[Analysis of the mechanism of the fixation of membrane structures using osmium tetroxide. II. An electron microscopic and x-ray structural study of myelin frozen and lyophilized at low temperature]. Comparative electron microscope and X-ray studies were made on the frog sciatic nerve myelin after freeze-drying technique. The specimens were fixed with OsO4 before and after freeze-drying. In the latter case, osmium was used as a hydrophobic solution (OsO4 in CCl4), or in the high vacuum during osmium sublimation. The results obtained in this study do not fit in the accepted mechanism operating during osmium fixation of membranes. Another mechanism is proposed by the authors, and the problem of osmium localization within the space of the myelin repeated unit is discussed.


[Polarized ultraviolet fluorescence microscopic study of the structural changes in muscle fiber contractile proteins. V. The possible nature of the conformational rearrangements in heavy meromyosin in fiber relaxation]. The mode and degree of tryptophanyl orientation relative to muscle fiber axes within hydrophobic and hydrophylic sites of myosin macromolecule in the presence of a fluorescence quencher (acrylamide, NO-3) during rigor and relaxation of glycerinated muscle fibers were studied using the polarized ultraviolet fluorescent microscopy. It was shown that myosin tryptophanyls both in LMM and HMM are oriented with their short axes along the longer axis of muscle fiber. Tryptophanyls in LMM have a more pronounced anisotropy of orientation in comparison with the fluorophore orientation anisotropy in hydrophobic sites of HMM. During the muscle fiber relaxation, conformational changes in HMM take place owing to which a section of polypeptide chain with a hydrophilic fluorophore is probably submerged deep into the macromolecule and becomes unapprochable to the quencher.


Immunology and male infertility.

Immunology and male infertility. This article has attempted to review evidence that suggests that immune factors may be operative in a small but significant number of infertile men. Although our current understanding of the possible processes by which autosensitization to previously sequestered reproductive antigens occurs is incomplete, there are laboratory assays presently available that give an indication, but do not prove, that immune factors may be contributing to the infertile state. Continued research is needed to develop new assays and more purified sperm antigens, which might enhance our knowledge of the underlying immunoreproductive changes. Until these are available, the following procedures should be considered when investigating a patient with infertility of suspected immune origin. The patient's history should be taken, and a physical examination should be performed. A complete blood count, urinalysis, and complete semen analysis and culture should be taken. Next, in vivo cervical tests (Sims-Huhner) are performed, followed by sperm antibody assessment (serum, semen) and perhaps in vitro cervical mucus sperm assays (especially the crossed hostility test). After the tests have been completed, the following possibe treatments exist: 1. Treatment of underlying infections 2. Correction of obstructions 3. Corticosteroid (or testosterone?) therapy 4. Washed sperm insemination 5. First portion of fresh ejaculate insemination 6. Artificial insemination with homologous donor 7. Adoption.


Medical treatment of the subfertile male. Specific and effective medical treatment is available for some subfertile males. Reproductive physiology should be reviewed with all patients and exposure to drugs and toxins known to impair testicular or accessory sex gland function should be terminated. Appropriate treatment of retrograde ejaculation, chronic infections of the genital tract, or gonadotropin deficiency is indicated. Accurate diagnosis and treatment of the impotent patient may restore potency and fertility. Pregnancies have been achieved in association with each of the empirical regimens; however, we believe that each must be viewed as experimental at this time, since results may be no better than those observed in the absence of treatment. It is our experience that patients with elevated serum levels of FSH, peritubular fibrosis, and hyalinization are unlikely to achieve fertility regardless of treatment; however, there are exceptions. As our knowledge of basic reproductive biology and clinical pathology increases, it is hoped that better guidelines and more rational and effective medical treatment for the subfertile male will evolve.


Vasovasostomy.

Vasovasostomy. As vasectomy continues in popularity, requests for restoration of fertility increase in number. Anastomosis of the vas deferens is a demanding, technically difficult operation. The principles governing it are different from those of other anastomoses in the body. The suitably equipped surgeon can expect, with practice, to achieve a pregnancy rate of 50% or better for his patient's wife. The operation can easily be performed under local anesthesia in either an office or hospital operating room. Hospitalization is unnecessary, and merely adds unnecessary expense. Disability is minimal, and discomfort minor. The technique of Belker is recommended for practice, since it permits one to inspect the anastomosis from within afterwards.


[Combined drug treatment of far-advanced forms of breast cancer]. Seventy patients with breast cancer (stage IIIb--IV) were randomized by an "envelope" method into 2 groups, each including 35 persons. Patients of the first group were injected vincristin, 5-fluoruracil, methotrexate (once a week), cyclophosphane (3 times a week) and prednisolone daily during 3 weeks. The duration of the course of treatment was 4 weeks. The therapy course was repeated with an interval of 1--2 months. Patients of the second group in addition to the analogous treatment were subjected to ovariectomy with subsequent continuous administration of prednisolone, testosterone-propionate or synoestrol. An objective effect was noted in 24 patients of the first group (71.4%), the complete remission being gained in 4 of them. An average duration of the remission--7.6 months. An objective effect was noted in 31 patients of the second group (88.5%), the complete remission--in 4 of them. An average duration of the remission--10.7 months. Primary mammary tumors and metastases in regional lymph nodes proved to be mostly susceptible to the conducted therapy. Lung and pleural metastases were found to be less susceptible. No grave complications due to this kind of treatment were noted.


[Clinical trial of the preparation clofazolin used intravenously]. The authors studied the hypotensive effect of the Bulgarian preparation Chlophazolin in ampoules of 0,15 mg, administered i. v. The study covered 50 patients, 44 of them with hypertonic disease II and III stage and the rest (6)--with renal and renovasal hypertension. The i. v. administration of chlophazolin was established to have a marked hypotensive effect and be expedient for the treatment of hypertonic crises and hypertension with high values. In a dose of 0,15 mg i. v. the preparation leads to a sharp decrease in the first 20 min, whereas during the following hours it is kept to lower values: systolic pressure-an average decrease of 30-40 mm Hb in a lying position, to 45-50 mm Hg in an erect position; the diastolic pressure-an average decrease of 10-15 mm Hg in a lying position to 20-25 mm Hg in an erect position. The hypotensive effect is better manifested in higher initial values of the pressure. It lasts approximately more than 13 hours but in 1/5 of the patients, with higher values of blood pressure, its effect is exhausted within 6-8 hours. Side effects of the preparation were registered in 26 per cent of the cases; orthostatic disturbances, sleepiness, dryness of the mouth, nausea. I. v. administration of chlopazolin does not change the excretion of urea and creatinine, diuresis and serum levels of sodium, potassium and chlorine.


[Dynamic study of the hypothalomo-hypophyseal-gonadal axis in patients with Klinefelter's syndrome]. Detailed clinical and hormonal studies were performed in 30 male patients with Klinefelter syndrome, proved by karyotyping. Diagnostic tests with LH-RH were carried out with application of 100 microgram of LH-RH as single stimulation and as long-term application for 7 days. Plasma levels of LH, FSH and testosterone were measured by specific radioimmunoassay. Th single LH-RG application stimulated both LH and FST secretion, while testosterone level remained unchanged in patients with Klinefelter syndrome. Long-term stimulation decreased basal LH and FSH levels and pituitary response to LH-RH . became close to normal. The testosterone level increased significantly in most patients with Klinefelter syndrome. This suggests that the Leydig cells in Klinefelter syndrome improved their activity, showing some functional reserve.


Studies on the deoxyribonucleic acid-bearing portion of the cell envelope of Escherichia coli. The envelope components of nuclear bodies which were obtained from Escherichia coli W7 by a mild lysis method were investigated. By using 2,6-diaminopimelic acid (DAP) as precursor which is incorporated only into peptidoglycan in this strain it was found that the particles contained about 14% of the murein layer of the cell. The percentage of phosphatidylethanolamine was enriched at the cost of the other phospholipids in the nuclear bodies compared to whole cells. If lipids were labelled with 3H-palmitic acid the cytoplasmic and the outer membrane could be found after isopycnic centrifugation; however, when the cells were incubated with chloramphenicol, only the outer membrane was seen. The peptidoglycan and the proteins could be assigned only to the outer membrane. The DNA is also bound to the outer membrane. From these results it was concluded that (1) in all lysis methods the cytoplasmic membrane is more easily dissolved than the outer layers of the envelope, and (2) that there is a firm binding between DNA and the outer membrane in vivo.


Adaptation of glomerular forces and flows to renal injury. The mechanism of glomerular ultrafiltration in normal kidneys or after renal injury is reviewed. The role of increased glomerular plasma flow in mediating increases of nephron filtration rate is evidenced under experimental conditions resulting in filtration pressure disequilibrium along glomerular capillaries. The increase of nephron filtration in hypertrophied kidneys appears to be due mainly to a rise of glomerular plasma flow and, to a smaller extent, to an increase of glomerular capillary hydrostatic pressure, the ultrafiltration coefficient remaining unchanged. In contrast, in the early phases of experimentally induced nephrotoxic serum nephritis, a decrease of the ultrafiltration coefficient was observed; nephron filtration rate, however, remained within the normal range, as a consequence of a higher hydrostatic pressure in the glomerular capillaries of the nephritic kidneys.


The role of renal "work" in compensatory kidney growth. In a series of studies designed to test the role of renal "work" in compensatory kidney growth we examined the relationship between absolute sodium reabsorption-which constitutes the bulk of renal energy expenditure, and growth of the remaining kidney at various intervals after contralateral nephrectomy.The increase in weight of the remaining kidney preceded the rise in sodium reabsorption and these two processes took place at different rates between 24 hours and 21 days after uninephrectomy.Absolute sodium reabsorption did not change during the first hours after contralateral nephrectomy, at a time when biochemical alterations are known to occur.The rate of [(14)C] choline incorporation into renal phospholipid, an early biochemical indicator of compensatory kidney growth, increased significantly one hour after contralateral nephrectomy but remained unchanged after sham-nephrectomy, regardless of the magnitude or direction of the concomitant change in absolute sodium reabsorption ("kidney work").These results indicate that renal work expended in the reabsorption of glomerular filtrate is neither the initiating, nor the primary controlling factor, of the compensatory kidney growth that follows unilateral nephrectomy.


Changes in renal function in early pregnancy in women with one kidney. In healthy women the 24-hour endogenous creatinine clearance is elevated by some 50 percent within 6 weeks of conception and an analogous increase of the 24-hour glucose excretion occurs. 24-hour glucose excretion later reverts to normal, reflecting a delayed onset of increased tubular reabsorption.Following unilateral nephrectomy there are marked increases in RPF and GFR in the contralateral kidney. Single hypertrophied kidneys apparently can adapt still further as in normal pregnancy. We have studied 5 women, in satisfactory general health prior to the pregnancy, each with only one kidney, before conception and during early pregnancy. Three had had unilateral nephrectomy for renal trauma 6-9 years earlier. two had received renal allografts 3 years earlier. In all cases the endogenous creatinine clearance began to rise in the second half of the menstrual cycle and when pregnancy supervened it rose rapidly to a peak value of 30-40 percent above the midcycle level within 7-10 weeks of the last menstrual period. That early peak was not always sustained and GFR subsequently fell to a level of 25-30 percent above the midcycle level. These changes in renal function were slower and smaller than in healthy women with 2 kidneys but were compatible with a successful outcome of pregnancy in these five cases.


[The development of neurology since A. v. Strümpell and its relation to internal medicine]. A. v. Strümpell is appreciated as one of those internal specialists who inaugurated neurology in Germany and furthered decisively its development. Issuing from the opinions which Strümpell expressed at the end of his life the further way of the German neurology up to an independent clinical discipline is described in short. Here the partly historically, partly really proved relations of neurology to internal medicine as well as to psychiatry are taken into consideration. Integration is characterized as an actual request, since with progressing differentiation and specialisation of medicine the adherence to the traditional structures and borders of the specialities becomes more and more questionable.


The effects of hydrocortisone and dopamine on circulatory alterations in experimental acute endotoxin shock in dogs. In our study of experimental endotoxin shock we tried therapeutic control of reversible acute endotoxin shock. In a standard model in the dog, in which endotoxin shock had been induced by intravenous injection of E. coli endotoxin dosed 1.75 mg/kg, the effects of hydrocortisone and dopamine administered concurrently were investigated. It was found that endotoxin shock elicited primarily haemodynamic alterations; arterial hypotension, reduction of renal arterial blood flow, elevation of central venous flow, decrease in left ventricular pressure, and vasodilatation. Dopamine plus hydrocortisone prevented development of alterations, primarily of haemodynamic ones, already in the initial phase of shock. Dopamine plus hydrocortisone raised the survival quota of animals in endotoxin shock, enhanced the renal arterial blood flow, maintained the diuresis, enhanced myocardial contractility, and elevated left ventricular blood pressure. After higher dosages of dopamine the peripheral blood pressure rose as well. The dosage of dopamine has to be adjusted with respect to the actual state of haemodynamics. The developing tendency to acidosis was not brought under control within the three-hour monitoring period.


Macromolecular metabolism in compensatory renal hypertrophy. 1. The initial biochemical changes of compensatory hypertrophy occur well within 1 hour of unilateral nephrectomy and perhaps within the first few minutes.2. The initial increment in rRNA is from decreased metabolism rather than from increased synthesis.3. Changes in the processing of mRNA precursors are probably also important.4. Compensatory hypertrophy is regulated by a humoral stimulus or stimuli.5. The stimulus needs to be present virtually all of the time during the early phases of compensatory hypertrophy.6. The stimulus is related to loss of renal mass, not to loss of renal function.


[Parent-child-interaction in infancy (author's transl)]. On the basis of many experimental studies it is demonstrated that not only mother-child-relationship in infancy but also father-child-relationship is important for child development. Different patterns of mother-child-interaction as well as father-child-interaction during the first weeks after birth are reported and intervening variables are discussed. Kind and degree of interactions of both parents with the newborn and infant influence the emotional, social, and cognitive development of the child. On the other hand the birth of child and the behavior of the newborn determine personal development of father and mother, too. The growth of the family is to be regarded as a process which is based on the differentiated net work of conditions. The concentration of research on mother-child-contacts has to be rejected in the light of these new findings and has to be regarded as hostile against the family as a whole.


Introduction: history and problems of compensatory adaptation of renal functions and of compensatory hypertrophy of the kidney. The history of observations and experimental work on compensatory changes following the loss of renal mass, and the historical reasons for the distinction between the concepts of compensatory adaptation (of renal functions) and of compensatory hypertrophy (of nephrons) are outlined. While the effector mechanisms of both types of compensatory changes are being elucidated at a rapid pace, many questions concerning the primary changes initiating these events, the control mechanisms implied and the interrelationship between functional adaptation and hypertrophy remain unanswered.


[Fetal parasystolia--uncommon case of fetal arrhythmia with polyhydramnios and hydrops fetalis (author's transl)]. By direct fetal electrocardiography an arrhythmic pattern comparable with parasystolia was observed during the 38th week of pregnancy. The gestational course was only complicated by polyhydramnios. The record of the FHF was considerably disturbed. The normocardic pattern showed poor irregularity, rarely accelerations and decelerations during labor activity. The ectopic QRS-complex was broadened (0,06--0,08 sec) and frequently raised. Beginning the record the frequency of the parasystolia was lower than the activity of the sinus node. A hydropic neonate was delivered by vacuum and died after bradyarrhythmia 37 minutes after parturition. In spite of intensive clarification the cause of pathology was not detected.


[The effect of some antiarrhythmic drugs on systolic time intervals in normal subjects (author's transl)]. Eleven healthy volunteers (mean age 30.1 +/- 4.3 yrs.) were repeatedly studied by measurement of systolic time intervals (QS2c, PEPc, LVETc, PEP/LVET) and arterial blood pressure (cuff method) before and after 24-hour oral application of four antiarrhythmic drugs (quinidine, disopyramide, prajmaliumbitartrate, propafenone) and two beta-blocking agents (propranolol, atenolol). The studies were repeated in the same group of volunteers with a different drug after an interval of one week. PEPc significantly increased after all antiarrhythmic agents at therapeutic doses by 6.1 to 9.4 ms (p less than 0.05 and p less than 0.01 resp.), whereas LVETc did not change significantly. PEP/LVET increased on an average by 0.033 +/- 0.006 (p less than 0.01). QS2c increased by 7.5 and 7.6 ms resp. (p less than 0.05) after prajmaliumbitartrate and propafenone. Heart rate remained unchanged after disopyramide and propafenone whereas it increased significantly (p less than 0.05) after quinidine and prajmaliumbitartrate. Blood pressure did not change significantly after any of these antiarrhythmic drugs. After application of the two beta-blocking agents propranolol and atenolol, no significant changes in STI could be observed. Mean arterial blood pressure significantly dropped after both, propranolol (minus 2.8 mm Hg) and atenolol (minus 9.7 mm Hg; p less than 0.05 and p less than 0.01, resp.). Heart rate decreased by minus 8.1 b.p.m. after propranolol (p less than 0.01) and minus 11.5 b.p.m. after atenolol (p less than 0.01). The results clearly indicate that at the dosage used, the four antiarrhythmic agents (quinidine, disopyramide, prajmaliumbitartrate, propafenone) exert a negative inotropic effect on left ventricular function as far as it can be judged from the measurement of STI. The lack of a significant negative inotropic effect of an oral treatment with beta-blocking agents on the STI can be explained by opposing effects of a decrease in blood pressure and a negative inotropic action.


[Fully automatic computer-analysis of electrocardiograms in clinical routine (author's transl)]. A fully automated Ecg recording and interpretation system (Hewlett Packard HP 5) consisting of a central computer and two peripheral units was evaluated during a four-month period. Ecgs were transmitted via public telephone lines, as was the report from central station to peripheral recording and print-out unit. Within a few seconds after recording and print-out unit. Within a few seconds after recording and transmission a preliminary report is available in printed format. The transmitted Ecgs are stored at the central computer and are being retrieved and evaluated manually there. Three cardiologists read the tracings and furnished final reports. 468 Ecgs were thus compared in our test time of 10 days for statistical evaluation with the following results: 1. 73.1% of all statements were read correctly by the computer. 2. There is a large range of diagnostic accuracy between 0% and 100%. 3. The evaluation of Ecg changed by cardiologists reflects the individual experience of the controllers regarding the Ecg statements as well as computer-dependent possibilities like modification etc. of Ecg. 4. As an example the diagnosis "myocardial infarction" is compared with other Ecg computer programs by means of a quality index calculated from sensitivity and specificity: HP 5 with 158.5 points reaches a similar level as the Pipberger program with 162.6 and the Bonner with 159.5 points. 5. Referring to false negative results this program is acceptable in all diagnostic groups with ca. 8%, except conduction defects with 17.7%. 6. Referring to false positive results the diagnostic groups myocardial infarction/ischemia and conduction defects are not satisfactory with 36.5% and 23.4%. 7. In all the tested system seems to be very useful in routine Ecg interpretation of bigger hospitals.


[Differentiation by microimmunofluorescence of T. cruzi and T. cruzi-like strains from T. conorhini and T. rangeli, using protection from the sponge Aaptos papillata (author's transl)]. Carbohydrates containing terminal nonreducting D N-acetylgalactosamin or D N-acetylglucosamin were identified at the cell surface of Trypanosoma cruzi by an indirect immunofluorescence test using the lectin of the sponge Aaptos papillata. With the method described in this study T. cruzi and T. cruzi-like strains are easy to distinguish from T. rangeli, but not from T. conorhini. The immunofluorescence test presented here may be very helpful for certain diagnostic problems.


[Establishing prevention in federal legislation]. History and present situation of legislation on the cantonal and federal levels are briefly discussed. Special attention is given to the planned federal law on prevention which should provide a frame for various measures aiming at primary prevention of illnesses and accidents.


[Split brain and the problem of interhemispheric relations]. For the last 15-20 years the study of interhemispheric relations made a big progress. This progress was facilitated by use of new methods in combination with midsagittal sections of comissural connections at different levels. An assumption is made that interhemispheric exchange of sensory information is of certain importance for the short-term memory and for compensatory mechanisms of the brain. The importance of hemispheric interaction for coordinated motor reactions and for subtle spatial orientation of animals is determined. Observation of patients with surgically dissected brain is a big contribution to further study of interhemispheric relations.


[Vascular changes in experimental renal ischemia and after renal homotransplantation (experimental angiographic study on animals)]. Which consequences result from these experimental results from practice? In the acute angiography in postoperative functional distrubance after transplantation of a human kidney is at first probably always to be reckoned with a rejection process, though this immunological process by no means must be in the foreground of the causal connection of several pathogenetic factors. Therefore, in our opinion it would then be assumed an ischaemia-conditioned cell damage of the tubulus by a longer lasting prefinal circulatory depression or due to a not optimal preservation, when there is in the angiogramme a clear discrepancy to the severity of the postoperative functional distrubance, i.e. when angiographically exists only a slight cortical ischaemia in an otherwise good arterial filling picture and a widely normal capillary filling phase.


[Value of hemodynamic parameters in determining kidney transplant function (animal experiments and clinical observations)]. From the demonstrated results is to be concluded: 1. The haemodynamic and functional inquiries on animal experimental and clinical kidney grafts suppose that the tubules and the renal vascular system are comparably affected by the damaging influences of the different preservation methods. 2. This pathogenetic relationship is apparently maintained also in the regeneration phase; i.e. the tubular restitution is connected with an improvement of the blood-supply of the organ. 3. The discrepancy between the morphologic and functional findings of storage and perfusion preserved kidneys shows that the efficiency of the graft is not only defined by definitive structural changes, but also by other factors, such as metabolites, enzymatic and humoral influences, changes of the local blood composition, regional conditions of blood-supply, and so on. 4. Due to the significant relation between restrictions of the renal blood-supply and the renal function after transplantation haemodynamic parameters are suitable for the judgment of renal preservation methods and for the prognostic estimation of renal grafts.


[Electron microscopic studies on long-term perfused dog kidneys]. In the applied preservation technique of kidneys used the fine-structural changes on main epithelial cells and glomeruli are relatively insignificant and appear reversible or reparable after a storage preservation up to 4 hours and permanent perfusion of 24 hours. After a storage preservation of 10 hours and an additional permanent perfusion of 24 hours and after a renal permanent perfusion during 48 hours compared to it most frequently irreversible damages in form of dystrophies and necroses on tubuli and glomeruli are the result, so that the conservative condition of the organ can no more be regarded as optimal. Such kidneys are certainly only conditionedly suited for a transplantation.


[Hemodynamic studies on the preservation effect of Fürtig perfusate on transplanted dog kidneys]. From the experimental results is evident that the Collins-III-solution and the perfusate conceived by Fürtig achieve a comparable preservation effect. This may be traced back to the fact that they are of the same value in their kational composition as well as in their osmolarity.


[Modification of the Gambro perfusion apparatus PF-3A for use in experimental studies]. The demonstrated modifications of the Gambro perfusion apparatus PF 3A can be used with great success in the field of experimental research. By means of the measurings which can now be performed the course of the perfusion is to be established from the point of view of measuring technique.


[Analysis of trends in the immunologic supervision of organ transplantation]. Immunological methods of the rejection diagnostics are discussed. The humoral as well as cullular immune response against the graft is taken in consideration. The tests described up to now in literature are not suited or must still be confirmed, respectively. Thus the aptitude of the nucleolar test, of the leucocyte aggregation test, of the MLC-MEM and the rosette inhibition test for the rejection diagnostics should be increasedly examined. The immunological rejection diagnostics is complicated by the immunosuppressive therapy.


[Immunologic course of kidney transplants studied by means of cellular and humoral immunity tests]. In 10 human-allo-transplanted persons and evaluation of the postoperative course was done with the help of specific and unspecific, cellular and humoral immune tests which were compared with clinical parameters. While the E-rosette-test did not show any correlation to the typical courses in the immunoglobulins postoperatively after a clear decrease at the time of the clinically diagnosed first set reaction an increase above all of the IgM could be observed. Unspecific tests, such as CRP and FSP may, concerning the rejection diagnostics, confirm the suspicion in as far as other factors, such as infection of the urinary tract were excluded. By choice of a suitable relation system the evidence of the immunoglobulins could possibly be proved, whereas for the cellular demonstration methods the E-rosette test does not seem to be recommendable in the performed way.


[Perfusion technic during clinical intra- and extracorporeal tumor removal from a solitary kidney]. On the basis of own experiences in operations of tumour-carrying kidneys two perfusion techniques for the intra- or extracorporal renal surgery are exolained and weighed one to another. In the in-situ-perfusion the pulsatile mechanical perfusion with supervisable flow, perfusate pressure and under direct measuring of temperature on organs has proved. The disadvantage of the in-situ-perfusion in contrast to the extra-corporal surgery consists in the impossibility of the local after irradiation.


[Distal ureteral stenosis following kidney transplantation]. 75 patients after renal allotransplantation were investigated for postoperative urological complications. 11 patients were found to have a stenosis of vesicoureteral anastomosis. According to clinical and radiological findings a classification into three stadiums was performed. Stage I indicates no necessity for operation. Two patients in Stage II and three patients in Stage III underwent surgical treatment for stenosis of ureteroneocystostomy. Treatment led to improved renal function and loss of urinary tract infection in 4 patients. The results of the study indicated treatment of stenosis after ureteroneocystostomy in Stage II prior to severe damage of renal allograft.


[Diagnostic value of determining urinary fibrin split products in glomerulonephritis, pyelonephritis and graft rejection]. On 112 patients with bioptically ascertained chronic proliferative glomerulonephritis, 94 with pyelonephritis and 23 patients with kidney transplantation altogether 1,050 times the fibrin fission products in the urine were estimated by the passive haemagglutination after Merskey. It was the aim of the investigation to test the diagnostic evidence described in literature concerning the floridity diagnostics in glomerulonephritis and the recognition of rejection in kidney transplantation as to its reproducibility. In comparison to the latent glomerulonephritis (0.3 microgram/ml) the florid glomerulonephritis (12.3 microgram/ml) as well as the acute pyelonephritis (9.2 microgram/ml) in comparison to the chronic pyelonephritis (1.3 microgram/ml) has significantly higher values. On account of the numerous "falsely positive" and "falsely negative" values in contrast to the data of other authors an activity diagnostics is not possible. Only in the glomerulonephritis with nephrotic syndrome a prognostic use is to be expected: Patients with steroid-sensitive nephrotic syndrome do not secrete any fibrin fission products in the urine and patients with steroid-resistant nephrotic syndrome secrete them in a large number. We could confirm that an increase of the fibrin fission products in the urine after kidney transplantation refers to an acute rejection crisis. Since 10 of 27 rejections were fibrin fission product-negative, in the lacking fibrin fission products in the urine a rejection is not be excluded, by which the diagnostic value is restricted.


Epidemiological studies on rheumatic heart disease and streptococcal carriers among school-children in Addis-Ababa, Ethiopia. Preliminary communication. The results of the first part of epidemiological follow-up studies on rheumatic heart disease and streptococcal carriers in Addis-Ababa are presented. In 1012 school-children relatively low morbidity of rheumatic heart disease (0.49%) and relatively small percentage of carriers of A-beta-hemolytic streptococci (4.24%) were found. There was no statistically significant difference in the morbidity of rheumatic heart disease as well as in the percentage of streptococcal carriers between the two basic social groups--children of well-to-do and of poor parents. No correlations with overcrowding were found. Serological types 5/12/27 and 3/13/B3164 of group A-beta-hemolytic streptococci were isolated most frequently.


[Felix Marchand--a retrospect in occasion of the 50th anniversary of his day of death (author's transl)]. In consideration of an autobiographical study of Felix Marchand and of ideas presented by him in various publications his importance for the pathological anatomy and medicine was discussed. His talent of deducing from analytical observations for the detection of generally valid principles was remarkable. His contributions to the theory of inflammation and diseases, to the significance of general and experimental pathology as a basis of pathology, and his understanding for the nature of pathological state as a dynamic event when he is speaking about pathological processes are to emphasize. In our view, Felix Marchand represented besides Rudolf Virchow the most outstanding personality of German-speaking pathology.


[Experimental aspects of pathogenesis and prophylaxis of gastric stress ulcers (author's transl)]. The prophylactic efficacy of various treatments was examined in porcine haemorrhagic shock [13] by measuring total and regional gastric blood flow with radioactive Microspheres. All 24 animals of the control-group (no treatment) developed extensive haemorrhagic lesions of the stomach. Total gastric blood flow fell almost by 90% during shock. By methods improving the circulation during heamorrhagic shock, a nearly total prevention of gastric stress lesions was possible. After splanchnicectomy (n = 7) and by application of the H2-receptor antagonist Cimetidine (n = 8) total gastric blood flow during haemorrhagic shock fell only by 38% and 44%, respectively, when compared to control values before shock. Only 2 piglets of these both groups developed minor changes, whereas in all others no lesions were seen macroscopically or histologically. Conversely truncal vagotomy (n = 9), which impairs gastric blood flow, had no prophylactic effect on the occurence of gastric mucosal lesions, induced by haemorrhagic shock. -- This study supports the suggestion, that gastric ischaemia due to sympathetic overactivity especially in corpus and fundus of the stomach plays an important role in the pathogenesis of gastric stress lesions. An improvement of gastric blood flow during shock could become a useful treatment in man.


[Fibrin glue protection of digestive anastomoses (author's transl)]. In animal experiments the additional sealing of colonic anastomoses using fibrin glue resulted in especially fast healing with formation of a delicate scar. Between April 1, 1976 and March 31, 1977, this method was used in 118 out of 355 patients undergoing extensive abdominal procedures. Suture line leakage was seven times less frequent than in the control group. This resulted in a considerable decrease of postoperative mortality.


[Partial gastrectomy (BI) with jejunal interposition (author's transl)]. Until now pathogenesis and the choice of surgical procedure in the management of gastric ulcer has suffered due to lack of resolution. The pathogenetic value of duodenogastric reflux for example has been underestimated and has not been considered in the operative technique. In order to close this gap the primary of secondary isoperistaltic orthograde interpositon of a jejunal loop between gastric remnant and duodenum is recommended.


[Experimental microsurgery in rats (author's transl)]. Experimental microsurgical techniques using a magnifying glass and surgical microscope enable nearly all abdominal operations and organ transplantations to be performed in rats. Vascular and prosthetic segment implantations, portocaval anastomoses, heterotopic heart-, kidney-, spleen-, pancreas-, and liver transplantations some with superselective organangiography, are excellently demonstrated. Continuing research in microsurgery has considerably expanded experimental surgery and given new impulse to clinical surgery.


[Present state of lung transplantation (author's transl)]. Lung allotransplantation is still an experimental method. Immunologic rejection makes it highly lethal in experimental animals as well as in man. Its present state can in no way be compared with renal transplantation in man.


[Gonadotropin secretion in patients with testicular feminization]. FSH and LH were functionally examined in 5 women with feminizing testis and compared with the peripheral sex steroid hormones. The oestradiol levels were found decreased, while those of testosteron were elevated. FSH disclosed no significant differences while the basal levels of LH and its stimulatory response to LH-RH were increased in the patients.


Detection of conjugative R plasmids conferring chloramphenicol resistance in Escherichia coli isolated from domestic and feral pigeons and crows. A total of 87 domestic pigeons of 2 lots and 184 feral pigeons of 15 lots were examined from 1975 to 1977 for the presence of drug-resistant (especially chloramphenicol resistant) Escherichia coli. 20 (23.0%) of the domestic pigeons of the 2 lots, and 39 (21.2%) of the feral pigeons of 5 lots (33,3%) showed resistant E. coli. Usage of selective media containing chloramphenicol, streptomycin or tetracycline resulted in the increase in isolation frequency of resistant E. coli excepting one lot of domestic pigeons in which isolation of chloramphenicol resistant E. coli was very frequent without selection by the drug. Among a total of 106 resistant E. coli isolates from pigeons, 64 (60.4%) were multiply resistant and 58 of the 64 isolates were resistant to chloramphenicol. 58 (90.6%) of the multiply resistant E. coli carried conjugative R plasmids, including 13 thermosensitive R plasmids. 8 (19.0%) of 42 singly resistant E. coli isolates had conjugative R plasmids. 10 crows of 2 lots were examined similarly. Half of them had resistant E. coli. 15 (78.9%) of a total of 19 resistant E. coli isolates were multiply resistant. Of the 15 multiply resistant E. coli isolates, 5, from 2 Japanese jungle crows, were resistant to chloramphenicol. 11 (73.3%) of the 15 multiply resistant isolates carried conjugative R plasmids, including one thermosensitive R plasmid. Difference of drug resistance status between Salmonella and E. coli isolated from pigeons was discussed.


[The differentiation of clostridial microcultures on nuclepore-filters by fluorescent antibodies as a rapid screening test for spores. I. Method of producing microcultures (author's transl)]. Spores of 32 strains of 11 different clostridial species (Table 1) were allowed to germinate as microcultures on Nuclepore membrane-filters to ascertain whether they could be differentiated according to their patterns of growth. The questions dealt with in the preliminary studies, investigated which pore-size of filters would be best for this purpose and which time necessary for each species to produce microcolonies of 10 to 20 cells from a single spore. Nuclepore-filters with a pore-diameter of 1 mu gave the best results and the times for producing microcolonies of the desired size ranged from 4 hours with Cl. septicum up to 10 hours with Cl. tetani (Table 3). The final result of the study was, that the differences in the patterns of growth were not great enough to allow identification. Only Cl. perfringens formed specific and distinctive compact colonies (Tables 4 and 5).


[The differentiation of clostridial microcultures on nuclepore-filters by fluorescent antibodies as a rapid screening test for spores. II. Application of fluorescent antibodies (author's transl)]. The study deals with the question of whether a combination of microcolony-cultivation on polycarbonate-membrane-filters with the fluorescent-antibody-method will lead to a rapid-diagnosis method for clostridial-spores. Formaldehyd-inactivated vegetative cells of eight different clostridial-strains (Table 1) were used for the immunisation of rabbits according to the method published by Böhm and Strauch (5). The results of the immunisation procedure, developed for aerobic-sporeformers, showed, that satisfactory results could not be obtained in all cases (Table 2). The eight conjugates were tested against microcolonies of 32 strains of different clostridial-species on membrane-filters, produced by the technique described in the first communication. The results showed (Table 4) that differentiation was always possible when homologous antisera were used. In most cases, in order to differentiate between the various species, conjugates of several serotypes had to be employed together. However due to their uniform antigenic nature, Cl. feseri and Cl. tetani could both be identified by using one strain for each to immunize. With clostridial-spores the species could be identified within a period of 6 to 12 hours by using the membrane-filter-fluorescent-antibody technique.


[Analysis of penicillin and ampicillin resistance in bacteria i. resistance and beta-lactamase production in clinical isolates (author's transl)]. The penicillin beta-lactamase (PBL) activity of the clinical isolates was measured at the same time by colorimetric microtitration, the iodometric method and chromatographic analysis. The minimal inhibitory concentration (MIC) of ampicillin (Ap) was determined for each isolate, the character of the coupled resistances, their frequency and distribution in the PBL producing and PBL-negative strains were also investigated. It was found that 1. the MIC value was 100 microgram/ml in 87.5 per cent of the Penicillin (P) and Ap resistant clinical isolates, 2. PBL was produced by 55--75 per cent of the P and Ap resistant strains depending on the species of the bacteria, 3. less than 50 per cent of the E. coli isolates produced PBL; in the case of other species this value was higher, about 65--70 per cent, 4. resistance to Su, SM, Tc, Nm and Cm was most frequently coupled to Ap and P resistance, 5. the distribution curve representing the number of the coupled resistance to the Ap and P shows a peak with 6 coupled antibiotics in the PBL-negative strains and 2 peaks in the PBL-producing strains.


Stepless antibody determination with the stick-ELISA technique. Results expressed as multiple of normal activity (MONA). A means is presented whereby results of antibody determination with ELISA (enzyme-linked immunospecific assay) can be expressed as the multiple of normal activity (MONA) contained in a normal serum pool, assessed by an internal standard. The procedure combines the advantage of stepless titration, inherent in the method of ELISA, with the opportunity to provide the clinician with an imaginable antibody result. It is discussed that independent of ELISA with the evolution of serology as an aid for the diagnosis of parasitic disease the clinician is faced with an evergrowing variety of normal antibody titers caused among others by different sensitivities of the methods and techniques employed. To preclude these differences result communications as MONA is suggested.


[Experience in application of electronic data processing in routine medical microbiology (author's transl)]. Experiences in a two years application of electronic data processing in medical routine microbiology are reported. Optical mark reader forms serve as request forms as well as workprotocol. On the left two thirds of these forms (Fig. 1 and 2) the patients data including clinical statements, and the kind of specimen to be investigated (sputum, smear etc.) as well as results not essential for the printout of laboratory reports are filled in. On the right third of the optical mark reader form, in which area the Bell & Howell document reader can read pencil marks, the patients identification number, the tests requested and all results are marked right at the work bench. As shown in the flow diagram (Fig. 3) after completion of the investigation the date on the mark reader forms are read mechanically and the test results are printed (Fig. 5) by means of the computer. In addition, the data processing system, which proved to be very flexible, performs all necessary types of administrative work as filing of laboratory data in a coded form on cards for permanent storage (Fig. 7) statistics and the printout of bills (Fig. 6). The processing of routine microbiology date is achieved by a Siemens DVA 404/3 (64 kbt) connected for magnetic disc device (2993 Mio bytes), and a line printer (60,000 lines per hour) and dialog display monitors, which are used simultaneously for the on line and off line handling of all the data in clinical chemistry-, serology- and hematology-departments of the same institute.


High frequency of K15 antigen in enterotoxigenic Escherichia coli: lack of correlation to adherence to epithelial cells or sensitivity to bactericidal effect of normal serum. Typing of E. coli O and K antigens, testing of sensitivity to bactericidal effect of normal serum and adherence to uroepithelial as well as buccal epithelial cells was performed in enterotoxinogenic (ETEC) and normal E. coli strains. The 99 ETEC faecal strains were obtained from Swedish and Ethiopian children and adults and Swedish soldiers in Cyprus with diarrhoea. The reference faecal strains were isolated from 120 healthy Swedish children. E. coli K15 was significantly more often seen in ETEC strains than in the reference strains, always in combination with O6 antigen. K15 is hardly ever seen in nonenterotoxinogenic strains. There was no significant difference in sensitivity to bactericidal effect of serum or adherence to epithelial cells between ETEC strains and normal strains. The epidemiological significance of the findings is discussed.


[Incidence of intestinal disease due to Yersinia enterocolitica (author's transl)]. Enteropathogenic bacteria have been identified in 413 of 7054 patients (5.9%) with intestinal disease who were examined at the Institute of Hygiene and Microbiology, University of Würzburg (South Germany), during the period November 1975 to November 1977. Salmonella was most frequently isolated (304 cases = 4.3%), followed by Yersinia enterocolitica (102 cases = 1.5%). Cases of shigellosis (7 cases) or infections with so-called enteropathogenic serogroups of Escherichia coli (20 cases) were rarely observed. Disease due to Yersinia enterocolitica occurred in 57 male and 45 female patients. Sixty-two patients were children of less than 15 years; among them, the age-group of 1 to 3 years (31 cases) was most frequently attacked. -Mild to severe enteritis was prevalent in 84 cases. Thirteen patients developed pseudo-appendicitis or abdominal cramps without diarrhea, three of whom had appendectomies. One female patient suffered from mild diarrhea followed by fever and arthritis; in three other subjects intestinal symptoms were lacking. In the two years' period the highest incidence of salmonellosis was observed during August to October. On the other hand, most Yersinia cases occurred during September to December. At the end of the year (December 1976 and November 1977, respectively) Yersinia enterocolitica became the most important agent of bacterial enteritis. The results are discussed in view of the current Federal German Public Health Regulations.


Group B streptococci in the female genital tract and nosocomial colonization of newborns. In a long-term study, rates for group B streptococcus prevalence in the vagina and/or anus of nonpregnant women and pregnant women in the first trimester and in the second trimester were found as follows: 7.1%, 7.3% and 5.4% respectively. At delivery, positivity rates of 4.8% and 3.8% were found for mothers and newborns, respectively. Each pair of strains isolated from mother and newborn was of the same serotype. In 13.6% of newborns nosocomial colonization of the upper respiratory tract occurred during their stay in the maternity home. The sources were other positive newborns sharing the same boxes, the nosocomial spread proceeded in clusters. Detailed type-antigen analysis of isolates allowed identification of index cases and their direct contacts. Types Ib, Ic, II/R, III + Ic predominated. Sexual transmission was demonstrated by findings of identical serotypes in both partners: 23% of male partners of nonpregnant positive women and 9.1% of partners of pregnant positive women had positive urine samples. A control male group consisting of psychiatric sanatorium patients without sexual contact repeatedly exhibited a positivity rate of 2%.


[Therapeutic studies on two different models of experimental pyelonephritis (author's transl)]. By transurethral instillation of a suspension of a serum resistant E. coli strain (serotype O25:19:12), chronic pyelonephritis is induced in rats, if systemic and local defense mechanisms are impaired by estradiol application. Without hormonal treatment a similar infection can be achieved with a more virulent E. coli strain (serotype O2:1:4). Due to the chronic course of the renal infection in either model, beginning of therapy may be delayed (e.g., 10 days after infection) thus imposing difficult therapeutic conditions on the efficacy of antibiotics to be tested. Evaluation of antibiotics in both models produced differential therapeutic results. In spite of equal MIC's for the applied E. coli strains, gentamicin and particularly cefazolin treatment was less effective in the estradiol treated rats than in those without hormone application. Cefuroxime therapy produced favourable results in either model. The different therapeutic efficacy in both models is to be explained by differences in host resistance to infection. It is suggested that by simultaneans testing of antibiotics in either model, it will be possible to estimate to what extent the therapeutic efficacy of antibiotics depends on the support of intact host defense mechanisms.


R plasmids in enterobacteriaceae from the hospital environment. R plasmids have been demonstrated in several group of strains of enterobacteriaceae from hospital environment. R + enteropathogenic strains of Escherichia coli were isolated from several items of baby-care as well as from the pre-prepared baby food in a newborn unit. Strains from environmental samples are thought to be identical with those causing nosocomial gastroenteritis of babies. From hospital waste waters of another larger country hospital we could isolate R + strains of Salmonella typhimurium and R + protei, both associated with occurence of gastrointestinal or urological hospital infections. R-factor-carrying strains of E. coli have been isolated also from surface water samples from the area surrounding the hospital monitored.


Immunoglobulin type of anti-Candida albicans antibodies in candidal vaginitis. Immunoglobulin G(IgG), immunoglobulin A (IgA) and immunoglobulin M (IgM) fractions of sera from patients with candidal vaginitis were tested by the immune adherence and agglutination tests for presence of anti-Candida albicans antibodies. The anti-Candida albicans antibodies were found in the IgG and IgM fractions.


[Fenbendazole therapy of experimental larval echinococcosis. 3. The antibody titer in the indirect immunofluorescent test (author's transl)]. Echinococcus multilocularis-infected NMRI-mice treated with Fenbendazole show a lower antibody titer in the immuno-fluorescence test than the untreated controls. Between animals, which were infected with different parasite strains, also differences in the antibody titer are to be seen. The same applies to animals, which were dissected at different times p.i. as well: With increasing duration of the infection it was observed a higher titer. The mentioned differences are chiefly due to the close positive correlation between worm burden, gamma-globuline content of the serum and antibody titer.


[Evaluation of bacteriological examinations of bathing-water from lakes in Carinthia (author's transl)]. The evaluation of the bacteriological examinations relates on 2330 water-samples, which were taken from 76 bathing-places of 23 Carinthian lakes in the course of 11 years. The examinations were performed for the purpose of hygienic control. After a short supervision on the methods of examination and of sampling the base of judgement is discussed. A relation to the limnological classification of the lakes could be made from the hygienic point of view. In bathing lakes in the alpine region the experiences proved a lower border-value for the indicators of fecal-charge more from the reason of lake-protection than from the reason of protection of the human health. A proposal for the judgement of bathing-water from lakes is made, including the significance of enterococci, and a scheme for recording the results is given.


[State of systemic and cerebral hemodynamics in patients with transient cerebral circulatory disorders]. In 50 patients with transient disorders of cerebral circulation due to hypertensive disease (27 cases), and combinations of hypertensive disease with atherosclerosis (23 cases) the authors by means of diluting Ewans blue stain (T-1824) studied the indices of general hemodynamics compared to that of REG data . For control purposes 10 patients with hypertensive disease in concomitance with atherosclerosis without transient disorders of cerebral circulation and 20 normals were studied. The study permitted to detect signs of disturbed general and cerebral hemodynamics which were most expressed in patients with severe cerebro-vascular crises, accompanied by a drop in the cardiac and pulse index, an increase of the general and specific peripheral resistance, a slowing of the blood flow rate on the segment hand-ear, an increase of the tone and drop of elasticity in the cerebral vessels, a decrease of cerebral blood repletion. Insufficiency of general hemodynamics leads to disorders of cerebral hemodynamics and unfavourably influences the development of the disease and the outcome of cerebrovascular crises.


Fluorimetric characterization and influence of Cu2+ binding on the fluorescence of inorganic pyrophosphatase from baker's yeast. The denaturation characteristics of inorganic pyrophosphatase from baker's yeast and the interaction with Cu2+ were investigated with fluorimetric methods. The position of the fluorescence emission spectrum with a maximum at 328 nm together with a quantum yield of 0.12 led to the conclusion that most of the tryptophan residues of the protein are buried in nonpolar inner regions of the molecule. The contribution of the tyrosine residues to the fluorescence of pyrophosphatase is only about 7%. Denaturation of the protein with denaturants or changes of the pH value cause a red shift of the fluorescence emission maximum. In the presence of Cu2+ ions a fluorescence quenching is observed. Thereby, a specific binding of one Cu2+ per subunit may be distinguished from further unspecific Cu2+ binding. The Cu2+ binding to the latter sites shows a time dependence according to a slow, reversible exposure of additional binding sites. This time dependent binding characteristics was also verified by following the free Cu2+ concentration with the fluorescent "metal indicator" epsilon-ADP.


Correlation of islet size and biochemical parameters of isolated islets of Langerhans of rats. [3H]-Leucine incorporation, insulin secretion, insulin content and DNA content of isolated islets of Langerhans of rats were determined. All these parameters are linearly correlated with the cross-sectional area of the isolated islets measured by means of an ocular micrometer.


The donor kidney: I. Morphology of adequate preservation. The structure of the dog kidney can be preserved in hypothermic intracellular-type solutions, but after 6 hours the appearance of pathologic focal changes such as mild oedema, lesions of the cellular elements, podocyte heteromorphism, vacuolization, disintegration of the basal membrane and of the cytomembrane structrues and even cell degeneration, is unavoidable.


The donor kidney: II. Structural and functional changes in the actue reperfusion period. Acute reperfusion of the dog kidney preserved under conditions of hypothermia reveals the structural changes suffered during preservation which have functional (reduced microcirculation, pathologic proteinuria) and structural (interstitial oedema, glomerular and tubular disintegration) consequences.


[Multiple primary brain tumors].

[Multiple primary brain tumors]. This is a write-up of 32 studies of patients suffering from multiple primary brain tumours. Such tumours are encountered quite rarely. Meningiomas, as well as their combination with tumours of another histological structure (neurinomas, gliomas) were most often studied among multiple primary brain tumours. Multiple gliomas occur even more rarely; they may be of a varying degree of malignancy and different in histological structure. Questions of histological structure, the peculiar features of the clinical picture, diagnosis and surgical treatment of patients with this pathology are discussed. A very rare case of multiple primary sarcomas of the brain is described.


The donor kidney: III. Angio-architecture and function of the reimplanted kidney. In the autogenous kidney preserved under conditions of hypothermia the development of a partial no-reflow phenomenon is unavoidable after reimplantation. The phenomenon is ascribed to ischaemic lesions induced by preservation. The consequences are functional disorders in the acute period (temporarily pathologic angiogram, nephrogram and proteinuria) and scars due to chronic focal necrosis. These unavoidable changes of the current preservation procedures are mostly of subclinical importance.


Concentrated or diluted heparin prophylaxis of postoperative deep venous thrombosis. A concentrated and a diluted heparin solution (Vitrum AB) have been evaluated in a controlled blind study, using a standard dosage of 5 000 IU, given every 12 hours subcutaneously. 167 patients undergoing abdominal surgery were randomized into three groups: 63 received diluted heparin 5 000 IU/ml, 43 received concentrated heparin 25 000 IU/ml and 61 patients served as controls. 80 per cent of the patients suffered from malignant disease. Deep venous thrombosis (DVT), diagnosed with the 125I-fibrinogen method, was found in 16% of the patients receiving diluted heparin, in 23% of those receiving concentrated heparin and in 33% of the controls. To evaluate the amount injected, an in vitro experiment was performed in which the intended dose was 5 000 IU. The measured amount of the concentrated heparin solution was significantly less than 5 000 IU. It is concluded that the frequency of DVT after gastrointestinal operations can be reduced significantly (in the present study from 33 to 16%) by administering diluted calcium heparin every 12 hours for 6--8 days. The concentrated heparin solution did not significantly reduce postoperative DVT, possibly on account of variations in the dosage. Diluted heparin prophylaxis can be achieved without serious side effects.


A comparison between subcutaneous low-dose sodium and calcium heparin. Prophylaxis of postoperative deep vein thrombosis and side effects of treatment. A controlled, randomized, prospective double-blind trial between subcutaneous low-dose sodium- and calcium-heparin was made. Heparin Vitrum was used. The only difference between the two heparins was the sodium or calcium ions. Postoperative thrombosis frequency, bleeding complications, and local reaction were analysed. For evaluation of local haematoma formation, 125I-fibrinogen uptake was measured over the injection sites. The only statistically significant difference between the two heparins was a larger haematoma formation at heparin injection sites when calcium heparin was used. Otherwise sodium- and calcium-heparin are equal in effect and side effects provided they come from the same heparin source.


Transthoracic suturing of bleeding esophageal varices without esophagotomy. Preliminary report. Suturing of bleeding esophageal varices by transthoracic esophagotomy is frequently followed by leakage in the suture line. To avoid this complication we suggest transesophageal suturing without esophagotomy. The technique was evaluated in five normal pigs and applied to two patients with bleeding esophageal varices. Esophagus both in the pigs and the patients tolerated the procedure well and the bleeding from the esophageal varices stopped. We suggest application of this procedure for bleeding esophageal varices instead of emergency portocaval shunt operation.


Phase contrast visualization of squamous cell microridges. A successful attempt has been made to identify microridges on squamous cells in routine smears using phase contrast microscopy. Microridges may be identified on mature cells of buccal mucosa and in cervical smears, either alcohol or spray fixed, and even in smears up to five years old. The features identified with phase contrast may also be observed with scanning electron microscopy. Identification of microridges may be of diagnostic interest in the evaluation of cervical smears.


Cellular content of the normal rabbit pleural space. The cellular content of the pleural space of five normal rabbits was studied by three cytopreparative techniques using different methods of collection (aspiration, irrigation) and fixation (95% ethyl alcohol, 50% alcohol: 1% polyethylene glycol). The method using aspiration, 95% ethyl alcohol fixation, and the Papanicolaou stain was simple and provided the best cytologic detail. With this method 70.1% of pleural fluid cells were monocytic, 7.5% were monocytic with morphologic features typical of macrophages, 10.5% were lymphocytes, 8.9% were mesothelial cells and 1.9% were polymorphonuclear leukocytes. Other methods were technically more difficult and provided less cytologic detail. The cellular content of the normal rabbit pleural space is described, providing baseline information for the study of experimental pleural disease.


Discrimination between human T and B lymphocytes by computer analysis of digitized data from scanning microphotometry. II. Discrimination and automated classification. Human B and T lymphocytes were purified and stained according to the Feulgen procedure. Stained preparations were scanned on a microphotometer and the digitized images were processed by analytical programs on a computer. Features of the cells relating to the chromatin distribution were extracted. Computer algorithms automatically derive classification rules and a machine recognition of B cells and T cells results in better than 80% correct assignments. The image data reveal a rich feature structure within both the purified B and T cell populations. Each population appears to contain several subpopulations of cells with distinctive and different chromatin texture.


Clonidine in the prophylaxis of migraine. The prophylactic effect of clonidine in a dosage of 0.05 mg twice daily was investigated in 49 patients using a double-blind, crossover trial carried out in four Departments of Neurology. Seventy-one patients were originally included but 22 patients withdrew, two of them due to side effects,the remainder because of inability to keep the requisite diary, lack of drug compliance or refusal to attend the checkups. Approximately equal numbers withdrew during the clonidine and placebo periods. There was no statistically significant difference between the number of migraine attacks or between the number of severe attacks (8 hours' duration or more) during the placebo and clonidine periods. This also applied to the patients with foodstuff-provoked migraine attacks. Sixty-three patients carried through a double-blind, crossover trial with capsules containing either 125 mg tyramine or placebo. There was no significant difference between the number of patients who developed attacks after the ingestion of placebo and the number who did so after the ingestion of tyramine. The same is true of the group with foodstuff-provoked migraine. As a rule side effects were few and mild. This study has not confirmed that clonidine has any pharmacological effect in prophylaxis of migraine.


Intracranial malignant lymphomas. A morphologic and immunocytologic study of twenty cases. Fifteen primary intracranial reticulum cell sarcomas and five cases with an additional solitary extracranial tumor mass have been studied. For comparison, seven extracranial malignant non-Hodgkin lymphomas and normal lymphoid tissue were included. The methods used on formalin-fixed paraffin-embedded tissue sections were an immunoperoxidase technique for the demonstration of intracellular immunoglobulins, microglial staining, Gomori's reticulin, methylgreen-pyronin, Giemsa, diastase resistant PAS, Mallory's PTAH and H&E. Electron microscopy was performed in one primary brain tumor. According to histopathologic criteria all tumors could be classified as malignant non-Hodgkin lymphomas, predominantly of the pleomorphic immunocytic or of the immunoblastic type; follicular lymphomas were notably absent. In all cases intracellular immunoglobulins were demonstrable in tumor cells and in a majority of the tumors these were monoclonal. Thus, all malignant lymphomas proved to be of B cell origin with demonstrable cytoplasmic immunoglobulin production. Based on the microglial staining more than half of the malignant lymphomas could also be classified as microgliomas. As a comparable staining was present in non-Hodgkin lymphomas outside the CNS, microglioma characteristics are not associated with intracranial growth.


A specific immunofluorescence technique for the demonstration of vasogenic brain edema in paraffin embedded material. Serum proteins as constituents of vasogenic brain edema were visualized both macroscopically and microscopically applying a double layer immunofluorescence technique to paraffin embedded material derived from three experimental series: peritumorous edema following xeno-transplantation of glioma cells, edema after cerebral embolization with micropheres, and edema after unilateral MCA occlusion. Exclusively cats were used as experimental animals. The staining procedures resulted in selective green fluorescence of vessel contents as well as edema protein, which was demonstrable even macroscopically at times, where edema formation reaches a maximum in each experimental series. Microscopically, serum protein could be traced up to the end of observation time ranging from 1 to 4 weeks, where the specific fluorescence was related to cellular structures. As compared to other techniques employed in brain edema localization, immunostaining mainly offers the following advantages: avoidance of in vivo tracing, better structural resolution in paraffin than in freeze sections, high specificity and sensitivity in antigen localization.


Monitoring corneal wound strength non-invasively. Intensity of light scattered from 24 healing rabbit corneal incisions progressively increased during six weeks following the operation. After the first week, the mean value for scattered light intensity from the wounds was highly correlated with wound tensile strength measured in another group of rabbits. The correlation coefficient was 0.95 at the 0.05 confidence level. It is hoped that a simple and reliable method of measuring scattered light intensity may provide a non-invasive tool for assessing the strength of a corneal wound in the future.


Reconstruction of a tuberculous thumb by free bone grafting. A case report. Tuberculosis with secondary staphylococcal infection destroyed the right thumb and index phalanges of a 24-year-old farmer. Four months after starting antibiotic therapy the index finger was amputated, and the thumb reconstructed by excising the disorganized phalanges and transferring the index metacarpal as a free graft to replace them. No previous report of this technique has been traced. A concurrent infection of the patient's left tarsus was treated by triple arthrodesis.


A recovered case of generalized BCG infection. A female infant was at the age of 8 months admitted with muco-cutaneous candidiasis. The applied therapy was inefficacious. Subsequent examinations pointed to a combined humoral and cellular immunopathy. At the age of 7 years the patient was readmitted with abdominal complaints. Diagnostic laparotomy revealed a tuberculous mesenterial growth. The isolated agent proved to be a BCG strain. Antituberculous therapy was beneficial, the tumour dissappeared and full recovery was attained. The mycotic process remained unchanged and still needs continuous treatment.


Immunohistochemical observation of lysozyme in macrophages and giant cells in human granulomas. Lysozyme activity of macrophages and giant cells in various human granulomas were examined with immunoperoxidase bridge method in tissue sections. Various numbers of epithelioid cells and giant cells of epithelioid cell granulomas of tuberculosis, sarcoidosis and Crohn's disease exhibited intense granular cytoplasmic lysozyme activity. Foreign body granulomas induced with various substances showed negative or faintly positive lysozyme stain. Macrophages and giant cells of aspergillus granuloma associated with thymus hypoplasia and T-cell depression contained no lysozyme. The results suggest that cell-mediated immunology plays an important role for the lysozyme synthesis of macrophages in granuloma.


Immunohistochemical observation of lysozyme in macrophages in leprosy. Lysozyme activities of skin granulomas of 24 patients in leprosy were studied. Lepra cells of all 15 lepromatous leprosy showed strong lysozyme activity in cytoplasma. In the specimens stained with lysozyme and Ziehl-Neelsen's carbolfuchsin double stain conspicuous lysozyme activity around M. leprae were observed. One borderline case was negative. Lysozyme of epithelioid cells and giant cells of 10 tuberculoid types were completely negative. These results suggest that lysozyme plays only a small role in the disposal of M. leprae in macrophages and other mechanisms than bacteriolytic function of lysozyme are responsible for the defence against these bacilli.


Bovine serum albumin (BSA) nephritis in rats. I. Experimental model. Proliferative glomerulonephritis with proteinuria was induced in Wistar rats by bovine serum albumin (BSA). Rats were first immunized with 1 mg or 2.5 mg of BSA and complete Freund's adjuvant (CFA) and eight weeks later 1 mg of BSA were given intravenously six times a week for four weeks. Immunofluorescence revealed granular deposits of IgG, C3, and BSA in the mesangial area with or without deposition of the same components along the capillary wall. Evaluation of the circulating antibody disclosed an apparent correlation between the level of antibody and histological findings. Rats with an intermediate amount of antibody production developed mesangial widening with mesangial immune deposits and no proteinuria. Rats with a low response developed proliferative glomerulonephritis with immune deposits along the capillary wall as well as in the mesangial area and proteinuria.


Effect of food, food constituents and fluid volume on the bioavailability of sotalol. The effect of food, some food constituents, and large volumes of fluid taken with the drug on the relative bioavailability of sotalol has been examined in five healthy volunteers. Each subject received an oral 160 mg dose in six different experimental schedules. Venous blood samples were drawn 1, 2, 3, 4, 6 and 8 hrs after the dosing, and sotalol concentrations in serum were determined fluorometrically. The results indicate that large volumes of fluid delay but do not affect the extent of sotalol absorption. Food, especially milk, decreases the bioavailability of the drug and an interaction with calcium seems to be the major reason for the reduced absorption.


Method and programme for compartment analysis of exogenously introduced indicator substance. The concept of the compartment structure of body fluids gives possibilities for finding the values of physiological characteristics such as volume of distribution, transport rate, kidney and intercompartment clearance. Their determination is made indirectly and it is based on the solution of a system of differential equations describing the behaviour of an open two-compartment system when an indicator substance is introduced. The determination of the coefficients of the equations involves a number of difficulties leading to inaccurate results due to the use of graphic-analytical methods. It is proposed to avoid this shortcoming by applying multiple approximation of the function describing the change in time of the concentration of the indicator substance in the intravasal space by a sum of two exponents, which corresponds to the system of differential equations. The approximation is performed by the least squares method, the precision criterion being the mean quadratic error of the approximation. An algorithm for which a computer programme is elaborated is proposed.


Laryngeal secretions. An immunochemical and immunohistological study. This study was designed to investigate properties of laryngeal secretion and secretory activity of IgA in the larynx. Laryngeal secretions were collected by adsorption method on filter paper during laryngomicrosurgery from 20 patients having an inflammatory lesion in the larynx. Contents of IgG, IgA, IgE, secretory component (SC), and lactoferrin in the laryngeal secretions were determined and compared with results of those in nasal secretions, tracheobronchial washings, and serum samples obtained from the same subjects. The laryngeal mucosae of 8 laryngectomized materials for cancer lesion were subjected to immunofluorescence studies including the cytoplasmic SC affinity test. Results of this study indicate that laryngeal secretions are characterized by exocrine secretion, resembling nasal and tracheobronchial secretions in the electrophoretic pattern and immunoglobulins content. The immunofluorescence studies and SC affinity test found that the larynx possesses secretory activity of IgA, particularly in the ventricle and subglottis.


Subjective effects and vigilance after diazepam and oxazepam in normal subjects. Twenty-two normal subjects were given single oral doses of diazepam 5 mg, oxazepam 15 mg and placebo in a double-blind cross-over trial. Subjective effects according to a rating scale and performance on a vigilance task were assessed. The results showed a difference between each of the two drugs and placebo, but none between the drugs, with regard to the vigilance test. The results from the rating of subjective effects showed an increase in "tiredness" for both drugs, and a decreased "well-being" for oxazepam.


The clinical pharmacology of oxazepam.

The clinical pharmacology of oxazepam. The benzodiazepines have been available now for about 15 years but new aspects of their actions are being elucidated all the time. Oxazepam has a short half-life and inactive metabolites and therefore differs from most other benzodiazepines. Some aspects of its clinical pharmacology are reviewed in outline. Firstly, the effects of the drug on psychological functioning is discussed. Next, the controversy regarding benzodiazepines and aggression is examined. Oxazepam appears exceptional here in that it is not associated with paradoxical release of aggression in patients. Finally, the ethical implications of the widespread use of these drugs is commented on, and the problem of dependence, physical and psychological, discussed. It appears that oxazepam is less likely than other benzodiazepines to induce dependence.


Biochemical and pharmacological properties of oxazepam. Oxazepam is the final metabolic product in vitro and in vivo of a large number of pharmacologically active benzodiazepines. Oxazepam shows antimetrazol activity varying in intensity and duration according to the animal species considered. This difference is in part related to different "sensitivity" and in part due to different disposition of oxazepam. Particularly relevant is the difference in biliary excretion by various animal species. Oxazepam is currently available as a racemate but two optical isomers can be separated as succinate half esters. The (+) form appears to be more active than the (-) form, probably because more oxazepam is released from the (+) than the (-) isomer in vivo. In vitro studies confirm that the liver hydrolyzes the (+) oxazepam succinate half ester more than the (-) form. Other work has aimed at analyzing the effects of oxazepam on brain chemical mediators, with particular reference to the cholinergic system. Finally it is shown that oxazepam, similarly to other benzodiazepines, increased aggressiveness in male mice during chronic treatment.


The clinical activity of oxazepam.

The clinical activity of oxazepam. Over the years, oxazepam has distinguished itself clinically from other benzodiazepines by virtue of its excellent tolerance. Recent research suggests that this is due to metabolic and pharmacokinetic differences rather than an intrinsically more favourable toxic-to-therapeutic dosage ratio. Because of its excellent tolerance, dosage is very flexible, and it is, therefore, possible to utilize oxazepam in a wide spectrum of anxiety-related disorders including the psychoses. The use of oxazepam in anxiety neurosis, depressive neurosis, psychotic disorders, alcoholism, and insomnia is discussed.


"Non-secretory" plasma cell dyscrasia with normal serum immunoglobulins. A well documented case of non-secretory myelomatosis with extensive skeletal lesions has been studied by immunohistologic techniques, electron microscopy, various electrophoretic procedures and different studies of serum and urine. In addition, the various lymphocyte populations have been studied by immunofluorescent techniques, rosette formation and stimulation with PHA and PWM mitogens. The ultrastructural studies revealed a well preserved structure of most of the plasma cells, often with a prominent nucleolus. The Golgi apparatus (GOL) was often large and in some cells there appeared to be a striking development of non-granular (smooth) endoplasmic reticulum in association with the GOL. Various non-crystalline inclusions were seen outside the cisternae of the endoplasmic reticulum. The cells contained large amounts of immunoglobulins of the IgG (kappa) class. No paraprotein was present in serum. Normal amounts of serum immunoglobulins were detected. No abnormalities could be demonstrated in the B or T cell system. It is concluded that the defect must be localized to the plasma cells themselves and not to the precursor cells of the B system.


Lymphoma of the small intestine in adult coeliac disease. Five out of 74 patients with adult coeliac disease (ACD) diagnosed from 1965 through 1977 developed intestinal lymphoma. The age at diagnosis of ACD was 54-63 years (mean 58) and in all patients an initial improvement was noted on a gluten-free diet. The interval between the diagnoses of ACD and lymphoma was 0.5-6 years (mean 3). In 4 patients the diagnosis of lymphoma was preceded by relapse of diarrhoea and loss of weight despite an adequate diet; 2 patients developed perforation of the bowel. In all patients who subsequently developed lymphoma a pronounced lymphocytopenia, 0.4-1.3 X 10(9)/l, was found at the diagnosis of ACD. It is suggested that ACD patients over 40 who have relapse of malabsorption symptoms despite an adequate diet should be investigated for the presence of an intestinal lymphoma. The suspicion of a malignant transformation may be especially strong if a previous, pronounced lymphocytopenia has been recorded. Three patients died 1-12 months after the diagnosis of lymphoma. However, 2 patients are in good condition 14 and 20 months, respectively, after laparotomy and removal of the tumour, indicating that an early diagnosis and treatment may have a reasonably palliative effect in some cases.


Lymphocyte subpopulations in chronic lymphocytic leukemia (CLL). Relation to the activity of the disease. The blood lymphocytosis in CLL is caused mainly by a rise of immunoglobulin (Ig)-bearing leukemic lymphocytes. Most cells carry Fc-receptors, while the percentage with receptors for human complement is very low with the present technique. The leukemic lymphocytes carry only one of the light chain types, which suggests a monoclonal origin. CLL patients with lymphocytes expressing kappa light chains may have a more benign disease than lambda-CLL. T-lymphocyte levels are high during the early course of the disease but decrease with its progression and are low in patients with "active" disease.


Effect of amiodarone in the Wolff-Parkinson-White syndrome. A clinical and electrophysiological study. Six patients with Wolff-Parkinson-White (WPW) syndrome were given long-term treatment with amiodarone. Symptomatic relief was obtained in all. Tolerance to the drug was good. Reversible corneal changes appeared after some weeks' treatment in five patients. No thyroid side-effects were noticed. Prior to treatment, dual atrioventricular (AV) conduction was demonstrated on His bundle electrograms in all six patients. Recordings were made at varied heart rates, using atrial and ventricular pacing. Reciprocating tachycardia was readily provoked by properly timed extra stimuli in all patients. When amiodarone treatment had become clinically effective, a second comparative study was made in four patients after 26--85 days' treatment. Amiodarone reduced heart rate and second degree AV block appeared at a lower atrial pacing rate. It increased the refractory periods of right atrium, AV node, and the accessory pathway in proportion to the duration of treatment. Induction of tachycardia was effectively prevented by the drug. It appears that amiodarone in chronic treatment has a predictable and unique depressant action on cardiac conduction, supporting the opinion that this compound, despite side-effects, has an important role to play in the treatment of refractory arrhythmias in patients with the WPW syndrome.


Effect of oral verapamil on ventricular irregularity in long-standing atrial fibrillation. In patients with chronic atrial fibrillation (AF), symptoms and cardiac function may be improved by regularizing the ventricular rhythm, even though the AF persists. This study concerned effects of i.v. and oral verapamil (V) on ventricular regularity. A regularizing effect was observed in 5 out of 10 patients after 0.15 mg of V/kg b.wt.i.v., but in only one patient after 80 mg of V By mouth. V in a dose of 240 mg by mouth resulted in ventricular regularity in 6 out of 10 other patients, 320 mg in a further 2 and 400 mg in the remaining 2 patients. Six patients were given chronic oral therapy in progressively increasing doses. Although ventricular regularity and symptom relief were obtained, intolerable side-effects precluded the evaluation of subjective long-term effects of this therapy in all but one patient. Further investigations, particularly concerning the pharmacokinetic mechanisms of V, are needed before the treatment can be recommended for patients with chronic AF.


Evaluation of quinidine Lipettes -- a sustained release preparation. A new sustained release preparation (Lipettes) of quinidine has been evaluated with regard to dissolution, absorption, serum concentration and side-effects. The serum levels of quinidine after single oral doses and after long-term treatment have been compared with the serum levels after administration of some other quinidine preparations on the Swedish market. The side-effects of the sustained release preparations have also been studied. Results indicated that this new sustained release quinidine preparation yields more even serum concentrations of quinidine and seemed to cause less troublesome side-effects than the marketed preparations.


Long-term clinical experience with atenolol--a new selective beta-1-blocker with few side-effects from the central nervous system. During the last four years we have used a new cardioselective beta-adrenergic blocking substance, ICI 66.082 (atenolol or Tenormin), alone or in combination with other drugs for treatment of hypertension in a total of 104 patients, including 15 with a chronic obstructive lung disease. Fifty-one patients started treatment with atenolol because of side-effects--especially from the central nervous system--during previous treatment with non-selective beta-blockers, mostly propranolol (Inderal). Mean duration of treatment was 16 months (range 8--36) and mean dosage 163 mg/day. In 18 patients treatment with Tenormin was withdrawn, but only in 10 of them could this be referred to side-effects. Of the 51 patients who complained of or showed side-effects from another beta-blocker, 80% were improved after changing to Tenormin. Of the patients with side-effects from the central nervous system, 73% improved, especially those who complained of nightmares, hallucinations, insomnia or mild depression.


Treatment of refractory anemias with methenolone. A therapeutic trial with methenolone (Primobolan) in 19 consecutive patients with different types of refractory anemia is reported. The remission frequencies were: pancytopenia 3/6, bicytopenia 2/4, refractory anemia with hyperplastic marrow 1/5, myelofibrosis 1/4. There was no obvious prolongation of survival in the patients responding. Side-effects were negligible.


Detection of hepatitis B surface antigen in isolated hepatocytes. HBsAg was detected by indirect immunofluorescent method in liver biopsy specimens of 60 symptom-free HBsAg positive volunteers. An effort was made to separate from the material intact cells suitable for studying HBsAg localization in the liver cells.


Epidemiology of the inherited ataxias.

Epidemiology of the inherited ataxias. Current epidemiologic studies of the inherited ataxias are limited by complex and confusing systems of nomenclature and by the lack of minimal diagnostic criteria. Despite the difficulties of comparing one study to another, most descriptive investigations provide a prevalence estimate of less than 6 cases/100,000. In isolated, inbred populations, a prevalence as high as 23 cases/100,000 has been reported. Neuroepidemiologic techniques and current knowledge concerning the epidemiology of the inherited ataxias can be applied to future studies in three broad areas--definition, classification, and etiology. Future etiologic investigations based on a goal-oriented, collaborative effort following a case-control format offer the greatest likelihood of success.


Cross finger flaps.

Cross finger flaps. Proper fingertip reconstruction requires good skin and soft tissue coverage, preservation of function and as normal an appearance as possible. The cross finger flap results in negligible joint stiffness, minimal morbidity and little work-time loss. An important factor is the conservation of finger length permitted by this technique. This method of repair is underutilized. It is indicated in several types of fingertip amputations where bone shortening would be detrimental.


Pharmacological aspects of immune reactions. "Immunopharmacology" evolved as a field of research in its own right when it was appreciated that pharmacological methods can contribute to the understanding of immune mechanisms on the one hand or can be used to influence or even control immune reactions at all stages and levels. The best studied subjects of immunopharmacology are release and effects of the chemical mediator substances which are responsible for the reactions of effector cells thus causing the clinical symptoms in allergic or inflammatory diseases. In the type I allergic (anaphylactic) reactions the primary target cells are tissue mast cells or basophil granulocytes which discharge their granular contents upon interaction of immunoglobulin E fixed to their surface with the specific antigen or--in the anaphylactoid reaction--upon stimulation with an appropriate chemical substance (so-called histamine-liberator). In both cases the stimulus leads to an influx or intracellular shift from one compartment to another of calcium ions, which in turn trigger membrane fusion and degranulation. This process can vary from a physiological secretion (in the case of IgE-antigen-interaction) to a pathological cytolysis (in the case of high concentrations of activated complement components or other chemical histamine releasers). As long as it is secretory it is subject to vegetative and hormonal modulation and regulation, mainly by catecholamines and other substances which increase cellular cAMP levels or inhibit calcium fluxes. Although cholinergic stimuli under certain circumstances induce mast cell degranulation and histamine release no definite role has yet been established for cholinergic mechanisms in type I allergies. Type II (Cytotoxic) and type III (immune complex mediated) allergies share the complement requirement. As far as mast cells and basophils are involved in such reactions their sensitivity towards pharmacological modulators is comparable to reactions induced by chemical histamine releasers. Otherwise these types of allergic reactions are dominated by phenomena of general inflammation. In those mainly cytotoxic effects of lipases and hydrolases are involved. cAMP active agents have, therefore, only limited modulating effects and steroid hormones are more effective in inhibiting the acute lesions in type II and III allergies. Only during the last decade the involvement of chemical mediators in type IV (cellular immunity) allergic reactions has been appreciated. 26 different factors called lymphokines have been discovered and classified as mediators of cellular immune reactions. However, rather little is yet known about their chemical nature and about the influence of drugs on their production or action.


Sustained effect of orally administered isosorbide dinitrate on exercise performance of patients with angina pectoris. The efficacy of oral isosorbide dinitrate was evaluated in nine hospitalized patients with chronic angina pectoris and positive maximal bicycle exercise tests. Patients were randomized double-blind to receive either 20 mg of isosorbide dinitrate or placebo on successive days after a control maximal upright bicycle exercise test. On each day hourly exercise tests were performed for 4 hours after drug administration to an end point of fatigue or angina pectoris. Mean systolic blood pressure 4 hours after the administration of isosorbide dinitrate was 25 mm Hg less than the control value (P less than 0.001). The values for resting heart rate and exercise-attained heart rate-blood pressure product were not significantly different from the values after placebo. The duration of exercise was prolonged (P less than 0.025) for at least 3 hours, and less ST depression (P less than 0.01) was observed up to 3 hours after the administration of isosorbide dinitrate compared with control values. The demonstration of sustained imporved exercise performance and previously described hemodynamic effects with the use of higher doses suggests that adequate blood levels of isosorbide dinitrate or mononitrate metabolites may be important for the efficacy of oral organic nitrates.


Developmental correlation between hypothalamic gonadotropin-releasing hormone and hypophysial luteinizing hormone. Considerable evidence indicates that the pituitary-gonadal axis is active in the fetus, but little is known about the relative times in development when the brain begins to secrete gonadotropin-releasing hormone (GnRH) and the hypophysis begins to secrete gonadotropin. The objective was to correlate the time of appearance of GnRH in the median eminence and organum vasculosum of the lamina terminalis (OVLT) with differentiation of LH-gonadotropes in the hypophysis of the fetal mouse by means of immunocytochemistry. Mice were studied at 15, 16, 17 and 19 days of gestation with the peroxidase-antiperoxidase (PAP) method of Sternberger, GnRH was first detected at 17 days of gestation in presumptive axons and axon terminals located adjacent to the superficial portal capillaries near the surface of the median eminence and close to the capillaries of the OVLT. LH-gonadotropes also were found initially at 17 days of gestation. They were prominent in the ventral half of the pars distalis. Most of these cells were ovoid or slightly angular, and almost all abutted one of the numerous sinusoidal capillaries present at this age in development. The number and staining intensity of both LH-gonadotropes and GnRH foci increased by 19 days. The close temporal relationship between the developmental appearance of GnRH and its target cell, the gonadotrope, provides further evidence that the potential for neuroendocrine control of gonadotropin secretion exists in the fetal mouse as early as 17 days of gestation.


Introduction to mechanisms of association of indigenous microbes. Indigenous microorganisms of numerous types associate with epithelial surfaces in the gastrointestinal tracts of mammals and birds. Some of the microbial types, e.g., Lactobacillus sp. in the stomachs of laboratory rodents, adhere to a surface without altering it ultrastructurely. In such cases, the adherence is mediated undoubtedly by macromolecules on the bacterial surfaces, possibly polysaccharides in most cases, interacting in specific ways with receptor macromolecules on the epithelial surface. Other microbial types that associate with epithelial surfaces without altering them ultrastructurally, e.g., Clostridium 109-2 in the mouse large bowel, may adhere to the surface only weakly or not at all, and maintain the association because they are motile and attracted to the epithelium by chemotactic substances. Microbial types that alter the ultrastructure of the epithelial cells to which they attach interact intimately with the membranes of the epithelial cells. In such cases, the microbes have specialized segments or ends for adhering to the membranes, and probably elaborate systems for stabilizing the membranes and cytoplasm at the site in the epithelial cell to which they attach. Some such organisms may have evolved unique reproductive mechanisms to maintain their populations on the epithelial surface.


Lectins as probes in studies of intestinal glycoproteins and glycolipids. The abilities of lectins to combine specifically with particular carbohydrate residues have made them valuable probes in the analysis of the surface components of intestinal epithelial cells. Fluorescence microscopy studies using FITC-labeled lectins have shown that the surfaces of these cells change as the cells move up the villi and that these changes are dependent upon the region of intestine in which the villi are located. The lectins have been used in radioassays developed to quantitate these cell surface components and have proven useful in monitoring the extraction and purification of these substances. Lectin affinity columns have been successfully used to isolate some of these components. Although lectins offer the advantage of specific recognition of relatively small defined carbohydrate units on complex molecules, they have the limitation of not being able to distinguish among different molecules bearing the same carbohydrate units. It is thus necessary to use the lectins in conjunction with other tools as one proceeds further in the analysis of the complex carbohydrates that constitute the cell surface.


Evidence of a role for permeability factors in the pathogenesis of salmonellosis. Two clinical isolates of Salmonella typhimurium were shown to produce two skin permeability factors. One factor was heat stable and rapid in onset while the other was heat labile and elicited maximal induration by 18 to 24 hr. The rapid, erythematous permeability factor (PF) response could not be prevented by antisera to cholera toxin or Salmonella antisomatic serum, but it could be simulated by high concentrations of lipopolysaccharide from S. typhimurium. The appearance of the delayed PF reaction was indistinguishable from that of purified cholera toxin. Histological comparisons of rabbit skin injected with Salmonella-delayed PF and cholera toxin revealed that both toxins resulted in gross edema and infiltration of polymorphonuclear leukocytes after 18 hr. The Salmonella-delayed PF was shown to be resistant to a variety of enzymes, sensitive to extremes in pH, and had an isoelectric point of pH 4.8. Unlike Salmonella lipopolysaccharide skin activity, the Salmonella-delayed PF was destroyed at 100 C and was neutralized by monospecific cholera antitoxin. The Salmonella-delayed PF, which shares antigenic determinants with cholera toxin, appears to be elaborated by living S. typhimurium cells in the rabbit ligated intestine, since rabbits immunized with procholeragenoid were protected against fluid loss from live cell challenge. Finally, production of the rapid PF is a stable genetic trait, while delayed PF production is apparently an unstable characteristic among the salmonellae.


Diarrhea and colitis associated with antimicrobial therapy in man and animals. Antimicrobial agent-induced ileocecitis of laboratory animals and colitis of man share common features. The significance of a newly described toxin in these two entities, the apparent source of the toxin (Clostridium difficile) and characteristics of the toxin are reviewed. Methods of toxin detection, isolation and rapid identification of C. difficile, and possible modes of therapy for antimicrobial agent-associated colitis of man are discussed.