Pirenzepine in duodenal ulcer. A multicentre double-blind controlled clinical trial. Second of two parts.

Ninety-six patients with endoscopically proved active duodenal ulcers were admitted to a multicentre double-blind trial with either pirenzepine (100 mg/day, 25 mg in the morning and midday and 50 mg at bed time) or placebo for 4 weeks. Ninety-two patients (46 in each group) completed the trial. After 4 weeks, complete healing had been achieved in 70% of the pirenzepine-treated patients and in 32% of the placebo-treated ones (P less than 0.01). No important side-effects and no abnormal changes in blood values or urinalysis were observed during treatment. The difference in the ulcer healing rates observed in the two parts of this multicentre trial is briefly discussed.


Pirenzepine and carbenozolone in gastric ulcer. Preliminary results of a multicentre double-blind controlled clinical trial.

Pirenzepine (PRZ) 75 mg/day for 1 week followed by 50 mg/day for 3 weeks did not show a good activity in gastric ulcer healing in comparison to carbenoxolone (CB) (300 mg/day for 1 week followed by 200 mg/day for 3 weeks). The tolerability of PRZ seemed to be better than that of CB. The increase in the daily dose of PRZ to 100 mg/day for 4 weeks led to better results in the patients who have completed satisfactorily the treatment up to now. PRZ's tolerability was greater than CB's. The results of this study are preliminary to further trial.


Pirenzepine in the treatment of benign gastroduodenal diseases. A double-blind controlled clinical trial.

Pirenzepine (PRZ, 75 mg/day for 10 days followed by 50 mg/day for 20 days) was compared with placebo (PL) in the treatment of endoscopically confirmed active gastroduodenitis or duodenal ulcer and with carbenoxolone (CB, 300 mg/day followed by 200 mg/day) in the treatment of gastric ulcer in a 30-day double-blind clinical trial. Ninety-seven of 112 outpatients completed the trial. The results can be summarized as follows: a) Gastroduodenitis. Complete normalization of the endoscopic picture was observed in 61% of the 28 patients on PRZ and in 30% of the 27 on PL. b) Duodenal ulcer. Complete endoscopic healing was observed in 75% of the 12 patients on PRZ and in 44% of the 9 on PL. In both studied PRZ induced improvement in clinical symptoms in more patients than PL. c) Gastric ulcer. PRZ and CB induced complete healing in a similar percentage of patients (64% of 11 and 70% of 10 patients). Better results in dyspepsia were observed in the PRZ group than the CB group. No major side-effects and no pathological changes in blood and urine analyses were observed in PRZ-treated patients.


Pirenzepine in the treatment of duodenal ulcer.

The effectiveness and safety of pirenzepine (PRZ) at 150 mg daily in the treatment of active duodenal ulcer was studied in an open pilot clinical trial followed by a double-blind trial against placebo. The open pilot study showed that pirenzepine was well tolerated and promoted ulcer healing in the 45% of patients within 2 weeks of treatment and in 90% within 4 weeks. The double-blind trial against placebo (PL) Confirmed these results: 60% of the patients in PRZ group and 10% of the patients in PL group showed endoscopic ulcer healing after 2 weeks. This difference was significant. Ninety per cent of the PRZ patients and 50% of the PL patients were completely healed after 4 weeks. In the PRZ group, gastric secretory tests showed a significant decrease in B.A.O. (69%), M.A.O. (33%) and P.A.O. (34%) after 2 weeks. In the PL group, the same parameters had only a small decrease, without statistical significance. There were no pathological changes in laboratory findings in either the open or the double-blind studies. Mild and transient side-effects were observed in 7 of 30 patinets receiving pirenzepine (diplopia and dryness of the mouth).


Pirenzepine (LS 519) in severe duodenal ulcer and in gastric ulcer. A double-blind clinical trial.

Duodenal ulcer. Forty-five of 49 adult outpatients with active, severe, endoscopically proven duodenal ulcers completed a 4-week double-blind trial comparing two doses of LS 519 (75 and 150 mg/day) with placebo. After 2 weeks, 1 of 15 patients given LS 75 mg and 4 of 15 given LS 150 mg/day had healed (P = 0.09). No patient given placebo had healed. After 4 weeks, 6 of 15 (40%) on placebo, 9 of 15 (60%) on LS 75 mg and 13 of 15 (86.7%) on LS 153 mg had healed (P less than 0.01). Patients given the highest dose of LS had significantly more pain-free days and nights and took fewer antacid tablets than those receiving the lowest dose of LS or placebo. Gastric ulcer. 19 of 20 adult outpatients with endoscopically proven active benign gastric ulcers completed a double-blind 4-week trial with either LS 519 (75 mg/day) or carbenoxolone (300 mg/day). Six of 10 (60%) given LS and 6 of 9 (66.7%) given carbenoxolone had healed after 4 weeks (N.S.). Symptomatic improvement was significantly faster in the LS group than in the carbenoxolone group. Hypokaliemia, increases in alkaline phosphatase and SGOT were observed in the carbenoxolone group.


A double-blind, short-term clinical trial of pirenzepine in duodenal ulcer.

The effectiveness of pirenzepine in the treatment of duodenal ulcer was assessed in a double-blind clinical trial in comparison with placebo. Twenty-nine of 30 patients satisfactorily completed the trial. There was endoscopic ulcer healing in 4 of 14 pirenzepine treated patients (29%) after 2 weeks of treatment and in 11 of 14 (79%) after 6 weeks. There was no healing in 15 patients treated with placebo after 2 weeks and there were two ulcers healed after 6 weeks. The difference between pirenzepine and placebo was significant in both 2nd and 6th week. Duodenitis (evaluated by endoscopy) markedly improved in the pirenzepine grouu after 2 (4 of 9 patients) and after 6 weeks of treatment (8 of 9), while no, or only slight, improvement was observed in 8 of 8 patients in the placebo group. When evaluated by ulcer symptom relief and antacid tablet comsumption, pirenzepine proved to be considerable more efficacious than the placebo. The results of this study demonstrate that pirenzepine promoted duodenal ulcer healing, that it markedly improved peptic duodenitis and promoted rapid regression of symptomatology in parallel with endoscopic findings.


Pirenzepine in the treatment of gastric ulcer. A double-blind short-term clinical trial.

The effectiveness of pirenzepine in the treatment of gastric ulcer was assessed in a double-blind 6 weeks' clinical trial in comparison with placebo. After 2 weeks of treatment 1 patient in each group showed a complete healing of gastric ulcer. After 6 weeks of treatment 9 out of 10 patients in the pirenzepine group (90%) and 4 out of 10 patients in the placebo group (40%) healed (P less than 0.05). The relief of ulcer symptoms was significantly better in the pirenzepine group than in the placebo group. From the second week on, the pirenzepine-treated patients stopped taking antacid while placebo-treated patients went on taking it (P less than 0.02). The results of this study demonstrated that pirenzepine promotes gastric ulcer healing and induces a rapid regression of ulcer symptoms.


Pirenzepine versus cimetidine in the treatment of duodenal ulcer.

Fifty-five patients with active duodenal ulcer have completed, up to today, a one-month double-blind trial to compare the effects of pirenzepine (150 mg daily), cimetidine (1 g daily) and placebo on the healing of duodenal ulcer. Fifteen (71%) of the 21 patients treated with pirenzepine had healed ulcers compared with 14 (82%) receiving cimetidine (P less than 0.05. In the placebo group there were 7 (41%) healed ulcers. Symptomatic improvement in patients given pirenzepine was as substantial as in cimetidine-treated patients. No adverse effects were noted.


Inhibition of pentagastrin and insulin-stimulated gastric secretion by pirenzepine in healthy and duodenal ulcer subjects.

The effect of i.v. pirenzepine infusion both on basal and pentagastrin and insulin-stimulated secretion was studied in 19 healthy and duodenal ulcer subjects. Following an overnight fast, gastric juice was collected for 30 minutes prior to the i.v. administration of pirenzepine (16 mg plus 2 mg/h for 2 hours) and the subsequent stimulation of gastric secretion by means of i.v. pentagastrin infusion (6 microgram/kg/h) or i.v. insulin injection (0.2 U/kg). Mean acid output was reduced--in comparison to placebo--by 22% after pentagastrin stimulation and by 34% after insulin stimulation.


Pirenzepine in peptic ulcer. Introduction to clinical trials reports.

The main pharmacodynamic characteristics of pirenzepine are briefly reported and the experimental plan of the clinical trial on pirenzepine in peptic ulcer is discussed.


Phase II trial of Prednimustine. Leo-1031 (NSC-134087) in acute non-lymphocytic leukemia.

18 patients with acute non-lymphocytic leukaemia were treated with Prednimustine, a chlorambucil ester of prednisolone, as a single drug. 5 patients responded with falling blast counts in peripheral blood, but only 1 obtained a complete remission of 3 months' duration. Since the activity of Prednimustine is lower than that of other commonly used drugs in acute non-lymphocytic leukaemia, future studies should concentrate on other aspects, such as treatment of patients with steroid receptor-positive blast cells or other types of leukaemia.


Humoral and cellular immunity to intrinsic factor in myasthenia gravis.

Myasthenia gravis (MG) is an autoimmune disease often associated with other autoimmune disorders. A case history of MG with a coexisting atypical megaloblastic anaemia with vitamin B12 deficiency and anti Intrinsic Factor (IF) antibodies, led to a study of humoral and cellular immunity to IF in 81 MG patients. Within this series, 3 other patients had a disturbed humoral and cellular immunity to IF. These 3 patients presented no other features of pernicious anaemia. The possible origins and significance of the anti IF antibodies in MG patients are discussed.


Bacterial lipopolysaccharides bind selectively to lymphocytes from lipopolysaccharide high-responder mouse strains.

Three different concentrations of horseradish peroxidase-labelled lipopolysaccharide (LPS-HRP) were added in vitro to spleen cells from the LPS high-responder strain C3H/Tif and to cells from the low-responder strain C3H/HeJ. After being washed and fixed the cells were exposed to the substrate and prepared for electron microscopy. After addition of 7 and 0.7 microgram/ml of labelled LPS only lymphocytes from the high-responder strain were labelled. About 5-10% of the cells from C3H/Tif bound LPS, which is in accordance with the known frequency of B cells possessing the genetically determined LPS receptor. At the highest dose of labelled LPS (70 microgram/ml) a large proportion of lymphocytes from the low-responder strain also bound LPS. Erythrocytes from both strains bound LPS at all concentrations. It is concluded that LPS-HRP allows the detection at the cellular level of LPS binding to the genetically controlled membrane receptor for LPS.


Human monocyte-mediated cytotoxicity to K-562 cells: activation by lymphokines.

Human monocytes purified by adherence and prolonged in vitro monolayer culture were activated by supernatants of autologous lymphocytes stimulated with live bacillus Calmette-Guérin or killed Corynebacterium parvum. Activated monocytes expressed increased ability to lyse K-562 cells prelabelled with methyl-3H-thymidine in a 48 h assay. Activation could be detected at a 1:64 dilution of lymphokine supernatants. Target cell killing by activated monocytes was strongly influenced by the density of the monocyte monolayer. Monocytes at an intermediate stage of in vitro differentiation seemed to be most response to lymphokine activation. Morphological studies indicated that a considerable number of K-562 cells attach firmly to monocytes. The monocyte-mediated lysis of K-562 seems to be extracellular, as phagocytosis was not observed. Freshly isolated adherent blood mononuclear cells (greater than 90% monocytes) were strongly cytostatic to K-562 cells, as determined by inhibition of methyl-3H-thymidine uptake. Considerable cytolytic activity was also found with freshly isolated adherent cells, strong enhancement being produced by performing the assay in the presence of newborn calf serum, as opposed to human AB serum.


Hyporesponsiveness to virus antigens in rheumatoid synovial and blood lymphocytes using the indirect leucocyte migration inhibition test.

Mononuclear cells (MNC) from rheumatoid synovial tissue and peripheral blood were tested plasma pneumonia by the indirect leucocyte migration inhibition test. MNC from the eleven rheumatoid synovial tissues tested had deficient leucocyte inhibitory factor production against all antigens tested for, and this was also the case in the peripheral blood of seven juvenile rheumatoid arthritis patients (JRA). In the peripheral blood of eight rheumatoid arthritis (RA) patients there was also generally low reactivity. However, significant differences in migration indexes were found with rubella viral antigen and with PPD at 5 micrigram/ml when zero-hour  and overnight incubations of the culture were compared. In contrast, MNC of peripheral blood of control donors had significant responses to PPD (19/19), mumps virus (7/11), rubella virus (10/19), cytomegalovirus (4/11), and herpes simplex type 1 virus (4/11) antigen after zero-hour culture, and no differences was seen after overnight incubation.


The effect of pulsed electromagnetic energy (Diapulse) on the survival of experimental skin flaps. A study on rats.

Experimental skin flaps in rats were treated with an active/non-active Diapulse unit in a double-blind trial to clarify whether or not pulsed electromagnetic energy had any effect on the surviving length of flaps. The observed differences in surviving flap areas between the Diapulse treated group and the untreated group as compared to the predicted survival by fluoresceine and/or vital capillary television microscopy were not statistically significant (p less than 0.10) in a set up, that on a significance level of 5%, would have detected an enhancement of flap survival of greater than or equal to 10% in 98% of trials.


The free abdominoplasty flap and its use in breast reconstruction. An experimental study and clinical case report.

In search for a free microvascular flap which would give abundant reconstructive material as well as a satisfactory donor site the free abdominoplasty flap was developed. The flap is designed on the area between the umbilicus, the pubic region and the anterior superior iliac spines and is based on the inferior epigastric vessels on one side only. In eight regular abdominoplasty procedures elevation of this flap and keeping the blood flow intact through the isolated vessels did not jeoparding the viability of the flap. Angiography of the specimens showed a good perfusion. The free abdominoplasty flap has been used for breast reconstruction in 2 cases of radical mastectomy. The first was failure because of venous thrombosis. In the second case 3 veins were anastomosed, 2 venae comitantes to the inferior epigastric vein and the contralateral superficial epigastric vein and the result was favourable.


The iron content of split skin grafts after general infiltration and percutaneous anaesthesia.

The iron content of split skin grafts from guinea pigs has been studied by flameless atomic absorption spectrophotometry from the time the grafts were cut until the transplants had been in contact with a standardized recipient area for 7 days. The iron content was taken as a measure of the blood content of the grafts. In order to relieve pain, general anaesthesia with ether, local anaesthesia by infiltration and local percutaneous anaesthesia with a solution of ketocaine. A2358, were used. At the time of cutting the grafts the iron content was highest when percutaneous anaesthesia had been used. After a decrease in the iron content in all grafts during the two first postoperative days there was an increasing level from the third day as a sign of revascularization. A stabilization of the values when general and percutaneous anaesthesia had preceded the operation was noted from the fifth postoperative day. The level was highest in the grafts cut after percutaneous anaesthesia.


Intrathoracic approach for subclavian and innominate artery reconstruction.

A subclavian or innominate artery obliteration may cause a retrograde flow in the vertebral artery, a subclavian steal. The steal has been associated with cerebral symptoms indicating vertebrobasilar ischaemia, the subclavian steal syndrome. As there still are no objective means of measuring the effect of the steal on the brain circulation, the syndrome can only be proved by experience from the results of surgical attempts to correct the steal. The steal was at first eliminated by direct reconstruction of the subclavian and innominate arteries through a thoracic approach. As the mortality was high, many surgeons have used cervical bypass procedures with considerably lower mortality. The present report is based on 15 years' experience with 85 patients operated on with direct artery reconstruction through a thoracotomy. A low mortality (1.3%) for the last ten years, a high patency of the reconstruction (80%) 8 years postoperatively and rather high rate of improvement (72%) in patients with subclavian steal syndrome were found. The study shows that the mortality rate with the thoracic approach need not necessarily be higher than with the cervical one. The high patency and the haemodynamically correct type of the reconstructions favour the thoracic approach. However, the direct reconstruction demands a technically advanced surgeon, who is well aquainted with the method. The results also showed that surgery still may be an alternative in patients with symptomatic subclavian steal.


Relief of chronic arterial obstruction using intravenous brinase. A control study.

A therapeutic trial using placebo or the thrombolytic enzyme brinase was carried out in a group of patients with chronic arterial obstruction. The patients were observed for 3 months before receiving six intravenous infusions of either saline or brinase over a period of 2 weeks. Ankle blood pressure, Doppler ultrasound scanning, and arteriography were used to establish diagnosis in the patients. No changes were observed during the 3-month pre-observation period. After six brinase infusions, recanalization of 17 out of 27 obstructed arterial segments was recorded and the number of patent segments increased from 11 to 27. No improvement was observed in the placebo-treated patients. The differences between brinase and placebo treatment was statistically significant.


Superficial mycoses in a southern New Zealand district.

A total of 2,709 pathogenic fungi were isolated from 8,762 patients suspected as having mycotic disease, over an 8 year period in Christchurch, New Zealand. The district is climatically designated as temperate with average mean temperatures of 17 degrees C in summer and 8 degrees C in winter. The predominant species of fungi were relatively small in number with Trichophyton mentagrophytes var. interdigitals as the major pathogen. Fungi other than true dermatophytes, particularly Candida spp. and Malassezia furfur, were included to demonstrate the full spectrum of superficial mycoses presenting for diagnosis at the mycology clinic.


Cineradiography in odontology.

Using cineradiographic equipment with 35 mm film, the application of cineradiographic technique in odontology has been investigated with special reference to observation of bolus-position, the mandibular movement pattern, chewing velocity and the stability of full dentures. The study is divided in two parts. In the first part an assessment is made of the theoretical and practical error of the method and the radiation dose is determined. In the second part limited studies are performed on test-subjects before and after different types of oral rehabilitation. The mathematically estimated geometrical errors almost coincided with the results of the clinical test of the distortion and, together with the tracing error, were of such magnitude that high precision measurements were not possible. By using metal indicators the error could be reduced and movements or differences in the X-ray film greater than 1 mm could be observed with good accuracy. The absorbed dose was determined using the method of thermoluminescent dosimetry and was found to be approximately 5 rad for a cineradiographic investigation of the cranium. The studies of bolus position, mandibular movements etc. revealed, that after oral rehabilitation the patient's oral behaviour may change dramatically. New occlusal surfaces were in most cases used for mastication after a short period of adaptation after rehabilitation. The mandibular movement pattern was also markedly influenced. It is concluded that cineradiography is very suitable for observations of intra-oral behaviour, such as bolus position, and for functional movement analyses. For high-precision measurements other methods should be used.


Recent advances in sympathetic ophthalmia.

Recent advances in understanding the pathogenesis of sympathetic ophthalmia are helping to remove the pigmented cloud which has obstructed the view of researchers on this disease for many years. Clinical features, diagnostic testing, histopathologic variations and principles of treatment are evaluated in the context of our increasing understanding of the pathogenesis of this disease. The relationship of sympathetic ophthalmia to Harada's disease and phacoantigenic uveitis are reviewed.


Methyl prednisolone and lung function after cardiopulmonary bypass.

Thirty-one patients who were undergoing cardiopulmonary bypass for elective aortic valve replacement were studied. The effects on some aspects of lung function of intravenous methyl prednisolone, administered immediately before bypass, were assessed by measuring alveolar-arterial oxygen differences and shunt fractions. No significant differences in pulmonary function were found between the treated and control groups. The use of methyl prednisolone in this context is not justified.


Effect of an inhaled antihistamine (clemastine) as a bronchodilator and as a maintenance treatment in asthma.

Although intravenous chlorpheniramine can cause bronchodilatation, oral and parenteral antihistamines have not proved useful in treating asthma. Inhaled antihistamines may cause throat irritation, but a recent study of the antihistamine, clemastine, showed it to be an effective bronchodilator without irritant effects. We have extended these studies to determine the site of action of inhaled clemastine and to assess its potential usefulness both as a bronchodilator and as a maintenance treatment. Eleven stable asthmatic patients received inhaled clemastine and placebo and the effect was assessed by serial maximum expiratory flow volume (MEFV) curves breathing air and a helium/oxygen (He/O2) mixture. There was no significant improvement in peak flow rates during air breathing after clemastine and no significant difference between the responses to drug and placebo. Minor but significant changes were seen in some flow measurements on the downslope of the MEFV curve during air and He/O2 breathing, and these are tentatively ascribed to a dilating effect of clemastine on peripheral airways where flow is laminar. Subsequent administration of inhaled isoprenaline showed the patients to be still capable of significant bronchodilatation. The addition of clemastine, from a pressurised aerosol, to the patients' therapeutic regimen for two weeks was no more effective than placebo in controlling airflow obstruction, and did not reduce the need for standard bronchodilators. In our patients clemastine was not a clinically useful bronchodilator either acutely or as a maintenance treatment for asthma.


Use of BCG as an immunostimulant after resection of carcinoma of the lung: a two-year assessment of a trial of 500 patients.

BCG (Glaxo) (0.5 ml = 5 X 10(6) organisms) was given subdermally to 250 patients ten days after resection of a lung carcinoma to stimulate the immune system. Increased activity of lymphocytes and macrophages could possibly result in the destruction of small extrapulmonary tumour deposits that were previously unidentified. The two-year survival of this group of patients was compared with 250 controls not receiving BCG after operation. A comparative analysis of the sex, histological types, and lymph node involvement in relation to the survivals occurring in these two groups showed that the administration of BCG by the method described produced a numerically greater survival rate, which was particularly noticeable in the women. None of these figures, however, is statistically significant. It would be unwise to draw any final conclusion until a five-year survey has been completed.


First pass uptake of 14C-propranolol by the lung.

Uptake of 14C-propranolol by the lungs during a single passage through the pulmonary circulation was measured in ten patients at cardiac catheterisation. Mean lung uptake of propranolol was 75% in seven patients who were not previously taking the drug and 33% in three patients who were taking it as regular oral treatment. Lung uptake of propranolol in man is therefore considerable and is partly saturable by normal oral doses. This may alter the dose response relation for propranolol and a wide range of other drugs when given intravenously. The method used to study lung uptake is simple and might be suitable for studies of endothelial cell function in disease.


Vitamin metabolism and therapy in ophthalmology.

Vitamin deficiency states are important in the genesis of many ocular disorders. Deficiencies may be due to poor dietary intake, or to alterations in metabolism produced by some commonly prescribed medications or by certain diseases. Furthermore, some vitamins may exert important pharmacologic effects on the normal eye. The ocular effects of deficiencies and excesses of specific vitamins, and the therapeutic uses of each vitamin, are reviewed.


A comparison of ampicillin and amoxycillin in acute on chronic bronchitis.

Twenty-five patients with an acute exacerbation of chronic bronchitis completed a double-blind trial of amoxycillin 1.5 g v ampicillin 4 g daily. After treatment for one week there was no difference between the treatments in the rates of achieving mucoid sputum, reduction in sputum volume, improvement in peak expiratory flow rate, or duration of hospital stay. In the doses studied ampicillin and amoxycillin are effective drugs of about equal cost.


The optimal therapeutic range in oral anticoagulation. History and proposal.

For patients on oral anticoagulation controlled with Quick's prothrombin time test using rabbit brain thromboplastin American clinicians proposed in the early 1940s that the lower limit of prolongation be taken at 1.5 and the upper limit at 3, corresponding to 10-30% prothrombin activity on a saline dilution curve. Thromboplastins derived from other tissues and species were later introduced, methods were modified, and adsorbed plasma was used instead of saline in the construction of the dilution curve to obtain percentage prothrombin activity; ratios and percentages lost their initial significance, but too often without the clinicians' awareness. With the detection of PIVKAs, finally, it became clear that transformation of prothrombin times into percentage activity, as obtained from dilution curves, could never be a valid means of standardization. It also became evident that only direct comparison of thromboplastins with (fresh) plasma from patients on stabilized oral anticoagulants could be used to determine equivalent therapeutic ranges for different types of thromboplastins. Reference thromboplastins were established and calibration procedures developed. A series of well-controlled clinical trials has provided sufficient information to define, in terms of these reference thromboplastins, therapeutic ranges for the prophylaxis and treatment of venous as well as arterial thrombosis. Definition of the ranges in terms of the biochemical defect induced by coumarin congeners remains, however, to be established.


Effect of weak-, non-, and co-carcinogenic chemicals on 2-acetylaminofluorene-induced mutation in Salmonella typhimurium.

The effects of various weak, non-, and co-carcinogenic chemicals on 2-acetylaminofluorene-induced mutation in Salmonella typhimurium were studied. We found that a single co-mutagen could provide for either enhanced or decreased mutagenesis. A differential effect on mutagenic expression was dependent upon: (1) the type of inducer of S-9 (supernatant from liver homogenate centrifuged at 9000 x g) liver enzymes; (2) the amount of S-9 enzyme preparation employed; and (3) the combined dose of mutagen plus co-mutagen studied. No effect was observed in the absence of S-9. Our data suggest that in S. typhimurium a primary factor in the alteration of mutagenesis by a combination of chemicals is changes in metabolism of the principal mutagen.


Electron microscopic studies on Blastocrithidia triatomae Cerisola et al. 1971 (Trypanosomatidae).

In the bug Triatoma infestans developmental stages of Blastocrithidia tritomae, which can be mistaken for T. cruzi during xenodiagnosis, were studied by means of electron microscopy. It turned out that three different forms appeared during the progressive divisions: "micro-", "pro-" and epimastigotes. The morphological study revealed significant criteria for a distinction from T. cruzi stages. Furthermore cyst-like bodies were observed often attached to the flagella of the different stages. As revealed by the presence of labyrinthine structures found in flagellated stages and in the cyst stages the latter were suggested as being specific cysts to be excreted with the feces and thus to establish new infections in other bugs. Apart from the cyst-like structures a comparison with the organelles known from other Trypanosomatidae showed only slight variations. A tubular cytopharynx-like structure, which was lined by microtubules, and the way of attachment of the flagellum to the surface of the host cell has not been described in Blastocrithidia before.


Antimalarial activity of the optical isomers of chloroquine diphosphate.

Optically pure d- and l-Chloroquine Diphosphate were examined for their efficacy against Plasmodium berghei in mice. The d-enantiomer is significantly more effective than the corresponding l-enantiomer, and in subcurative doses the d-enantiomer is also signficantly more active than the racemate. This increased activity  has however no influence upon Chloroquine-resistant strains of P. berghei. The LD50 in non-infected mice is higher for the d-enantiomer than for either the racemate or the l-enantiomer when mice were treated orally one and 4 times. These differences in efficacy and toxicity between the d- and l-enantiomer of Chloroquine are however not as pronounced as those found for the enantiomers of many other drugs and furthermore these differences are limited to subcurative doses.


The effects of endogenous hypergastrinemia and hypogastrinemia on the exocrine and endocrine rat pancreas.

The effects of endogenous hypergastrinemia and hypogastrinemia on the exocrine and endocrine pancreas were studied in the rat. Hypergastrinemia was induced by antral exclusion, and hypogastrinemia by antral resection. The studies were made 14 weeks after surgery. The total weight of the pancreas was increased both in hypergastrinemic and hypogastrinemic animals, due to hypertrophy of the exocrine cells. In contrast, the volume and total weight of the pancreatic islets were decreased. There was no numerical difference in the A-, D-, PP-cells between the hyper- and hypogastrinemic animals, respectively, and the controls. The number of insulin-producing (B-) cells was certainly reduced after the induction of hypogastrinemia. There was, however, signs of increased B-cell activity, which might contribute to an underestimation of the number of B-cells with the technique used. These findings do not support the hypothesis that antral gastrin has trophic influence on either exocrine or endocrine pancreas.


Comparison of glucose tolerance, serum insulin, serum lipids and skinfold thickness between 50- and 60-year-old men.

Two apparently healthy male groups, one 60 (n = 67) and one 50 (n = 367) years of age were compared with respect to blood glucose, serum lipid and serum insulin concentration and intravenous glucose tolerance. These groups were recruited from two health surveys performed on male populations of these ages in the municipality of Uppsala. The prevalence of diabetes mellitus in the two health survey populations were 4.5% and 0.9%, respectively. No significant differences in serum triglycerides, serum cholestrol and fasting serum insulin concentrations were found between the two age groups. Significantly higher k-values and higher early serum insulin response to i.v. glucose were found in the younger than in the older age group. The older age group was more obese, than the younger group. It is concluded that the prevalence of diabetes increases considerably in males between 50 and 60 years of age. In parallel, the prevalence of decreased glucose tolerance is increasing, which might partly be explained by increased body weight and partly by an impaired pancreatic beta-cell function.


[Immunobiological activity of various blood serum fractions from cattle and swine. The dynamics of Ig in specific serum against colibacillosis in pigs].

The level of the IgM and IgG agglutinating antibody specific hyperimmune serum against coli-bacteriosis and its fractions were studied. The serum was obtained at various stages of the preparation, hyperimmunization and exploitation of serum producing swine by using the 2-mercapto-ethanol test. It was established that serum of the total globulin, alpha-beta-globulin and gamma-globulin fractions contains IgM and IgG agglutinating antibodies against E. coli. These immunoglobulin classes are synthetized at all stages of serum producing swine preparation, hyperimmunization and exploitation. The quantitative IgM:IgG ratios at the individual stages vary. At the initial stages and until the 10th cycle of exsanguination (phlebotomy) IgM antibodies predominate. After that, at the following stages IgG antibodies begin gradually to predominate. Up to the 20th cycle of exsanguination both globulins are synthetized, but the 2-mercapto-ethanol non-sensitive IgG antibodies are in greater quantity.


An example of 'naturally occurring' anti-Jsa (K6) in a Japanese female.

Anti-Jsa was found in a Japanese female who had never received a transfusion and had borne 3 Jsa-negative children. The antibody agglutinated Jsa cells suspended in saline and treated with proteolytic enzymes as well as reacting with those cells by the indirect antiglobulin test. This example is the first reported 'naturally occurring' anti-Jsa.


[Brain peptide-hydrolase activity in hypothermia].

The cooling of rats to the body temperature of 30 and 25 degrees C does not change acidic peptide-hydrolase activity in tissue homogenates of cerebral cortex, hypothalamus, thalamus, hippocampus, midbrain, cerebellum and medulla oblongata. In deep hypothermia (to 20 degrees C) there occurs a significant increase in the peptide-hydrolase activity in tissue of the studied brain areas both in an incubation sample at 37 degrees C, and at temperature corresponding to the body temperature of cooled animals (20 degrees C). But the enzyme activity remains unchanged in homogenates of medulla oblongata incubation at 37 degrees C.


[Hormonal and functional parameters in hyperprolactinaemia (author's transl)].

58 women with raised serum prolactin levels and normal hypophyseal X-ray parameters were subdivided into three groups according to the serum prolactin level (16 to 40, 41 to 80, greater than 80 ng/ml). In addition to the determination of LH, FSH, oestradiol, progesterone and testosterone in the serum and thyroid diagnostic procedures the following hormonal tests were performed: 1. response to gestagen; 2. response to clomiphene; 3. Gn-RH-test for hypophyseal function; 4. ovarian response to administered gonadotropins (only in cases with prolactin levels administered gonadotropins (only in cases with prolactin levels greater than 80 ng/ml). The grade of menstrual cycle disorders depends on the severity of the observed hyperprolactinaemia. Slight disorders like luteal phase insufficiency, anovulatory cycle and oligomenorrhoea are associated with low- or medium-grade hyperprolactinaemia. Mainly secondary, but also primary amenorrhoea is found in cases with higher serum prolactin levels (greater than 80 ng/ml). In these cases the hypophyseal response to Gn-RH is frequently found (61%) to be negative and, moreover, the ovarian response to administered gonadotropins seems to be diminished. Increasing HPRL levels often appear to be associated with a negative response to the other above-mentioned tests.


Chitin structures of the cell walls of synchronously grown virgin cells of Saccharomyces cerevisiae.

The ability of a lytic beta-glucanase of Arthrobacter GJM-1 to dissolve cell walls of Saccharomyces cerevisiae with exception of the chitin-containing fraction was employed for the isolation of chitin-rich residues of the cell walls of synchronously growing populations of virgin cells. Electron microscopical examination of such wall residues isolated from cells at various stages of the budding cycle showed that the first phase of chitin deposition in the wall corresponds to the formation of an annular structure found as a part of the bud scar after cell division. The annular chitin-rich structure could not be isolated at cell cycle stages preceding the bud emergence and at earliest stages of bud development. The observations confirmed that the annular structure (chitin ring) formed during bud growth represents a major part of total chitin present in the bud scar after septum closure.


[Different composition of the cell wall polysaccharides in Saccharomyces cerevisiae S288 and in an osmosis sensitive mutant].

Determination of the polysaccharide contents and structural studies on the mannan by acetolysis and permethylation analysis shows an altered polysaccharide biosynthesis of the osmotic-sensitive mutant VY 1160 of Saccharomyces cerevisiae S 288. The mutant contains more glucan, less mannan, and less alkali-soluble glycogen. Its mannan is characterized by more short side chains and less long side chains. Its main chain is 1 leads to 6-linked, but its side chains consist of more 1 leads to 3- than 1 leads to 2-linked mannose units.


Dynamics of anaerobic growth of Saccharomyces cerevisiae in the chemostat.

A kinetic Monod model has been used to describe the dynamic response of a continuous stirred tank fermentor (CSTF) to changes in dilution rate. A general analytical solution of a linearized model was obtained. Experimental results (Vairo et al. 1977) of continuous anaerobic culture of Saccharomyces cerevisiae have verified the model quantitatively. For step disturbances on the dilution rate the responses of biomass concentration and the outlet substrate concentration were calculated on a digital computer and compared with the experimental data.


[Hormone analyses and ultrasound examinations in high-risk early weeks of pregnancy (author's transl)].

The serum concentrations of HCG, HPL, progesterone and oestriol and ultrasonic findings were compared with one another in 42 women with normal pregnancy course, 51 women with haemorrhages and abortion and 27 women with haemorrhages and delivery on time. Correct diagnosis was most frequently possible with the help of ultrasound examination. However, it was possible to improve the accuracy of the diagnosis before the twelfth week of pregnancy by means of hormone analysis. If the hormone concentrations were normal, whereas ultrasound findings were either negative or not clear, intact pregnancy could be assumed. HCG and progesterone determination possessed the advantage of being reliably measurable even before cessation of menstrual bleeding. From the eighth to ninth weeks of pregnancy, determinations of HPL were also suitable for assessing endocrinal functions. After the twelfth week of pregnancy, the pregnancy conditions could be judged most safely by the ultrasound method.


Behavioral parasitology and perspectives on miracidial host-finding.

This paper proposes and outlines a new interdiscipline, 'behavioral parasitology,' and presents some interpretations in one of the leading themes of this field, miracidial chemosensitivity to snails. Controversies over miracidial attraction and species-specificity are considered from the standpoints of the distinction between taxis and kinesis, the need for a stimulus gradient, and the possibility of an early phase in a miracidium's behavior adapted for dispersal rather than host-finding. Some of the many possible organic stimulants are discussed with regard to quantitative production by snails, sensory thresholds of the parasites, and possible interaction with inorganic ions. Organic and inorganic stimulants are considered to possibly form qualitative as well as quantitative gradients. A thermodynamic interpretation of miracidial klinokinesis as a function of stimulant concentration suggests the existence of two or more separate types of receptors for the same stimulant, one with a higher affinity for the stimulant and mediating a weaker klinokinesis (possibly a long-range receptor as compared to the other.


Pathology of Anopheles stephensi after infection with Plasmodium berghei berghei. I. Mortality rate.

The mortality of P. berghei-infected Anopheles stephensi females can be about 30% higher during the first three days than in normal blood-fed mosquitoes. As expected the mortality is higher after feeding on highly infected mice but also depends on the date of feeding and the temperature. Infected mosquitoes kept at 25 degrees C die more often than those kept at 21 degrees C. On the other hand sporozoite production needs the low temperature of 21 degrees C. So the sporozoite production rate falls with increasing temperature, and the mortality rate increases.


Pathology of Anopheles stephensi after infection with Plasmodium berghei berghei. II. Changes in amino acid contents.

Infection with Plasmodium berghei results in the disease of a relatively high percentage of mosquitoes depending on the experimental conditions. The damage caused by the parasites may be so severe that the host dies. It can also become manifest for instance in a change in the amino acid content of the mosquito homogenate. The amino acid content of mosquitoes fed on a glucose solution, normal mouse blood, or the blood of infected mice was analysed qualitatively and quantitatively over a period of 14 days. The amino acids lysine, phenylalanine, proline, threonine, and tyrosine are always found in higher concentrations in infected mosquitoes. The content of leucine (and/or isoleucine) increased from the 6th day and glutamic acid from the 9th day compared to the controls. Lower concentrations were found for alanine, aspartic acid, glycine, and serine as compared to uninfected mosquitoes. Further investigations on this subject might help to find the causes for the susceptibility or resistance of individual mosquitoes to plasmodia.


Differential survival of Salmonella typhi, Escherichia coli, and Enterobacter aerogenes on lettuce in the field.

Artificial contamination of young lettuce plants with Salmonella typhi (ST), Escherichia coli (EC), and Enterobacter aerogenes (EA) in the field in winter and summer resulted in presence of the pathogen and increased density of the two indicator bacteria (IB) in harvested produce. Viable counts of the three bacteria/g fresh weight declined at a decreasing rate with increasing time after contamination. The overall pattern of variation of the ST/IB ratio was correlated more closely with changes in the ST/EA than in the ST/EC ratio values. When viable counts were expressed as a proportion of the contaminating dose at different times after contamination, however, a closer similarity existed between ST and EC than between ST and EA values throughout winter and through the early part of summer experiments.


Some biological characteristics of Escherichia coli strains isolated from acute diarrhoeal diseases of infants.

The aim of this study was to evaluate the methods of biological characterization of Escherichia coli strains, in order to use them as screening tests in clinical microbiological laboratories. In two thirds of the 45 E. coli, isolated from acute intestinal infection of infants, different factors of virulence were found. The strains showed prevalently an enterotoxigenic character (66,6%), which was in correlation with the increased permeability (62,2%). Adhesive properties were present in 20% of E. coli independent of their enterotoxigenicity; only 11,1% of the strains had penetrating abilities. The rabbit skin model seems to be accurate and quick for ETEC screening purposes, as is the guinea-pig eye for the EIEC. The mouse intestinal loop has been found sensitive but time-consuming. The infant mouse model is simple and quick, but in this study it has not given optimal results. The Vero cell culture system is simple and easy to perform, but at least for some strains the preparations should be concentrated. The investigation of adhesiveness by haemagglutination is possible to conduct in every small clinical laboratory. Our opinion is, however, that after the isolation of E. coli from different pathological materials, the determination of the antigenic structure of the strains is necessary and later on the additional biological characterization should be performed.


[Differentiation of Klebsiella pneumoniae variatio "oxytoca" (author's transl)].

Altogether 268 strains of Klebsiella were investigated with respect to their ability to ferment dulcitol and to produce indole, gelatinase, and brown pigment on a medium containing gluconate and ferric citrate. In addition the capacity of the strains to use m-hydroxybenzoic acid as sole source of carbon and energy was tested. Of the 83 indole-positive Klebsiella strains 72 (87%) were able to grow on the m-hydroxybenzoic acid medium, whereas only 2 (1%) of the indole-negative strains did so. Late liquefaction of gelatin occurred in 66 (80%) of the indole-positive strains. The ability of the indole-positive Klebsiella strains to use m-hydroxybenzoic acid as sole carbon source supports the view that these strains should be grouped in a separate taxon, which may be named Klebsiella oxytoca; it also provides a simple additional test for the identification of these strains.


Serotyping of Serratia marcescens: simplified tube O-agglutination test and comparison with other serological procedures.

A simplified tube O-agglutination test was developed and evaluated for the determination of somatic serogroup (O) antigens of Serratia marcescens. Use was made of Tryptic Soy broth (TSB)-grown O-cells that had been boiled for 1 hour; 0.145 M NaCl proved a satisfactory diluent. Various technical parameters of this test were examined as well. Rabbit anti-O immune sera, that had been elicited with 5 x concentrated, TSB-grown, 1 hour-boiled O-cells of all 15 currently employed O-antigen reference strains of S. marcescens yielded satisfactory O-agglutinin titers. The tube O-agglutination test compared favorably with the indirect hemagglutination technic, although the latter technic yielded significantly higher O-agglutinin titers with merely 7 of the 15 O-antigens of S. marcescens. The tube O-agglutination test permitted detection of higher O-agglutinin titers than a microtiter O-agglutination test utilizing O-cells that had been stained with safranin O. Conversely, titers obtained with TTC-stained O-cells in a microtiter agglutination procedure approximated those yielded by the tube O-agglutination test, but O-cells of the various S. marcescens strains were stained nonuniformly by triphenyltetrazolium chloride (TTC). As before, there existed marked serologic cross-reactivity between O-antigens O6 and O14. A new O6 candidate strain, S. marcescens isolate S 1i, serotype O6:H20, was proposed. Contrary to O-agglutinins of human control serum, the O-agglutinins of rabbit anti-O immune sera proved refractory to treatment with 0.1 M of 2-mercaptoethanol (2-ME) and 0.01 M dithiothreitol (DTT) respectively. Dual absorptions of rabbit anti-O immune sera with killed cells of Staphylococcus aureus Cowan I (protein A), failed to significantly reduce O-agglutinin titers, although human IgG and IgM was bound by protein A. It was tentatively concluded that the 2-ME- and DTT-refractory rabbit anti-S. marcescens O-agglutinins resided in the IgM immunoglobulin class.


A finding of Yersinia pseudotuberculosis in well water.

From a sample of non-treated, non chlorinated well water a Yersinia pseudotuberculosis II strain was isolated. The water had been apparently massively contaminated because the strain was isolated from 1 ml of the sample. The serotype II of Y. pseudotuberculosis occurs very rarely as aetiological agent of human and animal infections.


[High voltage power station to study the influence of the DC-field with superimposed AC-field on humans (author's transl)].

Due to the great progress in electrical engineering man is exposed to electric fields in a high degree. However, the effect of the electric field has not been definitely cleared up till now. The following parameters are of decisive importance: Field intensity- Frequency-Shape of curve-Boundary conditions. As scientific investigations can only be reproduced and accepted when the experimental conditions are clearly defined, a station meeting these requirements has been developed. It consists of Testing room: Electric screen damping higher than 80 dB-Magnetic screen damping higher than 45 dB-large, cased ceiling electrode. Control room: Same as testing room, but no screening. High voltage generator: a) DC-Voltage 0-20 kV ripple & noise less than 0.01%; b) Alternating voltage 0-300 Vss frequency 5 Hz-50 kHz; c) combination of a) and b).


Combined test of hypothalamic-pituitary function in growth retarded children treated with growth hormone. I. Secretion of growth hormone and somatomedin before and after treatment.

In 23 growth retarded children two consecutive insulin tolerance tests (ITT) were performed to establish a diagnosis of growth hormone (GH) deficiency. Nine children did not respond (GH peak value less than 8 mU/1), whereas 14 were classified as having partial GH deficiency (GH peak value less than 20 mU/1). All were treated for an average period of 40 months with human growth hormone (HGH). In a combined stimulation test at the end of the treatment period 9 children demonstrated a persistent GH deficiency, whereas a normal response was found in 14 of the previous partial GH deficient children. During treatment the monthly growth rate rose from 0.21 cm 0.58 cm in the GH deficient children and from 0.31 cm to 0.70 cm in the partial deficient children, in most of whom spontaneous pubertal development occurred during treatment. Somatomedin (SM) values were decreased in the GH deficient children before and after treatment but increased to normal levels during treatment. Growth velocity in these children during treatment was correlated to SM values before treatment. In the partial GH deficient children SM values were subnormal before but normal after treatment. This supports the assumption that in some children with constitutional delay in puberty a reversible functional hypopituitarism exists, which is normalized after the onset of puberty, due to androgens sensitizing growth hormone releasing mechanisms. Treatment with HGH may induce increased growth velocity in some of these patients.


Endotoxin fever in the rat.

In rats intravenous injections of E. coli endotoxin at thermoneutral or slightly warmer environmental temperatures resulted in biphasic febrile response: two rises of temperature being separated by a transient fall. At an ambient temperature of 20 degrees C the change in body temperature still had a biphasic pattern, however, the fall was the dominant change. Each part of the response was the result of a coordinated reaction which involved heat production mechanisms (including interscapular and periaortic brown fat thermogenesis) and heat loss effectors (tail vasomotor changes) separately or in combination. Beside ambient temperature, the initial body temperature at the start of endotoxin action exerted an important role in determining which of the effector functions would be involved in the response.


Nutritional state and endotoxin fever of newborn rabbits.

At thermoneutral environments 6-10 day-old well-fed rabbits responded to 20 microgram/kg I.V. E. coli endotoxin with biphasic fever: temperature peaks at 60 and 120-150, and a transient fall between 60 and 90 min after endotoxin injection. In rabbits starved for 24 hours, and in runt rabbits body temperature did not rise, but a decline started 60 min after endotoxin administration, corresponding to the transient fall observed in well-fed animals and continuing until about the 100-120th min; thereafter body temperature tended to stabilize at the low level.


Species differences in the effect of isoproterenol and pindolol on renin release in vitro.

The effects of selective beta adrenergic receptor stimulation with isoproterenol (3 X 10(-8) M) and of beta adrenergic blockade with pindolol (3 X 10(-5) M) on the renin release in vitro were investigated in incubated canine and rat kidney slices. Bioassay was used to measure the renin content of the tissue samples and incubation media; renin content in the canine incubation medium was measured also by radioimmunoassay. Isoproterenol in a concentration of 3 X 10(-8) M brought about a significant increase in the renin content of the incubation media as well as the tissue slices obtained from canine kidney, however, there was no change in these parameters under similar conditions if rat kidneys were incubated. Pindolol, on the other hand, in a concentration of 3 X 10(-5) M caused a significant decrease in the renin release from as well as in the renin content of the rat kidney slices, while canine kidney slices failed to respond to the same dose of the drug. The differences between the two species is suggested to be due to the differences in basal renin levels.


Changes of plasma renin and renal renin concentration in HgCl2 induced acute renal failure in rats.

Acute renal failure (ARF) was produced by the single intraperitoneal injection of 3 mg/kg mercuric chloride (HgCl2) in male Wistar rats. Immediately after, and in the 1st, 3rd, 6th, 24th and 48th hour after HgCl2 administration the following variables were monitored: plasma renin concentration (PRC), renal renin concentration (RRC) blood-urea nitrogen (BUN), plasma sodium (PNa), plasma creatinine (PCr) concentrations and haematocrit (Ht). Haematocrit and PNa increased during the first hour and returned to the control value in the 3rd hour. Thereafter, their level remained unchanged. Plasma renin concentration increased threefold during the first six hours after the HgCl2 injection, however, by the 48th hour it returned to the control value. In the first 24 hours of ARF, RRC remained unchanged. However, by the 48th hour its level increased four times the control value. After mercury injection BUN and PCr increased progressively. We were not able to establish any significant correlation between the changes of PRC and BUN. A gradual increase of RRC was observed in the course of ARF.


Shigella dysenteriae 1-like cytotoxic enterotoxins produced by Salmonella strains.

A Salmonella enteritidis strain produced a cytotoxin in addition to heat-labile (LT) and heat-stable (ST) enterotoxins. Two strains of serotypes Salmonella kapemba and Salmonella thompson were LT and ST negative, but exhibited a cytotoxic effect. After Sephadex G-100 fractionation of the crude S. enteritidis material, some high and low molecular fractions had both cytotonic and cytotoxic activities. Of the two other salmonellae, only some high molecular fractions contained the cytotoxic substance. Neutralization experiments revealed an antigenic relationship between the cytotoxins studied and Shigella dysenteriae 1 enterotoxin. On the basis of cross neutralization and other data, it seems that cytotoxic and LT-like characters are carried by the same molecule. In S. thompson and S. kapemba the LT fails to exert a biological effect, although it is antigenically related to the LT of Escherichia coli.


Antitoxic immunity against the so-called lung toxin produced by Escherichia coli.

Cross neutralization test with antisera to crude haemolysins produced by some Escherichia coli strains indicated that there were no antigenic differences among the haemolysins tested. These crude preparates showed definite cytotoxicity which could also be cross neutralized by "antihaemolysin" sera. Neutralization experiments were performed in mouse lung test with homologous and heterologous anti-haemolysin sera, and with O and OK sera to the wild type strain and its toxic R mutant. The results showed that the immunity in the mouse lung model is antitoxic and antibacterial.


The effect of continuous human lymphokine treatment on skin graft rejection in mice.

Continuous intraperitoneal treatment with human lymphokines produced by Con-A stimulated peripheral human lymphocytes caused the acceleration of skin graft rejection in mice.


An altered heart-labile enterotoxin (LT') produced by Escherichia coli serogroup O55 strain.

An Escherichia coli serogroup O55 strain produced heat-labile enterotoxin only, which exerted unusual effects on cell cultures; it caused elongation of CHO and HeLa cells but no changes in Y-1 cells. Injection of this substance, designated LT', into mouse foot pad and rabbit skin caused a well-expressed necrotic effect beside the LT-like activity. LT' showed no cytotoxic effect and failed to produce mouse lung oedema. The strain was not haemolytic. According to Sephadex G-100 fractionation, the LT' had a high molecular weight. The LT' and the necrotic activities could not be separated by fractionation. Neutralization experiments suggested an antigenic relationship between LT and LT'. The antigenic deficiency of LT' was closely related to the common antigenic component of LT and choleragen. The necrotic effect caused by crude LT' was neutralized only by the homologous serum.


[Carl Heinrich Stratz (1858 to 1924), one of the first researchers in growth and development--chronological tables of his life and work (author's transl)].

Review of education, life and work of C.H. Stratz. First a clinical gynecologist and always earning his living from this profession, he was interested in the problems of somatic and regional anthropology. After 1900 he became more and more engaged in observations of the child's development from the new-born to the adolescent. His publications, especially his graphs and pictures of morphological changes in the childs body and the signs of puberty, have the following years deeply influenced our knowledge on "orthology" within the medical problems of youth.


The development of early Chinese Communist health policy: health care in the Border Region, 1936-1949.

This paper examines the health care policy and program of the Chinese Communists in their earliest stages of development. An assessment of 1) political policy, 2) public health campaigns, 3) medical services, 4) public health education, and 5) medical education, indicates that the role of the health delivery scheme was primarily to mobilize mass support for the government, and to change popular health behavior, thereby improving the health of the people and lessening demand on scarce medical facilities. An analysis of the Border Region's health program from 1936 to 1949 gives us an insight into the strategy of a revolutionary government to win popular support and to effect social change.


Histopathology of CNS leukemia and complications of therapy.

An understanding of the pathology of central nervous system (CNS) leukemia has evolved slowly. Observations in the 19th century clearly established CNS leukemia as a disease involving the leptomeninges. Although infiltration of the leptomeninges by leukemic cells remains the principal CNS lesion in patients with this disease, other histopathologic changes have become evident with the development of antileukemic therapy. During the early years of chemotherapy, as patient survival increased, the effects of chronic meningeal leukemia, e.g., increased intracranial pressure, became prominent. Only recently, following effective control of CNS leukemia with chemotherapy and irradiation, did it become clear that current methods of treatment can produce neurotoxic effects. Two specific examples are leukoencephalopathy and mineralizing microangiopathy, both apparently induced by the effects of radiation on the microvasculature. Only through careful prospective studies can the consequences and actual incidence of these two lesions be determined. These results will permit sounder judgments of whether the risks of CNS radiotherapy outweigh the known benefits.


Treatment of overt CNS leukemia.

At this time, methotrexate and CNS radiotherapy used together offer the best chance for prolonged remissions in children who develop overt CNS leukemia. Toxicity is a major problem. Unless a lower dose of radiation is used, the contribution of radiotherapy to neurotoxicity cannot be reduced. However, the toxicity of intrathecal methotrexate can be reduced by using Elliot's B as a diluent, combining methotrexate with hydrocortisone, and using a standard dose after the age of 3 years rather than a dose based on body surface area. Fortunately, the incidence of CNS leukemia has decreased over the years due to prophylactic CNS therapy. However, when a CNS relapse does occur, it carries a grave prognosis and is therefore still a significant problem necessitating continued research.


Radiation in the treatment of meningeal leukemia.

At the present time, a successful regimen for the eradication of occult meningeal leukemia, following induction of a first complete remission in acute lymphoid and undifferentiated childhood leukemia, is the combination of cranial radiotherapy in a dose of 1800 rads in 10 fractions in 12--14 days with six doses of intrathecal methotrexate. This regimen, when given with prednisone and vincristine with or without L-asparaginase for induction and daily oral 6-mercaptopurine and weekly methotrexate for maintenance, can be expected to give a relapse rate for isolated meningeal leukemia of approximately 5% during the first 2 years of follow-up. A modification of this regimen utilizing craniospinal radiation with prior and concurrent intrathecal methotrexate is given for the treatment of overt meningeal leukemia at diagnosis or for an isolated first relapse with meningeal leukemia. Radiation technique and morbidity are discussed.


Role of membrane vitamin E and cytoplasmic glutathione in the regulation of phagocytic functions of neutrophils and monocytes.

Neutrophils and monocytes are the prime defenders of the body against suppurative bacterial and fungal infections. To accomplish their role in inflammation, they must respond appropriately to chemotactic signals elaborated from complement and bacteria. This response predictably results in the adherence and subsequent directed movement of the phagocytes toward the infected area where they recognize opsonized microbes. Attachment of the microbes to the membrane of the cell leads to their ingestion and subsequent demise, principally by the reduced oxygen by-product H2O2, which is generated by the neutrophils and monocytes during phagocytosis. Optimal killing requires the translocation of granule myeloperoxidase into the phagocytic vacuole containing the bacteria and a suitable halide ion. Degranulation is controlled, in part, by assembled microtubules whereas ingestion requires assembly of submembrane microfilaments. Deficiency states resulting from vitamin E results in diminished membrane-related chemotaxis and ingestion, whereas depletion of cellular GSH results in defective microtubule assembly preventing the normal increase in adherence, chemotaxis, degranulation, and microbicidal activity of the phagocytic cells. Deficiency states resulting in dysfunction of the microtubule system include neutrophil glutathione synthetase deficiency, rodent glutathione peroxidase deficiency, and the Chediak-Higashi syndrome.


Vitamin E and platelet function.

In both animals and humans, vitamin E deficiency is associated with platelet hyperaggregability. In six E-deficient children, thrombocytosis was associated with marked hyperaggregability of their platelets to ADP, epinephrine, and collagen. Platelet malonyldialdehyde (MDA) formation was used as an indicator of prostaglandin formation, and was found to be increased during the E deficiency state. Following E repletion, both platelet aggregation and platelet MDA formation returned to normal. The addition of vitamin E to platelets in vitro has been associated with inhibition of platelet release, aggregation, and MDA formation. Extending these in vitro observations further, six normal controls were given 1600 units of vitamin E orally daily for 2 weeks to elevate their plasma E levels and the E content of their platelets in vivo. Concomitant with the elevation in their plasma E levels, there was an inhibitory effect of 12--20% on platelet MDA formation following E ingestion. These studies suggest that E deficiency increases the in vivo synthesis of platelet endoperoxides and prostaglandins, and that E excess has the opposite effect, i.e., inhibition of the endoperoxide intermediates of prostaglandin synthesis.


Prophylactic CNS therapy in childhood acute leukemia: review of methods used.

By use of prophylactic CNS therapy in children with ALL, the incidence of central nervous system relapse was dramatically reduced and the length of the initial bone marrow remission was significantly prolonged. Following thin's Research Hospital. Ten additional CNS therapy regimens were found which gave results equivalent to, but not better than, the St. Jude results. Our knowledge of CNS leukemia in general has greatly increased, but the last 8 years have brought us no further significant progress as to an improved regimen for prophylactic CNS therapy. Thus, 5--10% still show CNS relapse and one-third of children with ALL still have hematological relapse within the first 5 years following initiation of therapy.


Neurotoxicities of current leukemia therapy.

While major advances have been made in the treatment of acute leukemia, complications of therapy are significant. One of the most worisome complications is the neurotoxicity which is related to both central nervous system prophylaxis (cranial irradiatif neurotoxicity may be acute or delayed, and may range in severity from mild headaches ann of treatment-related neurotoxicity is important since this may permit amelioration of otherwise irreversible neurological sequelae in some patients. We review the clinical, phyh irradiation and chemotherapy, and offer recommendations for monitoring, evaluating and treating patients with potential or proven neurotoxicity.


Vitamin E and platelets: cooperative interactions with nitroblue tetrazolium on inhibition of adhesion, aggregation and secretion.

We have evaluated the influence of NBT, vitamin E, and the combination of NBT and vitamin E on the fine structure and biochemistry of platelets during incubation, and the effects of these compounds on the aggregation and secretion of platelets stimulated by collagen, thrombin, epinephrine, and ADP. Results demonstrate that NBT and vitamin E, rather than injuring platelets, appear to protect them during incubation. Togheter NBT and vitamin E blockedaggregation by epinephrine, collagen, and thrombin, but permitted a small first wave stimulated by ADP. This pattern of response to aggregating agents was similar to reactions observed in platelets pretreated with aspirin and indomethacin, both potent inhibitors of platelet prostaglandin synthesis. The findings support the concept that conversion of arachidonic acid to an activated state is an important step in prostaglandin synthesis and that electron transfer or oxidation--reduction reactions are intimately involved in the development of platelet stickiness. Although vitamin E alone does not block prot to regulate formation of endoperoxides and thromboxanes.


Neonatal thrombosis.

Abnormalities in blood flow, in blood vessel walls, in procoagulants, in circulating anticoagulants, and in the reticuloendothelial system may contribute to the thrombotic tendency of newborns. However, the importance of the role of each of these factors or other unmeasured factors is largely unknown. Most infants may be protected by their physiologic platelet dysfunction, increased fibrinolysis, and deficiencies in coagulation factors.


Cycochemical profiles in acute lymphoblastic leukemia.

Lymphoblasts from 61 untreated patients with acute lymphoblastic leukemia (ALL), classified according to the French-American-British (FAB) morphologic classification, were studied for cytochemical characteristics and membrane surface markers. Seventy-three % (eight of 11) of patients with E-rosette positive lymphoblasts (T ALL) had strong focal  paranuclear acid phosphatase (AcP) activity in more than 75% of their lymphoblasts; lymphoblasts from only 6% (three of 48) (p = 0.005) of patients with E-rosette negative, surface immunoglobulin negative lymphoblasts (non-T, non-B ALL) exhibited this characteristic AcP activity. The non-T, non-B ALL cases that manifested focal paranuclear AcP activity had clinical features more characteristic of the T ALL cases. The distribution of beta-glucuronidase activity in the lymphoblast cytoplasm was similar to that of AcP for T ALL and non-T, non-B ALL but the stain was generally more difficult to interpret THan the AcP and was a less reliable indicator of immunologic type of ALL. The periodic acid-Schiff (PAS) and nonspecific esterase stains were not useful in distinguishing between T ALL and non-T, non-B ALL but PAS negativity was associated with certain clinical features within the non-T, non-B ALL group. Cytochemical evaluation of the lymphoblasts at diagnosis in patients with ALL may be useful in identifying subsets of ALL that have distinct immunologic and clinical characteristics and important therapeutic and prognostic implications.


Immunofluorescence studies in transient acantholytic dermatosis (Grover's disease).

Abnormalities were found by immunofluorescence in five of 11 (45%) patients with transient acantholytic dermatosis. There was no consistent pattern to the abnormalities; for example, they were circulating antibodies to intercellular and basal cell antigens in a third. Deposits of Ig and/or C3 were present in lesions of three patients and C3 was present in the intercellular substance in the lesions of a fourth patient. These findings suggest that different immune mechanisms may be involved in the pathogenesis of transient acantholytic dermatosis.


Error measures for objective assessment of scene segmentation algorithms.

Scene segmentation is an important element in pattern recognition problems. Previous efforts to evaluate and compare scene segmentation procedures have been largely subjective. Quantitative error measures would facilitate objective comparison of scene segmentation algorithms. A theoretical discussion leading to a new generalized quantitative error measure, G2, based on comparison of both pixel class proportions and spatial distributions of "true" and test segmentations, is presented. This error measure was tested on 14 manual segmentations and 40 gynecologic cytology specimens segmented with five different scene segmentation techniques. Results indicate that G2 seems to have the desirable properties of correlation with human observation, categorization of error allowing for weighting, invariance with picture size and ease of computation necessary for a useful scene segmentation error measure.


Numerical evaluation of cytologic data: II. Comparison of profiles.

Results of cytologic studies are often presented as profiles of some type. The numerical characterization of these profiles may be statistically compared using methods of multivariate analysis. This article describes the determination of the statistically significant differences between portions of profiles, the computation of the Mahalanobis distance measure between profiles and the use of the chi-square statistic as a measure of the typicality of a profile. Fully worked numerical examples suitable for execution on a pocket calculator are given.


Structure analysis and classification of cervical cells using a processing system based on TV.

This paper presents preliminary results of a cell classification experiment using a new approach for feature extraction. The algorithm takes into account the special requirements of a fast parallel processing system (processor-oriented algorithms). A cell image is described by several hundred features derived from the nucleus only. The most significant features with respect to classification are determined by statistical analysis. Applying principal axis transform, a new feature set is computed, reduced considerably in dimensions. The data base (1,925 cell images of Papanicolaou-stained cervical specimens) was divided into a training set (963 images) and a test set (962 images). The classification results of the test set show that the recognition rate for the two-class problem (normal, suspicious) is better than 91%, using only ten morphologic features.


Free groin flap for the reconstruction of the scalp following tumor resection.

A free inguinal flap was transferred to correct a skull and scalp defect following resection of squamous cell carcinoma.


The theoretically ideal donor site dressing.

Many of the choices for managing split-thickness skin graft donor sites are satisfactory, but none is ideal. Epidermal regeneration in a donor site is readily available for clinical study. We have reviewed experimental studies of epidermal regeneration and applied those results to the clinical study of a new donor site dressing. This dressing is a vapor-permeable, transparent, polyurethane film with a polyvinyl ether adhesive. Used on 100 patients, it was found to be safe and effective in allowing rapid and painless healing. Although the dressing is occlusive and theoretically could promote infection in a contaminated wound, no infections were encountered. Comparison was made with 15 patients managed by other methods. No marked difference in healing time was noted clinically. The striking advantage of the new dressing was painless healing.


A simple method of producing a monolayer of cervical cells for digital image processing.

A manual method of producing a monolayer of isolated and evenly distributed cervical epithelial cells has been developed for use in an automated digital image analysis system. The cervical scrape specimen is vortexed from the spatula into a solution of Mucosol. The suspension is filtered through a 10 micro nylon mesh to remove polys and debris and then syringed to disaggregate epithelial clumps. The cells are plated out on a Nuclepore filter. The filter is touched directly onto a glass microscopic slide to transfer cells, which are then fixed and stained in a routine manner. Cell counts reveal elimination of 92% polys, with only 2% loss of squamous cells.


Numerical evaluation of cytologic data. III. Selection of features for discrimination.

The proper selection of variables is important in assembling a profile to best describe a given group, whether of patients or cells, vis-à-vis other groups. The need often arises to determine which variables in comparable profiles best discriminate between the profiles. Three techniques for the evaluation and selection of variables on the basis of their potentiality for discrimination are discussed in this article. The Kruskal Wallis test is useful in determining if a certain feature (variable) has any statistical significance between groups. The ambiguity function after Genchi and Mori and the measure of detectability (d') are discussed as direct measurements of a feature's ability to discriminate between groups. Fully worked numerical example suitable for execution on a pocket calculator are given.


Clinical study of a new antikeloid agent.

An old healing drug has been assessed and found to be of clinical value in stopping the inflammatory phase of hypertrophic scars and keloids. So far, this drug has no known side effects other than occasional mild gastric intolerance and allergic reaction. Our findings are well supported in the literature. The effect of the drug on other forms of connective tissue anomalies that present an inflammatory phase is similar to that on keloids, gradually brining scars to the maturation phase. Our results on this will be published later. Madecassol has also been shown to have a preventive effect on burn and postoperative hypertrophic scars. It compares favorably in effectiveness with compression bandaging, and gives more lasting results than intralesional cortisone or radiation therapy. Finally, Madecassol has a placebo effect of 29%-well within acceptable limits.


Rhytidectomy: a better way to suture the earlobe.

We propose suturing the earlobe in facelifts into a deepithelialized area of the facial skin flap in order to achieve a less noticeable scar, fewer lobe deformities, and better blood supply to the postauricular flap.


Urinary cytology: the subjective diagnostic clues and their evaluation by computer.

Subjective diagnostic clues of cells contained in the urinary sediment are summarized and correlated with the clinical data. The rationale, techniques and strategy of the automation process for cells in the urinary sediment are discussed. The encouraging preliminary results of the application of a high-resolution approach to automation by the TICAS system are briefly presented.


The use of percent volume analysis in Coulter sizing of cells in gynecologic cytopathologic cell suspensions.

The Coulter Counter model TA II was evaluated as a gynecologic cytodiagnostic tool. The instrument produces particle size histograms as plots of percent volume versus particle volume in 16 channels with each channel corresponding to twice the volume of the next lower channel. Cell volume distributions were obtained using cell suspensions from patients with cervicitis, inflammation, dysplasia or carcinoma and were compared with those from normal subjects. Although this method is superior to other methods of volume distribution analysis, it does not satisfy the stringent requirements of a cervical cancer mass screening method.


Pressure sores-a reappraisal.

Pressure sores are a common problem. They are casually accepted, their etiology is well defined, and treatment is standardized. How, therefore, can the subject justify reappraisal? On detailed review, evidence is presented showing that pressure sores can be minimized, that their pathophysiology is far from certain, and that their management is changing dramatically. During the past decade, new preventive measures have been adopted consisting of multidisciplinary tissue trauma clinics for paraplegic patients, based in rehabilitation hospitals, as well as early identification of the "at-risk" subgroup of geriatric patients who will require aggressive nursing care. Although pressure is the most widely accepted etiological factor, no sophisticated experimental studies have corroborated this hypothesis, and in fact, the majority of research conflicts with clinical observations. Recently, new surgical proceudres-myocutaneous and sensory skin flaps-have been devised to solve complex coverage problems which will possibly reduce the recurrence rate. An in-depth review of pressure sores is therefore warranted and will, we hope, stimulate renewed interest in this all-too-frequent clinical affliction.


Thread augmentation for facial rhytides.

Thread augmentation, a subsurface technique for correcting facial rhytides, is especially applicable to perioral wrinkles, melolabial furrows, and frown lines about the forehead. It is basically an augmentation technique which places a volume of well-tolerated, slowly absorbable or nonabsorbable sutures underneath the wrinkle. These threads produce augmentation by their volume and the mild local reaction of edema, lymphocytic infiltration, and fibrosis. This process gradually progresses to internal scar formation as the suture material is dissolved by slow hydrolysis in the presence of tissue fluid over a period of months; the nonabsorbable suture remains as a permanent implant. A high level of patient satisfaction with minimal complications has proved the value of this technique in over 100 cases.


The history of the artificial eye.

The history of the artificial eye, from antiquity to the present, is described. Around the beginning of the nineteenth century, glass eyes replaced the earlier metal ones--not always well tolerated. In 1835, cryolite glass was used instead of lead glass; to this day it remains the lightest and most desirable substance for making artificial eyes.


Lymphaticolymphatic anastomosis.

Lymphaticovenous anastomosis has proved valuable in the treatment of obstructive lymphedema. Histological studies of this anastomosis have shown the lymphatic component to be almost inactive in anastomotic healing. In order to clarify the role of the lymphatics, experimental lymphaticolymphatic anastomoses were performed in canine femoral lymphatics. The technique developed calls for eight to ten 19 mu sutures to prevent vessel wall collapse, and preservation of the vasa vasorum. Vessels were harvested from one hour to six weeks after anastomosis. Scanning electron microscopy and conventional light histology revealed the lymphatics to have active healing of the intima with complete reendothelialization by two weeks. The techniques developed in this study are directly applicable to human lymphaticovenous anastomosis.


Corrective cosmetic otoplasty: a simple and accurate technique.

The authors present a technique for cosmetic correction of protruding ears used in over 100 cases during the last ten years with good cosmetic results and no significant complications.


An update on wound healing.

The events of wound healing are defined as collagen metabolism, epithelialization, and contraction. Recent findings that further our understanding of these pheneomena are presented and correlated with the important clinical problems confronting plastic surgeons. The future direction of wound healing investigation and its application to practical surgical care are predicted.


A method of producing improved scars following excision of small lesions of the back.

Twelve benign lesions were excised from the back using the accepted elliptical excisions with suturing. At follow-up, all scars had stretched to become much larger than the original lesion. By contrast, 12 lesions of similar size were excised with minimal margin and the resultant defect allowed to heal by contraction and epithelialization. This method was quicker and less painful, and produced significantly smaller scars than the conventional method.


The dynamic Abbe flap.

A modification of the Abbe flap procedure is presented in which muscle-to-muscle union of the orbicularis muscle is obtained prior to inset of the flap. The technique consists in splitting the lip at the midline followed by dissection of the orbicularis muscle on each side from its abnormal position. The muscle is then rotated downward and sutured, restoring the oral sphincter. The flap is outlined on the lower lip and elevated. Following closure of the donor site, the Abbe flap is split in the coronal plane at the level of the muscle; this division is carried up to the mucocutaneous border, and the flap placed like a sandwich around the repaired muscle and sutured. The flap is usually divided in 14 to 16 days. The results have been good, with improved lip movement in 12 patients during animation.


Mutagenicity of 5,6-dimethoxysterigmatocystin, a metabolite from Aspergillus multicolor, in the Salmonella/microsome system.

The natural sterigmatocystin derivative, 5,6-dimethoxysterigmatocystin, was found to be a mutagen for Salmonella typhimurium strains TA98 and TA100 after metabolic activation in a mammalian microsome system.


Influence of fulvic acid on bacteriophage adsorption and complexation in soil.

The effect of fulvic acid, the major fraction of natural soluble organic matter, on the adsorption of MS2 bacteriophage to soil was investigated in controlled laboratory experiments. Batch experiments together with scanning electron microscopy-energy-dispersive X-ray analysis showed that fulvic acid complexed phage, which prevented its adsorption to soil. Phage strongly adsorbed to soil in the absence of fulvic acid. Phage which was complexed with fulvic acid was not irreversibly inactivated and could become viable under proper conditions, illustrating the importance of assay and elution procedures in the recovery of virus from aqueous solutions.


Antibacterial action of lactoperoxidase-thiocyanate-hydrogen peroxide on Streptococcus agalactiae.

Antibacterial activity of lactoperoxidase (LP)-thiocyanate (SCN)-hydrogen peroxide (H2O2) on Streptococcus agalactiae requires that the three reactants must be in contact with the cells simultaneously. Small but assayable amounts of LP adsorb to the cell surface and are not removed by washing. A diffusible antibacterial product of LP-SCN-H2O2 reaction was not found under our experimental conditions. Incubation of S. agalactiae cells with LP-H2O2 and 14C-labeled sodium SCN resulted in the incorporation of SCN into the bacterial protein. Most of the LP-catalyzed, incorporated SCN was released from the bacterial protein. Most of the LP-catalyzed, incorporated SCN was released from the bacterial protein with dithiothreitol. Cells that had their membrane permeability changed by treatment with Cetab or 80% ethanol incorporated more SCN than did untreated cells, i.e., approximately 1 mol of SCN for each mol of sulfhydryl group present in the reaction mixture. Alteration of membrane permeability caused protein sulfhydryls, normally protected by the cytoplasmic membrane, to become exposed to oxidation. The results suggest the LP-H2O2-catalyzed incorporation of SCN into the proteins of S. agalactiae by a mechanism similar to that reported for bovine serum albumin. Removal of reactive protein sulfhydryls from a functional role in membrane transport and in glucolysis in a likely cause of the antibacterial effect for S. agalactiae.


Comparison of homogenizing, shaking, and blending on the recovery of microorganisms and endotoxins from fresh and frozen ground beef as assessed by plate counts and the Limulus amoebocyte lysate test.

Of three methods studied, brisk shaking of samples in dilution blanks by hand and homogenization by a stomacher were compared relative to their capacity to recover the endotoxins and viable bacteria; blending with a Waring blender was compared with these two methods only on the recovery of viable cells. Aerobic plate counts were essentially the same by the three methods for fresh meats, with the stomacher producing slightly higher aerobic plate counts and significantly higher gram-negative counts determined by violet red bile agar. The stomacher produced significantly higher aerobic plate counts and violet red bile agar results on frozen meats than did shaking. Endotoxins were determined by the Limulus amoebocyte lysate test; results by shaking and stomacher on 15 single samples of frozen meat were identical. Of Limulus amoebocyte lysate-negative beef which was spiked with known endotoxin, a higher percentage of recovery was obtained with the stomacher. Although both aerobic plate counts and violet red bile agar counts were found by shaking and stomacher to decrease significantly in frozen meats, endotoxin content was not significantly affected. The stomacher was found to be the better method overall, especially when meats are to be examined for their content of viable gram-negative bacteria, endotoxins, or both.


Determining endotoxin content of ground beef by the Limulus amoebocyte lysate test as a rapid indicator of microbial quality.

Eighty-four samples of ground beef were placed into five half-log cycle groups based upon aerobic plate count (APC) results. Endotoxins were determined by the Limulus amoebocyte lysate test (LAL), and gram-negative viable counts were determined by a violet red bile agar overlay method. Ten samples with a log of APC of less than 5.50 had an APC mean of less than 5.24 and mean endotoxin content by the LAL of 51 ng/g. The 15 samples with APCs between a log of 5.50 and 5.99 had an APC mean of 5.79/g and an endotoxin mean of 103.8 ng/g. Twenty-eight samples had APCs between a log of 6.00 and 6.49 with a mean of 5.28/g and an endotoxin mean of 1106.4 ng/g. The 20 samples with APCs between a log of 6.50 and 7.00 had a mean of 6.77/g and an endotoxin mean of 5067.6 ng/g, while 11 samples had a log of APCs of greater than 7.00 with a mean of 7.53 and an endotoxin mean of 7,472 ng/g. Correlation of half-log cycle mean APC and violet red bile agar counts with mean endotoxin content were both highly significant, indicating that LAL-determined endotoxin content can be used to make a rapid approximation of viable plate counts. Because results can be obtained by LAL in 1 h, the finding of low levels of endotoxins can be taken to indicate low-count meat. The use of additional tests of microbial quality may be necessary when high endotoxin levels are found because the LAL detects both viable and nonviable cells.


Sampling culturable heterotrophs from microcosms: a statistical analysis.

The contributions of different sources of error in sampling mixed and unmixed bacterial microcosms were evaluated by using analysis of variance. Culturable heterotrophic bacteria from a turbid freshwater impoundment were sampled from 9-liter tanks that were unagitated or mixed with magnetic stirrers or pumps and from dilution bottles that were unagitated or agitated with a mechanical shaker. Axenic cultures of Enterobacter aerogenes were also sampled from manually shaken test tubes. In both agitated and unagitated tanks and in unagitated dilution bottles, dilutions made from the same sampling pipette were significantly different, showing a clumping of bacteria on the scale of millimeters. Also, microcosms within a single experiment differed from one another by a large margin. Dilution mean squares and tank or bottle mean squares were homogeneous for all types of tanks and unagitated bottles, indicating that the gentle mixing provided by pumps and stir bars did not reduce either millimeter scale or intermicrocosm variability over what prevailed in unagitated microcosms. By contrast, the vigorously shaken bottles and test tubes showed no millimeter scale variability. Intermicrocosm variability was undetectable in test tubes and two orders of magnitude less in shaken bottles than in unshaken bottles. When these facts are coupled with the inherent statistical advantage of replicating large rather than small experimental units, it is concluded that sampling error in the enumeration of aquatic bacteria in microcosms will be reduced by using numerous, small, violently agitated microcosms with a minimum of subsampling per microcosm.


Statistical procedure for evaluating the sensitivity of Limulus amoebocyte lysate by using a reference lysate.

A study was designed to estimate variability of the Limulus amoebocyte lysate test by comparing a reference lysate against itself. Three technicians performed parallel tests, i.e., titrated side by side, the contents of two vials of reference lysate on 4 different days using 24 vials of the United States reference lysate and 12 vials of the United States reference endotoxin. Each parallel test was replicated three times. From the sensitivity endpoints, ratios were calculated for each parallel test. These ratios were converted to the logarithm for estimating variability among technicians and among vials of endotoxin. By using the overall variability of log ratios, a statistical procedure was developed to evaluate the sensitivity of each lot of licensed lysate submitted to the Bureau of Biologics for release.


Plasmids in Escherichia coli controlling citrate-utilizing ability.

The citrate-utilizing ability of 19 out of 22 citrate-positive Escherichia coli strains isolated from pig sewage was transferred via conjugation to E. coli K-12. The conjugal transfer of citrate-utilizing (Cit) abilities was thermosensitive and concurrent with transfer of drug resistance. Weakly citrate-positive colonies were readily obtained in conjugation experiments. Their Cit characters could be transmitted to the other E. coli strains at a similar frequency in the retransfer experiments, and the transconjugants obtained still showed same characteristic growth on Simmons citrate agar plates. The 19 thermosensitive plasmids conferring citrate utilization and drug resistance were Fi-, and 16 of these plasmids belonged to incompatibility group H1. However, occasionally two conjugative plasmids (pOH3122-1 and pOH3124-1) carrying only the citrate utilization were also obtained in the conjugation experiments, and they were Fi+ and compatible with 19 reference R plasmids. In the two citrate-positive E. coli strains, it was suggested that the conjugative Cit plasmid showing Fi+ character and the more thermosensitive H1 plasmid conferring both the Cit character and drug resistance coexisted in the strain. The characterization of citrate utilization plasmids derived from pig farm sewage is discussed.


[Molecular aspects of carcinogenesis (author's transl)].

The mechanism of carcinogenesis is not yet understood. There is increasing evidence justifying the assumption that an unifying concept of carcinogenesis should be possible at the molecular level. New insights into the molecular mechanism of carcinogenesis were mainly obtained in studies on both chemical and viral carcinogenesis. In the present paper, selected results of these studies are reviewed. It is concluded that the interaction of different carcinogenic agents with the cellular DNA results in alterations of DNA. Only some of these alterations, however, seem to be relevant to carcinogenesis. Alterations of DNA can be caused by reaction of electrophilic agents with DNA constituents, by increased infidelity of DNA replication, by integration of viral genomes or by recombination events involving integrated proviruses.


[The significance of the enzyme histochemistry in the diagnosis of malignant non-Hodgkin's lymphomas (author's transl)].

The significance of histo- and cytochemical enzyme investigations in the diagnosis of malignant Non-Hodgkin's lymphomas (NHL) is evaluated. Histochemical enzyme methods complete the morphological diagnosis if some general principles of diagnostic histochemistry are observed. This is particularly true for the diagnosis of the hairy cell leukemia, the T-lymphoblastoma and the histiocytic reticulosarcoma.


Development of pancreatic endocrine cells in the rat fetus.

Prenatal development of rat pancreatic endocrine cells was investigated by the immunoperoxidase technique and the following results were obtained: 1) Glucagon immunoreactive cells are first endocrine element of the pancreas appearing already on day 11 of gestation, when the dorsal pancreatic bud is still quite small and the ventral pancreatic primordium is hardly swollen out. Most of the glucagon reactive cells are located in the epithelium of the foregut and the dorsal pancreatic bud but a few of them are attached to the base of the epithelium from the outside. 2) Insulin and pancreatic polypeptide (PP) immunoreactive cells are first demonstrable in small cell clusters budding from the exocrine tubules on day 14, whereas somatostatin and gastrin reactive cells on day 17 and 18, respectively. These findings support the hypothesis that the majority of pancreatic endocrine cells is derived from the epithelium of the foregut. 3) PP reactive cells, appearing first on day 14, assume gradually a peripheral position in the growing islet of Langerhans. Immediately before birth they attain the population and flattened cell shape comparable to those in adult pancreas. Their counterpart in the duodenum is found as open type basal-granulated cells in the rat fetus. 4) Noteworthily, glucagon-like immunoreactivity is found in some neuron-like cells of the Auerbach's plexus between the muscle layers of the duodenum on day 19.


In vitro drug resistance of salmonellae in Singapore.

Strains of Salmonella typhi isolated in Singapore were susceptible to chloramphenicol (except from two imported cases) and most of them also generally susceptible to ampicillin and septrin. Drug-resistant strains of Salmonella typhimurium appeared in 1971 and caused out-breaks among young children. However, decreasing drug-resistance of S. typhimurium was recorded in recent years following a drop in the number of cases. Other Salmonella serovers were found relatively susceptible to the antibiotics tested.