Ultrastructural and immunocytochemical characterization of circulating mononuclear cells in patients with myelomatosis.

The ultrastructure of blood mononuclear cells from two IgG myeloma patients was studied, and cells reacting with anti-idiotypic serum and polyspecific anti-Ig serum were characterized by immunoperoxidase techniques. Abnormal, mononuclear cells were present in the blood of both patients, which morphologically were classified as atypical small to medium-sized lymphocytes, polymorphic immature lymphocytes (lymphoblasts), predominantly of the lymphoplasmocytic type and atypical, plasmocytic cells or myeloma cells. Immunocytochemical observations showed that most of the abnormal cells, including atypical small to medium-sized lymphocytes, reacted with anti-idiotypic and polyspecific anti-Ig serum. Periods of relapse and remission were correlated with an increase and decrease, respectively, of the number of abnormal cells and cells which reacted with anti-idiotype and anti-Ig serum. The observations indicate that circulating lymphoid cells are part of the myeloma clone.


Limiting factors in bacterial phagocytosis by human polymorphonuclear leukocytes.

Limiting factors in neutrophil phagocytosis were studied using a sensitive assay by which attachment, ingestion and intracellular killing of bacteria could be separated. Phagocytosis was found to be limited by the attachment capacity of neutrophils. Ingestion and intracellular killing proceeded at a constant rate proportional to the number of bacteria attached to the neutrophils.


Binding of aggregated IgG to nephritogenic type 12 streptococci: influence of serum, C1 and C4.

The uptake of aggregated IgG by type 12, M protein positive (M + ve) streptococci was high in the presence of fresh serum, while the uptake by type 12, M-ve, type 1 and type 2, M + ve or M-ve streptococci was inhibited. Serum heated to 56 degrees C for 30 min inhibited the uptake of aggregated IgG by all strains tested. Purified C1q or macromolecular C1 added to heat-treated serum restituted the uptake of aggregated IgG. It was shown that C1 and C4 in fresh serum influenced the uptake of aggregated IgG by streptococci, resulting in the distinct reaction patterns observed.


Pizotifen as an antidepressant.

In a double-blind study the therapeutic effect and tolerance of pizotifen was compared with placebo in 20 outpatients of both sexes suffering from light to moderate depression. Pizotifen seems to possess certain antidepressive effects in dosages of 4-10 mg daily. These properties, and the well-documented effect of pizotifen in migraine, could make it an alternative in treating patients suffering from the often seen combination of vascular headache/depression.


Effect of chlorpromazine treatment on prolactin levels in cerebrospinal fluid and plasma of psychotic patients.

In psychotic patients, levels of prolactin in cerebrospinal fluid (CSF) and plasma were determined by radioimmunoassay before and after 2 and 4 weeks of treatment with chlorpromazine (CPZ). CPZ was given in one of three randomly selected fixed doses: 200, 400 or 600 mg per day. Before treatment, low levels of immunoreactive prolactin-like material (PRL) were found in the CSF of most patients. The concentration in CSF was about 20% of the plasma level. In CSF but not in plasma, the pre-treatment level of PRL was significantly higher in women than in men. During CPZ treatment, the PRL levels in CSF as well as in plasma were significantly elevated in both sexes after 2 as well as 4 weeks. The elevation was significantly greater in women, and was similar at the two time intervals studied. There was a significantly positive relationship between the dose of CPZ and the PRL elevation in both body fluids in both men and women. Before treatment no significant correlation between the PRL levels in CSF and plasma in either sex could be observed. During treatment, there was a significant correlation between the change in PRL levels in CSF and plasma in both men and women. CPZ treatment did not increase the levels of total protein, follicle-stimulating hormone (FSH), luteinizing hormone (LH), thyroid-stimulating hormone (TSH) or oestradiol-(17-beta) in either the CSF or the plasma.


Evaluation of the combination of tryptophan and ECT in the treatment of depression. I. Clinical analysis.

A double-blind evaluation of the antidepressant efficacy of treatment with a combination of orally administered L-tryptophan (L-TP) and electroconvulsive therapy (ECT) was made in patients suffering from endogenous depression. The patients were randomly assigned to two groups, one treated with L-TP (6 g daily) and unilateral ECT, the other with placebo and unilateral ECT. L-TP treatment was initiated at least 1 day before the first ECT and terminated 4 days after the last ECT. There was a good agreement between the two groups in several measures of antidepressant efficacy: doctors' and patients' ratings of depressive symptoms, and doctors' global rating of therapeutic effect 4 days and 1 month after the last ECT. In the L-TP group, however, there was a significantly better effect on retardation symptoms in the nurses' rating scale. This difference, which is not consistent with other measures of amelioration, contributes, at most, to a marginal therapeutic addition to the antidepressant effect of ECT. It is concluded that oral administration of L-TP, in the dose of 6 g daily, is not of practical value for potentiating the antidepressant efficacy of ECT.


Site of origin of deep vein thrombus in the calf.

A phlebographic technique is described for demonstrating as fully as possible the stem and muscle veins of the calf. The findings in 103 examinations containing calf thrombus demonstrated by this method are presented. It is concluded that calf vein thrombosis is as likely to originate in stem veins as from the soleal muscle veins.


Comparison of postoperative coumarin, dextran 40 and subcutaneous heparin in the prevention of postoperative deep vein thrombosis.

A double-blind study was carried out to investigate the effectiveness of several preventive regimens in postoperative deep vein thrombosis (DVT). The regimens consisted of postoperative (p.o.) acenocoumarin, dextran 40 + p.o. acenocoumarin, subcutaneous (s.c.) heparin alone and s.c. heparin + p.o. acenocoumarin. The 313 patients studied were stratified according to age (40-60 vs. less than 60 years) and type of operation (laparotomy, thoracotomy, hip replacement). Dextran 40 + p.o. acenocoumarin was more effective than p.o. acenocoumarin alone, which acted as control. Subcutaneous heparin alone or together with p.o. acenocoumarin was not more effective than p.o. acenocoumarin alone during the first part of the study, when about 4000 IU twice daily were administered accidentally. When the dose had been changed to 5000 IU twice daily, better results were obtained (DVT) incidence 5.9%). The results were strongly influenced by age and type of operation. Almost no DVT occurred in patients below 60 years of age with elective abdominal surgery. The incidence of perfusion disturbances in lung scans in patients with DVT was lowest in those treated with s.c. heparin in combination with acenocoumarin.


Controlled clinical study on antihypertensive treatment with a diuretic and methyldopa compared with a beta-blocking agent and hydralazine.

Twenty-eight previously untreated patients with essential hypertension were included in a randomized double-blind cross-over study comparing the results of treatment with the established combination of a thiazide and methyldopa (regimen A) with the combination of a beta-receptor blocker and hydralazine (regimen B). Three patients each developed intolerable side-effects on each regimen but they were all treated successfully on the alternative regimen. The remaining 22 patients obtained a significant reduction in BP at rest and during exercise on both treatments, with no significant difference between the two schedules. Heart rate was significantly reduced at rest and during exercise with regimen B, while a significant reduction was also obtained following exercise on regimen A. There was no significant difference between the two regimens as to tolerable side-effects during treatment, which were registered in about 60% of the patients on each scheme. However, 64% of the patients were treated satisfactorily without side-effects on either regimen. It is concluded that the combination of a beta-blocking agent and hydralazine is without obvious advantages compared with the combination of thiazide and methyldopa in obtaining initial BP control in patients with essential hypertension.


Glucose tolerance and insulin release in hypertensive patients treated with the cardioselective beta-receptor blocking agent metoprolol.

Blood glucose and plasma insulin levels were studied under fasting conditions and following an i.v. and an oral glucose load, respectively, in nine males with moderate hypertension before treatment, after one month on placebo and after three months on the cardioselective beta-receptor blocking agent metoprolol. The studies were performed under metabolic ward conditions. The reproducibility of blood glucose and plasma insulin values following an i.v. glucose load was very good. Medication with metoprolol caused no changes in the fasting levels of blood glucose or plasma insulin, nor in the blood glucose response following a glucose load given i.v. or orally. The initial and total integrated insulin response to the i.v. administration of glucose was similar before and during metroprolol. Following oral glucose both the total integrated blood glucose response and the insulin response were unaffected by treatment with metoprolol.


Bone marrow kinetic studies on three patients with myelomatosis. Indications for malignant proliferation within both the plasma cell and lymphoid cell compartments.

The proliferative activity has been studied in lymphocyte and plasma cell populations of purified bone marrow from three myeloma patients. In one of them, proliferation was also recorded in blood lymphocytes. Immunofluorescence studies, using idiotypic antisera against the M-component, were performed to identify lymphocytes and plasma cells belonging to the malignant cell clone. Pulse incubations with 3H-thymidine (3H-TdR) were made in vitro. Autoradiographic analyses revealed a higher overall 3H-TdR labelling index in the myeloma cell populations than in normal control cell populations. A few labelled plasma cells were observed in the myeloma cases (2.5-5%) but the major fraction (11.5-14%) and intensity of labelled cells were found among the lymphoid cells. This indicates that the proliferation of malignant cells in myeloma occurs not only within the plasma cell but also in the lymphoid cell population. The results provide additional support for the assumption that B-lymphocytes are part of the malignant cell clone in myelomatosis and most likely precursors to the myeloma plasma cells.


The architecture of the musculo-fibrous apparatus in the human orbit.

Combining the thick serial (60 mu) histological section technique with the 0.5 cm cleared section technique, a definite structural organization in orbital connective tissue and adipose tissue components lying in between, is revealed. Additionally, an interindividual uniformity and bilateral symmetry in the human orbital connective tissue structures was found. Finally, using the reconstruction technique it became clear that each eye muscle has its own connective tissue system in the orbit and that its architecture highly differs dependent on, which orbital area is approached. It is conceivable that in future the spatial architecture of the musculo-fibrous apparatus in the human orbit might prove to be of importance for clinical diagnosis and surgical approach.


Multilocular lesions in the therapy of cerebral palsy.

The cerebral pareses occurring in early childhood or produced subsequently by trauma or spontaneous cerebral haemorrhages, present a heterogenous symptomatic picture. In the forefront we find the spastic pareses associated with extra-pyramidal motor hyperkinesia (athetosis, dystonia, ballism). 36 C.P.-patients were surveyed from 1--4 years after operative intervention. It is shown that better results can be obtained when multilocular lesions during a single session in correspondence with the dominant group of symptoms are performed (thalamic and subthalamic target points of the extrapyramidal motor nuclei and dentate nucleus). The results are presented. Continuous physical therapy after the operation and a reasonable intellectual level are essential for improvement.


Combined transtentorial dentatotomy with pulvinarotomy in cerebral palsy.

For frequently associated spasticity with involuntary movements in cerebral palsy operations on cerebellar nuclei or on the pulvinar of the thalamus are recommended. We combined both approaches in 45 patients. The combination was possible after experiences with transtentorial dentatotomy, in which the electrodes are introduced into the deep structures of the cerebellum from a burr-hole on the lambdoid suture. The same lambdoid approach may equally well be applied for introducing electrodes into the pulvinar of the thalamus. The lesion in the pulvinar may moreover be combined with the target in the centrum medianum or in the nuclei VIM-VCP or VOP. Lesions are always asymmetric and multilocular. Their influence on the clinical picture is quite favourable.


Neurosurgical treatment of spasticity and dyskinesias.

122 Patients suffering from spasticity and/or dyskinesias underwent a total of 171 operations: 88 stereotactic dentatolyses, 24 posterior partial rootlet section D12-S1 or L1-S1, 16 posterior partial root section D12-S1 or L1-S1, 16 posterior cervical rhizotomies, 21 stereotactic pulvinolyses, 6 stereotactic associated V.L. thalamolysis and pulvinolysis. Results and indications are discussed.


Long-term assessment of stereotactic dentatotomy for spasticity and other disorders.

In the 60's stereotactic electrocoagulation of the dentate nucleus became a promising approach in the neurosurgical treatment of muscular hypertonicity, particularly when spasticity was evident. A relatively satisfactory improvement of spasticity has been reported earlier as a result and the authors were supporting these clinical results in previous publications. A long-term assessment of the results obtained in a large series of patients would permit a better evaluation of the effect of the operation. Analysing 109 stereotactic electrocoagulations of the dentate nucleus on 50 patients mainly in cases of cerebral palsy over a period of more than 10 years (most patients underwent a bilateral dentatotomy), the authors give a more realistic appreciation of the results, which depend on the criteria chosen. In 30% of the cases a clear improvement in the spasticity was obtained, and in 50% of all cases, nursing and rehabilitation were facilitated. The stereotactic dentatotomy never completely cured the spasticity and spectacular results were never observed, but the operation can be performed without complications and an unexpected neurological deficit did not occur. The role of the stereotactic dentatotomy and other neurosurgical methods in the treatment of spasticity has to be evaluated more critically.


Computerized graphic display of results of subcortical stimulation during stereotactic surgery.

An on-line computer programme is described and illustrated which is capable of displaying graphically in the form of Woolsey-type figurine charts stimulation-induced responses obtained during stereotactic surgery. Not only can these data then be optimally utilized for lesion localization but also the programme includes facilities for a variety of types of analysis of the tape-stored data pooled from all patients studied.


A computer programme system for stereotactic neurosurgery.

A computer programme system is reported which allows a simulation of a stereotactic operation. It incorporates the determination of intracerebral structures and the electrode tract by means of boney reference points as well as the calculation of the parameters for the stereotactic apparatus. It contains further a library of brain sections, by which the electrode tract within the target structures can be shown on a computer display.


EEG and evoked potential approaches to the study of neuropeptides.

EEG and event related potential (ERP) phenomena were considered here from the standpoint of possible applications to investigations of the central effects of neuropeptides in man. These electrophysiological phenomena were viewed from the standpoint that they provide an accessible intermediate level of observation between behavior and detailed neuronal events. Several general methodological issues were discussed. An attempt was made to describe the EEG and ERP phenomena that may be pertinent to future neuropeptide studies and to consider their functional significance. Available data concerning electrophysiological effects of neuropeptides were also discussed. Suggestions for future research were made, which emphasized comprehensive recording of EEG and ERP phenomena to permit examination of the patterning of electrocerebral events.


Acetaldehyde metabolism in vivo during ethanol oxidation.

The liver is the primary site for the oxidation of ethanol-derived acetaldehyde (AcH) in the rat. Only a small amount of the total AcH formed in this organ escapes into the rest of the body, but this amount increases with increasing hepatic ethanol concentrations. The bulk of the hepatic AcH output is eliminated extrahepatically, thus drastically changing the AcH level from that initially leaving the liver. Nevertheless, the extrahepatic blood AcH levels can be used as relatively accurate indicators of the corresponding hepatic AcH levels, since they are highly correlated with them. Significant levels of brain AcH occur only at very high arterial blood AcH concentrations.


The acute effects of ethanol on liver and brain tryptophan metabolism.

1. The effects of acute ethanol administration of liver and brain tryptophan metabolism are reviewed. 2. Ethanol enhances the activity of rat liver tryptophan pyrrolase by increasing the availability of circulating free tryptophan to the liver by catecholamine-mediated lipolysis followed by displacement of protein-bound serum tryptophan. 3. The response of the mouse liver enzyme to ethanol is strain-dependent. Ethanol activates the enzyme in CBA/CA but not in C57/BL mice. 4. Ethanol exerts a biphasic effect on the concentrations of rat brain tryptophan, 5-hydroxytryptamine and 5-hydroxyindol-3-ylacetic acid. 5. Both aspects of this biphasic effect are associated with an altered availability of circulating free tryptophan. 6. The initial enhancement  by ethanol of brain tryptophan metabolism may be due to the above-mentioned lipolytic mechanism, whereas the subsequent decrease in brain indoles may be caused by the enhanced tryptophan pyrrolase activity. 7. Brain tryptophan metabolism is decreased by ethanol in CBA/CA whereas no change is observed in that in C57/BL mice. 8. These results are discussed in relation to previous work on the acute effects of ethanol on rat and mouse brain 5-hydroxytryptamine metabolism.


Biologically important thiol-disulfide reactions and the role of cyst(e)ine in proteins: an evolutionary perspective.

Selected aspects of the reactions of thiols and disulfides are reviewed in an evolutionary context with special emphasis on the implications of the transition from a reducing to an oxidizing atmosphere on the earth. It is argued that thiols were important in prebiotic chemistry and in primitive metabolism but that disulfides, owing to their general instability in a reducing environment, came to be of importance as structural links in proteins only after the transition to an oxidizing atmosphere. The occurrence of glutathione is reviewed and discussed in terms of the role of glutathione in maintaining a reducing intracellular environment. The occurrence of cysteine and cystine in intracellular and extracellular proteins of bacteria and of animals is examined in terms of the redox state of the environment in which the protein functions. Thiol-disulfide changes associated with the dormant state are described and the role of cellular water content in dormancy is discussed. The potential significance of reactions between thiols and products of oxidative metabolism is discussed with special emphasis upon thiol additions to carbonyl and alpha, beta-unsaturated carbonyl groups and their possible role in steroid-receptor interaction.


Synthesis and application of cleavable and hydrophilic crosslinking reagents.

Bifunctional imidoesters are due to their mild reaction especially suitable for the crosslinking of proteins. Most often used are diimidates with a medium span (4 or 6 CH2-groups). Reagents with a wider span might be of interest. In such a case, however, the bridge should be more hydrophilic. Bifunctional imidoesters have, therefore, been prepared from dinitriles NC-(CH2)2-X-(CH2)2-CN; X being -O-, -O-(CH2)n-O- or -O-(CH2)m-O-(CH2)n-O-. The bridge of diimidoesters can also be labelled by coloured or fluorescent groups. Diimidoesters containing -S-S-bonds in the bridge can be cleaved more easily after their reaction with proteins. Dimethyl-3.3' -(8- delta -dithiahexamethylenedioxy)-dipropionimidate, a "long", cleavable and more hydrophilic diimidate, is a promising new reagent. In cases, where HS-(CH2)3-C(=NH)-OCH3- HC1 is is used for crosslinking of proteins, this reagent can possibly be replaced by 2-iminothiolane hydrochloride, a cyclic thioimidate, which is easier to prepare and to handle.


Crosslinked insulins: preparation, properties, and application.

Crosslinked insulins have proved to be valuable for structure-function studies and as proinsulin models. In the first part of the paper, a short review of the literature on analytical investigations, the preparation of A1-B1- and A1-B29-crosslinked derivatives, their biological activities in vivo and in vitro, and CD-spectral properties is given. The results of reduction/reoxidation studies with insulin derivatives containing irreversible and cleavable crosslinks are summarized. In the second part, new A1-B29-crosslinked monomers and 3 symmetrical dimers, linked between A1-A'1, B1-B'1 and B29-B'29, are described, as well as some results of tritium-labelling and of enzymatic degradation experiments with A1-B29-linked insulins.


Protein thiol-disulfide interchange and interfacing with biological systems.

Disulfide-containing proteins offer unique advantages for mechanistic studies of the formation of native three-dimensional structure from unordered, reduced precursors. The main advantage is that covalent intermediates are formed; by characterizing these intermediates, one obtains substantial information about the reaction pathway. Thiol-disulfide interchange is a major component of most oxidative mechanisms carrying thiol to disulfide; thus, it required some attention in its own right. Afinsen's descriptions of a "shuffle-ase" enzyme led us to examine the rates of the uncatalyzed exchange under physiologically plausible conditions. Somewhat surprisingly, we found that the rates for formation of several native proteins in uncatalyzed systems containing GSSG and GSH are as great as with the "shuffle-ase" enzyme, suggesting that a substantial portion of biological thiol oxidations proceed by uncatalyzed exchange. While thiol-disulfide exchange of course results in no net change in the oxidation level of a system, catalytic linkage of thiol or disulfide to other redox systems provides a mechanism for achieving net changes.


Identification of binding sites on the E. coli ribosome by affinity labeling.

Both electrophilic and photolabile derivatives of several different types of ribosomal ligands have been used in affinity labeling studies on the Escherichia coli ribosome. These studies have resulted in the localization of the peptidyl transferase center within a region of the 50S subunit, and the localization of the mRNA binding site within one of two regions on the 30S particle. In addition, labeling data have been obtained for GTP and streptomycin affinity labels. The affinity labeling results are discussed along with the results of other studies, and procedures are suggested for improving the resolving power of the affinity labeling technique as applied to ribosomes.


Disulfide bonds: key to wheat protein functionality.

Disulfide bonds in wheat proteins are major factors that determine the properties of the proteins and their functionality in wheat flour. The gliadin proteins contain mostly intramolecular disulfide bonds. In contrast, the high-molecular-weight glutenins are formed by disulfide linkages of several diverse polypeptide chains which have been separated and characterized. The linkage of these proteins in a fairly linear array contributes to the unique viscoelastic properties of glutenin. The glutenin has been separated into two fractions differing in molecular weight. The amount of highest molecular weight component is correlated with the rheological behavior of the flours from different wheat varieties. Various oxidizing and reducing agents are widely used to alter the functional behavior of wheat proteins by the action on sulfhydryl and disulfide groups.


[More on nutrition of children and youth in the 18th and 19th century, chiefly based on memoirs and contemporary recollections (author's transl)].

378 remarks on nutrition of children and youth found in personal recollections, letters a. s. o. of 42 authors of the 18th and 19th century are added to a former published sum of 760 items. Again, more mentions of protein (meat, fish a. s. o), fat and sugar are written down in the 19th century, compared with the three centuries before.


Experimental models for the study of diabetogenesis in laboratory animals.

The normal process of glucose-induced insulin release involves three major steps. First, glucose is identified by the pancreatic B-cell as an insulinotropic factor. Second, calcium accumulation in a critical cellular site triggers the release process. Third, a microtubular-microfilamentous system serves as the effector system for the translocation and eventual extrusion of secretory granules. It is possible to interfere rather specifically with each of these events. For instance, fasting results in an impairment of the process of glucose identification. Various pharmacological agents, including organic calcium-antagonists may uncouple the metabolic process of glucose recognition form the effector response. Last, experimental alterations of the B-cell microtubular-microfilamentous system cause severe disturbances in the dynamics of insulin release. It is proposed that such experimental models may help to elucidate the primary lesion in different types of spontaneous diabetes mellitus in laboratory animals.


[Human myopathy and animal muscular dystrophy].

Two hereditary muscular dystrophies similar to human progressive muscular dystrophy (P.M.D. Duchenne type) have been isolated in animals, one in mouse, the other in chicken. The decrease in the activity of glycogenolytic enzymes is similar to that observed in denervated muscle. Isozymic fetal types for several muscular enzymes have been observed as well in chicken as in man, but this fetal type may also be found in neurogenic atrophy. The release in circulation of muscle enzymes seems more specific. But the origin of the genetic lesion is still unknown. We describe here the three different theories about this problem: i.e. neurogenic, vascular, or myogenic. This last theory implies a trouble of membrane permeability.


Ventricular arrhythmia 24 hours before and after maximal treadmill testing.

To determine if maximal exercise treadmill testing influences the occurence of ventricular arrhythmia in the hours after exercise, 45 myocardial infarction and 22 angina pectoris patients (New York Heart Association Class I-II), and 23 normal subjects were examined with 24-hour ambulatory electrocardiographic Holter recordings before and after exercise testing. Comparison of qualitative and quantitative ventricular arrhythmia detected during identical chronological two-, four-, and 20- or more hour periods, before and after exercise testing in each patient, revealed no statistically significant difference in any patient group. The prevalence of ventricular ectopy in 80 per cent of ischemic heart disease patients and 30 per cent of normal subjects as detected by 24-hour Holter recordings was similar to previous studies. It is concluded that in ambulatory ischemic heart disease patients (New York Heart Association Class I-II) and normal subjects, maximal treadmill testing does not significantly affect the occurrence of ventricular arrhythmia in the hours after exercise.


Heparin neutralizing activity and coronary artery disease.

It has been previously shown and confirmed in the present investigation that the disaggregation of adenosine diphosphate (ADP)-induced platelet aggregates occurs at a slow rate more frequently in the platelet-rich plasma (PRP) of men with coronary artery disease. ADP-induced platelet aggregation was studied in the citrated PRP of 32 men (21 with and 11 without coronary artery disease) to determine the relation between release of heparin neutralizing activity (HNA) from platelets and the rate of platelet diaggregation. Each of the five PRP with slow (less than 10 per cent) disaggregation were from men with coronary artery disease. Platelets from these five PRP released from 34 to 51 per cent of their content of HNA during ADP-induced aggregation in contrast to the 27 PRP with more rapid disaggregation, only three of which had a detectable release of HNA. Of the latter 27 PRP, 21 had a second phase of aggregation which usually reached a peak of light transmission less than that of the first phase. These data are consistent with (but do not prove) the hypothesis that HNA released during aggreation may be one of the factors tending to prevent disaggregation of ADP-induced platelet aggregates.


Computer analysis of the orthogonal electrocardiogram and vectorcardiogram in 257 patients with aortic valve disease.

In most electrocardiographic studies of left ventricular hypertrophy the hypertrophy has had different causes. This study examined the performance of the Frank orthogonal electrocardiogram in 257 patients with aortic valve disease, 90 with predominant aortic stenosis and the remaining 167 with predominant aortic insufficiency. Optimal measurements suggested for routine electrocardiographic diagnosis of left ventricular overload resulted in recognition of 64 percent of cases of aortic stenosis and 74 percent of cases of aortic insufficiency with a 6 percent false positive rate. Multivariate analysis techniques improved performance: 82 percent of the aortic stenosis records and 78 percent of the aortic insufficiency records were correctly recognized as showing left ventricular overload; the false positive rate was 5 percent. Although many electrocardiographic measurements were significantly correlated with the aortic valve gradient, correlations were not high enough for use in predicting the severity of the aortic stenosis. Comparison of electrocardiographic variables in aortic stenosis and aortic insufficiency demonstrated a wide overlap between groups, and the electrocardiographic changes of aortic stenosis could not be differentiated from those of aortic insufficiency.


Effect of the vasodilator trimazosin versus placebo on exercise performance in chronic left ventricular failure.

The effect of the vasodilator trimazosin versus placebo on exercise duration until marked dyspnea was evaluated in a double blind randomized study in 16 patients with chronic left ventricular failure despite digitalis and diuretic therapy. Trimazosin caused a reduction in resting systolic and diastolic blood pressures and in resting product of systolic blood pressure times heart rate. The improvement in exercise duration from the average of values during the baseline and single blind placebo periods was greater after 3 and 6 weeks of trimazosin therapy (300 and 450 mg daily) after 3 and 6 weeks of double blind placebo therapy (P is less than 0.025). Four of eight patients receiving trimazosin had disappearance of pulmonary venous congestion on chest roentgenography compared with none of eight patients receiving placebo. These preliminary data suggest that trimazosin may be effective in treating chronic left ventricular failure.


Pathophysiological aspects of coxsackievirus B intestinal infection.

Our findings reveal that intestinal infection with coxsackie B5 results in decreased intestinal epithelial cell division in association with an increase in carbohydrate (glucose) and amino acid (leucine) absorption in the small intestine. These findings are contrasted with those occurring during Salmonella infection, which results in increased intestinal cell division rate but decreased carbohydrate (glucose) absorption. The changes in intestinal function and physiology that have been described occurred during an asymptomatic viral infection characterized by normal intestinal histology. A reasonable hypothesis is that these pathophysiological changes may be due not only to a variety of local factors but also to hormonal effects induced by systemic spread of coxsackievirus B.


Properties of the Ames Salmonella mutants lodged in the gastrointestinal tract of gnotobiotic rats.

An association of the histidine auxotroph of Salmonella typhimurium (strain TA1538) within the gastrointestinal tract of otherwise germ-free Sprague-Dawley rats is maintained during observations for up to 7 months. The bacteria exceed concentrations of 10(7)/g in the forestomach and exceed concentrations of 10(8)/g in the lower bowel and feces. When carcinogens are ingested, the number of revertants in the feces increases. The ingestion of structurally related compounds which are not mutagenic to the bacteria in vitro and for which no evidence of carcinogenicity exists does not increase the number of revertants in the feces. The numbers of salmonella are increased by the addition of Lactobacillus plantarum and Bacteroides fragilis but the salmonella disappear from the gastrointestinal tract when the rats are conventionalized. With the additional flora, there is a decrease in the number of revertants appearing in the feces in response to a given dose of carcinogen. This decrease may reflect an effect of the flora on the activity of the metabolic pathway responsible for the presence of the ultimate carcinogen or it may simply be an effect on the salmonella mutants themselves.


Alkaline phosphatase-positive malignant lymphoma. A subtype of B-cell lymphomas.

Alkaline phosphatase (ALP) activity was evaluated histochemically and cytochemically in concert with immunologic technics in 60 cases of non-Hodgkin's lymphomas and lymphocytic leukemias. Surface membranes of neoplastic cells were positive for ALP only in certain B-cell malignancies: 3 of 6 lymphocytic lymphomas of intermediate differentiation, 4 of 13 nodular lymphomas, and 1 of 7 Burkett's lymphomas. All other B-cell tumors, including chronic lymphocytic leukemia, well-differentiated lymphocytic lymphoma, and diffuse "histiocytic" lymphoma, were ALP-negative. The neoplastic cells of Sezary syndrome and lymphoblastic lymphoma were also consistently negative for ALP. In control lymph nodes ALP-positive lymphocytes were present only in primary follicles and in mantle zones of secondary follicles. ALP-positive lymphomas appear to be neoplastic counterparts of these normal lymphocytes, not only cytochemically, but also with respect to their morphologic and immunologic characteristics. Furthermore, histochemical inhibition tests suggested that the ALP activity demonstrated may reflect a newly recognized, unique isoenzyme.


Acute pulmonary complications in systemic lupus erythematosus. Immunofluorescence and light microscopic study.

Lung tissue obtained from eight consecutive patients with systemic lupus erythematosus complicated by severe, acute pulmonary disease was studied by both light and immunofluorescence microscopy. Light microscopic examination disclosed interstitial pneumonia in four cases, cytomegalovirus pneumonitis in one case, bronchiolitis and peribronchiolitis in one case, pulmonary infarction in one case and focal atelectasis in the remaining case. Direct immunofluorescence examination revealed focally bound immunoglobulins or complement (C3) within pleural and/or pneumocyte nuclei in each specimen. Immunohistologic studies in these cases may thus suggest a diagnosis of systemic lupus erythematosus with acute pulmonary complications, despite the lack of specificity of the pathologic changes seen by light microscopy.


"Lennert's lymphoma" with transformation to malignant lymphoma, histiocytic type (immunoblastic sarcoma).

Two cases of a recently described lymphoproliferative disorder called "Lennert's lymphoma" are presented. In both cases, the proliferation evolved into a frank malignant lymphoma of large lymphoid cells. This phenomenon has not been previously reported to occur in this disease. Immunohistologic study of the biopsy material in both cases suggest that it may be a T-cell proliferation. The possibility that "Lennert's lymphoma" is not a neoplasm but an abnormal immune reaction with similarities to angioimmunoblastic lymphadenopathy is raised. Whatever its nature, the potential for "Lennert's lymphoma" to transform into a frankly malignant tumor is documented.


Preleukemic granulocytic sarcomas of the gastrointestinal tract. Report of two cases.

Granulocytic sarcoma, or chloroma, is a tumor composed of immature cells of the myeloid series, which usually occurs as a secondary manifestation of acute myelocytic leukemia. Unique problems in interpretation of these lesions arise when the leukemic picture is absent in peripheral blood and bone marrow. In these cases, granulocytic sarcoma is usually misinterpreted as "reticulum cell sarcoma". Two cases of this neoplasm involving the small intestine and stomach, are reported. Signs of leukemia appeared terminally. The value of cytochemical stains in the differential diagnosis and the possible benefits of early recognition and treatment are emphasized.


Immunofluorescence tests in immune technics and applications.

The value of clinical laboratory tests as aids in diagnosis and prognosis depends on their sensitivity, specificity, and accuracy. Few tests fulfill the desirable criteria for use as screening tests in the asymptomatic, normal population. In the symptomatic patient a test of high sensitivity for detecting disease has great clinical value since a negative result tends to exclude the index diagnosis for consideration at that point in time. A test of high specificity for a single disease invariably has decreased sensitivity but has diagnostic value when positive. Data on the indirect immunofluorescent antinuclear antibody test (FANA) provide criteria to justify its wide application as a clinical laboratory test. A negative FANA result essentially excludes active systemic lupus erythematosus (SLE). Quantitation by serum titration of the positive FANA and attention to the nuclear fluorescence patterns provide indices of specificity for diagnosis of the various FANA-positive autoimmune diseases. Similarly, negative results of indirect fluorescent antibody tests for antithyroid antibodies essentially exclude Hashimoto's thyroiditis, and a negative test for antimitochondrial antibodies in biliary cirrhosis tends to exclude the surgically amenable form due to biliary stones.


T- and B-cells in immunologic diseases.

Three major subpopulations of lymphocytes have been identified in human peripheral blood: thymus-derived (T) lymphocytes, bursa-equivalent (B) lymphocytes, and null (neither T nor B) lymphocytes. T-lymphocytes are commonly identified by a surface receptor for sheep erythrocytes, and by heterologous antisera raised against human thymus cells and absorbed with human B-cell leukemias or lymphoblastoid cell lines. B-lymphocytes are routinely enumerated by immunofluorescent staining technics for surface immunoglobulin, or by assays for the receptor for C3. Null cells bear a receptor for the Fc portion of immunoglobulin, and are killer (K) cells in antibody-dependent cellular cytotoxicity. Accurate quantitation of T- and B-cells in disease states has been hampered by marked contamination of monocytes in populations of peripheral blood lymphocytes purified by density gradients, binding of autologous immunoglobulin to the surface of non-B cells, and disease-associated alterations of T- and B-cell surface markers. Assays for peripheral blood T- and B-cells may be of significant clinical value in the early diagnosis of lymphocytosis of unknown origin, congenital immunodeficiency disorders, organ transplant rejection crises, and Hodgkin's disease.


Father-to-son transmission of hypogonadism with anosmia: Kallmann's syndrome.

Gonadal and olfactory features of Kallmann's syndrome, usually considered to be inherited as an X-linked recessive trait, were found in a father and son who both had cryptorchidism, hypogonadism, and hyposmia. The father's fertility had been induced with chorionic gonadotropin, leading to the birth of three children. Olfactory and gonadal functions were normal in the mother and two siblings. The father had low basal plasma testosterone and subnormal follicle stimulating hormone (FSH) response to luteinizing hormone-releasing hormone (LH-RH). The affected son and his healthy brother were prepubertal. Their basal plasma total and free testosterone, serum FSH and luteinizing hormone (LH), and response to LH-RH were similar. The clinical presentation and formal olfactory function studies were considered most helpful for the suggestive diagnosis of Kallmann's syndrome in children. The occurrence of this syndrome in this family is consistent with autosomal dominant inheritance.


Primary pulmonary hypoplasia: report of a case with polyhydramnios.

We describe a case of extreme primary pulmonary hypoplasia. No other congenital anomalies and none of the conditions known to be associated with pulmonary hypoplasia were present. Pregnancy had been complicated by substantial polyhydramnios. The hypoplasia was due to a marked deficiency of the respiratory parenchyma in the presence of normal upper airways and bronchi. Virtually no parenchymal development had occurred and there were very few bronchioles, alveolar ducts, and alveoli. The changes differ from those seen in pulmonary hypoplasia secondary to congenital diaphragmatic hernia, bilateral renal agenesis, anomalies of the urinary outflow tracts, and malformations of the thoracic cavity, in which the pulmonary hypoplasia appears to be compressive in nature. While neither the etiology or pathogenesis of the pulmonary hypoplasia are apparent in this case, the presence of substantial polyhydramnios during pregnancy suggests the possibility that the developing lungs may offer an important surface area for reabsorption and recycling of constituents of amniotic fluid.


Diabetes mellitus, islet-cell antibodies, and HLA-B8 in a patient with systemic lupus erythematosus.

Evidence that autoimmune mechanisms may provide a possible explanation for the occurrence of some types of diabetes mellitus has included the clinical association of diabetes with other autoimmune conditions and the serologic demonstration of organ-specific antibodies. This article reports the case of a patient with systemic lupus erythematosus accompanied by diabetes and the presence of antibodies to pancreatic islet cells. This represents further evidence that autoimmune activity may play a role in the etiology of diabetes mellitus, which is especially interesting in light of recent HLA antigen studies that show a possible genetic link between the two diseases.


Effect of somatostatin on meal-induced gastric secretion in duodenal ulcer patients.

The effect of somatostatin, a growth hormone releasing-inhibiting hormone (GH-RIH) on basal and meal-, pentagastrin-, or histamine-stimulated gastric acid and pepsin secretion was studied in six duodenal ulcer patients. Intravenous GH-RIH infused in graded doses ranging from 0.62 to 5.0 microgram/kg/hr produced a dose-related inhibition of pentagastrin-induced acid secretion reaching about 15% of control level at the dose of 5.0 microgram/kg/hr. Acid inhibition was paralleled by a decrease in the pepsin output and accompanied by a dose-dependent reduction in serum growth hormone and insulin levels measured by radioimmunoassay. GH-RIH used in a single dose of 2.5 microgram/kg/hr produced about 85% inhibition of acid secretion induced by a meal (measured by intragastric titration) accompanied by a significant decrease in serum gastrin and insulin levels. The effect of GH-RIH on histamine-stimulated secretion was very modest and observed only after stopping the GH-RIH infusion. Thus GH-RIH suppressed acid and pepsin secretion induced by pentagastrin and a meal, and this effect was accompanied by a suppression of serum growth hormone and gastrin levels which may contribute to the inhibition of gastric secretion observed.


Isolation of Vibrio alginolyticus from wounds and blood of a burn patient.

Isolation of Vibrio alginolyticus from the wounds and blood of a burn patient is reported. Numerous tissue biopsy sites as well as one blood culture yielded the organism. The case history and a review of the hospital course of the patient is provided where relevant to the presence and identification of the organism. The bacteriologic, biochemical, and anti-microbial identification of the organism is described. Taxonomy, habitat, and pathogenicity of V. alginolyticus are discussed.


Fetal immunoglobulin synthesis following maternal immunosuppression.

Cord blood levels of immunoglobulin (Ig) A, IgM, IgD, and IgG classes and IgA and IgA subclasses were determined in the offspring of seven mothers who received azathioprine and/or prednisone during the entire pregnancy. Five of these women received the immunosuppressive therapy following kidney transplantation, and two received immunosuppressive therapy because of disseminated systemic lupus erythematosus. The fetuses appeared to have intact humeral immune function in that they had normal cord blood immunoglobulin concentrations and in one case responded with increased synthesis of IgA and IgM following premature rupture of the membranes.


The structure of mononuclear phagocytes differentiating in vivo. III. The effect of particulate foreign substances.

The response of mononuclear phagocytes to three inert particles--barium sulfate, talc, and thorium dioxide--was studied by correlated light and electron microscopy. All three particles induced maturation of the mononuclear phagocytes, which proceeded to the stage of the mature macrophage and required 7 to 9 days. Once established, maturation persisted as long as 45 days, as did the inert particles. The resultant lesions, dense aggregates of mature macrophages, were termed mature granulomas. The resultant maturation differed from that produced by digestible bacteria in tempo and extent but not in pattern.


Profile of intracytoplasmic lysozyme in normal tissues, myeloproliferative disorders, hairy cell leukemia, and other pathologic processes. An immunoperoxidase study of paraffin sections and smears.

Intracytoplasmic lysozyme (muramidase) may be readily identified in paraffin sections of tissues fixed in formalin or Zenker's acetic acid and in smears of peripheral blood or bone marrow using an immunoperoxidase technique. Sites of intracellular lysozyme in normal human tissues and in various specimens from patients with myeloproliferative and lymphoproliferative disorders, hairy cell leukemia, granulomatous diseases, toxoplasmic lymphadenitis, and other pathologic processes were defined by this method. Intracellular lysozyme was demonstrated in mature and immature neutrophilic and eosinophilic myeloid cells, in monocytic cells, and in some types of histiocytes and had a limited distribution in normal tissues. The neoplastic cells of hairy cell leukemia were devoid of intracytoplasmic lysozyme. Identification of intracellular lysozyme, as determined by  the immunoperoxidase technique, was compared with various cytochemical methods, particularly chloroacetate esterase and alpha-naphthyl butyrate esterase studies, for detection and characterization of myeloid cells, monocytes, and histiocytes.


Radiosensitivity of T and B lymphocytes. V. Effects of whole-body irradiation on numbers of recirculating T cells and sensitization to primary skin grafts in mice.

Whole-body exposure of mice to 50, 100, 300, or 500 rads results in an acute dose-related decrease in the number of viable recirculating T cells. The magnitude of this decrement becomes more pronounced with the passage of time. The dose-response relationship over this range of dosages appears to consist of three components: a steep drop between 0 and 50 rads, a plateau between 50 and 500 rads, and a second drop between 300 and 500 rads. The residual radioresistant cells are able to recognize a histoincompatible skin graft during the initial 5 days after irradiation. Low to moderate doses (50 to 300 rads) abrogate the partial tolerance noted in nonirradiated recipients exposed to the skin graft for 5 days and then regrafted from the same donor source 25 days after complete removal of the primary graft. A large (500 rads) dose results in prolonged graft survival in comparison with the nonirradiated group. It is suggested that the subpopulation fo recirculating T cells which develops partial tolerance during a 5-day exposure to a homograft is more radiosensitive than the effector subpopulation which is involved in graft rejection.


Antropyloric G-cell hyperplasia in hypercalcemic rabbits bearing the VX2 carcinoma.

The number of distribution and the numbers of G cells in the antropyloric region of the rabbit stomach were mapped employing immunoperoxidase localization and morphometric quantitation and compared to similar analyses in hypercalcemic rabbits bearing the VX2 carcinoma. In normal animals, G cells were confined to the lower third of the antropyloric mucosa, where they were randomyly distributed within the mucosal glands. In contrast, tumor-bearing animals showed an extension of these cells into the middle third of the antropyloric mucosa. The absolute counts of G cells in control rabbits were 5.3 +/- 0.78 (mean +/- SE) per unit area, while those in hypercalcemic tumor-bearing rabbits were 11.9 +/- 0.46, a statistically significant increase. It is concluded that rabbits bearing VX2 carcinoma have G-cell hyperplasia.


Differentiation in human myeloblastic leukemia studied in cell culture.

Normal adult hemopoiesis orginates in pluripotent stem cells; among the early differentiated descendents of such cells are progenitors committed to the erythropoietic, granulopoietic, or megakaryocytic pathways of myeloid differentiation. These may be detected in cell culture by developmental techniques, in which progenitors form colonies in viscid or semisolid media in response to appropriate stimulation. Certain diseases of hemopoiesis also originate in pluripotent stem cells; these include chronic myeloblastic leukemia, acute myeloblastic leukemia, polycythemia vera, and idiopathic myelofibrosis-the clonal hemopathies. The hypothesis is advanced that the distribution of cell classes among patients with clonal hemopathies is determined both by the differentiation potential of each pluripotent stem cell maintaining an abnormal clone and by random events occurring during clonal expansion. The latter process may account for the large variations observed between patients when committed progenitors are assayed in cultures of marrow from patients with acute myeloblastic leukemia (AML). This variation may also be used to estimate lineage relationships in the clonal hemopathies. When applied to myelopoiesis in AML, obvious differences from the normal are not detected. The analysis is consistent with the view that the blast cell population in AML is distinct from the leukemic myelopoiesis occurring within an abnormal clone. A new assay procedure is described for progenitor cells related to blast cell proliferation. Finally, these concepts are used to develop a model for the pathogenesis and cellular characteristics of AML.


Preleukemia. Cytogenetic clues in some confusing disorders.

A number of disease states are considered "preleukemic" because they carry a significantly increased risk for the subsequent development of frank leukemia. These include a variety of cytopenias, myeloproliferative disorders, and childhood syndromes. Cytogenetic data suggest that these preleukemic disorders may not be qualitatively different from leukemia but simply represent quantitative differences in the degree of selective growth advantage enjoyed by a proliferating abnormal hemic population. Recent chromosome studies have indicated that a) this proliferation is characteristically clonal in both preleukemia and leukemia, apparently resulting from a heritable change in a marrow stem cell that allows it to escape to some degree from normal growth regulation; b) genetic instability in the clone, with additional genetic change, may often underlie clinical progression from the relative indolence of preleukemia or chronic leukemia to an aggressive stage comparable to acute leukemia; and c) certain specific chromosome segments carry genes important in the acquisition of growth advantage by hematopoietic stem cells, and many of these are common to both preleukemia and leukemia. Expansion of hemic clones may also be influenced significantly by alterations in the growth control mechanisms themselves. For instance, in various preleukemic states, preexisting marrow hypoplasia may permit clones with only minimal selective advantage to reach demonstrable size. Chromosome findings may help to establish the diagnosis and prognosis in preleukemic disorders, but additional long-term data are needed.


Biofeedback: a guide to the clinical literature.

Biofeedback is defined and its historical development briefly described. Major literature reviews and comprehensive bibliographical resources are noted, and the literature is surveyed in regard to clinical applications, related relaxation techniques, and issues such as placebo effect, regression to the mean effect, differences between training for a specific or a generalized response, and the importance of theory in the use of biofeedback.


Somatostatin inhibition of glucose-induced electrical activity in cultured rat islet cells.

Electrophysiological studies of rat islet cells in monolayer culture were undertaken to determine the role of transmembranous ionic fluxes in the inhibitory action of somatostatin on insulin release. In the presence of somatotropin release inhibiting factor (SRIF) (2.5 nM), hyperpolarization occured with or without glucose (16.6 mM) in the medium. SRIF also inhibited the incidence of glucose-induced spike activity. The inhibitory action of SRIF occurred within 5 min and was readily reversible. An increase in extracellular K+ (5-13 mM) or Ca2+ (2.3-4.6 mM) prevented SRIF inhibition of glucose-induced electrical activity. The secretory response of cultured islets to glucose (16.6 mM) was completely inhibited by SRIF (2.5 nM). The presence of high [Ca2+]o or [k+]o enhanced insulin release in the presence of SRIF and glucose. Although phentolamine (5.0 microgram/ml) did not block the inhibition of glucose-induced electrical responses by SRIF, it prevented the inhibitory action of epinephrine (0.2 microgram/ml). It is concluded that the primary action of SRIF is to alter transmembranous cationic fluxes, as manifested by hyperpolarization and a decrease in the incidence of spike activity, which may prevent glucose from eliciting a normal secretory response.


Sites of cholinergic vasoconstriction in trout gills.

Sites of cholinergic vasoconstriction were investigated in isolated saline-perfused holobranchs of trout (Salmo gairdneri and S. trutta). Acetylcholine (ACh) always increased overall branchial vascular resistance (BVR) and, in addition, decreased the proportion of the total inflow appearing at the outflow cannula from the efferent arch artery. Since this was observed in both constant pressure and constant flow situations, it was concluded that ACh exerted most of its effect at a site downstream from the secondary lamellae, probably at the bases of the efferent filament arteries. Prussian blue dye injections indicated that, in addition, ACh caused a marked reduction in flow to the distal halves of the filaments and that flow within the proximal secondary lamellae was restricted during ACh administration to the inner and outer marginal channels of the lamellae. The results are discussed in terms of recent findings concerning the vascular anatomy of teleost gills.


A survey of tardive dyskinesia in psychiatric outpatients.

The authors found a high prevalence--43.4% of tardive dyskinesia in a sample of psychiatric outpatients, a population previously thought to be at nominal risk for development of this syndrome. There was no significant relationship between the presence of dyskinesia and age, sex, years of neuroleptic use, or various organic factors. The effects of dentures and of drug combinations are discussed, and it is noted that structured scales of dyskinesia and videotope recordings are important tools in diagnosing and following the course of dyskinesia.


1977 annivesaries.

The author recalls this year's anniversaries of events and individuals prominent in the history of medicine, psychiatry, and psychology and examines their practical and theoretical contributions.


Lithium treatment of patients with affective illness associated with organic brain symptoms.

Lithium was used to treat the manic symptoms of affective disorder in three patients with associated organic brain syndromes. In all three cases neuropsychological testing permitted evaluation of the degree of dysfunction during the acute and follow-up periods of treatment. Lithium was effective in controlling the manic symptoms of all three patients, and there was no evidence that it caused further organic deterioration.


The treatment of perceptual disturbances in schizophrenia with naloxone hydrochloride.

The authors treated 12 schizophrenic patients who had overt hallucinatory symptoms with intravenously administered naloxone hydrochloride, a narcotic antagonist purported to have antihallucinatory properties. They found no evidence of the effectiveness of naloxone in preventing hallucinations over that of placebo when administered in a randomized, double-blind fashion.


John Stuart Mill on the liberty of the mentally ill: a historical note.

The author discusses the quote from Mill's On Liberty that is often cited by libertarians in opposition to involuntary commitment of the mentally ill. This quote has been taken out of context; other statements in the document indicate that Mill excluded from his libertarian credo those "without the ordinary amount of understanding," i.e., those people who would now be considered mentally ill.


Suture technic and suture-holding capacity. A model study and a theoretical analysis.

The suture-holding capacity (SHC) of six representative surgical suture materials was analyzed. The single loop, the far-and-near, and the near-and-near suture technics were used in the study. The SHC was found to depend on: (1) the coefficient of friction between the suture strand and the tissue; (2) the distensibility of tied and untied fiber; (3) the holding capacity of the knot used; and (4) the strength of the untied strand. Knot-holding capacity (KHC) was of the greatest importance when the single loop technic was used and when the friction between the suture strand and the tissue was low. When the near-and-near or the far-and-near technic was used, the SHC was influenced little by the strength of the knot, especially when the coefficient of friction between strand and tissue was high. The near-and-near suture technic produced the strongest sutures for all materials except Dexon, for which the far-and-near technic produced the strongest sutures. With a correct suture and tying technic, one can optimally use the strength of the suture material and one can use thin strands.


Intraocular pressure reduction during treatment with pilocarpine and systemic propranolol. A comparative double-masked study.

Propranolol, pilocarpine, and placebo were tested on eight patients with ocular hypertension. The trial was performed in a randomized double-masked cross-over manner utilizing the double dummy technique. After 1 week's treatment with 40 mg propranolol administered orally twice daily a statistically significant decrease in intraocular pressure (IOP) was seen. Also after application of 2% pilocarpine eyedrops three times a day IOP was significantly reduced. Propranolol decreased the IOP to about the same extent as pilocarpine. Simultaneous administration of propranolol and pilocarpine caused a further decrease in IOP which was statistically significant compared with the corresponding values during administration of pilocarpine alone. The combination of pilocarpine and propranolol lowered IOP slightly more than propranolol alone. The difference was not, however, statistically significant. During treatment with propranolol a significant decrease in heart rate was observed and a slight reduction of systemic blood pressure. It is concluded that propranolol can additively decrease IOP during treatment with pilocarpine.


The maxillary interincisal diastema and its relationship to the superior labial frenum and intermaxillary suture.

From the analysis of histories, dental casts, and cephalograms of 471 children of the Burlington Growth Centre sample, interrelationships between the degree of spacing, crowding, diastema and frenum and suture type were derived and the following conclusions were drawn: 1. Suture type remains more constant through development than frenum type. 2. Frenum type is reasonably constant but may change from low to medium or high attachments, but only to a higher level of attachment. 3. Frenum and suture type are related; frenum types 5 and 6 (low attachment) are associated with spacing and with suture types 3 and 4. 4. The primary factors contributing to maxillary diastema appear to be degree of spacing or crowding in most cases, the specific types of sutures and frenum making a minor contribution.


Comparative study of acute effects of albuterol and isoproterenol sulphate aerosols in bronchial asthma.

Albuterol, a new bronchodilator drug known to cause beta2-adrenergic receptor stimulation, was compared with isoproterenol sulphate for their pulmonary and cardiovascular effects in patients suffering from bronchial asthma. In a double-blind manner 24 patients received as aerosol 170 micrograms of Albuterol or 150 micrograms of Isoproterenol or placebo on three different days. Spirometric, plethysmographic, heart rate and blood pressure measurements were made at 1, 5, 15, 30, 60, 90, 120, 300 and 360 minutes after drug inhalation. Baseline values for the various indices were not significantly different before administration of the drugs. Results demonstrate that Albuterol is an effective bronchodilator and its bronchodilating effect is significantly superior and of longer duration than that of Isoproterenol. Albuterol did not produce any significant changes in blood pressure and pulse rate, thus confirming its selectivity for beta2 receptors.


Absorption of horseradish peroxidase by neonatal pig intestinal epithelium: effect of Escherichia coli (055B5) on absorption.

The pathway of macromolecular transport through the neonatal pig small intestinal epithelium was examined, utilizing the cytochemical marker horseradish peroxidase (HRP). The marker was found adsorbed to the apical microvillous of the enterocytes, within apical tubules, and cytoplasmic vacuoles. Extracellular absorbed marker assumed a spherical appearance within the subepithelial spaces but was dispersed within the capillary lumens. Uptake of HRP into the enterocyte occurred in 48-hour old neonatal pigs, but transport into the circulation was not observed. Adherence of Escherichia coli to the surface of the ileal enterocyte did not totally inhibit HRP uptake. The E coli adhered to the surface of the enterocyte or within intercellular vacuoles appeared to be static in as much as they were not involved in the transepithelial migration of envacuolated HRP.


Resistance of neonatal calves given colostrum diet to oral challenge with a septicemia-producing Escherichia coli.

Twenty Holstein-Friesian male calves were obtained within 4 hours after bith (colostrum deprived) and allotted to 1 of 4 groups, each given a different feeding: colostrum, milk replacer, polyvinylpyrrolidone (PVP), and saline solution (0.85% NaCl). Each calf was fed 2 L of the respective diets every 12 hours. Rectal temperatures were recorded and blood samples were collected immediately before each feeding. At approximately 27 hours of age, all calves were inoculated orally with 1.5 X 10(10) viable organisms of a septicemia-producing Escherichia coli serotype O26: K60:NM. Within 8 hours, all calves had diarrhea. Coli-septicemia (E coli cultured from liver, spleen, and cardiac blood) was present in 1 of the 5 calves fed colostrum, in 5 or the 5 calves fed milk replacer, in 5 of the 5 calves fed PVP, and in 4 of the 5 calves fed saline solution. At necropsy of the calves (12 to 48 hours after oral inoculation), the same organism was isolated by cultural technique from small intestines of 19 of the 20 calves. Serum immunoglobulin G concentrations increased (P less than 0.01) in calves fed the colostrum diet in sharp contrast to the agammaglobulinemia occurring in calves fed the milk replacer, PVP, or saline solution. Results indicate that colostrum fed to the calf soon after birth provides protection from colisepticemia, but does not prevent the diarrhea of colibacillosis.


Use of the indirect fluorescent antibody test in the detection of bovine respiratory syncytial virus antibodies in bovine serum.

The indirect fluorescent antibody test was adapted for identifying bovine respiratory syncytial virus and its specific antibody, using goat turbinate (GTU) cells. The virus caused maximal cytopathic effects in GTU cells 4 to 8 days postinfection, but fluorescence was not readily detected during this period. Fluorescence was maximal in infected GTU cells at 24 to 36 hours postinfection, but could be detected 48 hours postinfection. Bovine serums (331) which had been submitted to the Oklahoma Animal Disease Diagnostic Laboratory were tested for antibodies to this virus, and 73.6% were found to be positive.


Influence of abdominal pressure and sympathetic vasoconstriction on the cardiovascular response to positive end-expiratory pressure.

The role of changes in abdominal pressure and sympathetically mediated vasoconstriction in the cardiovascular response to positive end-expiratory pressure was evaluated in 9 mongrel dogs. When the abdomen was widely opened, the decrease in cardiac output caused by positive end-expiratory pressure was the same as that found during control studies. When the abdomen was tightly bound, cardiac output was higher at any positive end-expiratory pressure than in control state (P less than 0.01), but the percent decrease produced by increasing positive end-expiratory pressure was the same. alpha-Adrenergic blockade with phenoxybenzamine produced a significantly greater decrease in cardiac output at any given positive end-expiratory pressure and thus appeared to inhibit the previously operative peripheral vascular adjustments to positive end-expiratory pressure. The major compensatory mechanism in the cardiovascular response to positive end-expiratory pressure thus appears to be mediated via alpha-adrenergic sympathetic factors.


Leukocytic response to inhaled bacteria.

Using histologic techniques, we have quantified the amount of infiltration of bronchi and alveoli by polymorphonuclear leukocytes during the 4 hours after an aerosol inoculation of mice with bacteria. Although the lungs of animals challenged with Staphylococcus aureus differed little from those of animals exposed only to a water aerosol, the lungs of animals exposed to Klebsiella pneumoniae or to Escherichia coli demonstrated significantly greater polymorphonuclear leukocyte infiltrations in bronchi and alveoli 2 and 4 hours afer exposure. These results suggest that the polymorphonuclear leukocyte may contribute to the early defense of the lung against some bacteria.


Pulmonary disease caused by Mycobacterium xenopi:two case reports.

Two cases of pulmonary disease caused by Mycobacterium xenopi are presented. One represents the first case report of Mycobacterium xenopi isolated from surgically resected lung tissue in the United States. The epidemiologic, bacteriologic, and clinical aspects of the disease are presented.


Subsensitivity to the bronchodilator action of albuterol produced by chronic administration.

Evidence of bronchodilator subsensitivity was sought in studies using the specific beta2 adrenergic agonist, albuterol. After a period of 1 or 2 weeks off all oral sympathomimetic agents, the mean response of the patients to the first dose of albuterol was consistently greater than the response after a period during which the drug had been administered regularly. Maximal decrease in response occurred after 2 weeks' of treatment, and there was no further decrease after prolonged treatment with the same dose of albuterol for periods as long as 1 year.


The tween opacity test as an aid in classification of mycobacteria.

The Tween opacity test can be used to differentiate (1) Mycobacterium flavescens from Mycobacterium gordonae and Mycobacterium szulgai, and (2) nonphotochromogenic strains of Mycobacterium kansaii from strains of the Mycobacterium terrae complex.


The bioavailability of folic acid added to wine.

Folate deficiency is a frequent cause of anemia in alcoholics, but little attention has been paid to its prevention. Folic acid was readily soluble in wines of high ethanol content at concentrations of 10 microgram/ml. Lactobacillus casei folate activity of folic acid added to wines was well maintained during a month's storage at room temperature and fell to 61% to 66% of original activity after 3 months. Pteroylglutamic acid, 10 microgram/ml, added to wines and given in doses of the beverages (4 ml/kg body weight that caused inebriation, was well absorbed by six normal human volunteers (mean maximal increment in serum folate concentration +/- SEM, 71 +/- 8 ng/ml) and by seven recently intoxicated chronic alcoholics (mean increment, 94 +/- 4 ng/ml). Folate deficiency in alcoholics could be prevented by the fortification of alcoholic beverages with the vitamin.


Renin-aldosterone profiling in hypertension.

Renin-aldosterone profiling was used to classify patients with hypertension: 243 patients with essential hypertension were classified by renin-urinary sodium indexing; 107 were reclassified by response to administration of furosemide and intravenous saline; 45 were further classified by response to a low-sodium diet. Arbitrary "normal ranges" were determined in 89, 32, and 38 volunteers, respectively. Patients with low-renin apparently do not have "high-volume" hypertension. Rather, they show a primary renal abnormality in renin secretion and become relatively deficient in angiotensin II and aldosterone when they are subjected to diuresis. They can maintain aldosterone secretion under normal conditions because their adrenal aldosterone receptor is supersensitive to angiotensin II. No evidence of abnormal sympathetic neural activity was found among the renin subgroups. Renin-aldosterone profiling in current clinical practice seems useful mainly in the detection of patients with curable forms of secondary hypertension. Aldosterone/renin ratios may be particularly helpful in diagnosis when obtained after a patient has undergone expansion or contraction of his extracellular fluid volume.


Toxicity of radiolytic products from 60 Co-treated starch on microorganisms.

The radiolytic products of a 60Co-irradiated starch are sensitive to the action of catalase, peroxidase and ferrous ions: extracts of irradiated starch so treated loss their toxicity for Escherichia coli. After eliminating the reductones, the toxic activity is attributed to the peroxides and more especially to hydrogen peroxide. Artificial reconstitution of an irradiated starch extract confirms this conclusion and reveals a secondary toxic action of formaldehyde.


Specular microscopic evaluation of donor corneal endothelium.

The corneal endothelium of intact isolated globes can be histologically evaluated with a specular microscope. The best observations are made within 6 to 8 postmortem hours; however, useful observations have been demonstrated up to 19 postmortem hours in a moist chamber stored eye at 4 C. The technique takes only a few minutes and enables one to see individual endothelial cell changes at magnifications of 120X to 400X. Endothelial screening can be done with this system for such changes as guttata, low cell populations, and trauma.


Suturing technique for extraocular muscle surgery.

A method for suturing extraocular muscles is presented which provides a safe, anatomically perfect means of reattaching extraocular muscles after recession, resection, or after disinsertion at retinal surgery.


[Current importance of resistance of group A streptococci to tetracyclines].

The resistance of group A streptococci to tetracyclines is a long-standing phenomenon, observed in numerous countries. Sixty strains of group A streptococcus, isolated in 1975 and 6976 at the Claude Bernard Hospital, were tested against natural and semi-synthetic tetracyclines and penicillin G. Whilst sensitivity to the latter was constant, approximately 30% of strains were resistant to tetracyclines. Amongst them, minocycline was nevertheless a little more active than natural tetracycline and doxycycline. The mechanism of this resistance would seem to be extra-chomosomal.


[Study of the transmissibility of multiple drug resistance and the capacity to ferment lactose in a clinical strain of Kl. pneumoniae].

The donor properties of K. pneumoniae PI 220 with multiple drug resistance were studied. It was shown that the above strain carried 2 plasmids, i.e. R-plasmid pPI 220 controling resistance to ampicillin, streptomycin, tetracycline, chloramphenicol, kanamycin and sulphanylamides and plasmid pPI 221 controlling lactose fermentation. Both plasmids can be transfered on conjugation to strain E. coli P678 at a temperture of 28 degrees C at a rate of 10(-5) for pPI 220 and 10(-4) for pPI 221. The drug resistance controlled by pPI 221 was transfered mainly in a "blocks" simultaneously to 6 drugs. Deletion of plasmid pPI 220 was observed rarely. The donor properties of the strain were defined by the conjugative plasmid pPI 220 controlling the self-transfer and mobilization of plasmid pPI 221 incapable of the self-transfer. E. coli P678 (pPI 220) (PPI 221) acquired the donor properties and transfered both plasmids to E. coli J62 on crossing simultaneously at a rate of 10(-2), as well as to S. typhimurium LT2 and P. rettgeri at a rate of 10(-5). In all the recipient strains studied the transfered plasmids were unstable and segregated also simultaneously at a rate being the highest for P. retgari PI 230. The clones with stable preservation of the plasmids could be obtained by selection.


[Use of a semisynthetic broad-spectrum penicillin (ampicillin) in surgical practice].

Parenterally ampicillin was used for the treatment of 87 patients with lung and abdominal diseases, liver abscesses, extremity phlegmonas, osteomyelitis and other diseases. The antibiotic was administered intravenously and intramuscularly. High efficacy of the treatment was observed in all the cases with ampicillin sensitive microflora. In some cases a satisfactory therapeutic effect was observed only with the use of ampicillin in combination with other antibiotics and aminoglycosides in particular. No side effects of the antibiotic were registered.


[Clinical use of rubomycin in neuroblastoma in children].

The results of treatment of 23 children at the age of 7 months to 11 years suffering from neuroblastoma are presented; 22 patients with tumors, relapses or metastases were subjected to the treatment and 1 child was treated prophylactically after radical operation. Four patients were subjected to roentgen therapy in addition to the treatment with rubomycin. The antibiotic was administered intravenously in doses of 0.7--1.5 mg/kg in 1--3 days or daily. The caurse dose (3--12 mg/kg) was determined by the treatment efficiency and the side reactions. The objective effect was observed in 68 per cent of the patients, including the pronounced objective effect (marks 3 and 2) in 41 per cent of the cases. Leucopenia (less than 4000 cells in 1 mm3 of the blood). thrombocytopenia, vomiting (or nousea) and changes in the ECG were registered in 20 (87 per cent), 4,9 and 2 patients respectively. When the results of the treatment were positive, repeated courses of the therapy within 1.5--2 years were carried out; 18 patients died within 4 months to 2 years after the first course of the treatment with rubomycin because of the disease development. No signs of the disease were observed in 4 children with in 3--6 years of observation.


Comparative susceptibility of Candida albicans to amphotericin B and amphotericin B methyl ester.

The in vitro antifungal activities of amphotericin B (AMB) and amphotericin B methyl ester (AME) were compared against 465 clinical isolates of Candida albicans. AMB and AME possessed comparable activity against half of the strains, but against the remainder of the strains the activity of AME was slightly lower than that of AMB. Rarely did AME show superior antifungal activity to AMB.


In-use evaluation of a prediluted quantitative antibiotic susceptibility test device.

An antibiotic susceptibility test (AST) device is described. Minimum inhibitory concentration results on 1,294 clinical isolates with seven antibiotics were rapid, reliable, and reproducible. Agreement with the disk diffusion test was 90%. Interlaboratory agreement for the AST was 94%. The AST provides minimum inhibitory concentration capability without the necessity of prior weighing and dilution of antibiotics.


Clinical and bacteriological evaluation of netilmicin in gram-negative infections.

A preliminary study was conducted with netilmicin, a new aminoglycoside antibiotic. Its effectiveness was evaluated in vitro against 546 strains of Enterobacteriaceae and Pseudomonas aeruginosa isolated from clinical material. Its effectiveness against gentamicin-susceptible strains was roughly similar to that of gentamicin and other newer aminoglycoside antibiotics. Cross-resistance to netilmicin was found in 9 of 44 gentamicin-resistant strains. A favorable clinical response was observed in 70% of the patients treated with a dose of netilmicin ranging from 4.5 to 7.5 mg/kg. However, the appearance of granular casts was seen in 7 of 10 patients receiving the higher dosage of netilmicin (7.5 mg/kg) and a rise in blood urea nitrogen or serum creatinine levels was observed in 5 of these patients.


Agar shake tube technique for simultaneous determination of aerobic and anaerobic susceptibility to antibiotics.

The broth dilution method of determining the minimum inhibitory concentration (MIC) of antibiotics has been adapted to an agar shake tube technique with semisolid media. This permits the simultaneous determination of the aerobic and anaerobic MICs for facultatively anaerobic bacteria such as staphylococci.


Cyclic thymineless death significantly increases frequency of R-plasmid elimination.

Thymine starvation of Escherichia coli strain C600 thy (R46) eliminated the R plasmid at a frequency of 17%. This was increased fourfold, to 68%, after the same culture was subjected to an additional three cycles of growth followed by thymineless death.


Chartreusin: production and microbiological assay.

Chartreusin was produced in the fermentation liquors of Streptomyces chartreusis at peak concentrations of 200 to 300 mug/ml. The titers could be increased by 200 to 300% or more by incorporating d-fucose, a part of the chartreusin molecule, into the fermentation media. A microbiological assay with Sarcina lutea could detect concentrations of the drug of 0.5 to 1.0 mug/ml.


Unusual effects of penicillin G and chloramphenicol on the growth of Moraxella osloensis.

Growth of exponential-phase liquid cultures of Moraxella osloensis was inhibited by 0.5 U of penicillin G per ml. For this organism, low concentrations of penicillin acted primarily in a bacteriostatic rather than in a bactericidal manner. At higher concentrations of penicillin some killing did take place, but the rate of killing was rather slow and appeared to be independent of penicillin concentration. Microscopic observation of cells from penicillin-treated cultures showed little or no cellular swelling or lysis. The total cell count did not decrease significantly during 6 h of incubation in 5,000 U of penicillin per ml. The rates of respiration, nucleic acid synthesis, and protein synthesis were not affected by the presence of penicillin. Attempts to counteract the bactericidal action of high concentrations of penicillin with growth inhibitory concentrations of chloramphenicol were unsuccessful, since chloramphenicol itself was more bactericidal than penicillin for M. osloensis.


Inhibition of acetylating activity in an enzymatic assay for aminoglycoside antibiotics.

The radioenzymatic technique using aminoglycoside-6'-acetyltransferase is suitable for determining serum concentrations of aminoglycoside antibiotics that have a 6'-amino group. Standard curves constructed for each drug in normal human serum are generally satisfactory, but we encountered a pool of human serum (designated IN pool) that inhibited the acetylating activity of the assay. Standard curves for amikacin, kanamycin, gentamicin, and tobramycin in the acetylating assay were all abnormal with standards prepared in the IN pool. Acetylating activity was also inhibited with amikacin standards prepared in a filtrate of this serum pool. Heat inactivation (56 degrees C for 30 min) of the IN pool did not eliminate the problem. When the IN pool was diluted 1:10 in normal human serum, the standard curve obtained with amikacin was comparable to the curve with standards prepared in normal human serum. With amikacin standards prepared in a 1:2 dilution of the IN pool in normal human serum, an intermediate level of acetylating activity was observed. When this IN pool was used for the preparation of gentamicin and amikacin standards in a bioassay with Klebsiella pneumoniae ATCC 27799 as the test strain, valid standard curves and concentrations were obtained. Furthermore, no differences in the biological activity of amikacin were observed with Pseudomonas aeruginosa or Bacillus subtilis as the test strain. Excellent agreement between the microbial assay and the enzymatic assay was obtained with serum specimens tested for gentamicin (r = 0.89), tobramycin (r = 0.96), and amikacin (r = 0.96). The results obtained with the IN pool illustrate the need for regular use of check samples of known performance, independent from the standards, when determining antibiotic levels in serum.


Rapid microdilution-colorimetric assay for yeast susceptibility to fluorocytosine.

Acid production by certain yeast species through the fermentation of glucose was used as the basis of an in vitro test for measuring susceptibility of these organisms to 5-fluorocytosine. Serial dilutions of 5-fluorocytosine in yeast nitrogen base broth, with bromothymol blue indicator dye, were made on microtiter plates. A fixed-concentration suspension of yeast cells was added to successive wells of the plates, and the color change from blue to yellow, indicating generation of acid, was noted. Eighteen hours after inoculation the lowest concentration of 5-fluorocytosine that completely inhibited the production of acid was recorded as the minimum inhibitory concentration. The results were reproducible in multiple trials with organisms of the genera Candida, Torulopsis, and Saccharomyces. This test is a rapid, inexpensive alternative to current 48- to 72-h methods in which broth turbidity is used as the end point.


Amikacin and cephalothin: empiric regimen for granulocytopenic cancer patients.

Amikacin (15 mg/kg per day) was used in combination with cephalothin (7 g/m(2) per day) as an empiric regimen for de novo febrile (>101 degrees F [38.3 degrees C]) episodes in 93 granulocytopenic (<1,000/mm(3)) cancer patients. Both drugs were given intravenously in four equal doses every 6 h. The response rate for all documented infections was 83%, including 11 of 17 (65%) bacteremias. Escherichia coli (14 cases) was the most common pathogen, whereas Pseudomonas aeruginosa (2 cases) caused fewer infections. Mean amikacin serum levels were 8.7 mug/ml at 1 h and 2.2 mug/ml at 5 h. Failure of bone marrow recovery in association with a bacteremia was a bad prognostic sign (only two of eight improving). Ototoxicity occurred in two (2%) patients, whereas presumed antibiotic-induced nephrotoxicity developed in six (7%) patients. Surveillance cultures (nose, gums axilla, and rectum) of all hospitalized patients revealed no significant change in the incidence of amikacin resistance. The combination of amikacin and cephalothin in this dose and schedule was safe and efficacious in these granulocytopenic patients.


Results of a clinical trial of cefoxitin, a new cephamycin antibiotic.

Cefoxitin was administered intravenously to 143 patients, 67% of whom were seriously ill. The rate of cure or improvement was 93%. The study was conducted in two phases; the first was an open, controlled clinical comparison of cefoxitin and cephalothin. In this phase, 28 patients received cefoxitin and 29 received cephalothin. In the second phase, cefoxitin alone was used for the treatment of an additional 115 patients. Twenty bacteremic patients treated with cefoxitin were cured or improved in 95% of cases. The infecting organism was eradicated in all bacteremic patients. All of 14 anaerobic or predominantly anaerobic infections were cured or improved. The infecting anaerobic organism was eliminated in 86% of the cases. Twenty-five patients infected by cephalothin-resistant, cefoxitin-susceptible gram-negative rods were cured. Three patients each with infective endocarditis and osteomyelitis were cured. The incidence of adverse experiences was: 1.4% drug eruption; 2% each asymptomatic serum transaminase elevation and leukopenia; and 2.5% asymptomatic eosinophilia. The incidence of severe thrombophlebitis was 5%. No permanent or serious adverse reactions were encountered. Although the numbers of patients in some categories were too small to permit statistical evaluation, I feel that cefoxitin may be a useful new antibiotic for treatment of infections caused by cehalothin-resistant bacteria and by anaerobic organisms.


Cholesterol-reducing bacterium from human feces.

An anaerobic, gram-positive diplobacillus that reduces cholesterol to coprostanol was isolated from human feces and rat cecal contents. The isolates closely resemble a cholesterol-reducing organism isolated by Eyssen et al. (H. Eyssen et al., Eur. J. Biochem. 36:412-421, 1973) from a rat's cecum. These organisms would not form colonies and were isolated and cultivated in an anaerobic medium containing homogenized pork brains (naturally high in cholesterol). These organisms require free or esterified cholesterol for growth. They were isolated by serially diluting feces or cecal contents and inoculating brain medium. Colony-forming organisms, which did not reduce cholesterol, were eliminated by addition of inhibitory agents to the brain medium cultures. This serial dilution procedure was performed until a pure culture of a cholesterol-reducing organism was obtained.


Recovery of spores of Clostridium botulinum in yeast extract agar and pork infusion agar after heat treatment.

Yeast extract agar, pork infusion agar, and modifications of these media were used to recover heated Clostridium botulinum spores. The D- and z-values were determined. Two type A strains and one type B strain of C. botulinum were studied. In all cases the D-values were largest when the spores were recovered in yeast extract agar, compared to the D-values for spores recovered in pork infusion agar. The z-values for strains 62A and A16037 were largest when the spores were recovered in pork infusion agar. The addition of sodium bicarbonate and sodium thioglycolate to pork infusion agar resulted in D-values for C. botulinum 62A spores similar to those for the same spores recovered in yeast extract agar. The results suggest that sodium bicarbonate and sodium thioglycolate should be added to recovery media for heated C. botulinum spores to obtain maximum plate counts.


Filtration removal of endotoxin (pyrogens) in solution in different states of aggregation.

Bacterial lipopolysaccharides are recognized as the major cause of pyrogenic reactions from parenteral solutions. Molecular filtration was used to remove these pyrogenic molecules (endotoxins) from contaminated parenteral solutions. Because bacterial lipopolysaccharides can exist in different states of aggregation, depending on the composition of the solution they are suspended in, the full range of possible states of aggregation was examined by using filters with a wide range of pore sizes. Filters of different pore sizes retained endotoxin lipopolysaccharide presumed to be in the vesicle form, the micelle form, or the detergent-solubilized form in aqueous solutions. Endotoxins (pyrogens) were successfully removed from artificially contaminated solutions of concentrated antibiotics by using filters of 10,000-nominal-molecular-weight limit.


Comparison of four-hour and twenty-four-hour refrigerated storage of nonpotable water for fecal coliform analysis.

The problem of extending the storage time of water samples for fecal coliform analysis was addressed. Included in this report is a literature review of the storage problem. Twenty-eight samples were analyzed in replicate to determine the effect of 24-h storage of water samples at 4 degrees C. A new statistical approach to data analysis, coupled with the concept of practical acceptability, is presented. According to our results, many samples can successfully be stored at 4 degrees C for 24 h.


Application of the rapid lysine decarboxylase test for early isolation and detection of salmonellae in sewage and other wastewaters.

A method for early isolation and detection of salmonellae in sewage and other wastewaters by using the rapid lysine decarboxylase test as a single biochemical reaction for screening the suspected Salmonella colonies is described. By this method, Salmonella isolation and identification can be completed within 2 to 3 days in contrast to the 5 to 7 days required for the conventional method.


Retention of bacteria in liquid films at agar surfaces.

The number of bacteria retained by agar dipslides immersed in bacterial suspensions was dependent solely on suspension population density and was unaffected by the nutrient status of the agar surface or liquid, disturbance of the liquid, or bacterial motility and chemotaxis.


Aerobic plate count and Escherichia coli determination on frozen ground-beef patties.

The aerobic plate count and Escherichia coli content of 604 samples of frozen ground-beef patties is reported. The results are discussed with regard to existing and proposed microbiological standards for raw meats.


Influence of continuous positive airways pressure treatment on ductus arteriosus shung assessed by echocardiography.

In a preterm infant with the respiratory distress syndrome complicated by patent ductus arteriosus, continuous positive airways pressure (CPAP) treatment relieved the signs of cardiac decompensation associated with left-to-right shunt. Echocardiography enabled the change in left atrial size, an indirect measure of the shunt, to be followed. In this way the rapid effect of CPAP in reducing left-to-right shunting could be monitored. This noninvasive technique could have many applications in neonatology.


Early neonatal bacteraemia. Comparison of group B streptococcal, other Gram-positive and Gram-negative infections.

All cases of neonatal bacteraemia associated with clinical illness occurring at Hammersmith Hospital, over a 9-year period, 1967-1975 inclusive, have been reviewed. The infants studied were those born in the hospital's maternity unit and those admitted from other hospitals from a wide area round London who were ill or of low birthweight. Positive blood cultures occurred in 91 infants, 47 of them in the first 48 hours of life. These 47 infants were analysed separately and divided into three groups, 13 with group B streptococcal infections, 11 with other Gram-positive infections, and 23 with Gram-negative infections. There were no significant differences in birthweight or gestation, in mortality, in incidence of clinically diagnosed respiratory distress syndrome or recurrent apnoea, or in the need for mechanical ventilation between the three groups. The age at which a diagnosis of infection was suspected, and the age at death were both significantly earlier in the group infected with group B streptococcus than in those obtained with other organisms (P less than 0-01 for both comparisons). There were no significant differences in the incidence of hyaline membrane formation or pneumonia seen at necropsy among the three groups. In some of the earliest deaths in the Gram-negative bacteraemic group, Gram-negative rods comprised the bulk of the hyaline membrane as did cocci in the group B streptoccal group.


Surgical jaundice in infancy.

The surgery of congenital malformations of the biliary system has undergone a revolutionary change during the past decade. Although Kasai's hepatic portoenterostomy operation for biliary atresia is the most dramatic example, radical departures from conventional surgical treatment also have been advocated for choledochal cyst, Caroli's disease, congenital perforation of the bile ducts and biliary hypoplasia. This communication describes the lesions responsible for obstructive jaundice in the early months of life, briefly reviews standard treatment and consolidates the available information about the new operative procedures currently proposed for congenital anomalies of the biliary tract.


Human renal allograft blood flow and early renal function.

Renal allograft blood flow (RBF) was measured at operation by electromagnetic flow meter and probes in 45 patients (34 cadaver donors and 11 living related donors). Mean RBF in 26 patients without acute tubular necrosis (ATN), was 412 +/- 80 ml/min and in 19 patients with ATN, 270 +/- 100 ml/min (p less than .001). Only two of 24 transplants (8%) with RBF greater than 350 ml/min had ATN; whereas, 17 of 21 transplants (81 per cent) with RBF less than 350 ml/min had ATN (p less than .001). In cadaver donor transplants, RBF did not correlate with duration of ATN, warm ischemia time, total ischemia time, pulsatile perfusion time or renal vascular resistance during perfusion. Measurement of renal allograft blood flow can predict presence or absence of postoperative ATN in 87% of patients.


Lymphocyte monitoring as a predictor of renal allograft rejection.

The ability to predict acute renal allograft rejection episodes or infectious potentials by immunologic monitoring was studied in 15 renal transplant recipients. Specifically, total circulating erythrocyte- (E) and erythrocyte-antibody-complement (EAC) rosetting cells were serially studied for the first two months after transplantation and related to immunosuppressive therapy and rejection activity. Total circulating, E-rosetting cells (T cells) were noted to be significantly depressed if rabbit anti-human thymocyte globulin (RAHTG) was used in the immunosuppression protocol. The rate at which these T cells repopulated the circulation was measured by calculating their slope (delta total E-rosettes/delta time). Patients with acute rejection had an average slope of 3.2 +/- 0.68 compared to those without rejection, whose slope was 0.74 +/- 0.35 (p less than 0.01). The rapid repopulation of T cells occurred about 10 days before clinical parameters of rejection were evident. The incidence of infection was greater in those patients with total E-rosettes less than 200/mm3. Serial monitoring of total E-rosetting cells after transplantation provides a diagnostic tool for predicting ensuing rejections and can also be used to gain information concerning the susceptibility to infection.


The effect of serum ALG concentrations on results following renal transplantation.

Seventy-three recipients of renal allografts from cadaver donors, and 121 recipients of kidneys from living related donors were studied to determine whether there were any differences in posttransplant results between patients that had a high average serum concentration of ALG (>/=800 microg/ml) during the two weeks of ALG therapy and patients that had low serum levels (</=799 microg/ml). Cadaver kidney recipients who had high serum ALG levels (average 1126 microg/ml) had significantly fewer rejection episodes three months posttransplant and less kidney loss three and six months posttransplant when compared to patients with low serum ALG concentrations (average 629 microg/ml). The tendencies after three and six months favored the group with high serum ALG levels, but the differences were not statistically significant. There were also significantly fewer rejection episodes and less kidney loss at three months in the group with serum ALG levels >/=800 microg/ml when high risk patients with diabetes mellitus were excluded. There were significantly also fewer rejection episodes at three months in recipients of living related kidney grafts that had serum ALG levels >/=800 microg/ml. When high risk diabetics or patients older than 40 were excluded from the related recipients, the number of rejection episodes was still significantly less in patients with high serum ALG levels. There was significantly less kidney loss 24 and more months posttransplant in recipients of kidneys from living related donors whether or not high risk patients were excluded. These results support previous reports from the University of Minnesota indicating ALG is a safe and effective immunosuppressive agent in renal allograft recipients.