabbit acrosome reaction showed that bovine follicular fluid was 3 to 4 times more effective than rabbit follicular fluid and that rabbit serum was totally ineffective in producing the acrosome reaction. The data support a physiologic role for follicular fluids in the process of fertilization and indicate that removal of sperm-bound seminal plasma components is a prerequisite to efficient induction of the acrosome reaction.


Factors in diminution of uteroglobin secretion in the rabbit. Uteroglobin was measured under various hormonal conditions: pregnancy, pseudopregnancy, pseudopregnancy with exogenous progesterone, pseudopregnancy with exogenous 20alpha-hydroxyprogesterone, ovariectomy with exogenous progesterone, ovariectomy with exogenous estrogen, ovariectomy with exogenous estrogen and progesterone, and ovariectomy with either exogenous progesterone or estrogen and progesterone, plus uterine trauma. In pregnant females, uteroglobin levels diminished sharply after day 9. In pseudopregnancy, high concentrations were maintained through day 14. Although exogenous progesterone did not prevent this decrease in pseudopregnant females, re-elevation occurred in the continued presence of progesterone. A similar pattern of decline and re-elevation was found in ovariectomized females that received injections of estrogen and progesterone. With an increase in estrogen dosage, the period of uteroglobin secretion was shorter and the magnitude lower. Ovariectomized females receiving only progesterone did not manifest a clear uteroglobin diminution. Uterine trauma on day 7 of exogenous steroid administration to ovariectomized females was followed by a diminution in uteroglobin. At the dosage level used, administration of 20alpha-hydroxyprogesterone did not affect the peak uteroglobin secretion occurring on day 5 of pseudopregnancy. Ovariectomized females receiving estrogen or sesame oil vehicle had barely detectable levels of uteroglobin. A uteroglobin-estrogen complex is suggested as a possible inhibitor of uteroglobin synthesis by a feedback inhibition pathway in pseudopregnant females and in ovariectomized females treated with progesterone plus estrogen. In pregnant females, a uteroglobin-estrogen complex and/or the uterine decidual response to implantation could control uteroglobin synthesis.


Effects of early treatment with antiserum to ovine follicle-stimulating hormone and luteinizing hormone on gonadal development in the rat. Neonatal rats secrete considerable amounts of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) between 5 and 15 days of age. Antisera to LH and FSH were injected during this 11-day period in an attempt to study the importance of gonadotropins for functional development of the gonads. Autopsies at 15 days of age revealed normal ovarian follicular histology after either antiserum treatment, but antiserum to LH significantly retarded differentiation of interstitial tissue. Uterine weights were increased, and some of the serum samples showed elevated FSH levels following the antiserum treatments. The testes of antiserum-treated rats were heavier at 15 days of age, while accessory sex organ weights were unchanged. Vaginal opening after antiserum treatment was more variable than in controls, but tended to be earlier. The first appearance of penile serum was not significantly changed. Both males and females were fertile as adults. Important limitations to the use of chronic antiserum injections were found in immature rats. The antisera were present for at least 34 days after injection. The ways in which this pool of antiserum might have influenced the results are discussed.


Sequential use of clomiphene citrate and human menopausal gonadotropin in ovulation induction. In an effort to diminish the incidence of multiple pregnancy, ovarian hyper-stimulation syndrome, and the excessive cost of human menopausal gonadotropin (HMG) administration, a sequence of Clomid-HMG-human chorionic gonadotropin (HCG) was used in 80 patients with infertility due to prolonged amenorrhea. Criteria for this therapeutic regimen were: (1) normal seminal fluid analysis and postcoital test; (2) lack of withdrawal bleeding from progesterone following amenorrhea of more than 6 months' duration; (3) normal x-ray of the sella turcica and visual fields; (4) low serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels; (5) normal endoscopic examination; and (6) lack of response to clomiphene in excessive dose (200 mg daily for 5 days) or prolonged dose (100 mg daily for 10 days) with or without HCG, or apparent ovulatory response to the above sequence for five or six consecutive cycles without pregnancy. Clomiphene was administered in a dose of 100 mg daily for 7 days. HMG was then given in the following manner: two ampules daily for 4 days, then one ampule daily for 2 days (75 IU of FSH and 75 IU of LH/ampule). After a 24-hour interval without treatment, 10,000 IU of HCG were given and 2000 IU of HCG 4 days later. Twenty-three pregnancies occurred in 80 patients. However, 15 of the first 25 patients became pregnant--in these patients the only abnormality noted was lack of ovulation. Six additional pregnancies occurred subsequent to one or more unsuccessful cycles. Multiple pregnancies occurred in only two patients (twins delivered at 32 weeks in one and an abortion of five fetuses at 20 weeks in another). However, multiple pregnancy did not occur in any patient whose urinary estrogen level was monitored and in whom the level was 100 mug or less when the HCG was given. The ovarian hyperstimulation syndrome did not occur in any patient.


Methyltestosterone treatment of infertility associated with pelvic endometriosis. Sixty-four patients who had infertility associated only with endometriosis were treated with methyltestosterone, 5 mg/day, continuously for a period of 6 months. The patients continued to ovulate while receiving medication and 12 patients became pregnant, on an average, 6 months after the initiation of therapy. A computer analysis indicated that approximately 30% of the patients could expect pregnancy within 2 years after the testosterone treatment was begun. The side effects of the low-dose methyltestosterone therapy were acne in 6% of the patients, mild hirsutism in 3%, and an occasional delay in ovulation.


Carbohydrate metabolism of Indian women taking steroid contraceptives. Three parameters, serum glucose, insulin, and growth hormone levels, were used to measure carbohydrate metabolism in 25 women not using steroid contraceptives, 48 women using combination oral contraceptives, and 27 women using low-dose progestogen oral contraceptives. Women in the combination contraceptives group had significant modifications in the responses of all three parameters studied. A bias toward modification was also seen in the normal tests of the combination group. The low-dose progestogen, megestrol acetate, did not cause similar changes in glucose, insulin, and growth hormone values.


Epididymis and seminal vesicle as sources of carnitine in human seminal fluid: the clinical significance of the carnitine concentration in human seminal fluid. Carnitine determinations in human seminal fluid were shown to be useful in assessing epididymal and seminal vesicle function and in locating blockages in the male reproductive tract. The carnitine concentrations in 50 samples of seminal fluid ranged from 15 to 530 mug/ml (as carnitine-HCl). The patients could be divided into four classes. Patients with normal seminal vesicle and epididymal function had values of 250 mug/ml or above. Those with a defective epididymis and a functional seminal vesicle had intermediate carnitine levels (100 to 200 mug/ml) and normal fructose values in the seminal fluid. Patients with a defective seminal vesicle but a functional epididymis had intermediate carnitine concentrations and low fructose levels. Extremely low carnitine values (less than 100 mug/ml) were found in seminal fluid from patients whose epididymis and seminal vesicle both were defective. The possible role of carnitine in sperm maturation was discussed.


Electrocardiographic changes induced by insertion of an intrauterine device and other uterine manipulations. A prospective study was carried out in normal women in order to investigate the effects of the following procedures on the electrocardiogram and blood pressure: (1) insertion of an intrauterine device (IUD)--the Lippes loop, Tcu-200, uterine progesterone system or Cu-7; (2) endometrial biopsy; and (3) uterine flushing. In groups in which a large IUD like the Lippes loop and/or a stiff IUD like the Cu-7 was inserted, the frequency of bradycardia was significantly higher than in any other groups. The severity of the bradycardia was similar in all of the groups and the frequency of this alteration was also similar among the nulliparous women or in those who complained of pain during the instrumentation, irrespective of the type of IUD inserted or the procedure carried out. No alarming modifications of blood pressure were observed and maintaining the patients in the recumbent position was sufficient to alleviate symptoms. In severe cases use of the Trendelenburg position should be enough to correct any alterations.


Postpartum contraception: subsequent pregnancy, delivery, and abortion rates. The first subsequent pregnancy rate in a group of women who accepted a variety of contraceptive methods after delivery and after therapeutic abortion is reviewed. Regardless of method chosen, 20 to 30% of postdelivery and 18 to 20% of postabortion patients were pregnant again after 1 year. In those patients who chose no method, 30 to 40% of postdelivery patients and 19 to 30% of postabortion patients were pregnant again 1 year later. When the postdelivery and postabortion patients were compared by outcome of this first subsequent pregnancy, there was no indication that subsequent therapeutic abortion was utilized to a greater extent by those who had had a prior therapeutic abortion than by those who had had a prior delivery.


Plasma glucagon and the insulin:glucagon ratio in gestational diabetes. The influence of pregnancy on serum glucose, serum insulin, and plasma glucagon concentrations was studied in eight normal women and 14 nonobese gestational diabetics. Each normal individual was subjected to an oral glucose tolerance test in midpregnancy, and all subjects were investigated late in pregnancy and again four to six weeks postpartum. As compared with the postpartum values, fasting glucose concentration decreased during gestation in the normals and increased in the gestational diabetics, but the changes were small and insignificant. In contrast, fasting insulin concentration increased equally and significantly in pregnancy in both groups. Likewise, the glucagon concentration was enhanced in the fasting state in both groups in pregnancy. However, the molar insulin-to-glucagon ratio was significantly elevated in both normals and gestational diabetics. In late pregnancy the magnitude of the insulin response to oral glucose (i.e., the incremental insulin area above fasting baseline) was equally and significantly enhanced in the normals and the gestational diabetics. However, when the insulin response during the first 60 minutes of the OGTT was expressed per unit of glucose stimulus (i.e., the delta insulin/delta glucose ratio) a significantly higher mean response was found in the normal pregnants than in the gestational diabetics. In pregnancy and postpartum, plasma glucagon always decreased to levels significantly below fasting levels after glucose ingestion. In normal midpregnancy the degree of suppression of glucagon was close to that of postpartum, whereas an exaggerated and prolonged suppression was found in late pregnancy in the normals as well as the gestational diabetics. These findings indicate that plasma glucagon and serum insulin concentrations are profoundly influenced by pregnancy. As the changes, however, lead to an increased insulin-to-glucagon ratio, the diabetogenicity of pregnancy is not explained by this relationship.


Relationship of serum glucose concentration to changes in refraction. The effect of chronic changes in serum glucose concentration on refraction was studied by increasing the dose of insulin or chlorpropamide in 10 diabetic patients who initially had relatively high glucose concentrations. In every case when serum glucose concentration was reduced the vision became less myopic or more hyperopic. To assess acute changes. 10 diabetics (including four with aphakic eyes) were given an intravenous injection of glucose. In patients with intact lenses the vision became more myopic or less hyperopic following the administration of glucose, but in the aphakic eyes hyperopia increased. It is concluded from both the acute and chronic studies that higher levels of serum glucose concentration produce myopia and lower levels produce hyperopia. Furthermore, these changes are related to changes in the optical properties of the crystallin lens.


Norepinephrine, epinephrine, and dopamine contents of the cardiovascular system in long-term diabetics. Norepinephrine, epinephrine, and dopamine concentrations were studied in the cardiovscular system of postmortem material obtained from six long-term diabetics and six control subjects. Norepinephrine concentration was considerably reduced in the cardiovascular system of the diabetic patients. The mean norepinephrine concentration in the apex of the heart, the radial artery, the posterior tibial artery, and the femoral artery in the diabetics averaged 6, 9, 12, and 20 per cent, respectively, of the corresponding mean values in the controls. Epinephrine was present in the cardiovascular system in the controls but in small amounts in comparision with norepinephrine. There was no correlation between the epinephrine and the norepinephrine concentrations in the tissue. In the diabetics the epinephrine concentration in the heart and in the arteries did not differ from the values obtained in the controls. The dopamine concentration averaged 11 per cent of the norepinephrine concentration in the cardiovascular system in the controls. There was a strong correlation between tissue concentrations of dopamine and of norepinephrine. In the diabetics the dopamine concentration was reduced, but relatively less than that of norepinephrine, and constituted 53 per cent of the norepinephrine concentration. It is suggested that the depletion of the norepinephrine stores in the heart in diabetic patients may in part be responsible for their reduced survival rate in acute myocardial infarction.


Insulin adsorbance to polyvinylchloride surfaces with implications for constant-infusion therapy. Because of the current interest in constant intravenous infusions of insulin for hyperglycemic conditions, we have re-examined the problem of insulin adsorption to the solid surfaces of commonly used infusion sets. Using both labeled and unlabeled insulin, we have compared solutions with and without albumin through various methods of delivery. An infusion system incorporating a 50-ml. wash-out with a solution of 25 U. regular insulin in 500 ml. normal saline permits delivery of at least 75 per cent of expected insulin for the first 50 ml. of the infusion and 100 per cent thereafter. After the first 20 ml. of the infusion, the per cent insulin recovered from the system is identical to that observed when albumin was added to the infusion solution at a concentration of 1.25 gm. per cent. From these date, we conclude that if an insulin concentration of at least 25 U./500 ml. is used, and if 50 cc. is washed through the infusion apparatus before treatment of a hyperglycemic patient is instituted, no extra protein additives are necessary.


Hepatic veno-occlusive disease originating in Ecuador. A case of hepatic veno-occlusive disease manifested by massive ascites is described in a 35-year-old female. She had consumed an herbal tea containing a Crotalaria plant species for 6 months prior to evaluation. Inferior vena cava and hepatic veins were patent by angiography. Liver biopsy showed histological changes typical of hepatic veno-occlusive disease, consisting of centrilobular congestion and sublobular hepatic vein obstruction. Complete clinical, biochemical, and histological recovery was documented 1 year after ingestion of the brew was discontinued. This is the first case known to be reported from Ecuador and the first to be diagnosed in the United States.


Colonoscopic polypectomy: silent perforation. The management of colon polyps has been completely revolutionized since the introduction of colonoscopic polypectomy. The reductions in patient time, cost, morbidity, and mortality are major advantages. Reported complications include primarily hemorrhage (1.7%) and frank clinical perforation (0.32%). This report describes a silent perforation after the removal of a broad based polyp through the colonscope.


Elevated serum acid phosphatase levels with rectal carcinoid tumor. A case of rectal carcinoid tumor with liver metastases is reported in which a markedly elevated serum acid phosphatase level was found. Tissue assays of the patient's tumor, liver metastasis, and uninvolved liver were performed which demonstrated very high tumor levels of acid phosphatase. The patient also had elevated plasma serotonin levels and urinary 5-hydroxyindole acetic acid levels and did not exhibit the carcinoid syndrome. Autopsy showed no prostate cancer or metastatic bone lesions. Serum acid phosphatase elevation may occur with carcinoid lesions of the rectum.


Ulcerative colitis in the Jewish population of Tel-Aviv Yafo. III. Clinical course. The clinical course of ulcerative colitis has been studied and analyzed in 504 Jewish patients in the Tel Aviv area. The length of follow-up was 1 to 46 years, with a mean of 7.8 years. The data are compared with other published series of the disease in different geographical areas. Differences in the incidence of serveral complications are noted. The trend in recent years toward a lesser mortality associated with the disease is discussed.


Does bacteremia follow colonoscopy?

Does bacteremia follow colonoscopy? In order to determine the risk of bacteremia from colonoscopy, we cultured blood specimens from 40 patients the day before laxative and enema preparation; right after such preparation; and 15 min, 1 hr, and 4 hr after colonscopy. Bacteremia was not induced by either the vigorous preparation or the colonscopy which, in 27 patients, included polypectomy, biopsy, and/or fulgurations. On the basis of our data, we conclude that the risk of bacteremia following colonoscopy is small, and we doubt the need of antibiotic prophylaxis for those with susceptible hearts.


Clinical presentation of diseases of the large bowel. A detailed study of 642 patients. This paper presents in detail the symptomatology and findings on examination of 642 patients suffering from a variety of lower gastrointestinal disorders, such as colonic and rectal cancer, diverticular disease, Crohn's disease, and ulcerative colitis. Location of precise sites of abdominal pain and tenderness was shown to carry a high level of diagnostic discrimination between the various disorders. Some surprising features emerged: almost half of patients with lower gastrointestinal tract disease complained of symptoms referable to the upper gastrointestinal tract, such as nausea/vomiting or anorexia. It is suggested that the provision on demand of such data to junior staff may benefit both diagnostic ability and decision making. As an incidental finding, just under 40% of patients with large bowel cancer had undergone previous (unrelated) abdominal surgery. The significance of this is unclear.


Circulating antibodies to bovine albumin in ulcerative colitis and Crohn's disease. Characterization of the antibody response. The presence of antibodies against a dietary protein, bovine serum albumin (BSA), was investigated in the serum of normal subjects and patients with inflammatory bowel disease and celiac disease. Antibodies to BSA were demonstrated in 28 of 30 patients with ulcerative colities (93%), 30 of 35 with Crohn's disease (86%), 5 with untreated celiac disease and in 12 of 28 normal subjects (43%). In patients with inflammatory bowel disease, antibodies to BSA were present in greater amounts in those with severe and moderate disease than in those with mild disease. Moreover, in those patients with high titers of circulating antibody, the serum anti-BSA activity was always associated with IgG and sometimes with IgA. These findings suggest that an increased absorption of antigenic material and stimulation of antibody production may occur in association with intestinal mucosal damage, not only in ulcerative colitis and celiac disease, but also in Crohn's disease.


The electrical potential difference across human ileostomy mucosa. Some of the characteristics of the electrical potential across human ileostomy mucosa were assessed by measuring potential difference (P.D.) between ileostomy lumen and forearm skin in 28 subjects, 19 of whom had had ulcerative colitis and 9 Crohn's disease. The mean P.D. at 3 to 5 cm from the tip of the ileostomy was 17.2 mv +/- 0.6 (SEM) in the ulcerative colitis group and 16.5 mv +/- 1.1 in the Crohn's disease group. The P.D. was highest at the tips of ileostomies and decreased to about half the tip level at 10 to 15 cm deep to the tip. Even at this distance from the tip, P.D. was apparently higher than values reported in normal ileum. P.D. rose during the first few weeks after colectomy and reached a stable value at about 2 months. Plasma aldosterone levels were normal in 6 subjects but despite this, administration of an aldosterone antagonist, spironolactone, caused a fall in P.D. These apparently conflicting observations suggest that the raised P.D. was maintained, at least in part, as a response to normal levels of aldosterone and an increased sensitivity to aldosterone by ileal mucosa near to an ileostomy is postulated. A significant correlation between P.D. and salivary Na:K ratios also supports a relationship between P.D. and aldosterone levels. Another patient, with a jejunostomy, also had a high transmucosal P.D., suggesting that jejunal mucosa may respond in a similar manner. No evidence in favor of active K secretion was discovered, because K concentrations in ileostomy ejecta were no greater than those which could be predicted as a passive response to the P.D. except in some subjects during the 1st week after surgery.


Effect of cholecystokinin and 16,16-dimethyl prostaglandin E2 on RNA and DNA of gastric and duodenal mucosa. Fasted rats were injected with either cholecystokinin-octopeptide (CCK-OP), 20 mug per kg; 16,16-dimethyl prostaglandin E2 (16,16-dimethyl PGE2), 0.2 mg per kg; pentagastrin, 250 mug per kg, or saline every 8 hr for 48 hr. The rats were killed and the incorporation of [3H]thymidine into DNA as well as the total DNA and RNA content of the mucosa of the oxyntic gland area and the duodenum were determined. Pentagastrin increased DNA synthesis 60% (P less than 0.001) in gastric mucosa and 90% (P less than 0.001) in duodenal mucosa when compared with rates for saline controls. Neither CCK-OP nor 16,16-dimethyl PGE2 altered gastric mucosal DNA synthesis. Pentagastrin significantly increased the DNA and RNA content of both the gastric and duodenal mucosa. CCK-OP and 16,16-dimethyl PGE2 caused a slight but significant increase in duodenal DNA synthesis, CCK-OP did not significantly increase duodenal DNA content, and 16,16-dimethyl PGE 2 increased duodenal RNA but not DNA content. CCK-OP (20 mug per kg) in combination with pentagastrin did not alter the stimulation of gastric DNA synthesis but significantly decreased the effect of pentagastrin on duodenal DNA. A dose of CCK-OP (370 mug per kg) equimolar to 250 mug per kg of pentagastrin did not stimulate DNA synthesis in either tissue and significantly inhibited stimulation by pentagastrin in both tissues. Low doses of CCK-OP (2.5, 5.0, 10.0, 20.0 mug per kg) caused statistically significant increases in DNA synthesis and DNA content of the pancreas, but had no effect on either mucosa of the oxyntic gland area or duodenum. 16,16-Dimethyl PGE2 did not inhibit the stimulation of DNA synthesis or the increases in DNA and RNA content stimulated by pentagastrin. From these results it appears that: (1) moderate doses of CCK have a weak trophic effect in the duodenum but not in the stomach, (2) physiological doses of CCK-OP stimulated pancreatic DNA synthesis and increased pancreatic DNA content without affecting these parameters in the oxyntic gland area or duodenum in the same animals, (3) in the stomach and duodenum CCK is not as potent a trophic hormone as gastrin and inhibits, probably competitively, the trophic effects of gastrin, (4) 16,16-dimethyl PGE2 does not stimulate growth and does not interfere with the trophic response to gastrin even though it inhibits acid secretion, and (5) 16,16-dimethyl PGE2 increased the RNA content of duodenal mucosa indicating that it may stimulate activity resulting in hypertrophy.


Marked alkaline phosphatase elevation with partial common bile duct obstruction due to calcific pancreatitis. This study characterizes a syndrome of partial common bile duct obstruction and marked elevation in serum alkaline phosphatase in 6 male alcoholic patients with calcific pancreatitis. In each patient, a marked elevation in serum alkaline phosphatase was associated with minimal, if any, elevation in serum bilirubin. In all cases, the alkaline phosphatase was hepatic in origin, and intravenous or operative cholangiography showed a dilated common bile duct. Liver biopsy showed canalicular bile stasis in 4 patients and bile duct proliferation in 2 patients. This study demonstrates that calcific pancreatitis may cause partial bile duct obstruction which differentially increases serum alkaline phosphatase without altering bilirubin or bromsulphthalein excretion.


Extraction of 125I-albumin microaggregates from portal blood. An index of functional portal blood supply in cirrhotics. Portal and hepatic indicator dilution curves (IDC) were obtained after injection of a mixture of 51Cr-labeled red blood cells ([51Cr]RBC) and 125I-albumin microaggregates (125I-AMA) into the cranial mesenteric artery in dogs. The extraction (E) of 125I-AMA from portal blood was measured during one passage through the hepatic reticuloendothelial system. Using [51Cr]RBC as a vascular reference substance, E-125I-AMA was calculated by comparing simultaneous [51Cr]RBC and 125I-AMA portal and hepatic IDC, and was expressed as percentage of 125I-AMA flowing through the portal vein. In 44 experiments (15 dogs), the colloid was almost completely extracted (E-125I-AMA = 92.3 +/- 1.0% (mean +/- SE)). This approach was applied in 15 patients with severe portal hypertension undergoing combined umbilicoportal, hepatic vein, and superior mesenteric artery catheterization. Eleven patients had alcoholic cirrhosis (AC) and 4 patients had idiopathic noncirrhotic portal hypertension (IPH). Using [51Cr]RBC-IDC, the portal fraction of hepatic blood flow varied between 34.1 and 100% (mean 62.6%) in AC patients and between 56.5 and 91.2% (mean 74.2%) in IPH patients. E-125I-AMA varied from 5.2 to 100% (mean 45.1%) in AC patients, although normal values were obtained in IPH patients (mean 93.2%). In all patients the extraction of Indocyanine green (E-ICG) was calculated using a continuous infusion for the estimation of hepatic blood flow. E-ICG was decreased in AC patients (mean 22.1%), although normal values were obtained in IPH patients (mean 49.5%). A highly significant correlation was found between E-125I-AMA and E-IGC (r = 0.977, P less than 0.001). Also, a significant correlation was found in all patients between E-125I-AMA and the relative clearance of ICG (r = 0.906, P less than 0.001). The correlations between the extraction or clearance of substances removed by two different cell population suggest that their decreases are mainly due to changes in liver microcirculation. In cirrhotics, the decreased E-125I-AMA can be related to part of portal blood bypassing Kupffer cells (intrahepatic portohepatic shunts) and/or to sinusoidal changes responsible for ineffective phagocytosis. Thus, E-125I-AMA can be used as an estimation of the functional portal blood supply to the liver in cirrhotics. Using portal and hepatic IDC after injection of [51Cr]RBC and 125I-AMA into the superior mesenteric artery, the portal fraction of hepatic blood flow and the functional portal blood supply can be estimated simultaneously in patients with portal hypertension before portacaval shunts.


Effect of bile duct ligation on the ultrastructural morphology of hepatocytes. The effect of severe cholestasis produced by bile duct ligation on surface membrane ultrastructure was compared to control. Isolated well preserved hepatocytes were prepared by boric acid dissociation and examined under the scanning electron microscope. Normal sinusoidal, intratrabecular, and canalicular surface membrane topography is described. In particular the bile canalicular microvilli were observed to be derived from two locations: a "marginal ridge" whose microvilli are unaltered after bile duct obstruction, and the bile canalicular surface whose microvilli are lost in obstruction and primarily account for the appearance previously described by transmission electron microscopy. Thus, newer techniques in tissue preparation and scanning electron microscopy demonstrate that bile canalicular microvilli are derived from two anatomical sites and respond differently to bile duct ligation.


Endoscopic features of gastroduodenal Crohn's disease. The clinical, roentgenographic and endoscopic findings in 14 patients with Crohn's disease of the stomach and/or duodenum are described. To date, this is the largest series of endoscopic findings of Crohn's disease of gastroduodenal region. The endoscopic findings include (1) mucosal nodularity or "cobblestoned" mucosa; (2) multiple aphthous-like ulcerations and/or linear ulcerations; (3) thickening of the antral folds; (4) antral narrowing with evidence of hypoperistalsis; (5) duodenal strictures. The diagnosis of gastric duodenal Crohn's disease is achieved by combining recognition of clinical features and roentgenographic and endoscopic features. The endoscopic features correlate well with the roentgenographic findings in our 14 patients. Tissue for histological diagnosis of Crohn's disease of the gastroduodenal area is rarely obtained by endoscopic biopsy, but peroral suction biopsy specimens may increase the rate of histological confirmation.


Contact inhibition of pleiotropin pinocytosis as a critical factor in metazoan cell ageing. For the biosynthesis of macromolecules in amounts sufficient for indefinite growth or survival in dividing as well as in nondividing metazoan cells, a specific serum protein is required. As the addition of this factor to the medium triggers off a chain of events which leads to RNA, DNA, and protein synthesis, we have called it the pleiotropin. Pleiotropin is taken into the cells by pinocytosis. Pinocytic uptake of pleiotropin is strongly inhibited by a mutual cell-to-cell contact; diploid cells in the stage of contact inhibition of pleiotropin pinocytosis are nutritionally limited, and some changes in life processes may be expected. In continouous culture and in tissues in vivo, these changes may accumulate and ultimately result in an irreversible damage of cells so that old cells are characterized by a low pinocytic activity and by a reduced formation of macromolecules. As pleiotropin increases the saturation density and prolongs the life span of diploid cells in vitro, it is suggested that the loss of division potential in metazoan cells is not a programmed event at the cellular level and that the ageing of static cell populations may be caused by the same nutritional deficiency as that of proliferating cells.


Changes in RNA synthesis during the life span of human fibroblasts in vitro. The prolongation of the life span of human fibroblasts in vitro by hydrocortisone seem to be associated with its stimulatory action on ribosome synthesis. The sustaining effect of the hormone on the latter remains, after withdrawal of hydrocortisone, for a time which is dependent on the age of the cells. When hydrocortisone is removed from cultures that have grown beyond the life span of the controls, the cells die within two passages. Hence, the events leading to the growth decline took place in spite of the presence of the hormone which does not seem to prevent the aging process but rather to delay it. The results could be compatible with either the error hypothesis or the theory which explains aging by an increased binding of histones to DNA with the subsequent blocking of genetic information.


In vitro senescence of mammalian cells.

In vitro senescence of mammalian cells. This review discusses the molecular and cytokinetic aspects of cellular aging of human diploid fibroblasts. Despite a large amount of data, the basis of their limited life span has not been defined. A replicative defect in aging cells lies in the mechanism(s) that initiates DNA synthesis, and the control of this mechanism(s) is mediated through an alteration in the sythesis of specific RNA and protein molecules. Two major groups of hypotheses have been offered to explain these findings. The differentiation hypotheses are based on the concept of a 'biological clock', while error hypotheses presuppose defects in genetic transcription or translation.


Thymidine labelling index as a criterion of aging in vitro. For logarithmically growing cultures of the human diploid cell lines WI-38 and WI-26, there is an exponential increase in the fraction of cells not incorporating [3H]dT under conditions of continuous labelling. Thymidine uptake, phosphorylation and incorporation into DNA can be correlated with cell proliferation. In addition, determination of the labelling index is reproducible within relatively broad limits of thymidine concentrations and specific activity. The plateauing phenomenon of the curve expressing percent-labelled nuclei versus time, which occurs in populations with less than 100% cycling cells, is largely due to radiation damage to the cells. The results of these studies provide insight into the population dynamics of aging fibroblast-like cell cultures. More importantly, however, the measurement of labelling index as described can be used as a reproducible and quantitative measure of the age of the diploid cell culture.


Mental health under the umbrella.

Mental health under the umbrella. In recent years many states, with the aim of integrating fragmented human services, have reorganized their human-service programs into comprehensive or umbrella agencies. The agencies vary widely in the number and kind of programs they include. Mental health staffs should not view these agencies as a threat, the author says, but as a chance to develop new linkages and allies and even new sources of funding. And the mental health field can exercise some leadership in the agencies' development because of its experiences in coordinating diverse and autonomous mental health services into comprehensive community mental health networks. The author lists some principles learned from that experience that are applicable to reorganizing all human services, including the need for common goals, written agreements, designated liaison staff, and a commitment to coordination.


A code of ethics for a community mental health program. The Orange County Department of Mental Health developed a code of ethics to give its variety of employees a single set of standards for patient care and professional behavior in a community mental health program. The need for the code grew from problems of role definition and interdisciplinary collaboration that repeatedly arose during the program's development. General principles for the code were extracted from various professional codes, from issues arising in the day-to-day workings of the program, and from existing laws. The code, presented here, defines principles related to confidentiality, professional conduct, quality of service, moral and legal standards, clients' rights, and therapist-client relationships.


Meeting training needs of foreign psychiatric residents in state hospitals. Foreign medical graduates entering psychiatric residency programs in the United States must cope with cultural, language, educational, and status barriers during their crucial first year of training. The authors point out the shortcomings of American residency programs for foreign trainees and describe how a program was developed to meet their special needs. It includes a more authoritarian form of instruction patterned after the educational structure the students were used to in their native countries and courses in American culture, English language, and problem-solving techniques.


Psychiatric consultation to a rehabilitation program for amputees. Staff on the rehabilitation unit for amputees at the Navy Regional Medical Center in Oakland, California, requested psychiatric consultation after a group of young patients had shown destructive behavior and resistance to the rehabilitation program. After two unsuccessful attempts at consultation, an approach was adopted in which a psychiatrist functions as a training consultant in group therapy to the orthopedic staff. The primary therapists are two orthopedic nurses, who conduct two weekly therapy sessions for the amputees under the consultant's supervision. The sessions have given amputees a chance to ventilate their feelings of alienation, powerlessness, and boredom, and have been effective in halting destructive behavior and increasing self-esteem.


An analysis of a state hospital population subject to release under Florida law. Section XI of the Florida Mental Health Act, or Baker Act, mandates the review of prior hospitalization orders for each resident patient. Those retained become voluntary patients, unless placed on involuntary status under procedures outlined in the act. As a result, many patients will probably be released. Staff from the Florida State University School of Social Work analyzed patients at Florida State Hospital from one catchment area and detailed their demographic characteristics, treatment needs, and interpersonal and financial resources. The researchers found that the area's one mental health center and four nursing homes would not be adequate community resources for meeting the patients' needs. They conclude that the release of many patients would create hardships both for the patient and for the service personnel in the community, and might be considered a violation of the intent of the act.


Production of guinea pig IgG1 homocytotropic antibodies to hapten-conjugated homologous serum albumin with different adjuvant combinations. The effects of various antigen-adjuvant combinations on the production of IgG1 antibody was investigated with p-aminobenzoate conjugated to guinea pig serum albumin. The results demonstrate the importance that initial exposure of antigen-adjuvant combination has on IgG1 production. Further, there is a synergistic effect when antigen adsorbed to alum and antigen with complete Freund's adjuvant were used in conjunction with one another. The result of this effect is discussed within the context of T and B cell activation by antigen-adjuvant combinations.


The fixation of heterocytophylic antibodies to macrophages. Using autoradiographic methods, heterocytophylic antibodies were found to be fixed to the peritoneal macrophages of the guinea pig. The heavy chain of the IgG molecule was responsible for the cell fixation which was inhibited by the autologous Fc fragment. The fixation of heterocytophylic immune complex (rabbit antibody IgG + homologous OA antigen) was also inhibited by the Fc fragment. Only some of the macrophages (35-50%) were able, however, to fix immune complex.


Structure and biological functions of human IgD. VI. Serum IgD in patients with allergic bronchopulmonary aspergillosis. Serum IgD levels were quantified in a large population of individuals with a variety of atopic and/or pulmonary disorders. As a group, patients with  allergic bronchopulmonary aspergillosis (ABPA) have markedly elevated (5.03 mg%) serum IgD when compared with serum IgD levels from either normal individuals (2.17 mg%) or patients with a variety of pulmonary and/or atopic disorders. Evidence is presented suggesting that the increased serum IgD levels in ABPA patients are not necessarily related to a hyper-IgE or panhyperimmunoglobulinemia common to most of all these patients, but is rather associated with an additional quantitative difference in the immunological responsiveness of some of these individuals. An understanding of why these patients produce supranormal levels of IgD may reveal the basis for inducing an IgD antibody response and subsequently help in elucidating the biological function(s) of IgD.


Delayed skin reactor from streptokinase-streptodornase: stability studies and amino acid analysis. Delayed skin reactor (DSR), the material in streptokinase-streptodornase responsible for eliciting delayed hypersensitivity reactions in man, is stable as a lyophilized powder or when stored at -70 degrees C. Storage at a pH above or below 6.0 leads to a decrease in the ability of DSR to stimulate lymphocyte proliferation in vitro. Its molecular weight is 30,000 as estimated by sodium dodecyl sulfate gel electrophoresis and it is composed of approximately 260 amino acid residues without apparent sulfhydryl-bridged subunits. The extinction coefficient of DSR (A 1% 280 nm) is 2.6.


Inhibition of cell division in rat lenses by prostaglandin E1. Prostaglandin E1 (PGE1) suppresses mitotic activity in the epithelial cells of rat lenses maintained in organ culture. At a concentration of 5 x 10(-5)M, PGE1 caused gradual inhibition of mitosis which was first evident after six hours of incubation and was maximum at 50 per cent of control values after 16 and 24 hours in culture. During this period prostaglandin-treated lenses showed no change in the number of cells labeled with H3-thymidine, but the amount of radioactive precursor incorporated per cell was reduced by almost half. At a higher concentration (1 x 10(-4)M) PGE1 evoked a transient mitotic inhibition within the first few hours of culture, but caused cell damage after 24 hours of incubation; a lower dose (1 x 10(-5M) had no influence on mitotic activity.


Some optical principles of the clinical specular microscope. The clinical specular microscope is used to examine and photograph human endothelial cells in vivo. An optical analysis is presented here in simple form to aid the ophthalmologist or visual scientist in understanding how this instrument can be used in a quantitative manner to measure the size of the magnified endothelial cells and the thickness of the overlying cornea. An error analysis is discussed in order to demonstrate some aspects of the precision of the determination.


Clinical study of porokeratosis: reports of 10 cases. Morphological and histopathological observations made over 4 years of 10 patients with porokeratosis are described. Absence of familial involvement was notable. Association of porokeratosis with tinea cruris, leprosy and epithelioma was seen, and their possible correlation is discussed.


Stereotaxic device for experimental eye surgery. A sterotaxic device for experimental surgery in enucleated eyes is described. This instrument is made entirely of plastic, is inexpensive to make, and has proved to be an invaluable help in teaching microsurgical procedures to ophthalmic residents.


Testicular and epididymal involvement in leprosy patients, with special reference to gynecomastia. Sixty-six male patients with leprosy were studied. Only those with the lepromatous type developed testicular and epididymal changes. Nine of the 38 patients showed decreased sexual function, and 7 developed gynecomastia. These changes were believed to be due to the altered gonadal state.


Surface ultrastructure of the human lens capsule and zonular attachments. The ultrastructure of the human lens capsule and zonular attachments was studied using scanning electron microscopy. The capsule was found to have two components; an organized mass of undulating, roughly parallel fibrils and a granular component. The undulation of the capsular surface and filament organization was much less evident near the anterior pole. The zonules were also found to be fibrillar and easily distinguishable from the capsular network. The three-dimensional aspects of the association between the zonules and the capsule as seen in these studies appear to meet the requirements of accommodation.


Sliding of the epithelium in experimental corneal wounds. The corneal epithelial cell has a unique sliding capability. The epithelial cell spreads and migrates in an amebic fashion without mitotic activity when the continuity of the epithelium is broken. This movement is demonstrated both in vivo and in vitro. Prompt sliding for sealing the wound defect is apparently the first step of the wound healing of the superficial cornea. Cut edges of collagen fibers show no sign of activity towards healing the wound. The energy source of the sliding is provided mainly from stored glycogen in the epithelial cells. Sliding is inhibited by removal of glycogen from the cell or by adding glycolytic enzyme inhibitors.


The fine structural localization of peroxidase activity in goblet cells of the conjunctival epithelium of rats. Cytochemical investigation of peroxidase was made on the conjunctival goblet cells, using the diaminobenzidine method. Many goblet cells in the conjunctiva demonstrated this reaction. The reaction was present in secretory granules as well as in the perinuclear cisterna, the rough endoplasmic reticulum, several Golgi saccules and adjacent small smooth-surfaced vesicles, and condensing vacuoles. Each secretory granule within a goblet cell showed a different degree of reaction, hence it is concluded that some goblet cells probably produce both mucous substance and peroxidase in one cell. The mode of production of peroxidase in goblet cells is concluded to be similar to that of secretory proteins in pancreatic exocrine cells. The enzyme, together with thiocyanate and endogenous hydrogen peroxide, is thought to serve as an anti-infectious agent in tears.


Alterations in adrenergic sensitivity of the rabbit iris after variation of environmental lighting conditions. After variation of the environmental lighting conditions, pupillary diameters of albino rabbits in response to progressively increasing doses of the sympathomimetics norepinephrine, epinephrine, and isoproterenol were measured. After maintenance of the rabbits under conditions of constant light for one week, an increased sensitivity of the iris dilator to the mydriatic effects of these adrenergic agents became evident. After maintenance of the rabbits in constant dark for one week, on the other hand, there was no change in the sensitivity of the iris upon administration of the same sympathomimetics. Norepinephrine levels measured in iris and ciliary processes after one week of either constant light of constant dark, moreover, did not differ significantly from those determined under normal lighting conditions. These results indicate that the sensitivity of the iris dilator can be altered by variation of the physiologic stimulus, light. In addition, the chronic interruption of contact between the normal neurotransmitter norepinephrine and its effector cells leading to supersensitivity in the dilator appears to be due to the removal of a trophic influence of norepinephrine, rather than its absolute loss.


Retinal degeneration in cats fed casein. I. Taurine deficiency. All cats fed a taurine-free casein diet for at least 23 weeks have shown granularity with a hyper-reflective white zone in the area centralis, nondetectable electroretinograms (ERG's), and structural changes indicating photoreceptor cell degeneration. The present study has demonstrated that cats fed this casein diet have a selective decrease in plasma and retinal taurine concentrations by five weeks; taurine levels were about 4 per cent of normal in plasma, and 60 per cent of normal in retina. After 10 weeks, taurine levels were 2 to 4 per cent of normal in plasma and reached a minimum of 20 to 30 per cent of normal in the retina. These biochemical changes occurred in association with a delay in the cone ERG implicit time at five weeks and reduced cone and rod ERG amplitudes at 10 weeks. During this period, retinal DNA content (as a measure of cell viability) and fundus appearance were normal. By 23 weeks, ERG's were nondetectable, retinal DNA content was reduced, and the fundus showed typical changes in the area centralis. These studies help to establish a biological role for taurine in maintaining photoreceptor cell function and viability in the cat.


Retinal degeneration in cats fed casein. II. Supplementation with methionine, cysteine, or taurine. All cats fed a taurine-free casein diet for 23 weeks have shown a nondetectable electroretinogram (ERG) in association with a plasma and retinal taurine deficiency. In the present study, the casein diet was supplemented with either taurine or taurine precursors (methionine or cysteine) for 23 weeks to see if retinal function would be preserved. Cats fed the casein diet supplemented with methionine or cysteine showed ERG's reduced in amplitude and delayed in implicit time and had plasma and retinal taurine levels that were well below normal by 23 weeks. Only those cats given taurine in the diet (i.e., those fed chow or casein supplemented with taurine) retained normal ERG function and normal plasma and retinal taurine concentrations. These findings establish a role for taurine in maintaining normal retinal function in the cat.


Pattern reversal visually evoked potentials in infants. Visually evoked potentials (VEP) were recorded from infants two to six months of age using a checkerboard pattern reversal stimulus. By six months, infants produced the largest amplitude VEP to checks subtending visual angles of 7.5 or 15 minutes of arc, as do adults with 20/20 acuity. This finding indicates that by six months an infant's sensory capacity for a visual acuity of 20/20 is established.


Survival of some photoreceptor cells in albino rats following long-term exposure to continuous light. Fischer albino rats, seven weeks of age, were exposed to continuous light at 65 foot-candle incident illuminance for up to 264 days. Other Fischer rats, seven months of age, were exposed to continuous light at 140 foot-candle incident illuminance for up to 147 days. In all cases, a small percentage of the photoreceptors survived. The identification of the surviving cells as photoreceptors was made by light microscopy on the basis of nuclear heterochromatin pattern and staining and by electron microscopy by the presence of ribbon synapses and ciliary basal bodies with ciliary filaments. No outer segment membranes were observed. The percentage of cones progressively increased from the normal 1.5 per cent to about 60 per cent with increasing exposure time, indicating that cone cells are more resistant than rods to destruction by constant light.


The biphasic intraocular pressure response of rabbits to epinephrine. A study has been made of the pupillary and intraocular pressure responses of conscious rabbits to daily topical applications of submaximal doses of epinephrine. On the first day, epinephrine caused rapid pupil dilation which preceded a prolonged -ecrease of intraocular pressure. On the second and subsequent days, the application of the same dose of epinephrine increased the duration of the pupillary response and caused a biphasic pressure response in all treated eyes; an initial increase of intraocular pressure lasting two to four hours followed by decrease of intraocular pressure below the initial value which lasted for more than twenty-four hours. The beta-receptor antagonist, propranolol, and the alpha-receptor antagonist, phenoxybenzamine, caused small and large reductions, respectively, in the hypertensive response to epinephrine. Phenoxybenzamine, but not propranolol, also inhibited the pupil dilation and the hypotensive response to epinephrine. Topical administration of phenoxybenzamine strongly inhibited the hypertensive response to epinephrine but left unaffected the pupillary response.


Menkes' kinky hair disease: a light and electron microscopic study of the eye. Light and electron microscopic studies of the ocular tissue of a case of Menkes' kinky hair disease are described. The copper deficiency responsible for this systemic and neurologic disease appears to cause a progressive degeneration of retinal ganglion cells, loss of nerve fibers, and optic atrophy. The pigment epithelium is also abnormal with only small and irregular melanin granules present among electron-dense inclusion bodies. Abnormal elastica is present in Bruch's membrane.


Corneal epithelial changes during midterm storage. The increased use of donor epithelium in keratoplasty for severe corneal disease has prompted an investigation of epithelial viability during midterm storage. Glycogen, ATP, and ADP have been used as indicators of the metabolic state of epithelial cells. These substances have been measured after conventional moist-chamber storage at 4 degrees C. for 1, 2, and 12 days and after immersion at 4 degrees C. in McCarey-Kaufman medium for 1, 2, and 12 days. In addition, recovery of glycogen and ATP stores has been evaluated after warming of the tissue in the storage solution to 37 degrees C. The evidence indicates that the corneal epithelium may recover these biologically important substances, despite depletion secondary to delayed cooling of donor eyes.


Physiological function of regenerating endothelium. A defined area, 4 mm. diameter, cryothermal injury was created on a rabbit cornea. Corneal thickness was measured at four distances from the limbus to the center of the cornea during the swelling phase after endothelial damage, and during the recovery period. Rapid initial swelling was followed by a period of stable maximum thickness over 24 hours. More swelling occurred centrally than peripherally. Eight days after injury the peripheral cornea regained normal thickness, and the central portion was normal thickness after 10 to 12 days. Histological examination of corneal endothelium showed that early migration of cells into the denuded area occurred 6 hours after injury. By 2 days, most of the denuded area was covered by endothelial cells, although the cells were large and irregular. The number of normal cells increased, and of irregular cells decreased, over the next five days, until two weeks after freezing all cells had a normal appearance. The recovery of physiologic endothelial function lags behind the histologic recovery by about four to five days, indicating that recovery of the normal endothelial permeability is possibly related to the status of the cellular junctions rather than covering of the posterior surface by cells per se.


Free grafts of autologous and homologous ureter. A functional study. A free graft of autologous ureter will survive functionally when implanted subcutaneously whether replacing ureter or urethra, provided that the adventitia containing its longitudinal blood supply has been removed. A free graft of similarly stripped homograft ureter, although surviving initially, will eventually stenose and be rejected in the usual manner.


A new concept of the anatomy of the anal sphincter mechanism and the physiology of defecation. III. The longitudinal anal muscle: anatomy and role in anal sphincter mechanism. A study of the longitudinal anal muscle was performed in 16 cadaveric specimens. The study comprised dissection and microscopic examination. The bundles of the longitudinal were found arranged in three layers: medial, intermediate, and lateral; each has a different origin and is separated from the other by a fascial septum. Four fascial septa related to the longitudinal muscle could be identified. They split and decussate below the lower end of the longitudinal muscle to form the "central tendon." The central tendon lies between the base loop of the external anal sphincter and the longitudinal muscle. It gives rise to multiple small fibrous septa in different directions; those which penetrate the base loop split and decussate to form the corrugator ani cutis. A mechanism of action of the corrugator is presented. The role of the longitudinal muscle in the anal sphincter mechanism and  during defecation is discussed. The muscle plays its major role during defecation. The part played by the muscle in anal fixation is considered. It helps to fix the anal canal to the side wall of the pelvis during defecation, thus preventing anal prolapse.


The response of the renal vasculature to prostaglandin E in man. Fifty micrograms of prostaglandin E1 (PGE1) dissolved in 10 ml of physiologic saline solution were injected into the renal artery of 33 hematuria patients. The serial films obtained before and after the injection of PGE1 were compared. The administration of PGE1 promoted the entry of the contrast medium into the renal artery as early as 0.5 sec after its injection. There were cases in which the time of the appearance of maximum arterial phase was shortned, even observed at the 0.5-sec interval. The maximum nephrogram appeared earlier after the administration of PGE1, and enlargement of the major axis of the nephrogram was observed. The time of appearance of the maximum venous phase was also shortened by the administration of PGE1. Thus, the increase of the renal blood flow with PGE1 was suggested roentgenologically. The mechanism of action and the clinical applicability of prostaglandin are discussed.


The effect of adrenergic drugs and hypogastric nerve stimulation on the canine urethra. A radiologic and urethral pressure study. A combination of fluoroscopy and measurement of changes in urethral resistance was used to identify the nature and location of the urethral response to adrenergic stimulation. Intraaortic norepinephrine or bilateral hypogastric nerve stimulation produced a constriction of the prostatic urethra in males and of the distal urethra in females. Intraaortic isoproterenol produced a dilation in the same regions. The adrenergically sensitive areas determined in this study appear more discrete than those determined by measurements of urethral pressure profile.


The influence of the progestogen gestonorone caproate on testosterone turnover in renal cell carcinoma. An in vitro study. To investigate the effect of gestagens on renal cell carcinoma 300-mg slices of normal, human kidney, renal cell carcinoma (RCC), and preoperatively irradiated RCC were subjected to a short term incubation with 200 pmoles of 3H-testosterone and 1 and 2 mug of gestonorone caproate. In the normal kidney 61.4 per cent of the testosterone added was metabolized, the oxidation products androstenedione and epitestosterone outweighing by 6:1 the reduction products 5alpha-dihydrotestosterone and androstanediol. In RCC only 22 per cent of the testosterone was metabolized, with 8.5 per cent being converted to 5alpha-androstanes. Gestonorone caproate essentially did not influence testosterone turnover. This can be explained by its action as an inhibitor of the reductive pathway of the testosterone metabolism only, which is insignificant in these tissues.


Cation exchange resin and calcium excretion. An experimental study. It has been suggested that cation exchange resins might be helpful in urinary stone prophylaxis. The effect of the cation exchange resin Dowex 50 WX8 upon calcium absorption and urinary excretion in guinea pigs was investigated. The mean fecal calcium concentration was very close in the Dowex-treated and control animals and the urinary calcium concentration was not reduced in the resin-treated animals. These findings suggest that Dowex was ineffective in binding calcium in the gastrointestinal tract.


The relationship of extrinsic nerves to motor activity of the upper urinary tract. In vivo studies on the pig. Ureteral activity in the anesthetized pig was monitored by indwelling open-ended nonocclusive fluid-filled catheters. After a preliminary control period, electrical stimulation was applied to the renal/ureteral nerves, anterior and posterior vagi, and the preaortic abdominal nerve plexuses. Such stimulation was uniformly without effect upon renal pelvis and ureteral activity as observed visually and also as recorded by the intraluminal catheters. Excessive mechanical stimulation of the ureter and collecting system on one side did not induce any change whatsoever in the motor activity of the contralateral system, i.e., no "reflex" activity was demonstrable between the two sides. After ensuring complete devascularization of one kidney (and hence halting urine production by the kidney) regularly spaced anterograde contraction complexes were recorded from the homolateral ureter for periods in excess of 40 min. This latter phenomenon is discussed in relation to the concept of an upper urinary tract pacemaker.


Torsion of the spermatic cord. An Experimental Study. Twenty-eight Hartley strain guinea pigs were divided into three groups. Group I animals had their exteriorized testes torsed for a variable period of time until a bluish black color was maintained after detorsion. Group II and III animals served as controls. Testicular hormone function was estimated by analysis of accessory sex gland weights and citric acid and fructose content. Spermatogenesis was assessed by testicular histology and sorbitol dehydrogenase activity and epididymal sperm number and motility. No apparent effect on either spermatogenic or hormonal function of the guinea pig testis resulted from the torsion of the spermatic cord to the degree and length of time described.


A brief note on the ultrastructure of renal glomeruli in acutely hyperuricemic rats. Male Wistar rats fed 2 per cent oxonic acid plus 3 per cent uric acid for 3 weeks developed hyperuricemia and an extraordinary uricosuria. The kidneys had gross abnormalities similar to those seen in humans with gouty nephropathy. The cortical surfaces were granular and the kidneys had uric acid and urate deposits in the intratubular and intestitial spaces of the medullary region. Both histologic and ultrastructural studies of the glomeruli failed to disclose any unusual morphologic changes. Glomerular cells were normal and glomerular basement membranes maintained the granular structure of the lamina densa with a clear demarcation between the lamina rara externa and lamina rara interna. These morphologic findings suggest that in acutely hyperuricemic rats with a lesion comparable to hyperuricemic tubular blockade, there is no associated glomerular alteration.


[The blood-xylose test in childhood: correlation between 1 hour blood-xylose levels and numbers of intraepithelial lymphocytes in intestinal mucosa in celiac disease]. In 59 children who underwent diagnostic small-intestinal biopsies the correlation between the intraepithelial lymphocyte infilration of the distal duodenal mucosa and the blood-xylose concentration 1 h after ingestion of 5 g D-xylose was investigated. 16 patients with active coeliac disease had blood-xylose values below 20 mg%, and the correlation between blood-xylose levels and the numbers of intraepithelial lymphocytes in this same group of patients was found to be highly significant. Provided that the methodology is meticulously followed, it is our experience that the one-hour blood-xylose test, in addition to the clinical investigation, facilitates the decision whether or not to perform a small-intestinal biopsy in the diagnosis and follow-up of coeliac disease in childhood. The test however cannot replace the intestinal biopsy which remains the only acceptable criterion for the diagnosis of this disease.


Control of plasma aldosterone in infancy and childhood. A study of plasma renin activity, plasma cortisol and plasma aldosterone. In order to elucidate the main factors controlling plasma aldosterone in infancy and childhood, plasma renin activity (PRA), plasma cortisol (PC, as a parameter of ACTH activity), plasma aldosterone (PA) and serum sodium and potassium were measured simultaneously in 84 healthy children (62 recumbent, 22 upright) ranging in age from 6 days to 16 years. 10 healthy male students served as adult controls. As compared to the controls, PRA levels were significantly higher in the children up to the age of 12 years. PA was also elevated in most children; the highest values for PA and for PRA were observed during the first 4 years of life. A significant positive correlation between PRA and PA (n = 84, r = 0,62, p less than 0.001) was found. There were no significant differences in serum sodium or potassium or in PC. All PC values were - with one exception - within the range found in healthy adults. Our results indicate that high PA values are freuqently observed in healthy children. They are mainly caused by elevated PRA. The physiological significance of increased activation of the renin-angiotensin-aldosterone system in infancy is not yet clear.