Intracellular pH of isolated rat diaphragm muscle with metabolic and respiratory changes of extracellular pH.

Relationships between intracellular and extracellular pH isolated rat diaphragms were determined both during respiratory and metabolic changes of extracellular pH. Metabolic changes of extracellular pH were produced by varying bicarbonate concentration of the suspending Krebs-Ringer solution and respiratory changes were produced by varying PCO2 of the suspending medium. At any defined extracellular pH, the bicarbonate concentration ratios between intracellular and extracellular space were the same during both metabolic and respiratory changes of extracellular pH. However, when extracellular pH varied within 7.15 and 7.4 intracellular pH remained essentially constant. In order to maintain the intracellular pH constant during extracellular pH changes, a bicarbonate efflux during metabolic changes from the intracellular compartment, and a bicarbonate influx during respiratory changes to the intracellular compartment must occur. The maintenance of identical intracellular/extracellular bicarbonate concentration ratios regardless of the mechanisms of extracellular pH changes (metabolic or respiratory) suggests an active mechanism for the transport of bicarbonate or H-+ ions.


Metabolic changes in avian blood and their effects on determination of blood gases and pH.

Oxygen consumption. MO2 and CO2 production rates, Cco2, of duck blood samples anaerobically stored at 41 degrees C were 0.041 and 0.036 mMol (L blood)minus 1 min minus 1, respectively, and were independent of O2 saturation in the range of 100 to 10% saturation; the resulting metabolic respiratory quotient of blood was 0.88. The pH decreased linearly with time at a rate of 0.0014 unit min minus 1. The lactic acid production rate was independent of Po2, and was about 0.033 MMol L minus 1 min minus 1. Errors were assessed that may be introduced in blood gas analysis when the high metabolic activity of avian blood is not accounted for. Thus the O2 dissociation curve established using the Van Slyke analysis will be shifted to the right; however, the displacement around P50 is only about 1 torr for a time lag of 5 min between sampling and analysis and is even less at higher Po2 values. When using electrodes, P02 will be underestimated and PCO2 overestimated. The magnitude of these errors depends on both delay time and slope of the dissociation curves. It is concluded that the standard blood gas analytical methods are applicable to avian blood, but that in some cases corrections for metabolic effects are neccessary. Any delay between blood sampling and analysis should be kept as short as possible; storage, if neccessary, should be on ice.


The effect of acetazolamide on myocardial carbon dioxide space.

Carbon dioxide, water and vascular space were measured in the heart muscle of the dog before and after the administration of acetazolamide. In contrast to the skeletal muscle whose CO2 space was markedly reduced by acetazolamide, cardiac muscle CO2 space was only minimally reduced. This suggests that cardiac muscle does not have extravascular carbonic anhydrase. Its presence in skeletal muscle and absence in cardiac muscle probably relates to the differences in cell size between the two types of muscle and their differing degree of vascularity.


Arterial blood gases in undisturbed resting birds: measurements in chicken and duck.

Arterial blood was sampled in resting, unrestrained and undisturbed birds using a remote-controlled sampling device. With this technique a blood sample of 0.45 ml was obtained for analysis of PO2, PCO2 and pH at the body temperature of the animal. In 5 domestic hens the following mean values were obtained: PA02-82 torr; PACO2=33 torr; pHA=7.52. The average body temperature was TB=41.0 degrees C. In 6 domestic ducks the analysis yielded values of PAO2=82 torr; PACO2=38 torr; pH2=7.49; Tb=41.0 degrees C. Although these values are close to those reported in the literature some discrepancies may be recognized; they can be attributed to respiratory and metabolic changes of blood composition possibly induced by classical sampling procedures.


Blood acid-base changes during experimental emersion and reimmersion of the intertidal crab Carcinus maenas (L.).

The time course of blood acid-base changes was studied in Carcinus maenas during experimental emersion and reimmersion at 15 degrees C by measuring pH and PCO2 and calculating bicarbonate concentration. During the first 4 hr of the emersion period, a marked rise of PCO2 entails a respiratory acidosis which is progressively compensated by a slow increase of the bicarbonate concentration; this compensation is completed after about 100 hr and the steady state mean pH value approximates that found for the immersed controls. Return to aquatic conditions is characterized by a rapid decrease of both PCO2 and blood bicarbonate concentration. During the first 2 hr of the reimmersion period, the decrease of blood bicarbonate concentration is accompanied by excretion of a significant amount of base in water, thus suggesting that readjustments of acid-base balance take place at least in part by ionic exchanges between the blood and the external milieu. Initial status was restored after 9 hr. These finding agree with the general views concerning the blood acid-base changes which must occur at transition from water-to air-breathing.


Mechanisms of O2 transport in Andean dogs.

Using previously inserted catheters, 11 dogs native to high altitude (7.5-23 kg bwt) were studied standing and unsedated in Cerro de Pasco, Peru at 4350 meters. Hemoglobin (Hb), hematocrit (Hct), O2 and CO2 contents, PO2, PCO2 and pH were measured in simultaneously obtained arterial and mixed venous blood samples. Blood pressures were measured in the pulmonary artery and the left ventricle and cardiac output (Q) was determined by dye dilution. Moderately higher values for Hb and Hct were found in these dogs. Hb-O2 affinity was no different than that found in sea level dogs: the P50 in the Andean dogs was 31.6 mm Hg at 38 degrees C and pH of 7.4. Because of the low barometric pressure at 4350 m (458 mmHg) the partial pressures of oxygen in inspired and in alveolar air were lower than at sea level: 84.3 and 56.4 mm Hg, respectively. PAO2 and PVO2, were 55.5 and 32.9 mm Hg while the SAO2 and SVO2 were 79.5 and 50.7%, respectively. Marked hyperventilation was observed (PACO2, 25.6 mm Hg) however, pH was normal. Cardiac output was normal (average 162 plus or minus 39 ml/min/kg). Moderate pulmonary arterial hypertension was observed in the presence of normal left ventricular end diastolic pressure suggesting increased pulmonary vascular resistance.


A study of the influence of various antirheumatic drug regimens on serum acute-phase proteins, plasma tryptophan, and erythrocyte sedimentation rate in rheumatoid arthritis.

In patients with rheumatoid arthritis neither indomethacin nor aspirin influenced the levels of the erythrocyte sedimentation rate (e.s.r) or serum acute-phase proteins fibrinogen, haptoglobin, C-reactive protein and alphaI acid-glycoprotein). Treatment with D-penicillamine, sodium aurothiomalate, or alclofenac produced a significant reduction both in acute-phase protein levels and in e.s.r. Each of the drugs displaced L-tryptophan from plasma proteins in vivo but withdrawal of indomethacin and aspirin was followed immediatley by excessive binding of this amino acid to circulating proteins:this phenomenon was not observed when alclofenac, sodium aurothiomalate or D-penicillamine were withdrawn. It has been demonstrated that disease activity in rheumatoid arthritis is reflected in acute-phase protein concentrations and in the extent to which L-tryptophan is bount to plasma protein. It is suggested that drugs which profoundly affect these parameters provide not only symptomatic relieft but also possible beneficial effects upon the disease process itself.


Comparison of benorylate and ibuprofen in the treatment of established rheumatoid arthritis.

Benorylate and ibuprofen appear to be useful drugs for pain relief in rheumatoid arthritis but benorylate would appear to have a slightly better effect on the pain score and it improved the grip strength more than the moderate doses of ibuprofen. It could be a most useful drug when gastric problems limit the dose of aspirin or of other analgesics.


Urinary excretion of hydroxyprolines in man under the influence of cold.

Urinary hydroxyproline excretion was studied in human subjects exposed to cold stress and was related to urine flow and tubular reabsorption of calcium and phosphate. The results indicate the occurrence of a calcium release from the bones, which does not seem to be caused by changed activity or immobilization. The cold-induced changes--calcium excretion, dehydration, and demineralization - are the same as those reported under space-flight conditions. Furthermore, it has also been possible to induce a similar response with psychological stress agents. These findings, together with recent observations on renal stone formation and hyperparathyrodism, indicate that different types of stress might have a direct influence on calcium homeostasis, possibly mediated by the adrenergic nervous system.


Antibacterial precipitins and autoantibodies in serum of patients with cystic fibrosis.

Sera from 84 patients with cystic fibrosis, 31 patients with other respiratory diseases and 21 control persons have been investigated for the occurrence of antibacterial precipitins and autoantibodies. Preciptins were studied by means of crossed immunoelectrophoresis, antinuclear factors by an indirect immunofluorescence technique and rheumatoid factors by the latex fixation slide test. A very heterogeneous antibacterial immune response was found in patients with cystic fibrosis, notably as regards Ps. aeruginosa. None of the other patients or controls had precipitins against this bacterium. The occurrence of precipitins against St. aureus and D. pneumoniae were more frequent in cystic fibrosis patients as compared with controls, but not as compared with other respiratory disease patients. No significant differences were found as regards precipitins against H. influenzae or the occurrence of rheumatoid factors. Antinuclear factors were more frequent in cystic fibrosis patients than in the other two groups investigated. A pronounced and heterogeneous humoral immune response against Ps. aeruginosa in cystic fibrosis patients chronically infected with mucoid strains of this bacterium was found to be correlated with poor prognosis and the reason for this is discussed.


[Dental plaque pH in patients with hereditary fructose intolerance].

There is little doubt that the initial cariogenic attack upon dental enamel is caused by acids stemming from metabolic activity of dental plaque microorganisms fermenting carbohydrates. However, a direct correlation between caries activity and pH changes of plaque has not yet been established. In-vio and in-vitro plaque pH was recorded in 4 caries-free HFI children by the method of Graf, R., and Graf, H. Application of 10% glucose were followed regularly by pH drops from the fasting range pH 6.2-7.2) reaching values of 4.7 to 6.5 after 20 minutes. These were comparable to values found in normal subjects. 10% sucrose treatment resulted in a slower and less pronounced pH lowering, reaching a pH between 4.8 and 6.5 compared to normal control subjects, which showed the classical drop down to pH 4.0 to 4.3 The results indicate that human dental plaque grown under sucrose- free conditions cannot metabolize sucrose (or its initial breakdown produce fructose) to produce an in-vivo pH drop below the critical range of enamel demineralization. The zero caries activity of the children may be explained by the lack of a demonstrable classical pH drop or acid attack.


Urinary lithiasis in childhood in the Bristol clinical area.

A series of 59 consecutive cases of urinary calculi in childhood is presented, being acquired from one local area (Bristol). These children were treated from 1950 to 1973. The peak presentation was in the 2nd and 3rd year of life, with a secondary peak in the 10th year. Anatomical (39%), metabolic (8.5%) or primary infective abnormalities (29%) were demonstrable, but 22% had to be left in an unsatisfactory "idiopathic classification''. The overall recurrence rate of 7% was reduced to 3.5% when those patients with cystinuria were excluded. The local water supply areas have been studied and a tentative association is suggested between patients and their environment when they live in an area where the water is not only hard but also alkaline (pHgreater than 8).


Tetrahedral intermediate in a specific alpha-chymotrypsin inhibitor complex detected by laser Raman spectroscopy.

Laser Raman spectroscopy indicates that inhibition of alpha-chymotrypsin by 2-phenylethaneboronic acid occurs in two steps: (i) the formation of a loosely bound complex, in which the boron remains in a trigonal configuration; and (ii) reaction of the boron with a functional group in the catalytic site of the enzyme, resulting in a reversible, stable tetrahedral adduct.


Anthopleurine: a sea anemone alarm pheromone.

The sea anemone Anthopleura elegantissima responds with characteristic contraction to a pheromone released by wounded conspecifics. The alarm pheromone was isolated by ion-exchange chromatography and identified by chemical and spectroscopic methods as the quaternary ammonium ion (3-carboxy-2, 3-dihydroxy-N, N, N-trimethyl)-1-propanaminium. Median effective concentration of the crystalline pheromone is 3.5 X 10-minus 10 mole per liter of seawater.


A new hyrogen ion telemetry technique for evaluating gastroesophageal reflux.

A new pH capsule telemetry technique was used to measure the pH fluxes in the upper part of the gastrointestinal tract in normal volunteers, symptomatic patients and in those with hiatal herniorrhaphy during the preoperative and postoperative period. The Darvon-sized pH capsule is swallowed with ease and with minimal discomfort by a fasting patient. The pH of the surrounding media activates an FM radio transmitter within the capsule to emit a continuous radio signal which is converted by a receiver to a linear graph on a strip chart recorder. This pH capsule telemetry test is easy to perform on an ambulatory basis and allows an accurate and reproducible determination of the presence or absence of esophageal reflux in patients with and without a hiatal hernia. Its correlation with symptomatic reflux is higher than that found with a conventional gastrointestinal series examination. The technique allows a much clearer distinction to be made between those patients with real symptomatic esophagitis secondary to actual reflux and those with other esophageal, cardiac or pulmonary symptoms existing withour reflux. This study also reveals a consistently lower fasting gastric pH in patients with signs and symptoms of reflux than in normal individuals without reflux. The technique enabled a more accurate assessment of the efficacy of hiatal hernia repair and revealed a reduced degree of esophageal reflux in those patients who had undergone successful repair with fundic plication.


Adrenergic mechanisms in the hindlimb circulation of baboons.

The effects of the adrenergic agonists norepinephrine, epinephrine, isoproterenol, and phenylephrine upon femoral arterial blood flow were measured in baboons before and after alpha (phenoxybenzamine) and beta (propranolol) adrenergic receptor blockade. Flow was measured with an electromagnetic flowmeter. Arterial and venous pressures were recorded simultaneously. Femoral vascular resistance was calculated from these data. Catecholamines were injected intra-arterially (10(-3)--10(0) mug, base, kg.(-1) and intravenously (1.0 mug kg.(-1) in a randomized sequence. All four adrenergic amines were vasodilators at low dose (10(-3) mug kg.(-1), intra-arterially) and this effect was abolished during beta adrenergic receptor blockade. Intra-arterial isoproterenol elicited dose-dependent increases in femoral flow; the other amines were vasoconstrictors at high doses. Alpha adrenergic blockade "reversed" the vasoconstrictor effects of these three amines. At the same dose isoproterenol increased flow more through the intra-arterial than the intravenous route. Conversely, norepinephrine and epinephrine were potent femoral vasodilators when injected intravenously. The findings indicate that the classical adrenergic amines are all vasodilators of the subhuman primate hindlimb at low doses due to their interaction with beta receptor sites. The fact that epinephrine and norepinephrine exert a greater increase in flow when given intravenously than when given intra-arterially is presumably secondary to increased arterial pressure, in turn due to the vasoconstrictor effects of these agents on other regional circulations.


Effects of pharmacological myocardial depression on coronary artery collateral formation.

Treatment of angina pectoris falls within two spheres: (1) increasing myocardial blood flow (direct bypass, vasodilators), or (2) reducing oxygen demand (beta blockade, propranolol). If the latter depresses the stimulus for collateralization without improving input, its use in certain forms of coronary disease may require reconsideration. To examine this hypothesis, 25 dogs (four groups) were evaluated by surface mapping, angiographic collateral mapping, and hemodynamic studies including cardiac output, systemic and coronary pressures, coronary flow, and left ventricular end-diastolic pressure, pressure to time (LVdp/dt). Collateralization was induced with ameroid constrictor placement in Groups I, III, and IV. Groups II and III received immediate propranolol treatment (3 to 5 mg. per kilogram per day for 6 weeks); Group IV received delayed treatment (4 weeks after constriction); and Group I received no propranolol (constrictor alone). Collateral formation was depressed significantly in the acutely beta-blockaded dogs (Group III) by surface and angiographic mapping and by hemodynamic evidence of depressed coronary flow and altered coronary retrograde pressures. Alterations in established collaterals (Group IV) were not consistent. These data suggest that pharmacological reduction of myocardial oxygen demand reduces coronary collateralization experimentally, requiring further evaluation of its usage in multivessel coronary disease to the exclusion of direct bypass.


Effect of aspirin, bile salt, and ethanol on canine gastric mucosal blood flow.

The effect of aspirin (20 mM.), sodium taurocholate (40 mM.), and ethanol (24 per cent w/v) on gastric mucosal blood flow was studied in an exteriorized, chambered preparation of canine fundic stomach. Gastric mucosal blood flow was measured by gamma-labeled microspheres and plasma aminopyrine clearance. All three test solutions caused a significant increase in microsphere-measured mucosal blood flow. The degree of increase in gastric mucosal blood flow was proportional to the severity of gross mucosal injury, being greatest with bile salt and least with ethanol. Plasma aminopyrine clearance determined only a small fraction of mucosal flow measured by microspheres following injury, particularly in sodium taurocholate and ethanol experiments, where the net hydrogen ion back diffusion was greatest. The results suggest that increased gastric mucosal blood flow may be a secondary defensive response to the damage caused by these irritants and that the plasma aminopyrine clearance is unreliable in quantitating mucosal blood flow changes in the presence of mucosal injury.


The role of acid and ischemia in production of stress ulcers during canine hemorrhagic shock.

Hemorrhage to a mean arterial pressure of 41 mm. Hg in ten dogs decreased Heidenhain pouch blood flow to 6 ml. per minute and aminopyrine clearance to 0.93 ml. per minute. Pouch oxygen consumption fell from 1.47 to 0.74 ml./min.-100 Gm. and total body oxygen consumption remained unchanged. Net ion fluxes during shock and reinfusion did not change significantly from control values of minus 89.8 muGq./30 min.-100 cm.-2 for H-+ and 88.6 muEq./30 min.-100 cm-2 for Na-+. However, PD decreased from 54 to 24 mv. in parallel with a fall in net Cl-minus flux from 56.8 to minus 11.7 muEq./30 min.-100 cm-2. Nine of ten pouches subjected to shock and instilled acid test solution (ATS) developed superficial mucosal erosions. No ulcerations were found in either seven control dogs (anesthesia + ATS) or in three dogs subjected to shock without ATS. Acid appears to be of prime importance in the production of stress ulcers during or following ischemia, even though there is no increase in mucosal ionic permeability.


The intestinal phase of gastric secretion: a pharmacological profile of entero-oxyntin.

In dogs with denervated fundic pouches, antrectomy, and gastrojejunostomy, feeding a meal of cooked liver and 5 percent bone dust stimualted acid secretion from the fundic pouches without increasing serum gastrin concentrations. Simultaneous administration of pentagastrin, histamine, octapeptide of cholecystokinin, or bethanecol produced potentiation of acid secretion, suggesting that the mediator of the intestinal phase is different from these secretagogues. Secretin and glucagon failed to inhibit the intestinal stimulus but both atropine and metiamide were potent inhibitors. We conclude that entero-oxyntin, the hormone responsible for the intestinal phase of gastric secretin, has a unique pattern of effects for acid secretion.


[Use of neuroleptic agents in modern pig-farming (author's transl)].

in pig-farming, the use of neuroleptic agents in conditions causing stress has increased. In the meaty type pig, this stress gives rise to specific symptoms such as acidosis, hyperthermia and muscle rigidity. This will result in death before or an abnormal meat quality (PSE-meat) after slaughter. The symptoms may also be produced in these pigs by having them inhale halothane (Fluothane), the symptoms being rapidly reversible. The inhibitory effect of various neuroleptic agents of the group of butyrophenone and phenothiazine derivatives on the appearance and course of the above symptoms is discussed. The extent to which the quality of the meat and mortality during transport is affected following administration of these agents to slaughter pigs as well as the degree to which hypersensitivity reactions to halothane are reduced in young pigs serve as models. Finally, public health and ethical aspects relating to the use of neuroleptic agents in farm animals are examined more closely.


[Fluid therapy (author's transl)].

An introductory part concerned with the distribution of fluid and electrolytes over the various compartments of the body and the acid-base regulation is followed by a discussion of the fluid balance and pathological losses of fluid and electrolytes. An assessment of patients showing dehydration is based on the histories, clinical examination and laboratory studies, in order to gain an impression of the state of hydration, electrolyte deficiencies, acid-base equilibrium, caloric requirements and renal function. The guidelines for fluid therapy include the scheme of this form of treatment, some comments on the available fluids and the techniques in large and small animals.


The ciliary-cone sensory cell of anemones and cerianthids.

An ultrastructural study of the tentacles of Stomphia and of Ceriantheopsis has revealed that the so-called 'ciliary-cone sensory cell' consists of a cluster of five to seven apparent receptors rather than just one cell as reported previously. At the center of a cluster is a single cell, whose dendrite bears one cilium surrounded by about ten large stereocilia. Surrounding this cell are a number of peripheral cells whose dendrites bear large numbers of small stereocilia and, in Ceriantheopsis, one cilium. The sensory apparatuses of all cells in a cluster unite to form a single unit projecting above the tissue surface: the ciliary cone. Their possible physiological role is discussed in relation to new behavioural observations.


Arbovirus infections in Sarawak, October 1968-February 1970: GETAH virus isolations from mosquitoes.

14 strains of Getah virus were isolated from a variety of mosquito species collected in Sarawak between October 1968 and February 1970. Ten strains were isolated from C. tritaeniorhynchus 7 of them at K. Tijirak. Single strains were isolated from C. gelidus, C. pseudovishnui, M. bonneae/dives and Aanopheles species. 6 of the isolates were obtained in October 1968 when Japanese encephalitis, Tembusu and Sindbis viruses were also very active. The available evidence suggest that Getah virus in Sarawak is maintained in a cycle similar to that of Japanese encephalitis virus and involves C. tritaeniorhynchus, C. gelidus and domestic pigs.


A purine nucleoside hydrolase from Trypanosoma gambiense, purification and properties.

A purine nucleoside hydrolase from Trypanosoma gambiense was purified 160-fold. Preferred substrates of the reaction were adenosine, inosine and guanosine with a maximum of activity at pH 5.4. Competitive inhibitors of the adenosine hydrolysis were dimethylallyl adenosine, 6-methylmercaptopurine riboside, tubercidin, formycin B, 6-mercaptopurine riboside and deoxyadenosine. A metabolic scheme of adenosine nomophosphate salvage synthesis is discussed.


The relationship between length of incubation, bacterial growth and tuberculin yield of a strain of Mycobacterium tuberculosis.

The relationship was studied between length of incubation in a liquid synthetic medium, amount of bacterial growth, pH of the culture filtrate and tuberculin yield of a single strain, DT, of Mycobacterium tuberculosis. No sinple relationship was found between the total crop of bacteria and the tuberculoprotein content of the culture filtrate. On the other hand, protein release and the pH of the culture filtrate were closely related. In each of two trials the bacterial crop increased rapidly during the early period of incubation, although maximum growth was not reached until 9 and 13 weeks respectively. The pH of the culture filtrate reached its maximum at a value of more than 9-0 after 5 weeks incubation and then fell until the 10th week; a second rise occurred until the 13th week when the pH dropped again and levelled off slightly on the alkaline side of neutrality. The rate of increase in tuberculin yield was most rapid during the first 7 weeks of incubation. After this, the rate of increase slowed down but the yield was still rising after 18 weeks. It is concluded that for the large-scale production of mammalian tuberculin by the method used in these trials, it is profitable to incubate production cultures for 14 weeks or longer.


Foreign bodies and urinary stones.

Experimental and clinical aspects of calculogenesis about foreign bodies are reviewed. Factors such as infections, urine dilution, urinary pH, and suture materials are discussed from an investigative point of view. The various kinds of clinical foreign body stones reported are categorized according to the manner of introduction into the urinary tract and anatomic locations.


Imipramine hydrochloride: pharmacodynamic effects on lower urinary tract of female dogs.

Our study of the pharmacodynamics of imipramine hydrochloride of the female canine lower urinary tract indicates the primary mode of action to be the stimulation of alpha adrenergic neuroreceptors in the bladder neck and urethra.  This stimulation results in increased resting urethral pressure, adequate sphincter closure, possibly an increase in the bladder capacity and efficient urinary control.  Imipramine had no anticholinergic effect on the bladder and the urethra.  It also appears unlikely that in enuretic patients imipramine acts by central augmentation of the adrenergic system.  No change was noticed in the intravesical or arterial pressures.


Use of methenamine hippurate in male infertility.

In sperm-freezing for infertility patients with low sperm counts, we found that semen containing high numbers of white blood cells, greater than 15 to 20 per high-power field, was both poor in quality and difficult to freeze. In examining these patients carefully, we found that many had smoldering prostatitis and some an overt history of prostatitis. We treated them with methenamine hippurate using various methods and found that by decreasing the white blood cell count in their semen, we could frequently improve the semen quality, particularly sperm motility, also achieve pregnancies in some cases.


Microsurgery in clinical urology.

Microsurgery is not a new tool to the urologist. Transurethral resection is probably the most challenging type of microsurgery, and we do it daily. The manipulations of microvascular dissections and anastomoses may be more intricate, but the basic concept of performing delicate procedures while looking down a tube is "old hat" to us. The new techniques discussed here may extend the range of operative solutions to difficult clinical problems in urology perhaps as transurethral resection did in the thirties and forties.


Urologic problems associated with imperforate anus.

A total of 120 children with both high, intermediate, and low types of imperforate anus were evaluated urologically. Genitourinary anomalies were associated with all types of imperforate anus but were found more often in children with high rectal deformities. Because the over-all incidence of genitourinary anomalies was high, early and complete urologic evaluation is necessary to achieve the best functional result.


Five-day partial bypass using a membrane oxygenator without systemic heparinzation.

These studies indicate that a heparin bound membrane oxygenator can be used in venovenous bypass circuit in dogs for a period of 5 days without systemic heparinization. The plasma SGOT, plasma hemoglobin, and MLW of the animals increased after initiation of bypass but returned to control levels. Oxygen transfer did not deteriorate in the membrane oxygenator, eliminating the necessity of membrane exchange during the 5-day bypass.


[Annual dynamics of acidobasic indices in the sheep blood].

Altogether 218 sheep were followed for a year and the values of their acidobasic indices were examined, the follow-up comprises all seasons of the year, gravidity period, time of nursing and milk production. The actual pH value in the sheep blood varied from 7.30 to 7.48, with 7.40 average. The average value of partial CO2 pressure amounted to 37.26 torr the individual values varying between 30.0 and 47.5 torr. Baz excess varies from +5.0 to -6.3 mval/1 blood with year average of 1.11 mval/1 blood. Buffer baz was 43.0 mval/1 on the average, with variations from 34.2 to 48.9 mval/1 blood. Standard bicarbonate showed a relatively broad range of values from 19.0 to 28.0 mval/1 plasma, with 22.85 mval/1 average. Actual bicarbonate manifested similar variation dynamics as SB. Annual average was 22.92 mval/1 plasma, with variations from 19.0 to 28.2 mval/1. Total plasmatic CO2 had balanced average monthly values, with year average of 23.84 mval/1. Generally it can be concluded that after the sheep being out to grass the acidobasic blood indices became regulated.


[Values of acido-basic balance in the blood of the beagle breed dog in comparison with the German shepherd dog].

The values of acidobasic balance were examined in 101 dogs of the Beagle breed and in 20 German Sheep-Dogs. The Beagle dogs were divided into five age groups. A difference was found between the values obtained in the group of the youngest dogs and those in older age groups. In comparison with Beagle dogs, the values were higher in German Sheep-Dogs (pH, base excess). A figure is attached representing the deviations of the values of acidobasic balance of blood in the two breeds.


Veterinary aspects of salmonid fish farming: husbandry.

A knowledge of environmental requirements is important in order to obtain good growth and health when farming salmonid fish. Biological requirements are discussed, including water quality parameters and nutritional aspects. The main techniques used for farming salmonids are described together with the annual cycle of operations undertaken on a commercial trout farm.


Studies on the modification of the cellular response to injury. II. Electron microscopic studies on the protective effect of acidosis on anoxic injury of Ehrlich ascites tumor cells.

Extracellular acidosis (ph 5.9 to 6.5) was found to be significantly retard the subcellular response of Ehrlich ascites tumor cells (EATC) to anoxic injury. The cells initially showed a reversible stage of cell injury with diffuse mitrochondrial condensation and swelling of endoplasmic reticulum (ER) at pH 7.9 by 1 h, while by 3 h at this pH all cells showed high amplitude and intramatrical flocculent densities of mitochondria, and fragmentation of membrane systems. At pH 7.4 cells were normal at 15 min., the mitochondria were condensed as above by 1 h, some cells still showed condensed mitochondria and dilated ER while others showed high amplitude swelling of mitochondria by 3 h and all cells showed irreversible changes by 4 h. At pH 5.9 to pH 6.5 mitochondria remained condensed until 3 h and only by 6 h did some cells show high amplitude swelling, whereas most cells showed persistent mitrochondrial condensation. Not until 8 h did all cells show high amplitude swelling of mitochondria. Furthermore, ultrastructural differences in the pattern of necrosis were seen at the lower pH values consisting of greater density of the cell sap, irregularly dispersed flocculent densities in apposition to fragmented cytoplasmic membranes and in mitochondria, and more prominent persistent clumping of nuclear chromatin.


Studies on the modification of the cellular response to injury. III. Electron microscopic studies on the protective effect of acidosis on p-chloromercuribenzene sulfonic acid-(PCMBS) induced injury of Ehrlich ascites tumor cells.

Extracellular acidosis (pH 6.5) was found to significantly retard the response of Ehrlich ascites tumor cells (EATC) to direct plasma membrane injury with the non-penetrating organic mercurial compound, p-chloromercuribenzene sulfonic acid (PCMBS). Treatment of cells with 1 mM PCMBS resulted in loss of viability of all cells by 45 minutes at pH 7.4, and by 90 minutes at pH 6.5. Pregression of cellular changes through the various stages of cell injury at the ultrastructural level was correspondingly slower at pH 6.5. The results support the concept that stage 3 of cell injury, associated with condensed mitochondria, dilated ER and swollen cell sap is compatible with cell survival, while stage 5 with high amplitude swelling of mitochondria, fragmentation of membrane systems, and beginning of karyolysis is characteristic of irreversible injury. All cells entered stage 3 at 7.5 minutes at pH 7.4, while essentially all cells entered stage 5 by 45 minutes. At pH 6.5, stage 3 was maintained for 45 minutes and 100% of the cells entered stage 5 by 90 minutes. Although the mechanism of the protection against PCMBS-induced injury is not known, the present electron microscopical results are compatible with the hypothesis that the extracellular acidosis acts to partially stabilize plasma membrane, perhaps by interaction with sulfhydryl (SH) groups.


Experimental porphyria induced by 3-(2,4,6-trimethylphenyl)-thioethyl)-4 methylsydnone.

Administration of 3-[2-(2,4,6-trimethylphenyl)-thioethyl]-4-methylsydnone (TTMS) induces hepatic porphyria in rats, mice and dogs. The protoporphyrin pigment in livers of rats and mice is found mainly in bile ducts and leads to bile duct proliferation and portal inflammation. Dog livers contain protoporphyrin predominantly in bile canaliculi. The birefringence of the pigment appears to be associated with bilamellar components within the pigment. The markedly depressed catalase activity in livers of rats does not increase after clofibrate administration. The catalase activity of mouse liver is depressed slightly and responds to clofibrate treatment.


Anticomplementary activity of human immunoglobulin G. I. Mechanism of the artifactual increase in anticomplementary activity of IgG during the assay.

The anticomplementary activity of IgG can be increased up to 20-fold by pipetting during the preparation of serial dilutions for the assay of this activity. Albumin, if added to the IgG solution before the serial dilutions, completely prevents this artifactual increase in activity. Polyethylene glycol, polyvinyl pyrrolidone, methyl cellulose, gelatin and octanol are also effective stabilizers of IgG. Repeated pipetting of IgG solutions caused marked linear increase in their anticomplementary activity. The formed anticomplementary activity was due to small amounts of highly aggregated protein. The amount of activity formed depended on at least four factors: [1] the number of pipetting steps; [2] the IgG concentration; [3] the level of albumin or other stabilizers, and [4] the pH, which influences the stabilization by albumin. The anticomplementary activity of IgG is increased up to 100-fold by exposure to gas-liquid, liquid-liquid and hydrophobic solid-liquid interfaces. Albumin and polyethylene glycol prevent the activity increase during these treatments. The tendency of IgG to aggregate at interfaces and the ability of albumin and other substances to prevent the aggregation paralleled their rate of adsorption to the air-water interface. Solutions of dansyl chloride in decane emulsified in aqueous solutions of IgG and albumin specifically label the proteins at the liquid-liquid interfaces. The mechanism of stabilization can be explained by preferential adsorption of surface-active proteins and polymers.


Studies on citrate-phosphate-dextrose (CPD) blood supplemented with adenine.

The effect of varying adenine concentrations in citrate-phosphate-dextrose (CPD) blood was studied in an attempt to optimize the storage conditions for human erythrocytes with regard to posttransfusion viability and oxygen release function. The maintenance of diphosphoglycerate (DPG) was impaired by adenine supplementation; this effect was closely related to the adenine concentration. A 0.25 mM adenine concentration in CPD blood improved the adenosine triphosphate (ATP) levels and the posttransfusion viability markedly, without appreciably impairing the DPG maintenance. The results suggest that CPD solution supplemented with adenine to give a 0.25 mM concentration in the blood is a better preservative for human erythrocytes than the commonly used acid-citrate-dextrose (ACD), CPD, and ACD-adenine solutions with regard to posttransfusion viability and oxygen release function. Adenine addition to this low concentration is not expected to cause renal damage even after massive transfusion.


Australia antigen 'ad' and 'ay' subtypes. Purification and partial characterization.

The two commonly-found Australia antigen subtypes have been purified by simple inexpensive, reproducible, physico-chemical methods involving ammonium sulfate precipitation, peptic digestion, calcium phosphate gel fractionation and molecular sieving on Sepharose 4B. The overall recovery of the two subtypes varied between 50 and 60% of the total antigen content on the starting serum. The purified antigens were found homogeneous by discontinuous gel electrophoresis, analytical ultracentrifugation, and isopycnic banding ultracentrifugation. No contaminating serum proteins could be detected by immunoelectrophoresis. The two purified antigen subtypes have similar Stokes radii and buoyant densities. The sedimentation coefficients for the 'ad' and 'ay' subtypes were found to be 33.0 and 40.1 times 10- minus 13 sec, respectively.


The non-Mendelian inheritance of Lewis-c blood group substance, as demonstrated in the case of a Bombay, Le(a-b-c-) saliva.

A Bombay, Le(a-b-) saliva was shown to lack Pneumococcus type XIV activity, an unusual situation, since this sample should be rich in this precursor to the ABO blood group substances. However, the sample was found to contain a new serological specificity, Le-c. It is argued that simple Mendelian inheritance does not occur with Le-c and single gene control cannot be demonstrated. Failure to repress a fetal gene at birth, as implicated by the similarity in structure between Le-c and carcinoembryonic antigen [SIMMONS and PERLMANN], has been excluded as the mechanism of inheritance of this blood group substance, due to the inability to detect carcinoembryonic antigen in the test saliva.


Biphenyl hydroxylations and spectrally apparent interactions with liver microsomes from hamsters pre-treated with phenobarbitone and 3-methylcholanthrene.

1. Metabolism of [14-C]biphenyl by hamster liver microsomes has been studied by t.l.c., quantitative fluorimetry and difference absorption spectrophotometry. 2. 4-Hydroxybiphenyl (major metabolite) and 2-hydroxybiphenyl (minor) accounted for at least 83% of total biphenyl metabolism. Small quantities of 2,2'- and 4,4'-dihydroxybiphenyl metabolites were also tentatively identified. 3. Biphenyl 2- and 4-hydroxylations exhibited different NADPH-NADH specificities and pH profiles. 4. Phenobarbitone preferentially induced formation of 4-hydroxybiphenyl, while 3-methylcholanthrene induced 2- and 4-hydroxylation almost equally by affecting both production and further metabolism of 2- and 4-hydroxybiphenyl. 5. Biphenyl, 2- and 4-hydroxy- and 2,2'-dihydroxybiphenyl gave both high- and low-affinity type I spectrally apparent microsomal interactions, whereas 4,4'-dihydroxybiphenyl promoted a reverse type I spectral change. There was an inverse correlation between the spectral dissociation constants (Ks) and lipid solubilities for the low-affinity type I interactions and a possible direct correlation for the high-affinity type I interactions. 6. Phenobarbitone and 3-methylcholanthrene induced cytochrome P-450 and cytochrome P-448 respectively and produced complex changes in the biphenyl type I interaction kinetics. No direct relationship was found in 'control' or 'induced' microsomes between biphenyl 2- or 4-hydroxylation, the type I interaction and cytochrome P-450 concentration. The results are discussed in terms of a 3-methylcholanthrene-inducible biphenyl 2- and 4-hydroxylase and a phenobarbitone-inducible biphenyl 4-hydroxylase.


Diagnosis and therapy of renal tubular acidosis in infancy.

While distrubances of the acid-base balance are frequently seen in infancy, renal tubular acidosis is a rather rare disease but should be considered as differential diagnosis if metabolic acidosis persists after adequate treatment. Proximal and distal tubular acidosis with primary and secondary forms can be differentiated. Proximal RTA is characterized by the loss of bicarbonate, distal RTA by a defect to establish a hydrogen ion gradient and thus to accomplish acidification of urine. In addition to these two basic forms a bicarbonate wasting state in distal RTA has been described. A patient with these clinical features is presented. He was admitted to our hospital at the age of 1 month with meningitis, enteritis and marked dystrophy. A persistant hyperchloraemic acidosis with concomitant hypokalaemia was present. The ammonium chloride loading test confirmed the diagnosis of primary distal RTA. Renal biopsy performed with 1 year of age revealed nephrocalcinosis of the inner medullary region of the kidney while the cortex was not affected. The patient first needed alkali doses of 12 mEq/kg/day which could be gradually reduced to 3.5 mEq/kg/day. Under additional potassium substitution of 5 mEq/kg/day he was thriving well. Differential diagnosis and the particular clinical features of this case are discussed.


[Effect of the antiarrhythmic agent propaphenone on cardiac conduction. clinical studies using bundle of his electrography].

The influence of the new antiarrhythmic agent Propafenon on cardiac conduction and sinus node function was studied by using His-bundle recordings and atrial stimulation in 14 patients with normal and diseases conduction system. Intravenous administration of Propafenon in therapeutic dose (1-2 mg/kg) produced a significant prolongation of the atrioventricular conduction time. Increase of the A-H interval was observed in 13 of 14 subjects during sinus rhythm. Second degree A-V block (Wenckebach form) during atrial stimulation occurred at lower frequencies after administration of the drug. The impulse propagagion within the His-Purkinje system was depressed significantly (H-V interval in 8, H-S interval in 10 of 14 subjects). Propafenon did not cause any alteration in intraatrial conduction, but depression of the sinus node automaticity was noted. Total reversal of the drug induced prolonged atrioventricular conduction and a decrease of the sinus rate was seen after administration of orciprenaline. Beta-adrenergic receptor blocking and local anaesthetic direct membrane actions are discussed as possible cause of the prolongation of atrioventricular and intraventricular conduction.


[Influence of CO2 and pH on the attachment response of the cercaria of Diplostomum spathaceum (trematoda) (author's transl)].

1. The attachment of the cercaria to artificial substrates (offered via dialyzing membranes) in definite media was investigated under conditions of variable pH and [CO2]. 2. A decrease of the pH of the substrate releases only attachments in CO2 containing media and consequently acts via CO2 systems of the medium. 3. As effective components of CO2 systems, dissolved CO2 + H2CO3 are confirmed. 4. The sensitivity of the reaction on gradients of the CO2 partial pressure (in solution) could be established by offering substrates with lowered pH in CO2 containing media. Thus, by raising the CO2 partial pressure from ca. 0,04% to 0,15% maximal fixation rates were obtained (Fig. 3). 5. The carboanhydrase inhibitor acetazolamide, when added to the medium, had no direct influence on the CO2 receptors.


Phosphatase systems in Paramphistomum explanatum Fischoeder, 1901.

Extracts of adult Paramphistomum explanatum have been shown to contain high concentration of acid phosphomonoesterase with maximum activity at pH 4.5. The enzyme has been characterized by an exhibition of an unexpected increase in the inhibitory action of a mercury at 1 mM concentration by EDTA. With a lower concentration of mercury (0.1 mM and below) EDTA gave partial protection against inhibition. Different concentrations of magnesium and cobalt activated the enzyme while fluoride, copper, arsenate, tartrate and p-mercuribenzoate brought about inhibition. EDTA, glycine, glutathione and sodium azide had no effect. There was an indication of the presence of alkaline phosphomonoesterase at pH 10.0. The Km for p-nitrophenyl phosphate hydrolysis was 0.45 mM at pH 4.5.


Reactions of n-hexanal with glycine in model systems.

n-Hexanal a common component of off-flavor of various foodstuffs forms in ethanol-water solutions brown coloured pigments with glycine very slowly. The changes in the ultra-violet region of spectrum, especially at the maximum at 280 nm are much quicker. Due to the fact that only the non-protonised amino acid reacts, the reaction rate is the highest in alkaline medium, especially at pH value 8.5-9. The primary product of the condensation of n-hexanal with glycine, the Schiff base, is not stable, as confirmed by the decreasing of the polarographic wave heights. The reaction rate constants of this decomposition were the highest at pH-value 8.5-9 similarly as the changes in the UV-Spectra. The effect of the temperature was negligible.


[A modified hydroxamic acid method for the estimation of the activity of lipase (E.C. 3. 1. 1. 3)].

Optimal conditions for a modified hydroxymic acid method have been worked out with respect to the stability of the substrate emulsion; by systematically varying the ratios of the components of the solutions it was possible to develop a homogeneous reaction system which could be directly measured by spectrophotometry.


Ribonuclease activity of Entamoeba histolytica.

Ribonuclease activity of Entamoeba histolytica was purified 65-fold by calcium phosphate gel, ammonium sulphate and acetone treatments. The enzyme was inhibited by metal ions, like Mg-2+, Mn-2+, Co-2+ and Ca-2+. Metal chelating and sulphydryl agents showed no effect. EDTA and alpha, a'-dipyridyl reversed the inhibition produced by Mg-2+, Mn-2+ and Fe-2+. Various sodium salts had negligible effect on the enzyme; however, sodium chloride activated the enzyme slightly. Amoebicidal drugs like enterovioform and chloroquine phosphate inhibited the enzyme completely, while emetine showed marked inhibitory effect. Neomycin exhibited a slight stimulatory action on this enzyme.


Clinical aspects of the disruptive effects of road accidents on the human body.

Knowledge of the patterns of injury from road accidents helps to reduce the risk of diagnostic error through oversight. Understanding the patterns of disruption of the body gives surgeons a better understanding of the nature of the injury and of the behaviour of the injuried tissues. This is of particular value in the diagnostic manipulation of fractures to decide whether they need internal fixation or whether external splintage will keep them in an acceptable position.


Cerebral blood flow and oxygen consumption in the rat in hypoxic hypoxia.

In order to measure cerebral blood flow (CBF) and cerebral metabolic rate for oxygen (CMRo(2)) at pronounced degrees of hypoxic hypoxia the Pao(2) of artificially ventilated and normocapnic rats was reduced to between 47 and 22 mm Hg for 15-25 min with subsequent measurements of CBF, using a -133Xenon modification of the Kety and Schmidt technique, and of the arteriovenous difference in oxygen content, the venous blood being obtained from the superior sagittal sinus. When the Pao(2) was reduced to minimal values of 22 mm Hg CBF increased 4- to 6-fold, the increase in CBF being unrelated to changes in blood pressure or Paco(2). The CMRo(2) remained unchanged at all levels of hypoxia. It is concluded that the maintenance of a normal, or near-normal, cerebral energy state even at extreme degrees of hypoxic hypoxia depends solely on a homeostatic increase in CBF.


Acid-base changes and excitation-contraction coupling in rabbit myocardium. I. Effects on isometric tension development at different contraction frequencies.

The effects of changes in acid-base parameters on the active force of isolated rabbit papillary muscles were studied at contraction frequencies of 12, 60 and 120/min. When extracellular pH was lowered from 7.4 to 7.0 and 6.7 in a bathing solution buffered with 10 mM histidine, the active force decreased at all contraction frequencies studied. After parallel increases of HCO3-minus concentration (up to 47 mM) and PCO2 at a constant extracellular pH of 7.4 the active force of the muscle increased at low and decreased at high contraction frequencies. None of these effects can be attributed to catecholamine release or to altered extracellular concentration of ionized calcium. The inotropic effects produced by bicarbonate were not reproducible by methyl sulfate (47 mM) or propionate (47 mM). It is concluded that: 1. a lowering of the extracellular pH has a negative inotropic effect at all frequencies, 2. HCO3-minus has a positive inotropic effect that is most pronounced at low contraction frequencies and 3. CO2 has a negative inotropic effect exceeding that produced by the mere reduction in extracellular pH. The cellular mechanisms involved in the various inotropic effects are discussed.


Acid-base changes and excitation-contraction coupling in rabbit myocardium. II. Effects on resting membrane potential, action potential characteristics and propagation velocity.

The effects of changes in acid-base parameters on the resting membrane potential, action potential characteristics and propagation velocity were studied in isolated rabbit papillary muscles. Lowering extracellular pH from 7.4 to 6.7 in a bathing solution buffered with 10 mM histidine did not alter the resting membrane potential or action potential characteristics but casused slight reduction in propagation velocity. A parallel increase in HCO3-minus concentration (up to 47 mM)and PCO2 at a constant extracellular pH of 7.4 caused a substantial decrease in action potential duration but did not alter the resting membrane potential or propagation velocity. The decrease in action potential duration was caused by the increase in HCO3-minus concentration. Propionate (47nM) caused a shortening of the action potential which was of the same magnitude as for HCO3-minus but methylsulfate (47nM) did not have this effect. The possible influence of these changes on the inotropic state of the myocardium and the cellular mechanisms involved are discussed.


Adenosine triphosphate dependent calcium uptake by subcellular fractions from bovine neurohypophyses.

Bovine neurohypophyses were fractionated by differential and density gradient ultracentrifugation and the Ca-2+ uptake and ATPase activities in the microsomal, mitochondrial and secretory granule fractions were studied. The microsomal and mitochondrial fractions accumulated Ca-2+ in the presence of ATP. The accumulation by the latter per mg protein was at least twice as large as by the former. This Ca2+ accumulation was accompanied by liberation of inorganic phosphate (Pi). In the presence of sodium azide (2 mM) Ca-2+ uptake and Pi liberation were inhibited in the mitochondrial, but not in the microsomal fraction. Further studies of the microsomal fractions revealed that the ATP-dependent Ca-2+ uptake and Pi liberation activities were temperature and pH-dependent and required Mg-2+. Both activities were stimulated by very low concentrations of Ca-2+ (1-10 muM) and were inhibited by EGTA (2 mM). N-ethylmaleimide (2 mM) inhibited both the Ca-2+ uptake and ATPase activities of the microsomal fraction. These results suggest the presence of a membrane ATPase that is stimulated by both Ca-2+ and Mg-2+. It is suggested that the observed Ca-2+ uptake activities are involved in maintaining a low axoplasmic free Ca-2+ concentration, thus playing an important role in the release mechanism of vasopressin by the neurosecretory terminals.


Brain carbonic acid acidosis after acetazolamide.

In cats in barbiturate anesthesia extracellular pH and potassium were continously recorded from brian cortex by implanted microelectrodes. Implantation of the electrodes preserved the low permeability of the blood-brain-barrier to HCO3-minus and H+ions as indicated by the development of brain acidosis by I.V. injection of HCO3-minus. Acetazolamide (25 mg/kg) i.v. was followed by a marked brain acidosis which after 10 min had progressed to a drop in pH of 0.203 plus or minus 0.046 (x bar plus or minus S.D., n equals 8). The slowness ofthe development of acidosis points to a direct effect of the carbonic anhydrase inhibition on the brain tissue. As a further support for this conclusion was considered the finding of a prolonged response time of brain pH to HCO3-minus i.v. to CO2-minus inhalation, and to hyperventilation after the acetazolamide inhibtion. No changes in brain extracelllular potassium were found.


Biochemical research into psychosis.

A strategy is presented for biological psychosis research with neuroleptics acting as a point of crystallisation like antidepressants do in biological depression research. The neuroleptics chlorpromazine, haloperidol and oxypertine were studied, and it was found that they influence central catecholamine (CA) metabolism in man. An increased central dopamine (DA) turnover was found to occur in psychotic disorders, mostly in the form of motor agitation. As the first of a planned series of studies, chlorpromazine with presumed ability to reduce both DA-ergic and noradrenaline (NA)-ergic transmission and oxypertine as a more selective blocker of NA-ergic transmission were selected for comparison. The overall therapeutic effect of oxypertine was inferior to that of chlorpromazine, whereas oxypertine proved more effective in cases where loss of initiative was predominant. On the other hand, chlorpromazine exerted a more marked influence on extrapyramidal motor functions than oxypertine. In chronic psychotic disorders with inertia, oxypertine thus seems to be a neuroleptic which is strong enough to prevent exacerbation of delusions and hallucinations while at the same time increasing the level of motivation. These findings were in accordance with our predictions. The comparative study is illustrative of the practical significance of the research approach in this study: The biochemical action profile of a neuroleptic seems to be a more reliable indicator of its clinical action than does its chemical structure.


Minoxidil--haemodynamic and clinical experiences with a new peripheral vasodilator.

Minoxidil, a new peripheral vasodilator, given orally to hypertensive men in single doses of 5-25 mg, produced no haemodynamic changes within one hour after administration. After repeated oral doses within 24 hours to a total of 15-45 mg and after 10 mg t.i.d. orally for one week, moderate decreases in BP were seen concomitant with tendencies to increased heart rate and cardiac output. Clinically, oral minoxidil 10-50 mg daily in combination with diuretics and adrenergic beta-receptor blocking agents achieved an improved BP control in five patients with sustained arterial hypertension and unsatisfactory response to previous treatment. However, in four of the five patients minoxidil had to be withdrawn because of side-effects. It is concluded that minoxidil, producing a hypotensive effect of slow onset, may find a place as a therapeutic addition to symptomatic patients with severe and therapy-resistant hypertensive cardiovascular disease, provided adequate measures are taken to counteract side-effects, especially water retention and development of oedemas.


Formation of aberrant neurotransmitters and its implication for alcohol addiction and intoxication.

The possible involvement of false neurotransmitters in the biological aspects of addiction to alcohol has been reviewed and discussed. Current evidence is somewhat ambiguous, although suggestive, of a cause-effect relationship between possible metabolic products of biogenic amines (i.e., tetrahydroisoquinoline derivatives etc.) and addiction. A novel hypothesis of the mode of action of these derivatives developed on the basis of experiments in the reviewer's laboratory is also discussed. According to the latter hypothesis, alkaloid formation may occur in vivo at the membranous level in situ, by interaction of indoleamines and (or) catecholamines with the products of polypeptide chains and thereby modifying the properties of plasmalemmal membranes.


Interaction of biogenic amines with ethanol.

Ethanol through its primary catabolite, acetaldehyde, competitively inhibits oxidation of aldehyde dehydrogenase substrates. As a consequence biogenic amines form increased quantities of alcohols rather than the corresponding acids. During this biotransformation, condensation reactions between deaminated and intact amines may occur which can yield tetrahydropapaverolines. These compounds are closely related to precursors of opioids which is cause to link ethanol abuse to morphine addiction. There is, however, no pharmacological or clinical evidence suggesting similarities between ethanol dependence or opiod addiction. Acetaldehyde plays an additional role in  alkaloidal formation in vitro. Biogenic amines may react with acetaldehyde to form isoquinoline or carboline compounds. Some of these substances have significant pharmacological activity. Furthermore, they may enter neural stores and displace the natural neurotransmitter. Thus, they can act as false neurotransmitters. Some investigators believe that chronic ethanol ingestion leads to significant formation of such aberrant compounds which may then upset autonomic nervous system balance. This disturbance may explain the abnormal sympathetic activity seen in withdrawal. While these ideas about the etiology of alcohol abuse have a definite appeal, they are naturally based on in vitro preliminary work. Much study of the quantitative pharmacology of these compounds in animals is required before judgement can be made as to the merits of the proposed hypotheses. In the meantime, pharmacological studies on the ability of ethanol to depress respiration in the mouse has revealed that unlike opioids or barbituates, respiratory depression induced by ethanol requires the presence in brain of serotonin. This neurotransmitter also mediates the respiratory effects of several other alcohols but curiously, not chloral hydrate, yet this compound is purported to alter biogenic amine metabolism much like ethanol. Thus, the response to ethanol can be pharmacologically separated from other major narcotic classes such as opioids and barbiturates by respiratory depression effects. The specific requirement for serotonin mediation exhibited by ethanol and several other alcohols opens the door for a rational therapeutic approach to the treatment of alcohol abuse. At the same time, this finding tends to lessen the probability that alcoholism is in some way connected with the formation of addictive alkaloids.


Microsomal ethanol oxidation: activity in vitro and in vivo.

Studies by several investigators have confirmed that the microsomal fraction of mammalian liver oxidizes ethanol to acetaldehyde in a reaction that requires NADPH and oxygen. Efforts to identify the enzymes involved have produced conflicting opinions of the reaction mechanism, however. Initially, the microsomal mixed function oxidase system was assumed to be capable of oxidizing ethanol in a mechanism that did not involve either alcohol dehydrogenase or catalase. Later evidence suggested that the oxidative enzyme was, in fact, catalase, a contaminant of microsomal preparations and that the mixed function oxidase system merely furnished hydrogen peroxide to the reaction. Much current research supports the latter interpretation. Other workers provide evidence that favors a system in which catalase does not participate. Attempts to define the reaction process have involved studies with catalase inhibitors, kinetic studies of the different reaction systems, and physical separation of catalase from the microsomal components. Questions of the mechanism of microsomal ethanol oxidation may prove to be purely academic, however. Efforts to prove that the system has significant in vivo activity generally have not been successful.


Four patterns of perinatal brain damage and their conditions of occurrence in primates.

The findings described in the present study are summarized in Table 1. It may be noted that anoxia or total asphyxia, whether in the newborn animal or in the (see article) adult, leads to patterns of injury in the brainstem. Hemispheral structures outside the thalamus seem to be entirely spared in those animals which survive. In contrast to this, situations leading to hypoxia associated with severe acidosis, usually of a mixed respiratory and metabolic type, cause brain edema; and when the edema is limited in its distribution, the damage is restricted to specific cortical loci. When the cerebral edema becomes more generalized owing to spread of the process, more and more extensive regions of the hemispheres are damaged until the entire cerebrum may become necrotic. On the other hand, clinical circumstances which lead to hypoxia but without acidosis of any great magnitude--usually due to the indolence of the process or to an associated hyperventilation of the mother--produce lesions which may be restricted to the white matter. These processes may be characterized by perivenular white matter hemorrhage and/or focal areas of periventricular leucomalacia. Finally, those clinical circumstances which lead to combined episodes of hypoxia plus anoxia with acidosis favor a predominance of lesions that affect the basal ganglia.


Vitamin E status of Alaskan Eskimos.

A survey was conducted during 1971-1973 on the vitamin E status of Alaskan Eskomos. The subjects were 315 residents of the northern coastal villages of Wainwright and Point Hope and the southwestern inland villages of Kasigluk and Nunapitchuk. Plasma vitamin E levels for the 6- to 17-year-old subjects at Wainwright, Point Hope, and Nunapitchuk were 0.81 plus or minus 0.26, 0.90 plus or minus 0.20, and 0.84 plus or minus 0.25 mg/100 ml (mean and standard deviation), respectively. The values for adults at Wainwright, Point Hope, and Kasigluk were 1.23 plus or minus 0.27, 1.23 plus or minus 0.27, and 1.27 plus or minus 0.33 mg/100 ml, respectively. No value less than 0.30 mg/100 ml was observed. Alpha-tocopherol was the only isomer present in significant amounts. Plasma vitamin E levels did not change significantly between 6 and 17 years of age; however, a steady increase with age was observed in the 18- to 69-year-old groups. Plasma alpha-tocopherol concentrations were significantly lower in children than in adults but there were no differences attributable to sex or geographic location. Vitamin E concentration in the blood plasma was linearly correlated with cholesterol concentration. Values are reported for the vitamin E content of some native foods. This study indicates that plasma vitamin E levels in Alaskan Eskimos consuming a high meat or fish diet are comparable to those in adults of the United States consuming a mixed diet.


Inhibitory effect of L-glutamine on gastric irritation and back diffusion of gastric acid in response to aspirin in the rat.

L-Glutamine given orally at 750 mg/kg significantly reduced the formation of gastric mucosal lesions induced by aspirin at 100 mg/kg at 1, 3, and 7 hours in pylorus-ligated rats. L-Glutamine markedly inhibited the loss of H+ and a corresponding increment of Na+ through the aspirin-damaged mucosal barrier, which suggests inhibition of acid back diffusion as the mechanism of action. In vagotomized rats, the diffusion of H+ from the instilled acid solution into the gastric mucosa and outflux of Na+ from the mucosa into the lumen was so strong that aspirin could not show any acceleration of a back diffusion of H+ in contrast to the aspirin-free group. However, L-Glutamine given with or without aspirin inhibited the group. However, L-Glutamine given with or without aspirin inhibited the back diffusion of H+ instilled into the vagotomized rat stomach.


Hepatitis-B-antigenemia with panarteritis, diffuse proliferative glomerulitis and malignant hypertension.

Fatal, rapidly progressive malignant hypertension, progressive renal failure and radiographic evidence of diffuse angitis, with persistent hepatitis-B-antigenemia, in a young man during his early recovery from documented type B viral hepatitis, is presented. At postmortem there was both light and electron microscopic evidence of systemic arteritis and proliferative glomerulonephritis.


Technetium-99m: basic nuclear physics and chemical properties.

The nuclear physics and chemical properties of technetium-99m are reviewed. The review of basic nuclear physics includes: classification of nuclides, nuclear stability, production of radionuclides, artificial production of molybdenum-99, production of technetium 99m and -99Mo-99mTc generators. The discussion of the chemistry of technetium includes a profile of several -99mCc-labeled radiopharmaceuticals.


Pharmacotherapy of essential hypertension.

Practical clinical aspects of the evaluation and treatment of essential hypertension are reviewed. Drug therapy discussed includes diuretics, and as adjunctive therapy, sympathoplegic agents, peripheral vasodilators and beta blockers. Also covered are treatment of less common forms of essential hypertension, other forms of antihypertensive therapy, and the use of fixed combinations of antihypertensive drugs.


Extemporaneous preparation of methyldopa in two syrup vehicles.

The stability of methyldopa in two extemporaneous syrup preparations was studied. Film-coated methyldopa tablets were triturated and incorporated into (1) unpreserved Syrup USP and (2) an equal mixture of simple syrup containing 0.5% citric acid and 0.2 N hydrochloric acid, in concentrations of 50 mg/ml. The preparations were stored in the dark, for 14 days at 5 C and 25 C. Samples were analyzed spectrophotometrically for methyldopa content at various intervals. Both preparations were stable under the conditions studied.


Properties of mannitol injection (25%) after repeated autoclavings.

The physical and chemical properties of mannitol injection 25% were examined after repeated autoclavings.  The product was found to be stable after five autoclavings of 250 F for 15 minutes each.  No extracts from the rubber closures were found.  It is advised that the product may be repeatedly heated or autoclaved if crystals appear as a result of storage.


The acid-base and biochemical characteristics of intrapartum fetal asphyxia.

The maternal and fetal acid-base, lactate, and pyruvate characteristics during the course of labor and at delivery were studied in 124 patients delivered of an infant with evidence of metabolic acidosis at delivery. This metabolic acidosis is principally caused by hyperlactatemia resulting from the tissue oxygen debt accompanying fetal asphyxia. Hypoxemia was one mechanism contributing to this fetal asphyxia and tissue oxygen debt. This evidence of fetal asphyxia developed during the last half and principally during the last two hours of the intrapartum period. Acid-base assessment of fetal blood with identification of a metabolic acidosis will provide an accurate objective diagnosis of intrapartum fetal asphyxia.


Clinical characteristics of pregnancies complicated by intrapartum fetal asphyxia.

The clinical characteristics of 124 pregnancies complicated by intrapartum fetal asphyxia have been reviewed. The evidence of fetal asphyxia tends to appear earlier in patients with maternal medical and obstetric complications than in those with labor complications. Evidence of clinical fetal distress was present in 36 per cent and was not related to the severity of the asphyxia. Low Apgar scores occurred in 40 per cent of infants with moderate asphyxia and in 80 per cent of infants with severe asphyxia at delivery. In the newborn infants, clinical evidence of cerebral abnormality was observed in 3 per cent, and evidence of the respiratory distress syndrome was seen in 3 per cent of the study group.


Response of the primate fetus to intra-amniotic saline injection.

The amniotic fluid was replaced with 20 per cent sodium chloride solution during the second half of gestation in 12 pregnant rhesus monkeys. This produced a congealing of the fetal blood in the small umbilical vessels which overlie in the placental chorionic plate. Death of severe asphyxia followed within 20 to 50 minutes in the younger fetuses due to a prompt cessation of umbilical blood flow. During this time, the rise in serum sodium of the fetus was moderate and could not be implicated as the cause of fetal death. In older fetuses, the asphyxia produced by the saline injection was transient and less severe, occasionally permitting survival. The caliber of the affected fetal umbilical blood vessels and their blood flow rates are presented as the principal determinants of the rapidity of development and the severity of the asphyxia produced by saline instillation.


Significance of meconium during labor.

Continuous fetal heart rate (FHR) monitoring and routine fetal scalp blood sampling was utilized in the evaluations of 366 fetuses during labor. One hundred and six patients had meconium in the amniotic fluid at some time during labor. A total of 26,110 uterine contractions were monitored during these 366 labors. The incidence of FHR patterns as a percentage of uterine contractions was calculated for the meconium and nonmeconium groups. Although there was a 3 1/2-fold increase in the incidence of low five-minute Apgar scores (less than 7) in the meconium group, signs of fetal distress were, with rare esception, not significantly different from those in the nonmeconium group. The presence of meconium in the amniotic fluid without signs of fetal asphyxia (late decelerations and acidosis) is not a sign of fetal distress and need not be an indication for active intervention. The combination of fetal asphyxia and meconium staining of the amniotic fluid, however, does enhance the potential for meconium aspiration and a poor neonatal outcome. Universal fetal heart rate monitoring and appropriate fetal acid-base evaluation is recommended for following patients with meconium in the amniotic fluid during labor.


Placental transport of alcohol and its effect on maternal and fetal acid-base balance.

The placental transport of alcohol and its effect on maternal and fetal acid-base balance studied in 10 sheep experiments by the maternal infusion of a 9.75 per cent solution of alcohol-dextrose at a rate of 15 c.c. per kilogram for 1 or 2 hours. Serial maternal and fetal blood sampling during and following the alcohol infusion revealed rapid placental diffusion of alcohol, a highly significant correlation between maternal and fetal blood alcohol concentrations, and a similar peak concentration of approximately 0.230 Gm. per 100 ml. in maternal and fetal blood that differed only in time of onset during the 1 and 2 hour infusion periods. Blood alcohol concentrations remained high for several hours during the postinfusion period. A significant maternal hyperlactacidemia and hyperglycemia were noted but did not result in significant alterations in maternal acid-base balance. An initial fetal metabolic acidosis and later mixed acidosis were observed during the alcohol infusion and worsened during the postinfusion period.


The use of 50 per cent phosphoric acid as an etching agent in orthodontics: a rational approach.

The chemical treatment of enamel surfaces is an approach used in obtaining increased adhesion of dental materials to tooth surfaces. One of the conditioning solutions extensively used prior to the direct bonding of orthodontic attachments is a 50 per cent phosphoric acid solution. The object of this investigation was to study the effect of various concentrations of phosphoric acid on the bond strength of an epoxy adhesive formulation developed for the direct bonding of orthodontic attachments. Furthermore, an attempt was made to quantitate the etching action of the phosphoric acid solutions by determining the depth of etch on polished enamel surfaces and recording the surface profiles of etched enamel surfaces by means of a surface-roughness measuring instrument. The use of 50 per cent phosphoric acid solution as a conditioning agent prior to the use of the epoxy adhesive formulation is advocated. The rationale supporting this recommendation includes (1) the bond strength of the epoxy adhesive system to enamel surfaces etched with 50 per cent H3PO4 is not significantly improved by the use of phosphoric acid at any other concentration; (2) the depth of etch obtained with 50 per cent H3PO4 is less than that observed with H3PO4 solution at concentrations which produce comparable bond strengths; (3) the surface roughness of enamel surfaces etched with 50 per cent H3PO4 is greater than that obtained with more dilute acid solutions. The optimal phosphoric acid concentration should be determined for each adhesive system.


Soteria: Evaluation of a home-based treatment for schizophrenia.

Data are reported from an ongoing study comparing outcome in two groups of young, first-admission schizophrenics - one receiving "usual" treatment (including drugs) on the wards of a good community mental health center, the other being treated by a non-professional staff (usually without phenothiazines) in a small home-like facility in the community. Six-month and one-year outcome data show few differences in symptoms between the two groups, but three measures of psychosocial functioning significantly favor the experimental group.


Mitochondrial permeability to chloride ion.

It is generally accepted that the inner membrane of the mitchondrion is not penetrated by chloride ion, in contrast to other biological membranes which are chloride permeable. In this report mitochondrial permeablity to chloride ion has been reevaluated by the measurement of passive swelling in isotonic chloride-containing solutions in the presence of an uncoupling agent. Under these conditions, mitochondria prepared from rat liver or beef heart show a definite uptake of wide variety of chloride salts. Mitochondrial chloride transport appears to be electrogenic, as is the transmembrane movement of the other halides. Therefore, the mitochondrial inner membrane shares with other biological membranes a definite permeability to this ubiquitous anion.


Transport of H plus and other electrolytes across isolated gastric mucosa of the rabbit.

The relationship of transmural and cellular phenomena to the rate of spontaneous luminal HH+ secretion by short-circuited gastric mucosa bathed in HCO3- and CO2-free Ringer solution was studied by the pH-stat technique. The bulk of luminal acidification can be accounted for by the appearance of H+ and not by organic acids. Acid secretion requires the presence of O2 and exogenous substrate but is not limited by endogenous CO2 production. The rate of H+ secretion is matched by the serosal appearance of alkali. The greater appearance of CO2 on the serosal side of the mucosa is consistent with hydroxylation of CO2 and greater permeability of the serosal border to HCO3-. Luminal changes in H+ concentrations affect H+ secretion but serosal changes do not, suggesting that the gradient produced by H+ secretion is at the luminal border. Steady-state isotopic Na+ and Cl- fluxes indicate net secretion of both ions, but net K+ transport is negligible.


Mechanisms of acid disposal in canine duodenum.

Distal duodenal pouches chronically excluded from the intestinal stream were perfused in seven awake dogs by a constant-circulation technique using isomolar solutions containing 60-120 mM HCl. The rate of disappearance of hydrogen ions (H+) and net ion movements was measured. In all experiments there was a loss of H+ from the perfusate accompanied by a gain of sodium (Na+), potassium (K+) and chloride (Cl-), together with an increase in volume and a decrease in osmolality. The magnitude of this H+ loss was a function of instillate [H+]. The H+ lost by neutralization was separated from that lost by diffusion by calculations based on the assumption that the observed changes in somolality were the result of neutralization by bicarbonate (HCO3-). The bulk of the acid (67%) was lost by neutralization, the remainder back-diffusing in a one-to-one exchange for diffusable Na+. This ability to dispose of acid decreased with increasing age of the pouches due to a diminished volume of HCO3- secretion, the magnitude lost by backdiffusion remaining unchanged.


Effect of histamine on microvasculature of isolated dog gracilis muscle.

Isogravimetric capillary pressure (Pci), capillary filtration coefficient (CFC), and plasma protein concentration were measured before and during adminisistration of histamine in an isolated, independently perfused canine gracilis muscle. Histamine produced an average decrease in Pci of 14.1 mmHg, an increase in CFC of 36-fold, and an increased rate of plasma protein escape of at least 24-fold. These results suggest that histamine reduces the reflection coefficient for protein at the capillary wall and are consistent with predictions of the theory of restricted diffusion assuming that 1-2.5% of available pores increase in radious from 40 to 240 A.


Anion effects on cation movements during correction of potassium depletion.

The differential effects of KCl vs. KHCO3 for intravenous K+ repletion were evaluated in a series of nephrectomized dogs previously depleted of 20% of total-body K by a 2-wk regimen consisting of K-free diet plus DOCA plus chlorothiazide. Twenty-four percent of K losses (5% of original TBK) were replaced by a 2-h infusion of either CKl or KHCO3. Blood pH was maintained at normal levels by controlling the rate of respiration. Skeletal muscle biopsies were taken before and 2 h after repletion, and blood samples were taken at intervals throughout. The following differences resulting from KHCO3 compared to KCl repletion were found: a) a greater cellular K uptake, a lower rate of increase, and a lower steady-state extracellular K+ concentration; b) a less increase in intracellular K+ concentration and a less decrease in intracellular Na+ concentration. These differences, which were independent of extracellular pH or kidney function, are thought to be secondary to unequal distribution of Cl- and HCO3-ions.


Interaction of O2 and CO2 in sustained exercise hyperemia of canine skeletal muscle.

The relative contribution of O2 and CO2 to the metabolic control of blood flow in long-term exercise was examined in the denervated gracilis muscle of the anesthetized dog. The data show that 1) on initiation of heavy exercise, the effluent blood PO2 and pH fall markedly and then rise slowly but remain depressed relative to control during 60 min of exercise hyperemia, while the initial increases in [K+] and osmolality rapidly approach and eventually reach preexercise levels. 2) The enhanced vasodilator activity of venous blood from exercising muscle is attenuated when effluent blood PO2 or pH is corrected to preexercise levels; it is completely abolished when both are corrected. 3) Induced reduction PO2 or pH in the arterial inflow, and thus venous outflow, of resting muscle produces a fall in resistance; simultaneous reductions of both to levels seen in heavy exercise produce a fall in resistance to near that observed during exercise. Since the enhanced vasodilator activity of venous blood from the contracting muscle was abolished by simultaneous correction of the PO2 and pH, it seems likely that these factors, acting directly or indirectly, are the principal chemicals responsible for the maintenance of the vasodilation seen in canine skeletal muscle during heavy exercise.


Cardiac lymph flow and composition in acute myocardial ischemia in dogs.

Cardiac lymph was obtained from 12 normal dogs (group 1) for two consecutive 2-h control periods and from 7 dogs (group 2) for 2 h before and 2 h after occlusion of the circumflex branch of the left coronary artery. Lymph composition was studied with reference to pH, red blood cell (RBC) concentration, total protein content, potassium and sodium ion concentrations, and creatine phosphokinase (CPK) and acid phosphatase enzyme activities. No significant difference was noted in any variable between the two groups during the firts 2-h period. In group 1, no significant changes occurred in any variable as a result of the passage of time alone. In group 2, 2 h of myocardial ischemia produced increases of 53.3 plus or minus 5.1% in lymph flow, 67 plus or minus 5% in protein content, and 418 plus or minus 27% in the RBC concentration, suggesting increased blood capillary permeability. Lactate rose 120.5 plus or minus 27%, potassium concentration increased 16.9 plus or minus 2.4%, acid phosphatase increased 30 plus or minus 3%, and CPK rose 61.6 pluse or minus 10.9%, suggesting ischemic injury of myocardial cells. These changes in lymph were statistically significant (P LESS THAN 0.05) and reflect both capillary and myocardial cell abnormalities.


Catecholamine release: mechanism of mercury-induced vascular smooth muscle contraction.

The mechanism by which mercuric ion (HgCl2) induces contraction of vascular smooth muscle was defined in the kidney of anesthetized dogs and in rabbit aortic strips. In vivo, HgCl2 injected into the renal artery induced a dose-related reduction in renal blood flow (electromagnetic flowmeter) and glomerular filtration rate (creatinine clearance). An intra-arterial infusion of phenoxybenzamine (POB) significantly reduced the vascular response to HgCl2 (P less than 0.001). In vitro, alpha-adrenergic blockade with phentolamine and POB prevented mercury-induced contraction, whereas agents that block serotonin, histamine, acetylcholine, and angiotensin did not do so. Norepinephrine receptor "protection" from phenoxybenzamine blockade sustained the response to HgCl2. Reserpine pretreatment produced a parallel reduction in the response of the aorta to tyramine and mercury. The results are consistent with an indirect action of mercuric ion via release of endogenous catecholamines.


Catecholamine effects on cyclic AMP levels and ion secretion in rabbit ileal mucosa.

Effects of catecholamines on cyclic AMP (cAMP) levels and ion fluxes were examined in isolated rabbit ileal mucosa. The base-line cAMP level was unaffected by epinephrine (Epi), norepinephrine (Norepi), and isoproterenol. The theophylline-augmented cAMP level was decreased slightly be Epi in one series of experiments but not in another. Propranolol did not enhance this effect. The increase in cAMP level produced by cholera toxin was almost completely reversed by addition of Epi or Norepi. This reversal was prevented by phenoxybenzamine. Epi also partially reversed the increase in cAMP level produced by prostaglandin E1. Effects of Epi on ion fluxes were determined following addition of secretagogues. Epi significantly decreased theophylline-induced but not cAMP or cholera toxin-induced Cl secretion. A decrease in short-circuit current was nonetheless observed in the latter two instances. The observed discrepancies between alpha-adrenergic effects on cAMP levels and ion fluxes suggest the following possibilities: 1) ion transport-related cAMP is only a small fraction of total mucosal cAMP; 2) cAMP-induced active ion secretion is only slowly reversible, or 3) effects of alpha-adrenergic stimuli on ion transport are not due to inhibition of cAMP accumulation.


[Aqueous humor pH in experimental lye burns and influence of different treatment measures (author's transl)].

300 rabbit corneas were burned for 1 minute by applying a filter paper of 10 mm diameter soaked in different concentrations of NaOH. The aqueous humor pH was then measured at certain time intervals and after different treatment methods until the physiologic pH of 7.6 was reached. The results were statistically analysed. Group 1, 2 and 3 were burned in 1n NaOH, 3n NaOH, and 6n NaOH respectively without any treatment. In these groups a "therapeutic" pH-level of 8.5 was measured on an average 0.5, 2.5 and 5 hours after the burn (Table 1 and Fig. 2). Group 4 and 5 again were burned with 6n NaOH. In group 4 the burn was followed by constant irrigation with physiologic saline solution by means of the Morgan Therapeutic Lens (Fig. 1a and b). With this regimen a pH of 8.5 was reached after 2.5 hours (Table 1 and Fig. 3). In group 5 the physiologic saline solutions was replaced by a buffer solution (Isogutt) and a pH of 8.5 was measured after only one hour (Table 1 and Fig. 3). Based upon these results it is felt that severe lye burns should be treated by constant irrigation with a buffer solution for several hours. A treatment that can easily be performed by use of the Morgan Therapeutic Lens.


Treatment of porcine malignant hyperthermia. A review based on experimental studies.

The metabolic and endocrine changes in porcine malignant hyperthermia are described and the importance of the catecholamine response emphasised. The relative effectiveness of several different therapeutic agents in the treatment of this syndrome in the Pietrain pig are described and the importance of a common link with the catecholamine response discussed.


The neuromuscular blocking properties of AH 8165 during halothane anaesthesia.

The time to onset, duration, time for reversal, and dose required to abolish twitch response for AH 8165 have been investigated. The drug is shown to be a rapidly acting agent, with a duration of action similar to pancuronium.


Lorazepam as a premedicant for day-case surgery: an assessment.

The sedative effect of 2 mg of lorazepam was assessed in eleven patients undergoing minor "day case" surgery and the results compared with a control group of eleven patients receiving a placebo. Sedation was assessed by a scoring method and quantified in terms of change in plasma cortisol levels. The results indicate that 2 mg of oral lorazepam produces good sedation (superior to nitrazepam in terms of plasma cortisol reduction) and has a postoperative anti-emetic effect but its prolonged duration of action makes it unsuitable for patients returning home within 8 hours of premedication.


Anesthetic solubility coefficients for maternal and fetal blood.

Solubility coefficients for seven inhalation anesthetic agnets were determined in maternal and fetal blood at 37 C.  Halothane, isoflurane, diethyl ether, and nitrous oxide were significantly more soluble in maternal than in fetal blood, while methoxyflurane, fluroxene, and cyclopropane were significantly less soluble.  Reasons for these differences cannot be accounted for by differences in the type or amount of hemoglobin present.


Postoperative alveolar-arterial oxygen tension difference: its relation to the operative incision in obese patients.

Forty-eight markedly obese patients for elective jejunoileal bypass were studied during spontaneous ventilation preoperatively and then postoperatively after 2 to 4 hours and on each of days 1 to 5 to determine the effect of the operative incision (midline versus transverse) on the alveolar-arterial oxygen tension difference (A-aDO2). Compared with control (Pre-op.) A-aDO2, there was a significant increase in A-aDO2 in all patients, beginning in the postanesthetic recovery area and continuing through postoperative (P.O.) day 4. Comparing the mean increase in A-aDO2 (P.O.-Pre-op.) between the two incision groups, patients with a midline incision had a significantly greater (p smaller than 0.001) increase in A-aDO2 on control (Pre-op.) value by day 5. The authors conclude that in markedly obese subjects, the midline incision can be expected to result in both more profound and more prolonged reduction in arterial oxygenation postoperatively.


Effects of patient age, pH of cerebrospinal fluid, and vasopressors on onset and duration of spinal anesthesia.

Two hundred twenty-two spinal anesthesias were administered with 10 mg. of tetracaine and 1 ml. of 10 percent dextrose to investigate the effects of vasopressors, patients age, and pH of cerebrospinal fluid on the onset and duration of spinal anesthesia. Neither the differences in overall age, cerebrospinal fluid pH, nor the addition of vasopressors had any significant effect on onset. Duration, however, was significantly prolonged by the addition of vasopressors, 53 percent prolongation by 0.2 mg. of epinephrine and 72 percent prolongation by 2 mg. of phenylephrine.


Venomotor changes caused by halothane acting on the sympathetic nerves.

Experiments were performed to determine whether depression of venomotor responses with halothane results from interference with sympathetic activation or from an effect on venous smooth muscle cells.  Changes in isometric tension of isolated canine saphenous-vein strips were recorded.  Adrenergic activation was achieved by transmural electrical stimulation, by addition of tyramine, and by addition of morepinephrine.  Halothane (0.5 to 3 per cent) did not significantly alter basal tension.  It lessened the reaction of the veins to electrical stimulation but not their response to norepinephrine; it increased the response to tyramine.  Since the responses to norepinephrine and tyramine were not decreased, halothane appears to act on the nerve terminal to prevent release of neurotransmitter associated with nerve-terminal depolarization.  Thus, halothane causes inhibition of electrically induced venoconstriction in cutaneous veins, probably by interfering with the release of norepinephrine from nerve terminals rather than by an inhibitory effect on the smooth muscle cells.


Systemic and regional blood-flow changes during spinal anesthesia in the rhesus monkey.

The radioactive microsphere technique was used to determine the distribution of cardiac output and regional blood flow in rhesus monkeys before and 10,20,40, and 80 minutes after induction of spinal anesthesia. Five monkeys were studied during low spinal anesthesia (sensory level T10) and five other monkeys were studied during high spinal anesthesia (sensory level T1). Each monkey served as its own control. There was no significant change in regional blood flow during T10 spinal anesthesia. During T1 spinal anesthesia, blood flow (per 100 g of tissue) to kidneys was significantly reduced at 20, 40, and 80 minutes, blood flows to liver and carcass were significantly reduced at 20 and 40 minutes and blood flows to miscellaneous organs (lymph nodes, salivary glands, etc.) were significantly reduced throughout anesthesia. Blood flows to heart, brain, and lower extremity during T1 spinal anesthesia showed only non-significant changes. Vascular resistance in the lower extremity was significantly reduced during both levels of spinal anesthesia, indicating arteriolar dilatation. Also, during both levels of anesthesia, the lungs received an increased proportion of the radioactive microspheres, suggesting increased peripheral arteriovenous shunting of microspheres due to the arteriolar dilatation.


Annals of allergy.

A review of the world literature regarding the relative efficacy, duration and toxicity of the available beta-adrenergic bronchodilator aerosols for the treatment of asthma is presented. Many of these agents will soon become available in the United States and some familiarity with their actions is necessary for optimal care of asthmatic patients.


In vivo erythrocyte sickling in the Japanese sika deer (Cervus nippon): methodology.

The Japanese sika deep (Cervus nippon) proved to be a suitable animal model for the study of acute phases of in vivo erythrocyte sickling. Ophthalmologic studies can be conducted during or after 1 to 6 hours of effective in vivo sickling. Intravenous administration of 1.75 to 3.5% sodium bicarbonate solution at a rate of 500 to 1,000 ml per hour produced a transient state of alkalosis and in vivo erythrocyte sickling in the sika deer. The percentage of sickled erythrocytes increased as the blood pH increased. Concurrently, the packed cell volume decreased. Sickling was enhanced by 100% oxygen ventilation after endotracheal intubation and light anesthetization. After the induction of erythrocyte sickling, a sickling-reversal phenomenon occurred despite continued bicarbonate administration. During the course of this reversal, the percentage of sickled erythrocytes steadily decreased, the venous blood pH decreased, and the packed cell volume slowly increased. Because of the sickling-reversal phenomenon, chronic erythrocyte sickling was not achieved.


Changes in motility and ph in the digestive tract of experimentally overfed sheep.

Motility of the digestive tract of 4 sheep was studied with radiotelemetric equipment. After base line records were made, each sheep was overfed with 70 g of grain per kilogram of body weight. The ruminoreticulum did not become static until the ingesta pH was less than 5. The cecum had the same patterns of motility and pH as did the ruminoreticulum, but these returned to normal more quickly in surviving sheep. The motility patterns of the abomasum and the small intestine were more erratic. Results indicated that considerable quantities of grain (substrate for microbial growth) reached the cecum before ruminoreticular motility was inhibited.


Physiologic studies of experimentally grain-engorged cattle and sheep.

Seven sheep weighing 34 to 41 kg, each, 3 steers and 1 heifer weighing 230 to 460 kg each, were experimentally, "overfed" (induced grain engorgement). The most significant changes occurred in ruminal ingesta pH, blood pH, packed cell volume (PCV), hemoglobin (Hb), carbon dioxide pressure (PCO2, total CO2 (volume %), blood D-lactic acid, blood HCO3, and base excess. There was no common denominator that was especially pathognomonic.


Erythrocyte metabolism in normal and glutathione-deficient sheep.

Glucose utilization and lactate formation in erythrocytes from normal and glutathione (GSH)-deficient sheep were similar. Significant differences were observed, however, between the 2 groups of sheep in the production of 14-CO2 from erythrocytes incubated with ascorbic acid or methylene blue, or both. The greater response of normal erythrocytes compared to erythrocytes deficient in GSH suggests that there are some metabolic differences in the pentose phosphate pathway (ppp) activity of the erythrocytes. The nature and site of these differences are, however, not known. When sheep were kept in a decompression chamber for 2 weeks and subjected to a simulated altitude of 7,000 m for 12 hours/day, the erythrocytes showed a four- to six-fold increase in the activity of the ppp.


The detection of cross-reacting material for alpha-antitrypsin in liver extracts by acid-starch electrophoresis.

Purified extracts of alpha-antitrypsin cross-reacting material (CRM) from liver of patients with MM, ZZ, and MZ phenotypes were studied by acid-starch electrophoresis and crossed immunoelectrophoresis. It is believed that CRM-M from liver is derived primarily from postmortem digested serum antitrypsin, whereas CRM-Z is a product of postmortem digested antitrypsin from hepatocytes. All extracts produced small bands of antitrypsin on the cathodal side of the gel: A single M band migrated faster than the single Z band, whereas CRM from an MZ heterozygote produced a combination of 2 mobile bands. The CRM-Z (from a ZZ phenotype) did not migrate toward the anode, in contrast to the presence of a broad plateau of antitrypsin protein with CRM-M (from an MM phenotype) or CRM-MZ. Thus, most of the CRM-Z protein could not be accounted for on routine acid-starch electrophoresis. However, an anodal peak could be seen on starch gels with CRM-Z at less acidic pH, suggesting that the anodal-migrating CRM-Z protein is denatured and loses antigenicity at lower pH.