[Sensitivity of different strains of the causative agent of plague to disinfectants].

Various strains of the plague microbe was found to have statistically significant differences in their sensitivity to phenol, formaldehyde and chloramine. These differences did not correlate with the origin, virulence and nutritional requirements of the plague strains. The sensitivity of the plague microbe to formaldehyde and phenol was found to be related to the permeability of its cell wall.


[Gastrointestinal tract microflora in nonspecific ulcerative colitis].

The species and quantitative composition of the normal and conditionally pathogenic microflora of the stomach, the proximal portion of the small intestine, in material obtained by biopsy from the mucosa of this portion, and in feces was studied in 10 patients with non-specific ulcerative colitis. The study was made before and after treatment. Before treatment in most of the patients gastric juice and the proximal portion of the small intestine were found to be greatly contaminated with microflora commonly present in feces, and in fecal microflora sharp dysbiotic changes were observed. As a result of treatment the microflora was essentially normalized (with the exception of Proteus and bifidobacteria).


[Time of formation of traumatic intracranial hematomas].

Biochemical study of the methemoglobin concentration (60 cases) and histological examination (40 of intracranial hematomas removed in different periods after the trauma confirmed the assumption that the main volume of these hematomas forms within the first minutes and hours after the trauma as a rule. The curve of the dependence of the methemoglobin concentration in the hematoma on the time of its formation allows the period of time which had elapsed after the trauma to be determined.


[Nature and outcomes of craniocerebral injury in a fall from a height].

The case records of 1,137 patients with trauma suffered as the result of a fall from a height were studied, 399 of them (35.1%) had a craniocerebral trauma. Isolated traumas with injury to the cranial bones and brain accounted for 74.4% of cases, multiple injuries (injuries to the cranial bones, brain, and facial skeleton) for 0.8%, and combined injuries (injuries (injuries to the skull, brain, weight-bearing and motor apparatus, and internal organs) for 24.8%. Severe craniocerebral trauma was encountered in 34.9% of the injured, trauma of moderate severity in 24.3%, and mild craniocerebral trauma in 40.8% of the injured. Death from a craniocerebral trauma suffered in a fall from a height occurred at the site of the accident in 17.2% of cases and in later periods at the hospital in 12.7% of cases.


[Potentials of hyperbaric oxygenation in correcting central respiratory disorders in ischemic stroke].

Changes in central respiratory disorders under the effect of hyperbaric oxygenation (HBO) were studied in 29 patients in the acute stage of ischemic stroke. Spirography, tetrapolar rheography, and examination of the blood gas composition were carried out. Before HBO was begun, various disorders of the respiratory function were found (hyperventilation syndrome, periodical rhythms: Cheyne-Stokes respiration, alternating respiration, etc.). It was revealed that HBO session causes a normalizing effect on the respiratory function in central disorders of respiration: the Cheyne-Stokes rhythm was replaced at the end of the session by wave-like respiration which is biologically more adequate, the regimen of hyperventilation changed to normoventilation, etc. There was parallel improvement in the indices of central hemodynamics and the blood gas composition.


Gallstone ileus. A retrospective study.

Eight patients have been admitted with gallstone ileus (GSI) to the Herning Central Hospital during the period 1960--1977. All of the patients were subjected to enterolithotomy only. One patient died postoperatively. On follow-up examination 6 months to 11 1/2 years after operation, one patient complained of a recurrence of cholecystitis, but refused operation. The other patients had no biliary tract complaints. We still consider, due to the above, that enterolithotomy alone is a sufficient primary procedure, and that only in cases of new biliary tract complaints can cholecystectomy and closure of an eventual fistula be considered.


[Dynamics of diencephalic-hypothalamic disorders after the removal of basal meningiomas].

Comprehensive dynamic examination of 27 patients after removal of basal meningiomas revealed some characteristic changes in the results of REG and EEG and in the neurological status. It was also found that the dynamics of the data studied differed with the course of the postoperative period. Some EEG and REG data of favourable prognostic importance were noted. The study of these data promotes objectivization of the course of the postoperative period and is thus also important in the choice of rational therapy in the postoperative period.


[New method of draining a syringomyelitic cyst].

A new method of operative intervention for syringomyelia is described in which after the syringomyelia cyst is opened its permanent drainage is accomplished by introducing into its cavity the free end of an adjacent posterior root transected before-hand directly at the site of the funnel-shaped transition of the dura mater from the spinal cord onto the cuff. As a result, all movements of the spinal cord are made together with this root, which prevents the draining root from falling out of the cystic cavity and does not create conditions for it to inflict damage to the cystic walls and the surrounding cerebral tissue. The method was used in operations on 9 patients.


Bile duct diameter and diagnostic reliability at cholangiography.

Cases of exploratory choledochotomy with widened bile duct as the indication have been assessed with respect to missed bile duct concretion in a retrospective study covering a period of five years. During this period 2,000 cholecystectomies were performed. The 110 cases, in which (a) pre-exploratory cholangiography was completely normal apart from a diameter of more than 10 mm, (b) exploratory choledochotomy was performed, and (c) secondary cholangiography had been carried out, were studied in detail. No calculi were demonstrable either at exploratory surgery or secondary cholangiography. With a good radiographic technique it does not seem likely that bile duct concretions would be missed in widened ducts at otherwise normal operative cholangiography--at any rate not with bile duct diameters up to 20 mm.


Interval appendectomy. A retrospective study.

79 patients were admitted with a periappendicular abscess at the Surgical Organic Department, Randers Centralsygehus in a 5-year-period from April 1, 1970 to April 1, 1975. Appendectomy à froid was not made on 9 patients. A questionnaire in 7 patients showed no recurrence after an observation period of an average 2.4 years. Appendectomy à froid was made on 70 patients with a complication rate of 13%. The operation could be regraded as quite unnecessary in 14%. Therefore appendectomy à froid cannot be recommended as a routine operation, but all patients ought to be controlled until the palpable mass has disappeared, and only in cases of doubt and in symptomatic cases the patients ought to be operated. All patients over a certain age, 40 years for instance, ought to have performed a colon X-ray with double contrast or coloscopy to exclude a coecal cancer.


[Technic for surgical intervention in severe brain contusions and crushing].

Basal contusions of the frontal and temporal lobes of the brain, occurring as a contrecoup as a rule, are particularly severe and are marked by a high mortality. The 10-year practice of the Sklifosovsky Scientific Research Institute of Emergency Aid in the surgical management of cerebral contusion was aimed at the search for a less traumatic craniotomy approach and the most sparing and radical, within reasonable limits, intervention on the cerebral focus. Analysis of the work done enables us to choose the method described in the article, comprising extensive infratemporal craniotomy which excludes the frontal, temporal, and parietal, lobes, and to recommend combining intervention on the focus with internal decompression and active aspiration of the wound discharge from the cranial cavity in the first 24 hours after the operation. The illustrations supplied show the stages of the operation: linear skin incision, incision and separation of the temporal muscle, resection of the squama of the temporal and frontal bones down to the base of the skull. The operation may also be carried out as osteoplasty (sites for forming the trephination openings are shown in Fig. 1, a).


Skeletal scintigraphy in the inital assessment of women with breast cancer.

The results of 99mTc bone scanning have been retrospectively analyzed on 467 women admitted with a newly diagnosed breast cancer. The outcome of skeletal scintigraphy has been studied with reference to various prognostic variables. 9.8% of the women exhibited a positive scintigram. We could not find any influence of the tumour position on the frequency of positive bone scans. Age in relation to the menopause affected the rate of positive scans in that about three times as many positive scans were recorded in post menopausal women than in those who had not reached the menopause. Clinical staging according to the TNM system as well as the histological status of the axillary nodes correlated well with the rate of scintigrams that indicated a disseminated cancer disease. The tumour size, as measured in the operation specimen, strongly affected the frequency of positive and suspicious scans in accord with the prognostic significance of this parameter. The role of skeletal scintigraphy for an adequate staging of breast cancer patients is discussed.


Active and inactive thyroid hormone levels in elective and acute surgery.

The changes in the plasma or serum concentration of thyrotrophin (TSH), thyroxine (T4), 3,5,3'-triiodothyronine (T3), 3,3',5-triiodothyronine (reverse T3, rT3) and cortisol were examined in patients undergoing elective cholecystectomy (n = 10) or acute laparotomy due to peritonitis (n = 11). TSH and T4 showed no essential changes in either group. T3 was reduced already during initiation of anaesthesia and continued to fall during and after surgery in both groups. In the peritonitis group, T3 was reduced already before medical intervention. rT3 displayed changes opposite to those of T3. An increase in cortisol peceded the changes in T3 and rT3 in both groups. T3 and rT3 returned towards normal levels when the patients recovered and resumed oral nutrition. It seems likely that both elective and acute uncomplicated surgery is accompanied by a transient reduction in the extrathyroidal production of the most active hormone, T3, and by a reciprocal increase in the levels of the virtually inactive rT3. The underlying mechanism behind this metabolic adaptation is unclear but may be related to adrenocortical activation and/or to changes in the mode of nutrition.


Intrathoracic goitre: a review of 29 cases.

Twenty-nine patients suffering from intrathoracic goitre who were admitted to a thoracic surgical clinic were studied. Most patients had respiratory complaints but as many as 28% did not have any symptoms and their goitres were revealed on routine chest X-rays. Only seven patients were operated upon with a thoracic approach, usually a sternal split. All others were operated upon with a cervical collar incision. Three of the goitres were toxic and one malignant. Two of the patients died, one when inducing anaesthesia and the other of pulmonary embolism six days after the operation. General anaesthesia with endotracheal intubation is preferred when operating for intrathoracic goitre. The operation is started with a cervical collar incision and the patients prepared for a sternal split. Lateral thoracotomy may be necessary only when the mass is situated in the posterior mediastinum.


Optimal regimen of low-dose heparin prophylaxis in gastrointestinal surgery.

Four low-dose heparin regimens were compared with respect to the postoperative frequency of deep venous thrombosis (DVT) diagnosed with the 125I-fibrinogen method and other thrombosis variables as well as to peroperative and postoperative bleeding. The study comprised 204 patients undergoing gastrointestinal surgery who received 5,000 IU of either calcium heparin or sodium heparin (Vitrum AB) subcutaneously 2 hours before the operation and either every 8 or every 12th hours afterwards for 6--8 days. DVT was diagnosed in 17 and 16% of the patients who received calcium heparin every 8th or 12th hour respectively and in 11 and 10% respectively of those given sodium heparin every 8th or 12th hour. The differences in the incidence of DVT between the four groups were not statistically significant. An 8-hourly regimen was not accompanied by more bleeding incidents than a 12-hourly regimen. Sodium heparin was associated with a significantly increased number of patients who required blood transfusion and had more bruising at the injection site. It is concluded that the safest, most practical and still effective of the four investigated low-dose heparin regimens is calcium heparin 5,000 IU/ml administered 2 hours before the operation and every 12 hours afterwards for the first postoperative week.


Hemodynamic evaluation of the Carpentier-Edwards bioprosthesis in the aortic position.

The Carpentier-Edwards bioprosthesis is a glutaraldehyde-fixed porcine xenograft with a fully flexible thin-walled stent. Cardiac catheterization studies were performed in 17 patients to evaluate use of this valve in the aortic position. Hemodynamic studies established a mean peak gradient across the prosthesis of 19 mm Hg (range 5 to 65). The mean effective orifice area was calculated to be 1.6 cm2 (range 0.8 to 3.3). All patients demonstrated an improvement in functional class after operation. Mean left ventricular ejection fraction increased from 51 +/- 16 to 68 +/- 9 percent (P less than 0.004) in eight patients operated on for aortic stenosis, but was not significantly changed in patients operated on for aortic insufficiency. Hemodynamic comparison of the Carpentier-Edwards bioprosthesis with the standard Hancock xenograft showed similar effective orifice areas for the 23 and 25 mm diameter valves. In two patients studied the 21 mm Carpentier valve demonstrated a greater effective orifice area than that previously reported for the standard Hancock xenograft. The Carpentier-Edwards bioprosthesis affords both clinical and hemodynamic improvement when used in the aortic position and may allow improved effective orifice area when used in the smaller aortic root.


Effect of androgen on growth hormone secretion and growth in boys with short stature.

The response of plasma growth hormone (GH) to insulin-induced hypoglycaemia (IIH) and arginine infusion (AI) was studied in 22 young males (ages 8 to 17 years) with short atature and absent or delayed sexual maturation, before and after androgen administration. During initial evaluation, 5 patients had blunted GH response to IIH, 12 responded subnormally to AI and 4 failed to respond normally to either stimulus. These same studies were repeated in each patient following androgen administration. The source of androgen was as follows: a) 5 days of testosterone propionate (25 mg intramuscularly daily) in 20 patients. b) Methyltestosterone, 10 mg t.i.d. orally for four days in the other 2 subjects. In almost every case, androgen administration resulted in raising the levels of fasting GH and enhancement of the GH responses to IIH and AI was observed. Patients manifesting subnormal GH responses to these stimuli before androgen consistently demonstrated a normal response when challenged with identical stimuli during androgen administration. Growth velocities during the year following these studies were significantly increased in most instances and the growth spurts correlated well with the progression of sexual maturation. Sustained improvement in the GH responses to IIH and AI were uniformly observed in 3 patients when repetitive studies were performed 8 to 12 months later during spontaneous advancing sexual development. The results indicate that brief androgen administration can be helpful in delineating the cause of growth retardation in boys with short stature and delayed sexual maturation, particularly when the diagnosis of isolated growth hormone deficiency is suspected. They also offer prognostic value in determining growth potential in this same group of young males.


Inhibition of prolactin and lactation by methylergometrine hydrogenmaleate.

Reports on the effect of methylergometrine hydrogenmaleate (MEM) on prolactin (PRL) secretion and lactation are still controversial. Therefore a prospective study was designed to follow the influence of MEM on post-partum PRL levels and milk production. MEM was given orally to 30 post-partum women from day 1 to day 7 in a daily dose of 0.6 mg. Thirty untreated women served as control. PRL plasma levels and milk yield were compared at day 1, 3 and 7. PRL levels were significantly lower in the treated group at day 7 (P less than 0.01), while the difference at day 3 was statistically not significant. Milk yield was significantly reduced at day 3 (P less than 0.05) and day 7 (P less than 0.01). These results indicate PRL inhibiting properties of MEM resulting consequently in reduced lactation.


A sensitive and specific in vitro bioassay method for the measurement of follicle-stimulating hormone activity.

An in vitro bioassay method for hFSH is presented. The method is based on the principles previously described by Dorrington et al. (1976b) and involves the assay of oestradiol produced from 19-hydroxyandrostenedione by dispersed Sertoli cells of 10-day old rats when cultured in the presence of graded doses of FSH. Using the 1st International Reference Preparation for human pituitary gonadotrophins (FSH and LH/ICSH) for bioassay (code no. 69/104) as standard, the useful range of the method is from 0.5 to 32 mIU/chamber (2 to 128 mIU/ml). The sensitivity of the method is 0.5 mIU/chamger. The mean index of precision (lambda) obtained from 16 multiple assays over 2 or 3 dose levels was 0.084. Parallelism was obtained between the 69/104 preparation and all preparations under study. The practicability of the proposed assay method is such that 15 preparations at 3 dose levels can be assayed by one person in 3 days. The specificity of the assay was investigated by determining the FSH activity in the following preparations: hFSH alpha- and beta-subunits, hLH, hCG, hTSH, ACTH, human growth hormone (hGH) human prolactin (hPRL) and luteinizing hormone-releasing hormone (LH-RH). The ACTH, hGH, hPRL and LH-RH preparations studied showed no detectable FSH activity in the assay. In the remaining preparations very low levels of FSH activity were found, corresponding to 0.004 to 0.6% of the weight of these preparations when compared with a highly purified hFSH preparation, suggesting that the method is specific for FSH. The possible synergistic or antagonistic influence of the above preparations when assayed in the presence of the 69/104 preparation was also assessed. No evidence of a synergistic or antogonistic effect was found. The assay of the hFSH potencies of a limited number of hFSH preparations of varying purity by the proposed in vitro bioassay, an hFSH radioreceptor method and an hFSH specific radioimmunoassay technique revealed that - although the relationship of the various potencies obtained with each method showed a close agreement - the bioassays yielded the highest potency estimates, and the radioimmunoassays the lowest ones. Since the proposed bioassay method is sensitive and considered to be specific for hFSH activity, it provides a suitable basis for the assessment of the specificity of other in vitro methods (radioreceptor and radioimmunoassay) currently used for detecting low levels of FSH activity.


Characterization of specific antisera to native human luteinizing hormone.

Antisera against highly purified native hLH (10 000 IU/mg = 0.5 mg hLH/mg protein) were raised in 4 rabbits. The antisera were invariably of high titre and high avidity. They were purified by affinity chromatography on a column with hCG-Sepharose 4 B. Before and after adsorption the antisera were tested in a double antibody radioimmunoassay. Before adsorption hCG cross-reacted in all antisera, but in none were the inhibition curves identical. No such cross-reaction remained after the affinity chromatography. These purified antisera made it possible to develop highly specific and sensitive assays for measuring native hLH. We conclude from studies of the effect of native glycoprotein hormones and their subunits that there are probably differences in the antigenic sites of the complete hLH molecule and in the isolated beta-subunit of hLH. The investigation also indicates that even highly purified preparations of hTSH may be contaminated with hLH and that the preparations of hLH-subunits may contain a certain amount of the native hormone.


Measurement of circulating 1,25-dihydroxyvitamin D in man. Changes in serum concentrations during treatment with 1 alpha-hydroxycholecalciferol.

A sensitive assay is described for measurement of circulating 1,25-dihydroxyvitamin D (1,25-(OH)2D) using rachitic chick intestinal cytosol binding protein. The metabolite was extracted from serum by diethyl ether and chromotographed on a Sephadex LH-20 column followed by high-pressure liquid chromatography. The concentration of 1,25-(OH)2D was then measured by a competitive protein-binding assay. The binding capacity of the protein was unchanged for 4 months. The inter- and intra-assay variations were both 11%. The standard curve was useful at serum concentrations ranging from 14 to 395 pmol/l (6 to 165 pg/ml). The normal mean concentration was 79.6 +/- 36.8 pmol/l (33.1 +/- 15.3 pg/ml). The serum 1,25-(OH)2D was studied in elderly subjects following administration of 1 alpha-hydroxycholecalciferol (1 alpha-OHD3) at different doses. Large variations occurred indicating individual rates of metabolism of 1,25-(OH)2D.


Inhibition of diphosphonate-blocked bone mineralization. Evidence that calcitonin promotes mineralization.

There is much experimental evidence which indicates that calcitonin in hibits bone mineral resorption, but there are few data available in support of the proposal that calcitonin may also promote mineralization. Ethane-1-hydroxy-1,1-diphosphonate (EHDP) administered to immature rats inhibited mineralization as evidenced by widened tibial epiphyseal plates and decreased bone ash to dry weight ratios. Concurrent dosing with salmon calcitonin (SCT) prevented or reversed the EHDP-blocked mineralization in a dose dependent manner. Administration of SCT during the period after EHDP treatment significantly improved mineralization of tibial epiphyseal plates as shown by plate width narrowing and increased uptake of radioactive calcium. These results suggest that SCT increased mineralization in EHDP-treated rats, and provide supportive evidence for the proposal that calcitonin may also promote mineralization, in addition to its well known ability to inhibit bone mineral resorption.


Ethanol elimination in regenerating rat liver: the roles of alcohol dehydrogenase and acetaldehyde.

The rate of ethanol elimination in vivo was studied with rats in which the energy consumption of the liver was increased by partial hepatectomy. Immediately after partial hepatectomy the activity of alcohol dehydrogenase in the liver remnant was not changed from that of the livers of sham-operated controls, but the rate of ethanol removal was significantly faster. Twenty-four h after the partial hepatectomy the activity of alcohol dehydrogenase was only 48 % of the activity measured in unoperated control rats. Therefore it is concluded that in normal liver the activity of ADH is in excess. In partially hepatectomized rats the rate of ethanol elimination was linearly correlated with the activity of alcohol dehydrogenase, which suggests that when the rate of NADH reoxidation is markedly increased, as in regenerating rat liver, the rate of ethanol elimination may be limited by the activity of alcohol dehydrogenase. The activity of aldehyde dehydrogenase and the concentration of acetaldehyde in the tail blood were not significantly changed from the level of unoperated rats during oxidation of ethanol.


[Presence of extracranial cerebral arterial lesions in patients undergoing open heart surgery: a planned approach to a single stage operation (author's transl)].

The combined approach of extracranial arterial lesions in patients undergoing open heart surgery decreases the high cardiac and neurological morbidity and mortality presented by patients operated sequentially. Besides the anatomically sound simultaneous approach of arch lesions and heart surgery, both to be operated by median sternotomy, the authors present their criteria used in the selection of neurologically symptomatic and asymptomatic patients with carotid and vertebral disease to be operated simultaneously. Results in 17 personal cases are presented.


[Revascularization of the extracranial carotid-, vertebral- and subclavian arteries in a small peripheral hospital (author's transl)].

A total of 21 procedures were performed on a group of 17 patients, 13 of them more than 65 years old, for mixed intra- and extracranial vessel disease. Ten had recovered from a frank stroke. Thirteen of them underwent one procedure, three two procedures and one a total of three revascularizations. Eighteen carotid endarterectomies, without patch angioplasty were performed. The determinant factor whether or not to use an intraluminal shunt was the peroperatory encephalographic monitoring by a neurologist. The shunt was used any time significant EEG changes occurred during a test clamping period of five minutes. The other procedures included a vertebral artery endarterectomy with patch angioplasty, a subclavian- subclavian vein by-pass, as well as a common carotid artery resection for elongation and kinking of the internal carotid artery combined with marked stenosis. The mortality was nihil. Postoperatively all patients did well with an improved mental and neurological status.


[Treatment of carotid artery arteriosclerosis 1966 to 1976. Early and late results (author's transl)].

Early and late results of surgery for carotid arteriosclerosis between 1966 and 1976 were reviewed in 154 patients (192 operations). The percentages of excellent and good early results were 96.7% (stage 0), 91.3% (stage I), 46.6 (stage II) and 51.6% (stage III). Overall mortality was 9.1% within the month (3.8% as neurovascular risk). In late results, out of 140 survivors, the percentages of excellent and good results were 69% in stage 0, 59.7% in stage I, 45.5% in stage II and 56.7% in stage III, the mean delay being 40.5 months. There were 3.6% cases of neurological disorders (0.7% corresponding to the side of the operated carotid artery), 7.1% of vertigo and arterial hypertension, 33 (new) deaths (23.6%) occurred after a mean 31.3 months, of which 16 resulted from some cardiovascular trouble. The cumulative survival curves parallel those of the normal population showing the protection yielded by the operation and the decrease in neurovascular risk.


[Five year follow-up of 104 cardial artery deobliteration (author's transl)].

From December 1, 1964 to December 31, 1977, 613 patients underwent 699 operations for stenotic lesions of the internal carotid artery. One hundred and four of these cases, operated before December 31, 1972, were reevaluated at 5 years. These include 9 patients stage 0 (asymptomatic), 45 patients stage I (transitory), 8 patients stage II (progressive), 22 stage III mild (mild deficiencies), and 20 stage III severe (severe deficiencies). The overall 5 year mortality is 34% with a survival rate of 65%, steadily decreasing from 87% in the first year. There is a fundamental difference to be made between results in stages 0, I, mild-III and the other, for immediate and for 5 year mortality: 19% versus 67%. The rate of local recurrences is low: 3% of patients operated on the same side. In contrast, 11 subjects underwent a bilateral procedure. Carotidal endarteriectomy improves long term survival only moderately, mainly as a result of coronary disease. However it has an undisputable effect in diminishing neurological accidents.


[Techniques for the diagnosis of cerebral ischemia (author's transl)].

The various techniques for the diagnosis of cerebral ischemia are reviewed. The methods for investigating the large cervical arteries are considered (angiography, ultrasonic Döppler technique, carotid compression test) as well as those concerned with intracranial circulation. The latter are divided in "functional" methods (Rheoencephalography cerebral blood flow measurements with Xenon or with microspheres) and "morphological" methods (Brain scintigraphy and CAT scan). The respective values of the various methods are estimated in a personal series of patients.


[Cerebral revascularization by extra-intra-cranial arterial anastomosis. Technique and results (author's transl)].

Extra-intra-cranial anastomosis introduced in 1967 by Yasargil and Donaghy consists in using a branch of the external carotid artery to anastomose it on one of the cerebral cortex. This procedure is indicated when there exists an obliterating lesion not in reach of a local technique. On clinical grounds two situations may exist: --the first is a regressive ischemic episod and the operation is then preventive; --the second is a confirmed deficit, non regressive: thecurative value of such an operation must then be discussed. The author reports his 5 year experience: 51 patients were operated amounting to 60 anastomoses. Eighty percent of the operated patients have a patent anastomosis. The operative risk is small (1 death, 1 worsening). The clinical criteria are discussed (Acta chir. belg., 1979, 78, 85-93).


[One stage operation of bilateral carotid lesions (author's transl)].

Bilateral one stage carotid endarteriectomy was performed in 11 patients presenting with bilateral symptomatics stenoses without neurological nor cardiac major complications. We only found one such experience in the literature (1). The choice of a simultaneous procedure is based solely on electroencephalogram analysis and on the residual pressure after the test of carotid occlusion; the side where occlusion is tolerated and/or where the residual pressure is highest, is operated first. This simultaneous bilateral procedure carries the theoretical risk of ischemia. It has the advantage of decreasing the cardiac complications and the risk of neurological deficit and at the same token avoids intercurrent controlateral thrombosis and recurrent symptoms between two non-simultaneous procedures. In cases of symptomatic lesions, the indication of surgery is evident; for asymptomatic lesions we only consider a simultaneous procedure in special cases where there exists a threat of neurological complications.


Transient liver deterioration induced by general anesthesia.

The disappearance rate of bromsulphthalein (BSP) has been studied in 43 patients before and during vaginal hysterectomy under three kinds of anesthesia: Halothane anesthesia, neuroleptanalgesia, and peridural anesthesia. Furthermore, serum enzymes were measured before and after surgery. The half-life of BSP in the elimination phase is significantly prolonged during general anesthesia but not during the peridural anesthesia in the same procedure. There were slight increases of gamma-glutamyltranspeptidase in the later postoperative days with no changes of transaminases and alkaline phosphatase. It can be concluded that the known post-operative transient liver dysfunction, detected only by the BSP-test, occurs during the performance of surgery and is caused by the influence of the general anesthesia on the intrahepatic cell metabolism and not by the operative procedure itself.


Liver injury and lipid metabolism: sex differences in the fatty liver induced by d-galactosamine.

The time-course of plasma lipid alterations and of triglyceride accumulation in the liver was investigated in male and female rats 12, 24 and 48 hours after treatment with 3.48 mmole/kg (0.75 g/kg) D-galactosamine (Ga1N). In the early stages of Ga1N-induced liver injury the concentrations of triglycerides, phospholipids and total cholesterol decreased, while in the later stages these values in the plasma increased above normal, especially in male animals. In contrast, glucose concentrations continually decreased, while free fatty acid (FFA) levels rose to twice those normal in female animals. Male animals had significantly lower FFA-values throughout the experiment. Consistently, the triglyceride accumulation on liver was 75 mg/g in female animals 24 hours after Ga1N administration, while male animals in the average showed only 33 mg/g triglycerides. Similar fatty infiltrations were obtained in female animals with the rather low doses of 1.16 and 2.32 mmol/kg Ga1N. It is concluded that the increase of FFA-influx after Ga1N administration is the main cause for fatty infiltration, the sex differences in the plasma FFA concentrations explaining the net differences in liver triglyceride accumulation. Additional effects in the pathogenesis of fatty liver might stem from disturbed glycosylation reactions and/or an altered secretion and metabolism of lipoproteins after Ga1N-induced liver injury.


Haem biosynthesis in cutaneous hepatic porphyria: comparison with alcoholism and liver disease.

The enzymes of haem biosynthesis have been measured in the peripheral blood of 13 patients with cutaneous hepatic porphyria. The activity of leucocyte delta-aminolaevulinic acid synthase was significantly elevated (p less than 0.001) as was that of erythrocyte porphobilinogen deaminase (p less than 0.05). Leucocyte ferrochelatase activity was depressed (p less than 0.001) and the activity of erythrocyte uroporphyrinogen decarboxylase did not significantly differ from control values. Similar enzyme activities were assayed in 12 chronic alcoholics and 8 patients with liver disease and the results differed markedly from those obtained from the porphyric patients. It is unlikely that the raised leucocyte delta-amino-laevulinic acid synthase activity can be attributed to alcohol ingestion or liver disease. A defect in the activity of uroporphyrinogen decarboxylase may exist in cutaneous hepatic porphyria but this could not be demonstrated in erythrocytes in this study.


Effect of glucagon on glycogen content of the dog and rat intestinal mucosa.

The effect of intraarterial glucagon injection on the glycogen content of the intestinal mucosa of the dog and the rat has been investigated. In both species significant glucagon-induced reduction of mucosal glycogen contents was revealed.


Functional analysis of organic sphincter systems by elastance-measurement. Evaluation of a new method.

The function of organic sphincter systems cannot be described by measuring a static pressure, but only by applying a dynamic procedure of measurement that takes into account the characteristics of smooth muscles. Therefore, the elastance-method has been developed. Experiences with this method and its clinical value are demonstrated when one applies this procedure to measurements in the lower oesophagus, the duodenal papilla and the anal canal.


Interaction of synthetic human big gastrin with blood proteins of man and animals.

Radio gel and affin chromatography were used to study big gastrin interaction with blood proteins of man and animals. The experiments showed that big gastrin interacts with serum proteins in vitro. The gastrin-blood protein complex is labile and readily dissociates (T 1/2 = 8--14 min). A more stable complex is found in acidic medium. Ceruloplasmin is one of the blood serum proteins able to interact with big gastrin. The stability of hormone-protein complex, formed by gastrin and ceruloplasmin, is dependent upon hormone concentration. With the addition of C-terminal penta--and octapeptides to labelled hormone, binding increased. It is speculated that formation of labile gastrin-blood protein complexes is necessary for selective gastrin transport from hormone-producing cells to target cells.


Gastric basal secretion during exercise and restitution in patients with chronic duodenal ulcer.

Gastric basal secretion was studied at rest, in the course of one hour's exertion and one hour's restitution in 10 patients with chronic duodenal ulcer, aged 21-52. The subject performed exercise on a Monark ergometer under a load that gave constant pulse rate acceleration equal to 50% of the age-related maximum. Gastric juice samples were collected with the subjects sitting, in three successive phase of rest, exercise, and restitution. It was found that during exercise there was an increase in the gastric juice volume, HCl levels in it, basal secretion volume, and overall sodium, potassium, chloride, calcium, and magnesium content, their concentration in the juice having remained constant. In the course of restitution the above values did not differ in any significant way from those obtained at rest.


Five patients with nonalcoholic diabetic cirrhosis.

Five nonalcoholic diabetic women were clinically and histologically verified as having micronodular cirrhosis. In this series all the patients were over 50 years of age, and showed obesity, hyperglycemia, enlarged liver and mild abnormalities of liver function tests. The histological findings differed from hepatitic cirrhosis. In two patients serial biopsies confirmed development of cirrhosis from centrilobular necrosis.


Serum gastrin in portal and peripheral veins after arginine in man.

Immunoreactive serum gastrin from portal and peripheral veins was determined in five controls and in five cirrhotic patients with indwelling portal catheters in basal conditions, during and after 30 min arginine infusion, in order to assess whether the human liver is involved in gastrin metabolism. A significant difference was found between portal and peripheral gastrin concentrations in controls at 0, 60 and 90 min; no significant differences were found in cirrhotics. Our findings support the hypothesis of an at least partial breakdown of endogenous gastrin in the human liver.


The fine structure of stratified ependyma in the ventricular wall of N-ethyl-N-nitrosourea-treated rats.

Ependymal stratifications, up to 15 cell layers in thickness at the floor of the lateral ventricle of rats treated transplacentally with N-ethyl-N-nitrosourea (ENU), are described. Ultrastructurally the constituent ependymal cells are well-differentiated and show no morphological signs of neoplasia. The possibility that these findings are due to the toxicity or carcinogenicity of ENU is discussed.


Spindle-shaped appendages of IIIab-pyramids filled with lipofuscin: a striking pathological change of the senescent human isocortex.

Brains from 30 mentally normal men, ranging in age from 18--90 years, were studied to assess the occurrence and development of lipofuscin-filled spindle-shaped appendages of pyramidal cells of the isocortex; these can generally be encountered in the senescent brain within layer IIIab. The number of pigmented spindles was determined in a circumscribed part of prefrontal area revealing a close association of this conspicuous pathological alteration with growing age.


Familial centronuclear myopathy: a haploid DNA disease?

In the same family three boys (ages 8, 11, 14 years), suffering from a slowly progressive weakness of the flexors of the head and distal muscle groups of the extremities, were found to have a myopathy characterized by the presence of central nuclei in type I fibres. Their mother showed no histopathologic signs but a myopathic pattern on electromyography could be demonstrated. Cytophotometric examination of the anterior tibial muscle of these siblings revealed a reduction in DNA content by 50% in the central and subsarcolemmal nuclei (haploid DNA content) when compared with subsarcolemmal nuclei (diploid DNA content) of the same muscle of their mother. Nuclear DNA concentration in fibrocytes did not differ significantly between members of the family. Therefore, it is assumed that the nuclei of muscle fibres are selectively affected by the disease process which is indicated by a haploid DNA content.


[Melanosis cerebelli. Ultrastructure and infrared absorption of the pigment (author's transl)].

The pigment present in melanosis cerebelli where it is deposited in the dentate nucleus and within the cerebellar granular layer is similar to that of S. nigra as judged from the typical infrared absorption bands near wave numbers 3.450 cm-1 and 1.650 cm-1, respectively. According to electron microscopic findings, this type of melanin arises within the astrocytes of the dentate nucleus. The astrocytic melanosomes exhibit a relatively monotonous substructure reaching diameters of 30 mu and more, and they differ in this respect from the triadic neuronal melanosomes of S. nigra that are strongly reminiscent of lipofuscin granules. These differences may be due to additional components of melanosomes, apparently specific of a particular cell type, and they are in turn accounted for by the dissimilar cellular metabolic make-up of nigral cells and astrocytes, respectively. This does not dismiss the possibility, however, that the melanin pigments of either type of melanosomes are the same or closely related to each other as far as their basic chemical composition is concerned. The cause of the melanosis of the dentate nucleus is not known. Possibly involutional tissue changes governed by endocrine factors among others may play an important part.


Late-onset malignant astrocytoma in a case of multiple sclerosis. Clinical, neuropathological, virological, and tissue culture studies.

An unusual case of concurrent MS and anaplastic astrocytoma is presented. MS was diagnosed in a female patient at the age of 22 years. A left side thalamotomy was performed for relief of severe intention tremor at age 28 and at age 32 she received immunosuppressive therapy for 1 year. At the age of 36 after a severe exacerbation of her symptoms a left side fronto-temporal tumor was diagnosed and a subtotal neurosurgical extirpation was performed. Histopathologically, the tumor was an anaplastic astrocytoma, which was further substantiated by electron microscopy and establishment of a permanent cell line in vitro. The cultured tumor cells were negative for measles virus by immunofluorescence. The relationship between the reactive astrocytes in MS plaques and astrocytic neoplasia is discussed.


Paraganglioma in the cauda equina region.

Some new ultrastructural observations are documented in paraganglioma in the cauda equina region. These include the presence of nerve fibers in the tumor capsule, clear vesicles and tubulo-vesicular structures in some cytoplasmic processes in the tumor, fenestrated endothelial cells, and numerous tubular bodies in some endothelial cells.


The morphopathologic substrates of concussion?

Neuronal inundation with i.v. infused horseradish peroxidase was studied following concussive brain injury by means of both light and electron microscopy. In animals sustaining mechanical brain injury of insufficient intensity as to elicit either microscopic intraparenchymal hemorrhage or other neuropathological change, yet of sufficient intensity as to provoke a physiological concussive response, vascular peroxidase exudation concomitant with neuronal peroxidase inundation occurred throughout the raphe and reticular core. Initially such inundated neurons were totally flooded with the tracer and as such appeared reminiscent of cells visualized in Golgi preparations. However, over the course of a 24-h period these peroxidae flooded neurons apparently organized the peroxidase into vesicles and vacuoles which assumed a perinuclear position from where the peroxidase ultimately reached both the nucleus and nucleolus. It was remarkable that these events occurred without any evidence of subcellular alteration. We interpret such initial inundation with this protein tracer, its ultimate reorganization, and its nuclear and nucleolar uptake as being consistent with some form of subtle and transient neuronal perturbation. We speculate that as such this neuronal perturbation may constitute a morphological correlate of the concussive episode.


The stathmokinetic (mitostatic) effect of vincristine and vinblastine on human gliomas.

Twelve patients with gliomas received 3H-thymidine intraarterially in combination with an i.v. mitostatic agent (Velban: 0.1 mg/kg or 3 mg/M2 of Vincristine) prior to tumor biopsy. The labeling index (LI) of each tumor was compared with the mitotic index divided by the elapsed time from administration of the mitostatic agent to biopsy (MI/t). Most of the malignant gliomas that had an LI of 5-15%, also yielded an MI/t value of 4-5 x 10(-3), whereas tumors with an LI of less than 5% generally showed very slight (0.1 x 10(-3) mitotic accumulation. Use of a mitostatic agent is suggested to differentiate the proliferative activity of various gliomas.


The perineuronal satellite oligodendrocyte. A role in remyelination.

Demyelination was induced in the superior cerebellar peduncles of weanling mice by the administration of Cuprizone. Remyelination occurred when the animals were replaced on a normal diet. Perineuronal satellite oligodendrocytes in the periventricular gray were clearly seen to be remyelinating axons. This study demonstrates for the first time the role of these cells in remyelination, and raises the possibility that they may be involved in normal myelination of the central nervous system.


Electron microscopical demonstration of nucleic acids in virus-like particles in the skeletal muscle of a traffic accident victim.

Picornavirus-like crystalline arrays were found in the skeletal muscle of a victim of a traffic accident. Individual particles measured approximately 22 nm in diameter and were arrayed in a hexagonal or triangular pattern. Cis-platinum (II) staining of these virus-like particles showed that these particles were not glycogen but contained nucleic acids, and the staining according to Bernhard also showed these particles contained RNA. Through the combination of the methods of Heinen (1977) and Bernhard (1969), we can confirm that virus-like crystalline structures found electron microscopically contain nucleic acids and possibly represent virions.


Scanning electron microscopy of in vitro grown cells from experimentally induced neurogenic tumors.

Serially transplanted neurogenic tumors of experimental origin were explanted in vitro and analyzed by scanning electron microscopy. In explants of intracerebrally transplanted gliomas, small stellate cells with branching processes were observed; in transplanted tumors of the peripheral nervous system, slender bipolar cells as well as fibroblasts emerged. The stereoscopic features were compared with the picture of conventional light microscopy. The findings are consistent with the assumption of the glial derivation of CNS-tumors induced with neurotropic alkylating carcinogens. The peripheral tumors are composed of Schwann-cell like elements and fibroblasts. The significance of the results for the cytogenetic derivation of brain tumors are discussed.


A quantitative study of the composition of cerebellar cortical dysplasias.

The areas of molecular and granular layers in four large cerebellar cortical dysplasias were measured with the planimeter and the Purkinje cells were counted. There was a relative deficit of molecular layer and a still greater deficit of Purkinje cells in three of the four dysplasias. The fourth one had normal numbers of Purkinje cells per molecular layer and a relative deficit of granular layer. These abnormal proportions in the composition of a dysplasia may relate to the timing of its origin.


Rosenthal fibers formation in the central nervous system. Its relation to Alexander's disease.

Subpial and subependymal gliosis with abundant Rosenthal fiber (RF) formation are described in two patients. In one, the process appeared as a narrow band over the entire neuraxis and was not accompanied by neurologic manifestations. In the other, the changes were mostly restricted to the lower medulla and upper cervical cord and displayed invasive features. The glial proliferation with RF in the second patient was associated with an inflammatory component, dense collagen deposition, perivascular Schwannosis and demyelination. Involvement of some of the medullary nuclei and their tracts may explain the patient's vague bulbar symptomatology. The underlying cause which led to astrocytic proliferation with excessive RF in these two patients remains elusive. Possible factors contributing to this phenomenon are discussed in the context of Alexander's disease.


Decay and recovery of the acoustic stapedius reflex in humans.

The time course of decay and recovery of ipsilateral and contralateral stapedius reflex responses to 2 000 Hz pure tone stimulation was studied in 10 normal-hearing subjects. Reflex responses were found to follow a closely similar time course with respect to both decay and recovery in simultaneous bilateral recordings. The similarity is compatible with the assumption that decay and recovery originate in the afferent auditory system, and not in the muscles. Recovery was 50% complete 250 ms after the end of the stimulus and most subjects had reached their initial amplitude after 1-3 s. The individual correlation between decay and recovery was negative but weak, which is interpreted as showing that these processes have a tendency to balance each other, but are based partly on different mechanisms. The implications of the present results for diagnosis of disorders of the lower auditory system as well as for the evaluation of the protective role of the stapedius reflex against noise damage are pointed out.


Behavioral auditory function after transection of crossed olivo-cochlear bundle in the cat. V. Pure-tone intensity discrimination.

This report describes the cat's ability to discriminate pure-tone intensity differences after transection of the crossed olivo-cochlear bundle at the floor of the fourth ventricle. Cats were trained by behavioral (avoidance) conditioning to detect intensity difference above 75 dB re 0.0002 dyne/cm2 of 10 000 Hz tones, using the repetitive method. Postoperative comparison of data from 5 experimental animals and 5 sham-operated control animals showed minimal differences which reflects merely functional biological variance. Neurohistological examination confirmed the accuracy of the lesion placement.


Békésy audiometry in evaluation of hearing in cases of raised intracranial pressure.

The paper reports findings in a Békésy audiometry study on 50 ears of 27 patients with raised intracranial pressure. The Békésy audiometry was done both preoperatively and after operation when the raised intracranial pressure had been controlled. The study showed a significant hearing loss in Békésy audiometry due to raised intracranial pressure. However, only low frequencies of 125-250-500 Hz showed a reversal of hearing loss which was statistically significant. The type II pattern of Békésy audiometry changed to type I after control of the raised intracranial pressure. The type IV and V patterns had a tendency to change to Békésy I or II, on control of the raised intracranial pressure.


Simulation of low-pass hearing loss in a Finnish speech discrimination test.

Three different degrees of clinical hearing loss of low-pass type were stimulated by a filter apparatus. The equipment to simulate a given hearing loss is described. The speech discrimination curves corresponding to the normal hearing and to the three degrees of hearing loss were measured in normal hearing adults using Finnish PB-words. The stimulation of a light hearing loss of low-pass type yielded a two-staged discrimination curve. The discrimination curves of a moderate and a severe hearing loss crossed at a very high output level. The cause of this phenomenon is discussed on the ground of the exceptional vowel/consonant relation and intensity/frequency distribution in the Finnish language.


A developmental study of the sound pressure transformation by the head of the cat.

The interaural intensity difference (IID) created by the imposition of a cat's body in a free sound field was measured in two age groups of kittens and one group of adult cats. For all animals significantly larger IIDs were obtained for high than for low frequency stimulation. The frequency at which peak IID occurred was higher for the younger group of kittens than for either the Old Kittens or the Adults. Above 4 kHz the Adults showed a marked variation of IID with azimuth, whilst the Young Kittens showed little variation of IID with azimuth at frequencies below 10 kHz. It was found that Adult-like IIDs are achieved before physical maturation is complete. The results are discussed with reference to the physiological development of sensory systems and the implications for a possible post-natal plasticity of the auditory system are examined.


Population differences in cellularity of the mastoid process.

Adult crania from four human skeletal population samples were radiographed in order to study variation of the air cell system in the mastoid process. Six types of processes were recognized, i.e., sclerotic, diploic, diplo-pneumatic, pneumatic, and highly pneumatic. Frequency of non-pneumatized (acellular) processes in Eskimos was significantly lower than that found in the other three populations. Female crania in each sample showed fewer acellular processes than male, but the differences were statistically significant only in the Whites, Eskimos, and total sex samples. While present in each population, frequency of asymmetry of type was significant in only Whites and Eskimos. These results provide some additional evidence that a genetic factor is operant in determining the degree of cellularity of mastoid processes.


Growth influence on tubal function.

The influence of growth on tubal function was studied in 26 children by means of tubal function tests in a pressure chamber and by geometric analysis of lateral cephalograms. Good tubal function coincided with mesoor brachycephalic skeletons, poor tubal function with dolichocephalic morphologic patterns. According to our results, tubal function seems to be strongly influenced by the growth processes of the skull.


Loss of visual suppression of caloric nystagmus in cats.

Loss of visual suppression (VS) of caloric nystagmus was produced after creating flocculus lesions. The flocculus receives visual signals through a climbing fiber pathway via the inferior olive (IO) and through a mossy fiber pathway (MF) presumably via the superior colliculus (SC). In order to elucidate the prefloccular nuclei responsible for VS of caloric nystagmus, VS of caloric nystagmus was investigated after making lesions in such nuclei as the SC and the IO in 42 cats. After the IO lesion, VS of caloric nystagmus was revealed in all IO-lesioned cats throughout the whole experimental course. After the SC lesion, loss of VS was constantly observed and persisted in 7 out of 9 cats. Hence, the MF pathway via the SC is believed to be the most likely candidate for the immediate modification of the vestibuloocular reflex by visual stimuli.


Peroperative drill-generated noise levels in ear surgery.

A simple technique for the measuring of sound intensities produced by drilling in ear surgery is presented. In 6 patients the sound level from drilling in the mastoid exceeded 100 dBA. The drilling device should be so designed as to avoid acoustic trauma. Furthermore, a surgical technique should be selected, which minimizes the noise levels and duration of exposure as far as is possible.


Cupula motion in the semicircular canal of the skate, Raja erinacea. An experimental investigation.

An upper bound on the magnitude of semicurcular canal cupula motion was experimentally determined in the isolated labyrinth of the skate, Raja erinacea. To visualize the cupula, a glass pipette was pushed through the ampullary wall, and local regions of the cupula were stained by slow infusion of small amounts of Alcian Blue dye. Caloric stimuli which produced large changes in single unit activity in the ampullary nerve and which often recruited several larger, previously silent units were found to produce on detectable cupula motion as seen through the ampulla wall. However when the cupula was first grossly displaced, motion was thereafter observed in response to identical caloric stimuli. Analysis of afferent responses indicates that the normal range of cupula motion in the skate is below the optical resolution of the method, conservatively estimated as 3--5 micrometers.


Some observations on negative endocochlear potential during anoxia.

The effects of anoxia on the endocochlear potential (EP) and +K and +Na concentrations in the endolymph were studied in three groups of guinea pigs: kanamycin-treated guinea pigs, waltzing guinea pigs and normal guinea pigs. The magnitude of the EP in kanamycin-treated guinea pigs and waltzing guinea pigs did not show marked deviation from that observed in normal animals. The +K and +Na concentrations in the endolymph in those animals with severe suppression of sound-evoked cochlear potentials were also within the normal range. The changes in +K and +Na concentrations in the endolymph in anoxic condition were similar in the three groups of animals. However, the rate of decline of the EP was slower in kanamycin-treated guinea pigs and old waltzing guinea pigs. In young waltzing guinea pigs showing moderate suppression on the cochlear microphonics, the decline of the EP during anoxia was comparable to that observed in normal guinea pigs. The results indicate that anoxia decreases +K and increases +Na concentrations in the endolymph in a similar fashion in kanamycin-treated guinea pigs, waltzing guinea pigs and normal guinea pigs. It is suggested that the decline of the EP during anoxia is correlated with the +K conductance of the organ of Corti.


Following eye movements on the absence of central vision.

Following responses to constant velocity and sinusoidally oscillating movements of the whole visual environment were examined in normal subjects wearing blinkers to obscure central vision or subjected to a photo flash to induce a central scotoma, in patients with central scotomas of pathological origin and in one patient with a central scotoma in an immobile eye which provided open loop testing. Good following and brisk nystagmus were produced in patients with central scotomas and subjects with flash scotomas; it was subjectively evident that the scotoma itself could be used as a target to generate open loop pursuit and augment peripherally induced following responses. Following responses in subjects with blinkers were weak, possibly reflecting that, in everyday life, eye movements induced by movements of the visual background have to be suppressed. Open loop responses were strong, suggesting that the periphery has the latent potential to mediate good following. The findings provide a unified explanation for the various patterns of optokinetic nystagmus.


The immunological status of allografts in the middle ear.

In a series of experiments using two inbred rat strains differing in respect of their major histocompatibility antigens, and a sensitive test for antibody directed against major histocompatibility antigens, it was shown that (i) grafts known to be highly immunogenic (10(7)) lymphocytes) regularly immunized their hosts when injected intratympanically; the immune response could not be ascribed to leakage of cells into either the external auditory meatus or the nasopharynx, (ii) immunization occurred at least partly via the regional lymphatics, (iii) single orthotopic or heterotopic incus grafts immunized their hosts sporadically, and (iv) the variable immunization which followed single ossicular grafts was due to their relatively low content of antigen.


Response of nasal airway resistance to hypercapnia and hypoxia in the dog.

Nasal airway resistance was calculated in 9 anesthetized mongrel dogs by measuring the pressure difference across the nasal airway while a continuous flow of humidified air was passed through the upper airway. Hypercapnia produced a significant decrease in nasal airway resistance (P less than 0.05, Wilcoxon signed-rank test), which was proportional to the Paco2 over the range of 40 to 70 torr. Hypoxia produced a decrease in nasal airway resistance only when there was severe depression of Pao2. Direct stimulation of peripheral chemoreceptors by intravenously administered NaCN (100 microgram/kg) resulted in a significant decrease in nasal airway resistance (P = 0.06, Wilcoxon signed-rank test). Interruption of the cervical sympathetic trunk bilaterally abolished or reversed the response of the nasal airway resistance to hypercapnia and to NaCN. The study indicates that the nasal airway can modify airway resistance in response to respiratory stimuli and that this reflex is mediated by the sympathetic nervous system.


The protective effect of acute phase reactants in neonatal sepsis.

Phase reactants were evaluated prospectively in babies suspected of having sepsis. Among 318 babies, there were 22 proven and 10 "very probable" cases of neonatal sepsis. Of the proven cases 14 survived and 8 died. The survivors had a positive latex C-reactive protein (CRP) in 11 cases and an alpha1-acid glycoprotein (AGP) level greater than 0.5 g/l in 12 cases. Among those who died, one had a positive latex CRP and none had AGP greater than 0.5 g/l. These findings were supported by positive CRP and elevated AGP in almost all "very probable" cases, all of whom survived. These data in newborn infants support the hypothesis that acute phase reactants have a functional role in combating infection.


Suppressed lymphocyte mitogen-responsiveness in urinary tract infections of children and its correlation to pyelonephritis.

Cell-mediated immunity (CMI) was studied in a group of 48 children with urinary tract infections (UTI) using a whole blood micromethod for lymphocyte stimulation in vitro. The patients were subdivided into pyelonephritis group (27 cases) and lower urinary tract infection (LUTI) group (21 cases) on the basis of fever, erythrocyte sedimentation rate, C-reative protein and renal concentration capacity. At the acute stage of infection the lymphocyte responsiveness to leucoagglutinin (LA) and concanavalin A (Con A) was suppressed in both groups, but the suppression was much greater in those with pyelonephritis. By 6 weeks after infection the lymphocyte responses were normal in most but not all cases. We conclude that an acute pyelonephritis is associated with marked suppression of CMI and that the latter can be used as an additional criterion for establishing the level of infection. Patients with UTI did not generally appear to have any primary defect of CMI but when suppression of CMI was present, it seemed secondary to an ongoing infection.


Biochemical characterization of the proliferation pool of lymphatic cells in the human tonsil and demonstration of the age-dependent pool size reduction.

The DNA and RNA content and also the thymidine and uridine incorporation kinetics were determined in peripheral lymphocytes and lymphatic cells of the tonsil. The existence of a proliferation pool of lymphoid cells in the tonsil could be established by the comparison of all data. An age-conditioned reduction of the pool size was assumed from the uridine incorporation rate which takes place faster than the organo-specific cell decrease likewise conditioned by age in the tonsil. The abscess tonsil could be explained as a pathological state with considerable reduction of proliferation.


Biomechanics of the human epiglottis.

The mechanism that folds the epiglottis down over the closed larynx in the course of swallowing has been unclear. Measurements of the force needed to fold the epiglottis in cadaver specimens exceed the estimated force available from the aryepiglottic muscle. Frame-by-frame analysis of cinefluorograms reveals that deglutitional epiglottic downfolding occurs at the time of maximal elongation of the hyoepiglottic ligament. The observations lead us to propose a conical model of epiglottic downfolding which also explains the conical shape of the epiglottis usual in early infancy. The infant shape may be part of a protective partially closed entrance adaptive to suckling, while maturational widening of the opening adapts to the growing respiratory demands of increasing physical exertion.


Clinical findings and intestinal immunoglobulins in children with partial IgA deficiency.

We studied the intestinal morphology, and the jejunal and rectal immunoglobulins of 16 children with partial IgA deficiency, defined as serum IgA concentration more than two standard deviations below the mean for age, but higher than the lower limit of sensitivity of single radial immunodiffusion (0.02 g/l). Five of the patients had been treated with phenytoin, 2 had juvenile rheumatoid arthritis, 2 had ulcerative colitis and 5 had recurrent upper respiratory tract infections. The jejunal morphology was normal in every case. In 6 cases normalization of serum IgA occurred during the follow-up, while in one patient with ulcerative colitis the concentration fell below 0.02 g/l. In patients with recurrent infections, there was a decreased frequency of infections when the level of serum igA increased. In 4 patients, IgM-containing cells prodominated in both the jejunal and rectal mucosa, and IgM was increased in the intestinal juice. In 6 patients a significant increase in IgM-containing cells or a decrease in IgA-containing cells or both were seen in either the rectal or jejunal mucosa. There was no correlation between the number of IgA-containing cells in the intestinal mucosa and the serum level of IgA.


The effect of ozone and photochemical oxidants on the interferon production by tonsillar lymphocytes.

In order to elucidate the biological effects of photochemical smog on the tonsil, lymphocytes from human tonsil were exposed to ozone and rabbits were exposed to ozone or photochemical oxidants. The tonsillar lymphocytes were studied for interferon production by Newcastle disease virus and blastoid transformation by PHA. Both interferon production by and blastoid transformation of the human tonsillar lymphocytes decreased markedly on exposure to ozone. Tonsillar lymphocytes from rabbits exposed to photochemical oxidants showed a significant decrease in interferon production. The decrease in interferon production in tonsillar lymphocytes from the rabbit exposed to photochemical oxidants was greater in magnitude than the decrease in interferon production in tonsillar lymphocytes exposed to ozone or non-irradiated automobile exhaust gas. The difference in blastoid transformation between the exposed groups and controls was not significnat. The results suggest that exposure to photochemical oxidants causes some functional changes in tonsillar lymphocytes.


A prospective study of individual courses of breast feeding.

A prospective study of the course of breast feeding was carried out in 75 randomly selected women. Weekly interviews were performed from the day after delivery until the termination of breast feeding, but in no case for longer than 6 months. In each case a detailed analysis was made of the factors leading to transient lactation crises or to complete cessation of breast feeding. A second group of 71 mothers, also randomly selected, was interviewed in retrospect only, 6 months after delivery, and served as controls. Twenty-four weeks after delivery 47% of the mothers in the weekly interview group were still breast feeding. The corresponding figure in the control group was 38%. In both groups only few mothers terminated lactation for medical reasons, while about one fourth stopped for some other reason and about one half because of a combination of factors. Brief case reports are presented to illustrate how varying the factors were that threatened breast feeding.


Smoking during pregnancy--effects on the fetus and on thiocyanate levels in mother and baby.

Twenty-eight mothers smoking 10--20 cigarettes daily during pregnancy had significantly higher serum thiocyanate concentrations at delivery compared in 25 non-smoking controls. The thiocyanate levels were positively correlated to cigarette consumption and inversely correlated to the birth weights of the infants. A highly significant correlation existed between serum thiocyanate levels of the mother and umbilical cord serum thiocyanate levels, reflecting a nearly complete equilibration. The thiocyanate concentrations in human milk on the 4th day after delivery were considerably lower than the serum concentrations, and no correlation existed between serum and milk concentrations. The infants of smoking mothers had significantly decreased weight and length at birth compared in infants of non-smokers. Birth weights were 3 344 +/- 434 g and 3 620 +/- 504 g respectively (p less than 0.05), and lengths 49.8 +/- 1.7 cm and 51 +/- 1.6 cm respectively (p less than 0.05). No differences were found between smokers and non-smokers in placental and umbilical cord histology, and umbilical cord artery medial area. It is concluded that serum thiocyanate concentration in smokers may be used as an objective measure for smoke exposure, and that maternal cigarette smoking acts as an exogenous factor which interferes with intrauterine development of the fetus in a dose related way.


Spontaneous labour and elective induction--a prospective randomized study. Behavioural assessment and neurological examination in the newborn period.

The effect of induction of labour on the foetus and the newborn was investigated in a prospective randomized study. 41 neonates were studied after induction at full term by amniotomy and intravenous oxytocin infusion. The infusion rate was regulated by the intraamniotic pressure using the Cardiff infusion pump system. 39 neonates served as controls where the labour started spontaneously followed by amniotomy. In both groups foetal heart rate monitoring intraamniotic pressure recordings were performed. There were no differences in Apgar score and pH in cord blood between the groups. The newborns were evaluated the first and the fifth day of life with the Brazelton Neonatal Behavioral Assessment Scale and with a modified Prechtl neurological examination. There were no differences in behaviour and neurological state between the two groups. However, within the groups there were significant differences between the first and the fifth day concerning both neonatal behaviour and neurological state.


Effect of intrauterine nutritional deprivation on neuromotor behaviour of the newborn.

The neurological maturation in 25 newborn babies born to severely undernourished mothers was studied by evaluating muscle tone and excitability status. These mothers had weight below the 25th percentile expected for height, haemoglobin less than 80.0 g/l and serum albumin less than 25.0 g/l. Twenty-three babies born to healthy mothers were studied as control. The babies of undernourished mothers demonstrated gross intrauterine growth retardation. There occurred parallel reduction in placental weight and its protein content. The neuromotor behaviour of these newborns showed significant alteration in the performance of most reflexes, resembling normal motor behaviour of preterm infants. As many as 72% newborns could be classified as hypotonic and 56% hypoexcitable. However, no newborn demonstrated hypertonia or hyperexcitability. The parameters of neuromotor assessment were found to have no correlation with the birth weight in both undernourished as well as control group. These observations suggest that muscle tone and excitability are better indices of maturation of central nervous system than the birth weight. It seems that the neurological evaluation becomes unreliable in babies who suffer from intrauterine nutritional deprivation.


Evidence of riboflavin depletion in breast-fed newborns and its further acceleration during treatment of hyperbilirubinemia by phototherapy.

Phototherapy in the treatment of newborns with hyperbilirubinemia, resulting in degradation of bilirubin, also appears to have other photodynamic effects on metabolism. We studied flavin adenine dinucleotide (FAD) saturation of erythrocyte glutathione reductase, which should reflect riboflavin nutritional status, in 28 healthy newborns, and followed 37 newborns with hyperbilirubinemia prior to the start of and during phototherapy. The results indicate that healthy newborns on human milk feeding, relatively poor in riboflavin, have evidence of a transient riboflavin depletion soon after birth. This effect is made more pronounced by phototherapy and partially prevented by parenteral or oral administration of moderate amounts of riboflavin.


A longitudinal study of manganese in human milk.

Flameless atomic absorption spectrophotometry has been applied to the analysis of manganese in human milk samples. Twenty-seven breast-feeding mothers donated 229 individual milk samples between the 2nd week and the 9th month of lactation. The milk samples were representative of every feed in a period of 24 hours, foremilk and hind-milk in equal proportions. The median concentration of manganese declined from the initial value of 5.9 microgram/l to about 4 microgram/l before the 2nd month of lactation, remained at this level up to the 5th--6th month of lactation and showed a tendency to rise thereafter. The values presented here are noticeably lower than most of those reported earlier. It remains an open question whether the manganese concentration is exceptionally low in Finnish human milk or whether the great difference from most earlier studies may reflect problems of contamination or technical difficulties when less sensitive analytical methods have been used.


Umbilical artery catheterization in newborns. I. Thrombosis in relation to catheter type and position.

Seventy-one sick newborn infants, who had an umbilical artery catheterized, were randomized in one of four catheter groups: long end-hole-, short end-hole-, long side-hole- or short side-hole catheter. A long catheter means a high position of the catheter tip (Th6--11) and a short catheter a low position of the tip (L3--5). An angiography through the indwelling catheter in order to diagnose thrombosis was performed before the catheter was withdrawn. Dissection of the aorta and its brances was performed on infants who died. The total frequency of thromboses was 26%. There were no thromboses among infants with long end-hole catheters while infants with short end-hole catheters had thrombosis in 26%, long side-hole catheters in 33% and short side-hole catheters in 64%. Long end-hole catheters functioned better than the others. Only 6 of 16 infants with thrombosis had physical signs from the legs, while 12 infants without thrombosis had similar signs.


Adynamia episodica hereditaria. Treatment with salbutamol.

Three sibs with adynamia episodica hereditaria are described. Treatment with salbutamol inhalation had a beneficial effect on the duration of their adynamic attacks. Continuous peroral treatment with salbutamol has been tried in these patients resulting in the almost complete prevention of attacks. No serious adverse effects have been recorded. Peroral treatment with salbutamol is recommended as the treatment of choice in young patients with adynamia episodica hereditaria and in patients with frequent attacks of adynamia.


Peak expiratory flow rate. Reference values for Swedish children.

Reference values for the peak expiratory flow rate assessed by the Wright-McKerrow peak flow meter have been established for Swedish children. The material consisted of 143 boys and 132 girls. We recommend the sexes be considered together. The equation of the regression line is 72.14 x height3 + 96.12. The coefficient of correlation is 0.93 and the residual standard deviation 13.7%.


Hemoglobin A1c (HbA1c) in children with long standing and newly diagnosed diabetes mellitus.

In 35 children with long-standing diabetes mellitus, a significant correlation was found between the hemoglobin A1c (HbA1c)--and the 24-hour urinary glucose excretion. By contrast, 11 newly diagnosed diabetic children had grossly elevated HbA1c-concentrations, but no correlations could be established between the levels of HbA1c and the duration of symptoms, blood glucose, glycosuria, ketonuria and the acid--base status. However, HbA1c and C-peptide were significantly correlated. The elevated HbA1c-concentrations decreased towards normal in all of these 11 children after 2--3 months following adequate therapy. The results suggest that the determination of HbA1c may serve as a valuable metabolic control index in children with long-standing diabetes mellitus, but adds little information in newly diagnosed patients. For the individual diabetic child during the early treatment period, HbA1c may be the index of choice for adequacy of metabolic control.


Spontaneous perforation of the common bile duct.

An 18-week-old baby boy suffered an episode of acute abdominal symptoms followed by a silent period with mild obstructive jaundice, abdominal distension and failure to thrive. During the clinical work-up he deteriorated suddenly, with progressive abdominal distension and ascites. At laparotomy a perforation of the common bile duct with bile peritonitis was found. Spontaneous perforation of the common bile duct is seldom listed as a cause of obstructive jaundice. The clinical picture is characteristic. Awareness of this diagnosis may help to avoid time-consuming and unnecessary investigations and to lead to surgical treatment in good time.


Scleroderma with massive regional lymphadenopathy.

Scleroderma in a two-year-old boy with gross enlargement of the right inguinal lymph nodes, as an early sign, is reported. Repeated lymph node biopsies revealed non-characteristic reactive changes and hyperplasia, but eventually histological examination of skin and muscle from the right leg were diagnostic. The effect of one year of D-penicillamine therapy is briefly mentioned.


Nonketotic hyperglycinemia. Clinical, biochemical and therapeutic aspects.

A patient exhibiting progressive cerebral depression from the first days of life is described. The diagnosis of nonketotic hyperglycinemia was established on the typical clinical presentation, elevated glycine concentrations in body fluids and diminished glycine cleavage activity in liver tissue. A series of therapeutic trials, including strychnine treatment, was tried on this patient without apparent effect on the clinical course.


Deletion of the long arm of chromosome 11: a clinical entity.

A deletion of the long arm of chromosome No. 11, an aberration undetectable in conventional chromosome staining, was identified with Giemsa banding in a female infant with multiple congenital anomalies. A survey is given of the clinical findings in the few cases so far reported.


Cellular aspects of rabbit Masugi nephritis. IV. Cell quantitation of proliferative glomerulonephritis.

Diffuse proliferative glomerulonephritis was induced in the rabbit with injection of goat nephrotoxic serum, and cell dynamics in the glomerulus were quantitatively investigated. The mean total cell number of a normal glomerulus in cross-section was 54.8, consisting of 24.1 endothelial cells, 16.0 podocytes, and 14.3 mesangial cells. In 5 selected nephritic rabbits, the mean total cell number of a glomerulus at the florid stage (7 to 12 experimental days) was 2.4 times as great as the control. It was revealed that the cells consisted of 27.9 endothelial cells, 14.9 podocytes, 21.1 mesangial cells, and 57.8 monocytic cells, indicating that about 76 per cent of the increased cells were of monocytic origin. Mesangial cells showed moderate increase in number (1.5 times) which persisted until 100 days, whereas endothelial cells increased only slightly. The monocytic cells promptly disappeared at 40 days correlating well with resolution of the proliferative change. Although the cellular compositions varied in each case, it was concluded that monocytes were essential in producing proliferative glomerular changes in the reversible type of Masugi nephritis.


The development of extranodal lymphoid follicles in experimental bronchopneumonia.

Extranodal formation of lymphoid follicles was morphologically studied in experimental bronchopneumonia. Control gnotobiotic mice had no peribronchial lymphoid follicles and only lymphatic vessels were traced from the terminal bronchiolar region toward larger bronchi. During the week after intranasal inoculation of mycoplasma pulmonis, lymphoid follicles developed in the terminal portion of the lymphatics by the accumulation of small lymphocytes. A loose network of mesenchymal cells and early infiltration of macrophages, following stromal edema, seemed to play an important role in the early accumulation of lymphocytes. Blastic transformation was seen frequently in the center of the accumulated lymphocytes. Two weeks after inoculation plasma cells emerged conspicuously in the periphery of the lymphoid follicles, and the acute phase of bronchopneumonia began to subside. Typical germinal centers with tingible body macrophages and dendritic reticulum cells developed when the bronchitis persisted in a chronical manner.


Malignant neurofibroma with glandular differentiation (glandular schwannoma).

A case of malignant shwannoma is reported with unusual elements in an 89-year-old female. A large mass was located in the subcutaneous tissue of the right lateral chest wall and measured 5 cm in the greatest diameter. Histologically the tumor was composed of neurofibroma and malignant schwannoma with glandular differentiation. Neurofibroma characterized by numerous hyaline neural nodules was located in the peripheral portion of the tumor, whereas malignant schwannoma occupied a large part of the central portion of the tumor. The glandular elements observed in some areas of malignant schwannoma consisted of cuboidal and columnar shaped cells and were arranged in tubular or tubulo-medullary fashion in which rosettes or pseudorosettes were found. Mucicarminophilic material was observed, both in the cytoplasm and in the lumen. Seven reported cases of peripheral nerve tumor with glandular differentiation are reviewed briefly.


Immunopathologic studies of renal glomerular change in liver cirrhosis with special reference to its pathogenesis.

The kidneys from 62 proven liver cirrhosis cases were examined by immunofluorescence (IF), and 94% of the cases were positive for some immune reactants deposition. Combined deposition of immunoglobulin(s), both or each one of C1q and C4, and further with C3 were observed in about 70% of all IF positive cases. The morphological alterations of the glomeruli correlated with the intensities of regional immune reactants depositions. Guinea pig C3 was frequently activated in vitro on the glomeruli of these cases. Immune reactants depositions in the glomeruli appeared to form immune complex locally. Smooth muscle and liver cell antigens in the immune complex at the glomeruli were examined by indirect method of IF using monospecific antibodies and positive cases concerning each antigen were found in about 1/3 of the kidneys from 21 liver cirrhosis cases. These facts suggest that the high rate of the occurrence of immune complex deposition type glomerulo-nephritis may be due to the glomerular deposition of some autoantigen-antibody complexes including smooth muscle and liver cell antigens.


Different histological manifestation of glomerular lesions in familial systemic lupus erythematosus.

Lupus nephritis in a sister and brother pair was histologically analyzed. The 12-year-old sister showed clinically progressive renal failure and her renal pathology disclosed segmental necrotizing and disorganizing glomerulonephritis. On the contrary, the 14-year-old brother exhibited nephrotic syndrome and his renal biopsy showed diffuse exudative and proliferative glomerulonephritis with segmental membraneous changes. Although the familial incidence of SLE suggests both genetic and environmental factors existing in the background of SLE of identical twins and siblings, the differences of clinical manifestation and histopathological findings imply that there might be little direct genetic and environmental control on determining the expression of the disease.


Tyrosinemia.

A case of tyrosinemia in a three-month-old boy is presented. The patient appeared jaundiced initially with markedly elevated levels of serum tyrosine and a positive Millon-reacting urine. Jaundice persisted and hepatosplenomegaly gradually increased. He died due to liver failure on the 51st day after admission. At autopsy, the liver showed the features of severe giant cell hepatitis including giant cell formation, fibrosis and bile retention. The pancreas and the brain showed characteristic postmortem findings as previously reported  in patients with tyrosinemia.


Nonpapillary carcinoma in situ of the urinary bladder. A histopathologic study and mapping of the urothelial lesions.

Three cases of primary nonpapillary carcinoma of the urinary bladder diagnosed by urinary cytology and multiple biopsies were reported. Bladder specimens of two of the patients were totally embedded for step-sections that were mapped after histopathologic study. Atypical hyperplasia and carcinoma in situ with foci of microscopic invasion affected the bladder mucosa and extended continuously to the distal ureters as well as prostatic urethra. Multicentric distribuion of the abnormal epithelium was definite in one case, and the bladder mucosa was extensively denuded in the other case. Metastasis to one of the regional lymph nodes was noted in the remaining one case. The origin of Pagetoid cells occurring in two of the cases is obscure, but we presume that these cells may represent transformed tumor cells showing differentiation toward the surface umbrella cells, or they are derived from Brunn's nests where the cells may gain potential to differentiate to glandular epithelium.


Non-traumatic uriniferous pseudocyst. Report of a case.

A non-traumatic uriniferous pseudocyst was incidentally found at autopsy in a patient with invasive urothelial carcinoma involving ureteral orifices. Massive paraaortic lymph node involvement by the metastic tumor in addition to the ureteral obstruction was considered responsible for the formation of uriniferous pseudocyst. The pertinent clinical history and autopsy findings are presented and a possible mechanism of pseudocyst formation is discussed.


C cell carcinoma of the thyroid--papillary type.

Two cases of papillary type of C cell carcinoma of the thyroid were reported. They showed papillary arrangement with fibrovascular stalk in properly fixed tissues. Histochemically argyrophil reaction was positive in the cytoplasm and amyloid deposited in the stroma. Ultrastructurally secretory granules were found in their cytoplasm. The papillary type is not an artifact but one of the histologic variations of this carcinoma.


Prolactin and 3-methylcholanthrene induced cervical carcinoma. Effect of bromocriptine.

Female mice of the NMRI strain were injected with estradil for the first five days after birth (estrogenized animals) and ovariectomized at the ages of 6-9 weeks. One week later, a cotton thread impregnated with 3-methylcholanthrene was inserted into the uterine cervix. Starting on the day of insertion of the thread, and for a further 6 days, the females were injected with estradiol (E2), ovine prolactin (P), or 2-bromo-alpha-ergokryptine mesylate (bromocriptine). Controls were injected with vehicles only. The animals were killed 4 or 8 weeks after insertion of the thread, and the uterine cervix was serially sectioned. A combined treatment with E2 and P resulted in an increased incidence of invasive epithelial lesions in the uterine cervix. This incidence was higher than in controls or females injected with either hormone separately. Bromocriptine reduced the incidence of invasions, and this reduction with either hormone separately. Bromocriptine reduced the incidence of invasion, and this reduction could not be restored to the contrl level by a simultaneous treatment with E2 anrogenized females was higher than that reported in an earlied study using non-estrogpenized females.


Response of pulmonary (circulating) megakaryocytes to experimentally induced consumption coagulopathy in rabbits.

The effects of slow temporary infusion of a tissue thromboplastin solution into the superior vena cava on pulmonary as well as circulating megakaryocytes were studied in 40 rabbits (2-48 hours after infusion) and related to 6 noninfused and 7 infused with normal saline. This is a simple and specific method of inducing a fall in blood platelet levels and thereby an activation of thrombocytopoiesis and megakaryocytopoiesis. The induced intravascular coagulation is probably counterbalanced by an activated fibrinolysis allowing the animals to survive the infusion and thereby offering the possibility of studying the long-term effects. An increase to about  300% of the normal values in circulating as well as pulmonary megakaryocytes was found 20 and 24 hours after the onset of the infusions respectively. The number of circulating and pulmonary megakaryocytes, showing great individual variations, however, dropped to normal levels within 28 hours after onset of the infusions, which means that megakaryocytes remain detectable for less than eight hours in the lungs. No increase was found in pulmonary megakaryocytes in the control (saline infused) group. In our opinion the entrance of megakaryocytes from the bone marrow into the blood circulation in an incidental event, the number in the circulation reflecting the activity of megakarycocytopoiesis. This experiment supports our suggestion that intravascular coagulation is one of the major pathophysiological mechanisms leading to an increase in pulmonary megakaryocytes.


Effects of cyclophosphamide on open, granulating skin wounds in rats.

The effect of cyclophosphamide on the healing of open cutaneous wounds was studied in rats. Following intraperitoneal injections of 25 mg/kg body weight every second day for 9 days, only about 7% of the wounds were completely covered by epithelium after 15 days, whereas in the control animals 60% of the wounds were completely epithelialized. Measurements of wound diameters in circular skin wounds revealed unhealed wound areas in the drug treated animals which were significantly larger than those of the control animals. Cyclophosphamide was found to reduce the occurrence of H3-labelled cells in the granulation tissue when evaluated after 11 days. At 15 days there was no difference in the labelling frequency between treated and control animals, indicating reversal of the drug effect.


Mechanical properties and hydroxyproline content of connective tissue in porous ceramic implants.

The present study describes a model applying ceramic implants (A1203) for in vivo studies of connective tissue regeneration. Two types of implants have been developed: a one-piece model for histological examination and chemical analyses, and a two-piece implant which can also be used for mechanical testing of connective tissue. When these were implanted subcutaneoulsly on the back of rats, a correlation was found between the mechanical strength and the hydroxyproline content of connective tissue in the implants. The peak synthesis occurred between the 7th and the 14th day after implantation, and a plateau was reached for both strength-increases and hydroxyproline-formation between the 14th and the 21st days. For histological examination, the implants were embedded in plastic materials and prepared as hard tissue specimens. The model presented can be applied to study connective tissue regeneration in normal and pathological conditions, including studies of the effects of various drugs on the connective tissue.


Surface ultrastructure of human arteries with special reference to the effects of smoking.

The surface ultrastructure of uterine arteries from 20 women was studied with scanning electron microscopy. Specimens were excised and fixed under pressure shortely after removal of the uterus during hysterectomy. Two groups of patients were selected: non-smokers and women who smoked more than 15 cigarettes a day. The prevalence of seven different morphological criteria was evaluated without knowledge of the smoking habits of the patients. Endothelial cells were usually well demarcated and distributed with their length axis paralledl to that of the artery. The cell nucleus was revealed by a gentle bulging into the lumen, and cell borders by the presence of rows of microvilli. Inter- and intracellular holes alon the cell borders were more common in arteries from smokers, whereas microvillie were more common on the cell surfaces of arteries from non-smokers. These differences might be related to cell injury. Previous studies indicate that holes are more frequent in injured than in non-injured cells, whereas the surface of injured cells is often smoother than that of non-injured cells. Therefore, these data may be taken to suggest that smoking can lead to endothelial injury in man.


Structural changes and ability to release renin in auto- and allo-transplants of mouse submaxillary glands.

In mice having a high renin content in the submaxillary glands allo- and autotransplantation of the gland showed identical histological changes of the tissue, comprising disappearance of acini and intercalated ducts as well as a reduction in the number and size of granules in the granulated ducts. No structural signs of rejection were found. Adenomas, possibly originating in the granulated ducts, were frequently present in the transplanted glands. The renin content of autotransplanted glands was invariably much higher than in allotransplants, and after noradrenaline injection renin was released only from autotransplants, never from allotransplants. Blockade of the renin system was accordingly followed by a decrease in blood pressure only in mice with autotransplants.


Cell proliferation in normal and diseased gastric mucosa. Autoradiography after in vitro continuous labelling with tritiated thymidine.

The rate of gastric epithelial cell proliferation was studied in healthy volunteers and in patients with different degrees of gastritis. Endoscopic biopsies from the antral and fundic part of the stomach were incubated in vitro with 3H-thymidine for 30, 120, and 210 minutes respectively. Autoradiographs were prepared, and the percentage of DNA-synthesizing cells (labeling index) in the progenitor cell region was estimated. From the successive labeling indices the rate of entry of cells into DNA-synthetic phase (S-phase) and the duration of the S-phase could be estimated. All the biopsies were classified according to the degree of gastritis. The mean (+/-SEM) length of the S-phase was found to be 7.4 +/- 0.3 hours in antral mucosa and 7.2 +/- 0.4 hours in fundic mucosa. There was no significant difference between the S-phase duration in normal mucosa, superficial gastritis, mild atrophic gastritis and severe atrophic gastritis. This observation suggests that the labeling index can be used as an expression for the rate of cell proliferation in human gastric mucosa. A significant correlation between the labelling indices and the degree of gastritis was found in both antral and fundic mucosa. In six cases, labelling indices estimated by cell counts performed on longitudinal or cross sections of foveolae were compared. Ther was no significant difference between the results obtained by the two different counting techniques.


Diaphragmatic blood flow at various levels of ventilation in the rabbit.

Diaphragmatic and renal blood flow were measured with Ytterbium-169 and Scandium 46 labelled 15 micron microspheres in sodium pentobarbitone anesthetized rabbits. The first measurement was performed during spontaneous breathing of air and the second measurement after 15 min of breathing 2-6% carbon dioxide in oxygen. The lung ventilation as well as the diaphragmatic blood flow increased significantly during breathing of the carbon dioxide-oxygen mixture. Arterial blood pressure and renal blood flow were not significantly altered by the induced hyperventilation. No significant correlation was found between the magnitude of lung ventilation and diaphragmatic blood flow. The results of the present study indicate that consecutive measurements of diaphragmatic blood flow with radioactive microspheres at various levels of breathing effort is an appropriate method for further exploration of the relationship between diaphragmatic perfusion and working performance.


Evidence for a cholinergic secretory innervation of the guinea-pig endometrium.

Uterine mucus secretion was studied by measuring carbohydrate release from everted guinea-pig uteri placed in organ baths. Field stimulation of the organ resulted in a significant increase in carbohydrate out-put, this increase was inhibited by tetrodotoxin, scopolamine and previous destruction of the paracervical ganglia. Previous section of the hypogastric nerve reduced the response to field stimulation, while interruption of the costouterine connexion or the pelvic nerve was without overt effect. Stimulation of the hypogastric nerve increased uterine carbohydrate secretion. Pelvic nerve stimulation produced no significant effect. Carbachol increased the carbohydrate secretion to the same extent as did field stimulation. Isoprenaline and methoxamine were without significant effect. It is suggested that certain endometrial cells have a cholinergic sympathetic secretory innervation with pre- and postganglionic fibers running in the hypogastric nerve.