Insulin secretion by isolated perfused rat and mouse pancreas.

A method for isolation and perfusion of a pancreas preparation consisting of pancreas, stomach, proximal duodenum, and spleen is described. Basic characteristics of regulation of insulin secretion from the perfused pancreas isolated from rats, albino mice, obese mice (ob/ob), and black mice were identical. Viability and stability of the pancreas preparation during perfusion were maintained as documented by measurements of oxygen consumption of the pancreas preparation, perfusion pressure, and pH of the perfusion medium. The insulin-secretory capacity of the pancreas of different animal species was compared. Insulin secretion by the perfused rat and obese (ob/ob) mouse pancreas was much more potent than that by the pancreas of lean albino and lean black mice. D-Glucose-induced insulin secretion from the pancreas was decreased after fasting of the animals and was dependent on glucose concentration and presence of calcium in the perfusion medium. D-Glyceraldehyde, tolbutamide, D-mannose, dihydroxyacetone, L-leucine, and L-arginine also induced insulin secretion from the pancreas. D-Fructose, D-galactose, L-glucose, 3-O-methyl-D-glucose, N-acetylglucosamine, D-xylose, D,L-glyceric acid, pyruvate, L-lactate, and theophylline did not provoke insulin secretion.


Osmotic and nonosmotic control of vasopressin release.

While the existence of an osmotic control for vasopressin (AVP) release has been long recognized, development of a sensitive immunoassay has allowed for better understanding of factors affecting the threshold and sensitivity of AVP release. Individual variation, genetic, environmental, and species differences, and the nature of the solute providing the osmotic stimuli can significantly affect the release of the hormone by altering the threshold and/or the sensitivity of the osmoreceptor. In addition to the hypothalamic osmoreceptor, AVP secretion is also controlled by an anatomically separate pathway which is responsive to nonosmotic stimuli. It appears that both low-pressure (left atrial) and high-pressure (carotid and aortic) receptors via the parasympathetic pathways provide the major nonosmotic pathway for vasopressin release. Such pathways are activated in response to acute systemic hemodynamic changes, stress, and hypoxia. The precise interaction between osmotic and nonosmotic AVP release remains to be clarified. A model of osmotic and nonosmotic interactions, based on available electrophysiologic studies, is presented and its clinical implications are discussed.


Effect of positive end-expiratory pressure on ventricular function in dogs.

Artificial ventilation with positive end-expiratory pressure (PEEP) reduces venous return by raising intrathoracic pressure. To determine whether PEEP decreases cardiac output further by depressing myocardial function, we constructed Starling curves, using rapid dextran infusion in 7 anesthetized dogs ventilated with zero (ZEEP) and 20 cm PEEP. The changes in stroke volume and in left ventricular stroke work (LVSW) when PEEP was added or removed were significantly greater than could be attributed to the corresponding change in transmural left ventricular end-diastolic pressure (LVEDPTM) on these Starling curves. To the extent that PEEP did not alter left ventricular diastolic volume-pressure characteristics, these data indicated PEEP depressed ventricular function. Identical changes with PEEP in cardiac output (-30%), esophageal pressure (+10 cmH2O), and left ventricular function were observed after pulmonary edema was induced with oleic acid. These results confirm and extend recent suggestions that high levels of PEEP depress left ventricular function in dogs, accounting for about half of the reduction in cardiac output before and during acute pulmonary edema.


Effect of temperature and clofibrate on Plasmodium berghei infection in mice.

Parasitemia counts established that 22 degrees C-acclimated mice subjected to cold exposure for a short time (-35 degrees C for 30 min) during Plasmodium berghei infection had significantly higher parasitemia levels than parasitized mice continuously housed at 22 degrees C. Parasitized 5 degrees C-acclimated mice also demonstrated higher parasitemia levels than parasitized 22 degrees C-acclimated mice. There was no correlation between plasma free fatty acid (PFFA) concentration and parasitemia in mice infected with P. berghei. The effect of clofibrate (an agent known to reduce PFFA levels in rats) in reducing PFFA levels in mice was inconclusive. However, the P. berghei-infected mice treated with clofibrate demonstrated significantly lower parasitemia when compared to parasitized mice that were not treated with clofibrate.


Host defenses in murine malaria: successful vaccination of mice against Plasmodium berghei by using formolized blood parasites.

Infections of normal ICR mice with the NYU-2 strain of Plasmodium berghei (Pb) are uniformly fatal. However, a proportion of mice that have been vaccinated with a formalin-killed antigen prepared from the blood stages of Pb survive an otherwise lethal challenge. Such immunity is not induced by immunization with normal mouse erythrocytes. The level of acquired anti-malarial immunity is related to the size and number of doses of antigen, and intravenous injection is superior to the subcutaneous route of vaccination. The addition of the adjuvants BCG and Corynebacterium parvum to the immunizing regimen improved the level of protection to a variable extent, depending on the batch of plasmodial antigen with which they were used. The adjuvants were most efficacious when used with batches of antigen which were poorly protective when used alone. These adjuvants were found never to protect ICR mice against Pb unless used in combination with specific antigen.


Longevity of Wuchereria bancrofti var. pacifica and mosquito infection acquired from a patient with low level parasitemia.

Two cases are reported which illustrate important epidemiological aspects of lymphatic filariasis--prolonged longevity of the adult parasite and the possibility of transmission by individuals with ultra-low level microfilaremia. These cases demonstrate that people can remain carriers of microfilariae in the peripheral blood for many years without reinfection, and even those with a low level microfilaremia can constitute a significant reservoir of mosquito infection. Such cases represent one of the most serious obstacles to the eradication of lymphatic filariasis in regions where control is based on chemotherapy.


Diabetic management by insulin infusion during major surgery.

In five insulin-requiring, uremic diabetic patients undergoing renal transplantation, we infused insulin intravenously at a low rate to maintain plasma glucose levels between 100 and 200 mg/100 ml. In those patients receiving 100 mg or more of prednisone per day and 5 per cent dextrose solution, the hourly infusion rate was determined from tthe following equation: insulin (U) = plasma glucose value divided by 100. When prednisone was not given or when the patient was thin, the ratio became: plasma glucose value divided by 150. Results were compared with those of nineteen similar transplant patients treated with conventional subcutaneous insulin therapy during surgery, and significantly better glucose control was achieved with the low dosage, intravenous infusion.


Comparison of Marlex mesh and microporous teflon sheets when used for hernia repair in the experimental animal.

A new prosthetic material, microporous expanded Teflon (PTFE) was compared with Marlex mesh in the experimental animal. Triangular pieces of each material were placed beneath the transversalis fascia in the right and left groins of seven white New Zealand rabbits (mean weight, 8 kg). The animals were sacrificed are two week intervals. PTFE was found to retain its position and shape without local or peritoneal reaction. By contrast, Marlex mesh showed marked inflammatory reaction and scarring with complete distortion of the graft. Microscopically, PTFE was completely invaded by fibroblast at eight weeks, with flat orientation of graft to the fibrous tissue forming a "neofascia". In contrast, Marlex mesh lacked fibroblastic incorporation of the graft with marked scarring and distortion. These findings suggest that PTFE could be a useful fascial buttress in inguinal hernia repair where Marlex mesh is now used.


The influence of donor age on graft survival.

Recent papers report differing conclusions concerning use of kidneys from different donor age groups. We analyzed graft survival of 652 consecutive cadaver kidney donor-recipient pairs. Overall cumulative graft survival was 45 per cent at two years post transplantation. Kidneys from donors aged less that fifteen, sixteen to thirty. thirty-one to forty-five, and forty-six to sixty years had a cumulative graft survival of 51, 44, 39, and 40 percent, respectively. The difference is not statistically significant. When both donor and recipient ages are controlled, the pediatric aged kidney may be superior in the pediatric recipient or the older normotensive adult recipient. Use of properly selected cadaver kidneys in patients of all age ranges is encouraged.


The management of inadvertent subcutaneous adriamycin infiltration.

Once the inadvertent infiltration of Adriamycin occurs, it is recommended to immediately treat the problem. This has been accomplished by wide excision and meshed split thickness skin grafting for resurfacing of the defect. Obtaining a healed wound alleviates the stiffness from lack of motion or ruptured tendons. Pain from the open ulcer, which is prone to infection in the immunosuppressed patient, is lessened. An analogy between pit viper envenomization and Adriamycin infiltration is discussed.


Suture technic to provide hemostasis after liver wedge biopsy.

A surgical technic for liver wedge biopsy is described. Vertical mattress sutures are placed to outline a triangular mass of liver with its apes 2 to 3 cm from the liver edge and its based formed by the edge. The suture is tied tightly until the mass blanches, and the biopsy is made within the mass. No additional suturing or hemostatic agents are needed.


The intraocular pressure responses of low-dose bupranolol (Ophtorenin) and methazolamide (Neptazane) in glaucomatous eyes. A controlled clinical study.

In a single-dose, double-blind study, the minimum effective doses of bupranolol and methazolamide were established. The beta-blocker bupranolol (Ophtorenin, Dr. Winzer, Konstanz) in an oily solution reduced IOP significantly in a concentration of 0.05%. The carboanhydrase inhibitor Methazolamide (Neptazane) did not change IOP in a peroral dose of 50 mg, while 100 mg p.o. gave a significant IOP decrease. Both drugs exhibited an additive effect in this low regimen. It is concluded that the combined application of both drugs will postpone or avoid side effects and prolong the time and the field of clinical usefulness. It appears possible that both have a different mechanism of action.


[Change of intracranial pressure in neurosurgical patients by hyperventilation, positive negative pressure ventilation and PEEP (author's transl)].

The effects of a hyperventilation, positive negative pressure ventilation (PNPV) and ventilation using positive endexpiratory pressure (PEEP), on intracranial pressure (ICP) was measured in 24 patients suffering from different neurosurgical disorders. The patients were given a basic anaesthesia including muscle relaxation. The investigations showed, that hyperventilation, followed by a PCO2 of 26 and 30 torr, clearly lowered the intracranial pressure. The pressure drop was much more pronounced when the preexisting ICP was high than when it was low, due to the form of the compliance curve of the brain. PNPV also lowered intracranial pressure, but a harmful effect of this technique on lung function and structure is known. Its use is justified only for short periods and in addition to other measures for lowering ICP. The results also demonstrated that PNPV possesses limited beneficial properties with regard to the subject discussed here. Ventilation by PEEP significantly increased ICP. This technique is to be employed with caution in neurosurgery. Arterial pressure (radial artery) and central venous pressure (subclavian vein) were also recorded.


[The influence of dopamine of kidney function during continuous positive-pressure ventilation (PEEP) (author's transl)].

In a group of 20 patients the influence of continuous positive-pressure Ventilation (PEEP) on cardiac output, kidney function and renal and intrarenal hemodynamics was investigated. During ventilation with PEEP 10 ccm H2O a reduction of cardiac output, glomerular filtrationrate, sodium excretion and urinary output was observed. Renal blood flow, especially the cortical fraction, also decreased. Dopamine infusion, in a dose of 4 ng.kg-1.min-1, during continuous PEEP-ventilation, induced an increase of cardiac output, glomerular filtrationrate, renal sodium excretion and diuresis. The decreased renal cortical perfusion particularly was improved by Dopamine application.


[Arterio-tracheal fistula during long-term intubation of an awake patient. Case report (author's transl)].

Because of anterior softening of the trachea due to thyroid swelling a patient was intubated with a "Lanz-" endotracheal tube with low-pressure cuff after thyroidectomy. The awake, eating patient developed severe endotracheal haemorrhage during the 17 days of intubation. Thoracotomy revealed a 2 cm long horizontal rupture probably at the site of the tube tip at the anterior wall of the trachea. The opening was connected to a rupture of the right brachiocephalic trunk at its bifurcation. Interpositions of dacron prostheses between the trunk, the subclavian artery and the carotid artery and suture of the tracheal wall controlled the situation. However, the patient died from acute hepatic failure, as shown at post-mortem examination. This case report is a warning against long-term intubation of awake patients, as sometimes recommanded.


[A simple self prepared IMV system using original parts of Bird including alternative ventilation under CPAP and PEEP (author's transl)].

A simple self prepared IMV system (intermittant mandatory ventilation system) is described. Only original parts of Bird are used. The system is in fact a combination of the original Bird-PEEP-system with the CPAP-system described by us [1]. The function, mounting and working of the IMV system is described. With this combined system it is now possible to apply different forms of assisted or nonassisted ventilation (CPAP, PEEP, IMV) utilizing the same system making by minor modifications. The FIO2 can be exactly regulated. It is possible to pass continuously from totally controlled ventilation to full spontaneous breathing with or without CPAP. Since original parts of Bird-gears are used in many intensive care units, new developments in artificial ventilation such as IMV can be realized without great expenses. The functioning of this system is demonstrated by several cases including the documentation of recorded changes of arterial oxigenation.


Anesthesia and the development of surgery (1846-1896).

The hypothesis that the introduction of anesthesia in 1846 accelerated the development of surgery was tested by compiling statistics on the types of operations performed in this country and abroad in the absence of anesthesia (prior to 1846) and over the 50-year period after 1846. Prior to 1846, surgery involved the extremities and superficial parts of the body almost exclusively. The same was generally true for 50 years following 1846. The introduction of anesthesia was necessary before surgery could advance, but control of infection, establishment of the sciences of pathology and physiology, and development of professionalism in clinical medicine and surgery based on research and teaching were also required. Almost a half-century lapsed after the introduction of anesthesia before surgery advanced significantly beyond the stage it was at prior to the introduction of anesthesia in 1846.


Stridor in pediatric patients.

We have presented a classification scheme to help in evaluating the diagnosis of stridor in the pediatric patient. The correct diagnosis can usually be arrived at on the basis of a careful and complete history, physical examination, appropriate radiographic studies and bronchoscopy. The anesthesiologist should be aware of the problems associated with all these conditions. In every instance prompt establishment of an adequate airway is imperative.


Ischemic myelopathy.

Ischemic myelopathy and Angiology of the Spinal Cord have recently drawn the attention of both paraplegists and angiologists, and their details are now fairly well known. Ischemic myelopathies increased with the rise of vascular surgery, but the means of prevention have been carefully studied and the incidence is now decreasing. Twenty-five hundred cases of cord injury have been reviewed, and among 92 nontraumatic cases, 16 ischemic myelopathies have been tabulated. The anatomy and physiology of the spinal cord circulation have been described.


Decreased venous distensibility in essential hypertension: lack of systemic hemodynamic correlates.

Venous distensibility in essential hypertension has been reported to be unchanged or decreased; its pathophysiologic role is uncertain. In 27 male hypertensive patients and 21 normotensive control subjects, forearm venous distensibility and capillary filtration rate at 30 cm of H2O distending pressure were measured by strain gauge plethysmography. Plasma renin activity (PRA), plasma volume (PV) by the Evans blue dye dilution technique, mean arterial pressure (MAP) by cuff, and cardiac output (CO) by the CO2 rebreathing method were also measured. Compared to values in normotensive control subjects, forearm venous distensibility in hypertensive subjects was decreased (P less than 0.05); the forearm venous pressure-volume curves (deflation phase) were shifted in the direction of the pressure axis (P less than 0.02); and the capillary filtration rate was increased (P less than 0.05). Venous distensibility changes in hypertensive subjects were unrelated to PRA, MAP, PV, CO, stroke volume, and total peripheral resistance. These findings confirm previous reports of decreased venous distensibility in hypertension and provide direct evidence for increased capillary filtration rate. In view of the lack of significant correlation between venous distensibility and the measured hemodynamic parameters, a patho-physiologic role for venous distensibility in hypertension could not be established.


The value of atropine in the documentation of reversible airways obstruction.

Thirteen randomly selected outpatient asthmatics were treated with nebulized atropine sulfate, isoproterenol and the combination of these drugs in a randomized double-blind trial. Sequential pulmonary function parameters, cardiovascular changes and side effects were monitored over a 60-minute period following drug administration. Both atropine and isoproterenol produced significant and equivalent improvement in mean forced expiratory flow rates; the combination of drugs produced significantly greater improvement at each time interval without producing significant cardiovascular changes or side effects. Four patients failed to show clinically significant increases in expiratory flow rates following  isoproterenol alone; two of these four improved following atropine alone,  while two improved only when given the combination of drugs. The addition of an anti-cholinergic agent may provide a more precise assessment of reversibility of obstructive airways disease in the individual patient.


Bupivacaine: a review.

A review of current significant literature concerning bupivacaine hydrochloride (Marcaine) is presented with particular emphasis on clinical use in oral surgery. The major advantages compared with other presently used local anesthetics are an increased duration of action and a favorable potency to toxicity ratio.


[Anti-Candida albicans IgM antibody: correlation between immunofluorescence and ultracentrifugation (author's transl)].

The indirect fluorescent antibody (IFA) technique for specific IgM anti-Candida albicans was applied to 158 sera and compared with sucrose density gradient centrifugation. For detection of specific IgM results of both methods were in agreement for 157 sera (99.36%). Specific IgM titers determined with IFA on unfractionated sera followed those found on fractionated sera. The results show that specific IgM anti-C. albicans can be identified and titrated by the immunofluorescent technique.


Procedure for processing of central nervous system tissue for immunofluorescence, light, and electron microscopic evaluation.

A rapid and simple procedure has been developed for the simultaneous localization of viral antigen in central nervous system tissues by immunofluorescnece and concomitant correlation with viral induced lesions in the contralateral brain hemisphere. In this study, one-half of the brain was excised from the dog under deep general anesthesia and samples were collected for immunofluorescence by snap freezing in liquid nitrogen. The other half of the brain was perfused under pressure with a buffered glutaraldehyde-paraformaldehyde mixture for subsequent light microscopic and ultrastructural evaluation. The technique was useful in studying central nervous system diseases in large outbred experimental subjects in which economic and other considerations developed for tissue processing in rodents was not feasible.


Management of lung contusion.

One hundred and thirty-two consecutive patients with lung contusion were admitted during the three-year period of 1972 through 1974. All were treated with early intubation and mechanical ventilation with positive and-expiratory pressure with the postulate that such management would minimize the progression of interstitial edema, and intra-alveolar hemorrhage. If progressive increase in the alveolar/arterial oxygen tension gradient was not observed over the ensuing 24 hours, and in the absence of other non-thoracic indications of continuance of mechanical ventilation, patients were extubated and removed from the ventilator. All other patients were further ventilated and followed by daily chest roentgenograms and blood gas studies. Mean ventilation time was 6.2 days. Progressive hypoxemia and deterioration of pulmonary function were not seen. The incidence of pneumonia and tension pneumothorax was low. Overall mortality was 10.6 per cent. The most common cause of death was brain death. No deaths were the result of hypoxemia.


The Philadelphia epidemic of Legionnaire's disease: clinical, pulmonary, and serologic findings two years later.

Clinical, pulmonary, and serologic findings in Legionnaires who attended the 1976 American Legion Convention in Philadelphia were studied 2 years after the Legionnaires' disease epidemic there. All 31 survivors of Legionnaires' disease studied became ill within 2 weeks after the convention, and 18 had not fully recovered 2 years after the epidemic. Twenty-five (28%) of 90 additional Legionnaires exposed at the convention but not diagnosed as having Legionnaires' disease became ill during the same time interval; five of these had symptoms during the next 2 years. Survivors had decreased diffusion capacities measured by the carbon monoxide single-breath method. These differences could not be accounted for by ventilation abnormalities or concurrent illness. Significant levels of IgG or IgM antibodies persisted in 94% of survivors of Legionnaires' disease and in 53% of Legionnaires exposed at the convention, which suggests a high prevalence of subclinical infection. Persistence of IgM antibody raises the question of latency or subclinical infection as part of the natural history of Legionnaires' disease.


The compromised host and Legionnaires' disease.

Pneumonia caused by Legionnaires' disease bacterium was recognized in eight patients during a 7-month period. The patients were immunosuppressed by their underlying illness, corticosteroid therapy, and other exogenous immunosuppressive agents. Five of the patients had received immunosuppressive therapy for less than 16 days. Clinical presentation was similar to that of other bacterial pneumonias in compromised patients. Legionnaires' disease progressed to necrotizing pneumonia with abscess formation and respiratory failure in two patients. Diagnosis was made by [1] culture of lung tissue and bronchial washings; [2] direct fluorescent antibody staining of lung tissue, sputum, and bronchial washings; and [3] serologic evidence of infection. Therapy with oral erythromycin was ineffective. Intravenous erythromycin was given to six patients, with a good response. However, two patients showed further clinical improvement after rifampin was added. Because this illness may be more severe in compromised hosts, open lung biopsy and special microbiologic tests should be done when Legionnaires' disease is suspected.


Legionnaires' disease in patients with associated serious disease.

Of nine patients with Legionnaires' disease, seven were receiving corticosteroids, and all nine had serious underlying diseases. Direct immunofluorescent examination of respiratory secretions, including sputum and transtracheal aspirates, showed the Legionnaires' disease (LD) bacterium in five of seven patients who seroconverted and in a sixth patient with a single elevated titer to the LD bacterium. All nine patients received erythromycin therapy, and five survived. Two patients showed persistence of their infection after receiving 2 weeks of erythromycin therapy, and two patients developed pulmonary abscesses. These cases of Legionnaires' disease show the occurrence of pulmonary abscesses, the possibility of relapse after giving only 2 weeks of erythromycin therapy, and the utility of direct immunofluorescence for early diagnosis.


Autopsy diagnosis of Legionnaires' disease in immunosuppressed patients. A paleodiagnosis using Giemsa stain (Wohlbach modification).

A diffuse pneumonia characterized by short Giemsa-stained, gram-negative rods that were not cultured was diagnosed at autopsy in the fall of 1975 in three immunosuppressed patients who had had renal transplants. An acute fibrinous exudate was found, with macrophages, neutrophils, and numerous short bacilli in each inflamed alveolus as shown by Giemsa's stain (Wohlbach modification). Transplantation was stopped for 1 month. The institutional infection control committee discussed the cases, and increased observation. After the Legionnaires' disease agent was identified in 1977, the bacteria were stained by Dieterle's method and identified as Legionnaires' disease bacteria by direct fluorescent antibody test. No further cases have been identified in the succeeding 62 renal transplantations at this medical center. Although Wohlbach's modification of Giemsa has given consistently good staining of the Legionnaires' disease bacterium in our cases, unclarified factors may interfere with good staining, and the May-Grünwald Giemsa stain was unsatisfactory.


Nosocomial Legionnaires' disease in Columbus, Ohio.

Three patients with severe pneumonia at a community hospital in Columbus, Ohio, were found to have Legionnaires' disease in late August 1977. A subsequent serologic survey of patients with pneumonia at this hospital identified three additional cases. Among patients with pneumonia, hospital exposure in the 2 weeks before onset of illness was significantly associated with Legionnaires' disease (P = 0.003). Serosurveys of hospital employees with a recent history of upper respiratory illness, healthy employees, and workers at the hospital construction site showed that one of 101, one of 107, and none of 114, respectively, has a single reciprocal titer of greater than or equal to 256 to the Legionnaires' disease (LD) bacterium. Serosurveys of patients with pneumonia at three control hospitals identified five additional patients with Legionnaires' disease, three of them with pneumonia that was apparently hospital acquired in a single renal transplant unit. A fourth patient from that unit without clinical illness had a fourfold rise in titer to LD bacterium.


Nosocomial Legionnaires' disease: a continuing common-source epidemic at Wadsworth Medical Center.

Forty-nine cases of Legionnaires' disease were identified from May 1977 through July 1978 in patients and employees at Wadsworth Medical Center. Cases clustered in October and November 1977. Fifteen patients died. All Legionnaires' disease (LD) patients were in the hospital before onset of illness (median time from admission to onset, 17 days; range, 3 to 276 days). Twenty patients were immunosuppressed or compromised by malignancy. In 1977, six of 12 renal-homograft recipients acquired LD pneumonia in contrast to three of 22 during the preceding 3 years (P = 0.031, Fisher's exact test). In a prospective survey of 1658 consecutive hospital admissions, seven cases of Legionnaires' diseases occurred (0.4%), including six among 14 patients who seroconverted to the LD bacterium. Prevalence of a reciprocal titer of 128 or above in Wadsworth employees was significantly greater than in a nearby control population (P = 0.044, Fisher's exact test). Exposure to the external hospital environment may be an important factor, and soil may be a reservoir for the LD bacterium. Legionnaires' disease at Wadsworth may be a nosocomial pneumonia affecting a small group of patients with particular risk factors.


Legionnaires' disease bacterium isolated in 1947.

The results of serologic, cultural, and DNA relatedness studies have shown that the Legionnaires' disease (LD) bacterium and an unclassified agent isolated in 1947 are the same species. Both organisms grew on charcoal-yeast extract agar, enriched Mueller-Hinton agar, and F-G agar, but neither grew on blood agar, trypticase soy agar, or in thioglycollate broth. Both agents reacted with convalescent sera from patients with Legionnaires' disease and convalescent sera from guinea pigs infected experimentally with the LD bacterium. The percentage of guanine plus cytosine in DNA preparations from each organism was ascertained by thermal denaturation to be 39%. In DNA hybridization reactions the 1947 isolate showed the same degree of relatedness to Philadelphia 1 strain of the LD bacterium as did three recent isolates of the bacterium. The LD bacterium was also shown to be antigenically related to another unclassified organism isolated in 1959.


Isolation of the Legionnaires' disease bacterium from environmental samples.

We analyzed 24 environmental samples collected in or near the Indiana Memorial Union, where an epidemic of Legionnaires' disease occurred in early 1978. We conducted fluorescent antibody analyses and culture on F-G and charcoal yeast extract agars of each sample directly; splenic tissue of guinea pigs inoculated with the sample; and yolk sacs from embryonated eggs inoculated with splenic tissue of guinea pigs injected with the sample. Legionnaires' disease (LD) bacterium was isolated from seven of the 24 samples: one water sample from the air-conditioner cooling tower of the Union; three water samples from a stream near the Union; and three mud samples from the same stream. The LD bacterium strains were of three different serotypes. These findings indicate that LD bacteria may be widespread in nature.


Pathologic findings in guinea pigs inoculated intraperitoneally with the Legionnaires' disease bacterium.

Tissues from guinea pigs inoculated intraperitoneally with the Legionnaires' disease (LD) bacterium were studied with light, immunofluorescent, and electron microscopy. The principal gross lesion was diffuse peritonitis of varying severity. Microscopically, the peritonitis of covered by a mixed inflammatory infiltrate of macrophages, neutrophils, fibrin, and cellular debris. Foci of inflammation and necrosis were consistently observed in the splenic parenchyma, and similar lesions were often found in the lungs, liver, lymph nodes, pancreas, heart, and other organs. Numerous LD bacteria were seen in the peritoneal exudate; fewer were found in disseminated lesions. In electron micrographs, the highest concentrations were seen in macrophages, with fewer organisms present in neutrophils or extracellular spaces. Although the lung is the primary organ konwn to be affected by Legionnaires' disease in humans, our findings indicate that the LD bacterium is capable of dissemination.


Immunologic factors affecting the in-vivo and in-vitro survival of the Legionnaires' disease bacterium.

Immunologic factors affecting viability of the Legionnaires' disease (LD) bacterium were studied in vitro and in vivo in mice and  guinea pigs. In bactericidal tests, fresh human serum quickly killed LD cells. Heating fresh serum to 56 degrees C for 30 min destroyed bactericidal activity; absorbing it with bentonite had little effect. Fresh normal human serum was more effective than guinea pig serum. Adding LD cells to fresh normal human serum caused a greater than 50% depletion in functional complement activity, apparently by activating the classic C-142 pathway, because human serum deficient in C4 was not bactericidal. Antibodies to the Knoxville 1 LD strain in guinea pigs showed enhanced complement-mediated bactericidal activity. Without complement, immune guinea pig or human sera prolonged in-vitro LD cell survival. Antibodies to Knoxville 1 in mice depressed in-vitro bactericidal activity of human complement against Knoxville 1. In-vitro bactericidal tests support in-vivo studies in subcutaneous chambers. Complement-deficient mice immunized with Knoxville 1 were (P less than 0.01) less resistant to homologous challenge than nonimmunized mice. Immunized guinea pigs had a greater than 80-fold increase in resistance to subcutaneous-chamber infection.


Scottish experience with the serologic diagnosis of Legionnaires' disease.

Four-hundred fifty-nine sera from 342 persons were examined at Ruchill Hospital, Glasgow, using an agar-grown heat-killed, ether-treated antigen derived from the Philadelphia 1 strain of the Legionnaires' disease bacterium. They were examined, in parallel, at the Center for Disease Control (CDC), Atlanta. Overall agreement (results agreeing +/- one twofold dilution) was reached with 90% of sera. Important differences were obtained with 10 (2.2%) sera. With three of these 10 sera the CDC alone obtained a significant titre (256) whereas with the other seven the Glasgow laboratory alone obtained a titre of 256. Altogether 28 persons (8.2%) with an agreed titre of 256 or higher were identified. However, some of these people had been ill 4 years before serum was obtained for examination. These persistent high titres make the serologic diagnosis of Legionnaires' disease difficult.


False positive reactions in the indirect fluorescent antibody test for Legionnaires' disease eliminated by use of formolised yolk-sac antigen.

The indirect fluorescent antibody (FA) technique for the diagnosis of Legionnaires' disease was used to investigate an outbreak of respiratory disease in a military population. The outbreak was later shown to be caused by an adenovirus. High titres were obtained using the ether-killed antigen supplied by the Center for Disease Control (CDC), Atlanta, but not with a formolised yolk-sac antigen prepared in out laboratory. The reactivity of these sera with the CDC antigen was removed by absorption with a partly identified gram-positive bacterium, whereas sera from persons with true Legionnaires' disease were unaffected by such treatment, suggesting that such reactivity is not specific for Legionnaires' disease. The lack of reactivity with negative control sera and strong reactivity from a small group of patients in whom seroconversion was demonstrated has led us to conclude that formolised yolk-sac antigen is a reliable antigen for the diagnosis of Legionnaires' disease by the FA method. Measurement of the sensitivity and specificity of the formolised yolk-sac antigen is still in progress.


Prevalence of antibodies to Legionnaires' disease. A seroepidemiologic survey of Michigan residents using the hemagglutination test.

The indirect fluorescent antibody test and a microhemagglutination technique detected antibodies in human sera to Legionnaires' disease antigen about equally. Since the hemagglutination technique was simpler, more rapid, and less expensive, we used it to ascertain the prevalence of antibody in 1200 sera from apparently healthy, nonhospitalized Michigan residents. Prevalence was analyzed by age, sex, geographic location (county or residence), and season of the year. There was a significant difference in prevalence between seasons: 91 of 600 sera (15.2%) from February to March 1978 had a titer equal to or greater than 1.16, contrasted with 179 of 600 sera (29.8%) from August to September 1978. This difference was independent of age and sex. There was no significant difference by geographic location, sex, or age except for decreased prevalence for persons 60 years or older.


Legionnaires' disease: one person's perspective.

Since July 1976 when an outbreak of severe, acute respiratory disease of unknown origin occurred among attendees at the 58th Annual Convention of the American Legion in Philadelphia, great progress has been made, including identification of the causative organism, Legionella pneumophila. Clinical features include not only respiratory involvement but often abdominal complaints, encephalopathy, renal disease, and rhabdomyolysis. Erythromycin appears to be an effective antimicrobial agent. Epidemiologic studies have defined epidemics as well as sporadic cases. Legionella pneumophila has appeared as an opportunistic pathogen. Organisms have been isolated from air-handling equipment and evaporative condensers in four instances. At present diagnosis usually is based on the demonstration of a fourfold rise in antibody titer between serum specimens obtained 3 to 6 weeks apart. Recent data suggest that organisms may be shown in tracheal secretions using a direct flluorescent antibody procedure and that antigen may be shown in urine using the microenzyme-linked immunosorbent assay (ELISA) technique.


Lessons from Legionnaires' disease.

In July 1976 a pneumonialike epidemic from a previously unrecognized microorganism erupted among Legionnaires who had attended a meeting in Philadelphia. There were an estimated 182 cases, in which 29 patients died. Among other things the episodes shows that even in a medically sophisticated industrialized nation, a bacterical pathogen can produce a small epidemic and defy identification for almost 6 months. One historical implication of the event is the need to consider the possibility of a return of large-scale epidemic disease rivaling the sweeps of bubonic plague in fourteenth-century Europe. Such epidemics could occur through any of a variety of microorganismic mechanisms recognized as operating at the present time. It is suggested that humans would react to such a disaster much as their progenitors did centuries ago.


Contamination of intravenous infusion fluid: effects of changing administration sets.

Daily change of intravenous (i.v.) infusion administration sets has been recommended by the Center for Disease Control since 1973 to reduce the risk of infusion bacteremia. To evaluate this recommendation, we undertook a prospective, randomized, controlled trial that compared the rates of i.v.-associated bacteremia, in-use i.v. fluid contamination, and phlebitis in 300 patients whose administration sets were changed every 24 h with those in 300 patients whose administration sets were changed every 48 h. No i.v.-associated bacteremia occurred. Twelve of 600 infusions (2%) had positive infusion-fluid cultures: five in one group and seven in the other. Both groups had comparable rates of phlebitis. In this study population with low rates of fluid contamination, no benefit accrued from changing the administration sets every 24 h instead of every 48 h. In hospitals with low rates of fluid contamination, the routine changing of i.v. administration sets every 48 h will result in substantial financial savings.


Effect of cimetidine on gastric hypersecretion and diarrhea in systemic mastocytosis.

Two patients had systemic mastocytosis and histamine excess, marked gastric acid and pepsin hypersecretion, and diarrhea. Cimetidine inhibited gastric acid secretion in both, but with only partial initial control of diarrhea. The other manifestations of mastocytosis were only partly controlled, even by combined H-1 and H-2 antagonist therapy. Basal and pentagastrin-stimulated acid and pepsin secretion before and after 5 and 14 months, respectively, of continuous and effective cimetidine therapy were essentially the same. Thus there was no evidence for an increase in the number of H-2 receptors during the long period of blockade or of involution of the parietal or peptic cell mass.


[Primary mycotic aneurysm of the abdominal aorta from salmonella injection. A new case successfully operated upon (author's transl)].

A double aneurism, located in the abdominal aorta and left common iliac was found complicating a salmonella typhimurium infection which had been present for 7 months. A by-pass operation between the inaffected iliac arteries was followed by resection of the two aneurisms. Cultures taken from the walls of the aneurisms showed the presence of salmonella typhimurium. The authors stress the particular seriousness of the spontaneous evolution of such mycotic aneurisms.


Gastroduodenal haemorrhage.

Before the First World War the treatment of gastroduodenal haemorrhage was predominantly medical, though the results, especially with recurrent haemorrhage, were far less satisfactory than was claimed by some physicians. It was not until Finsterer, in 1939, demonstrated the virtues of early operation that surgery began to take its place in the treatment of this condition, mainly by gastric resection. Results remained poor, however, until 1958 with the introduction of conservative treatment by vagotomy, pyloroplasty, and under-running of the bleeding point. Personal experience, both with partial gastrectomy in the 1950s and 1960s and with mainly conservative treatment between 1967 and 1970, is described and the results presented.


Hunterian Oration, 1979. Some controversial aspects of John Hunter's life and work.

John Hunter's life and work have been described extensively in more than a dozen biographies, in over ninety Orations, and in thousands of articles and lectures. In spite of this manifest acknowledgment of John Hunter's greatness there are nevertheless numerous aspects of his character, his health, and his opinions which have been the subject of criticism, misunderstanding, lack of appreciation, and even slander.


Kinetics of the complement fixing and immunofluorescent antibody response in experimental chlamydiosis in ewes.

Normal, 70 days pregnant ewes were inoculated i.v. with a chicken embryo grown Chlamydia psittaci strain. The ewes presented a biphasic febrile curve and aborted 30 to 68 days after inoculation. Chlamydiae were isolated from aborted fetuses and from vaginal swabs. Ewes developed CF and IF antibodies titrating 1:320 to 1:1024 two to three weeks after inoculation. A second antibody rise occurred one to two weeks before or after abortion and reached titers of 1:640 to 1:1024. Immunoglobulin fractions from the serum of the ewes were also tested by CF and IF. IgG antibodies were detected by both methods and the trend of their kinetics was similar to that of whole serum. IgM antibodies were present in very low titers in the immunoglobulin fractions of some of the animals. CF and IF were equally sensitive in detecting anti-Chlamydia antibodies in whole serum or immunoglobulin fractions.


[Histological and immunological aspects of allergic and non allergic nasal mucosae. A study of 64 biopsies (author's transl)].

Optical and immunofluorescent microscopy was used to examine 52 pathological nasal mucosae (41 allergic, 11 non-allergic), and the results were compared to the clinical, biological and allergic findings. It was noted that there were a large variety of histological lesions in each group of patients, their extent being related much more to the duration and severity of the aggression than to their nature. There appears to be a relation between the extent of the anatomical lesions and immunological activity, non-allergic mucosae being low in immunoglobulin levels.


[Compound grafts in laryngeal surgery (author's transl)].

Compound grafts were used during surgery for enlarging the larynx and after cordectomy.--During operations for re-establishment of laryngeal permeability, a compound graft taken from the auricle of the ear ensures rapid cicatrization of excellent quality. This technique was used in 26 patients and gave very good results in 25 of them.--After cordectomy, a perichondro-cutaneous graft from the auricle ensures optimal reconstruction of the anatomy of the larynx. Voice re-education would appear, however, to be necessary in many cases. Surgery of this type appears to be of great value, even when excision is made for cancer of the vocal cord, which was the case in 8 of our 16 patients.


Assignment of the human acid alpha-glucosidase gene (alphaGLU) to chromosome 17 using somatic cell hybrids.

Hybrid clones (MOGs) were made between the mouse line RAG and a primary fibroblast line from an individual of the rare alphaGLU 2 phenotype. Fifteen independent primary clones and 32 subclones were tested for the presence of human alphaGLU after separation of the human and rodent enzymes by starch gel electrophoresis. Twenty-three other human-mouse hybrids from six different crosses were analysed for the presence of human alphaGLU by exploiting a difference in the thermostability of the human and mouse enzymes. The hybrids were also analysed for up to 25 other enzymes which were used as markers for different human chromosomes. Two of the MOG hybrids were karyotyped and karyotype data were already available for a number of the other hybrids. The combined results demonstrate that alphaGLU is located on chromosome 17, and probably on 17q.


Inhibition of human factor B activity of the properdin system by human and guinea-pig sera.

The activity of factor B of the alternative pathway of complement activation was assayed in human and guinea-pig sera using the radial haemolytic assay with various MgCl2 and RB concentrations. RB were prepared by heating at 50 degrees C human or guinea-pig sera to render them deficient in factor B. Whatever concentrated RB and MgCl2 were, guinea-pig sera seemed unable to react while human sera gave an haemolytic reaction with both human and guinea-pig RB. We described an inhibition of human factor B activity by human and guinea-pig RB under certain conditions. This inhibition is more pronounced in the case of guinea-pig RB.


Increased release of lymphokines by allografted mouse spleen cells following concanavalin A stimulation.

Using a test proposed in this laboratory for following macrophage "activation" (intracellular beta-glucuronidase content) and quantitative dilution studies, we have shown that lymphocytes from mice presensitized by a skin allograft release far more macrophage activating lympholines than do normal lymphocytes when non-specifically stimulated by concanavalin A. This difference may be due to latent metabolic changes of sensitized lymphocytes, but it may also express a modified balance among the various lymphocyte subpopulations within the spleen of grafted mice.


Control of mucus secretion and ion transport in airways.

The output of secretions from the airway submucosal glands is regulated by vagal efferent nerves. Stimulation of cough receptors increases mucus output reflexly via the vagus nerves. Adrenergic agonists increase submucosal gland secretions in some species, which indicates that adrenergic receptors are present in these cells. However, evidence for adrenergic nervous pathways to the glands is limited. Irritants and drugs stimulate secretion from epithelial cells by direct effects. There is also evidence that the secretion of epithelial cells can be stimulated by parasympathetic nervous pathways in birds but not in mammals. Active ion transport of Cl- toward the lumen and of Na+ toward the submucosa results in net ion movement toward the airway lumen in unstimulated tracheal epithelia. Drugs and mediators increase the net movement of ions toward the lumen. No agents have yet been found that increase net ion movement toward the submucosa. The link between ion transport and water secretion in airway epithelia, although speculative, seems likely in view of the evidence from other epithelia. Since airway epithelium is a "tight junction" epithelium, modification of the tight junction may alter the transepithelial movement of water and ions. We suggest that the depth and consistency of the periciliary layer of airway secretions determine the ability of the cilia to propel the mucoprotein gel and thereby modify mucociliary transport. To achieve this, secretion of mucus must be controlled separately from the secretion of water. Studies are needed to determine which of the specialized functions of the epithelial cells interact to regulate the clearance of secretions from the airway. Is the sol maintained by secretion and reabsorption of fluid across the epithelium? Does the sol move with the gel by ciliary action or does it remain stationary? Do changes in the epithelial tight junctions influence net water movement and thus indirectly alter the depth of the sol layer? To answer these questions, techniques are needed to study subunits of the airway, including isolated surface cells and submucosal glands; and sensitive methods are required to analyze the very small samples of secretions for glycoprotein and electrolyte content. Intracellular measurements of electrolyte concentrations and electrical potentials may help to elucidate the mechanisms of transepithelial ion and water movement. The control system for the production and removal of respiratory tract secretions may be altered in disease. For instance, chronic stimulation of cough receptors causes reflex secretion and may be the cause of the hyperplasia of submucosal glands and of the abnormal secretions that occur in chronic bronchitis and asthma (50, 58). The abnormally viscid mucus in cystic fibrosis may be due to a defect in Cl- transport, which provides too little water for both the gel and sol layers. These speculations are intended to identify areas for further research, which hopefully will reduce the morbidity and mortality in these common lung diseases.


[Antibiotic resistance of Shigella in different regions of the USSR].

Shigella were most sensitive to polymyxin ceporin, ampicillin, neomycin and furazolidone and resistant to chloramphenicol, tetracycline and streptomycin. Shigella resistant simultaneously to two or three drugs mainly to tetracycline + chloramphenicol, tetracycline + streptomycin and tetracycline + chloramphenicol + streptomycin were most frequent. The frequency of the Shigella strains carrying R-plasmids increased from 28 per cent in 1969--1970 to 72.6 per cent in 1977. The Shigella strains isolated during the dysentery outbreak in 1973--1977 carried the R-factor controlling resistance to tetracycline + chloramphenicol, tetracycline + chloramphenicol + streptomycin, tetracycline + chloramphenicol + streptomycin + neomycin. Interaction between separate biochemical types, colicinogenicity and drug resistance classes was found in the Shigella isolates. The data on the effect of antibiotic (tetracyclines) intensive use in stock-raising defining wide spread of the R-plasmids controlling resistance to these drugs were obtained.


[Compaction of 2-chain DNA as a method of procedure in determining its binding constant with antibiotics].

The binding of antibiotics and dyes with a compact form of DNA produced in water-salt solutions containing polyethylenglycol (PEG) presents a possibility of studying antibiotic interaction with DNA molecules contained in biological objects, such as viruses and chromosomes, since the compact form of DNA reflects some DNA properties in vivo. Possibly the use of the compact and not the "open" or linear form of DNA in chemical reactions will provide data on the efficiency of the compound "action" under conditions close to intracellular ones. The results well be useful in screening substances with "optimal" pharmacological effect. The paper presents a method for determination of the constant of antibiotic or dye binding with DNA and two-chain synthetic polynucleotides in water-salt solutions containing PEG. The method is based on "elimination" of the DNA molecules in the form of compact particles bound in a complex with an antibiotic or a dye. Comparison of the data with the results of estimation of the constants of antibiotic binding with DNA by the routine methods showed close conformity of the binding constants determined by different methods. It was found that the value of the binding constant of the antibiotics studied slightly depended on the structural state of DNA. The value was practically the same for the linear and the compact forms of DNA.


[Effectiveness of the intramuscular administration of high doses of penicillin in treating pneumonia].

Clinical tolerance of benzylpenicillin administered intramuscularly in doses of 2000000--3000000 units every 4--6hours (12000000 units a day) was studied in 253 patients with pneumonia. Satisfactory tolerance of sodium benzylpenicillin and pronounced painfulness at the site of injection of potassium benzylpenicillin were noted. General toxic side effects in the form of asthenia, dizziness, pain in the heart region were observed in a part of elderly patients. The benzylpenicillin serum levels after administration of 2000000 units were 6--10 times higher than those after administration of 200000 units. The efficiency of benzylpenicillin elevated doses was studied in 193 patients. In 101 of them the previous treatment with usual doses of benzylpenicillin, i. e. 200000 units every 4 hours was not sufficiently effective. The elevated doses of benzylpenicillin proved to be effective in 78 per cent of the cases, the effect being observed in all the cases with acute pneumonia, in 88.5 per cent of the cases with neglected state and in 83 per cent of the cases with chronic pneumonia. The therapeutic effect was also observed in most of the patients with benzylpenicillin resistant microflora in the sputum. On the basis of high efficiency of penicillin therapy it was concluded that gram-positive cocci played the main role in pneumonia etiology.


[Use of carminomycin on children and adolescents with osteogenic sarcoma].

The therapeutic effect of carminomycin was studied in clinic at different treatment schemes with respect to 14 children and juvenile patients with osteogenic sarcoma. Pronounced local effect evident from disappearance of the pain and in some cases decrease of the metastatic tumor were noted in the patients with metastases of the osteogenic sarcoma to the bones or relapses of the primary tumor. Subjective improvement and objective effect were observed respectively in 90 and 53 per cent of the patients with metastases into the lungs and pronounced lung symptomatology.


Clostridium botulinum in the Gulf of Thailand.

A survey was carried out to determine the incidence of Clostridium botulinum in samples of mud, sand, and fish from the Gulf of Thailand. Enrichment cultures from 762 samples of mud and sand from seven different areas around the Gulf were tested. C. botulinum type D was present in 10 samples, and type E was present in 2 samples taken from the west coast at Hua Hin. Enrichment cultures from 16,773 fish grouped into 2,151 samples yielded 10 filtrates containing C. botulinum type D and 5 containing type E. All of the toxic filtrates were obtained from samples of fish taken from the west coast of the Gulf of Thailand.


Limitations of the Moeller lysine and ornithine decarboxylase tests.

A total of 40 fecal and environmental isolates, including 26 Escherichia coli strains, 9 members of the genus Klebsiella, and 5 members of the genus Enterobacter, were tested by enzyme assay for their endogenous and induced levels of lysine decarboxylase and ornithine decarboxylase when grown in Moeller decarboxylase medium. All of the coliforms examined had measurable lysine decarboxylase and ornithine decarboxylase activities whether or not they were positive in the Moeller test. In general, the Moeller lysine decarboxylase test reflected the inducibility of lysine decarboxylase whereas the Moeller ornithine decarboxylase test did not relect the inducibility of ornithine decarboxylase. Neither test measured the amount of intracellular enzyme; rather, they indicated whether the amount of polyamine liberated was sufficient to raise the pH of the culture medium above 7. Changing the growth conditions (i.e., the concentrations of glucose, lysine, and amino acids other than lysine) greatly influenced the lysine decarboxylase activity in coliforms. The limitations on the interpretation of the Moeller test results are discussed.


Deoxyribonucleic acid strand breaks during drying of Escherichia coli on a hydorohobic filter membrane.

Cells of Escherichia coli mounted on a hydrophobic filter membrane were dried under various vapor pressures. A mutant defective in deoxyribonucleic acid repair (uvrA recA) was more sensitive to drying at a water activity of 0.53 or below than the parent strain but not at a water activity of 0.75 and above. Sucrose gradient studies showed that single- and double-strand breaks of deoxyribonucleic acid occurred at a water activity of 0.53 or below, but no breaks could be observed at a water activity of 0.75 or above. These results were observed in all cells rehydrated with 0.03 M tris (hydroxymethyl) aminomethane-hydrocholoride buffer solution at 0 or 37 degrees C, in the presence or absence of oxygen, with saturated water vapor or with a hypertonic solution followed by a gradual dilution. Freezable water was detected in the cells only at a water activity above 0.75 by differential scanning calorimetry. Removal of unfreezable water of cells in the drying, therfore, might induce deoxyribonucleic acid strand breaks.


Histamine production by Klebsiella pneumoniae and an incident of scombroid fish poisoning.

A histamine-producing strain of Klebsiella pneumoniae was isolated from a sample of tuna sashimi implicated in an outbreak of scombroid fish poisoning. None of the other nine gram-negative bacterial strains isolated from the tuna sashimi was capable of equivalent histamine production. Bacterial histamine production was monitored in a tuna fish infusion broth (TFIB), and the implicated K. pneumoniae was capable of producing 442 mg of histamine per 100 g of tuna in TFIB in 7 h under controlled incubation conditions. Only 12 of 50 other K. pneumoniae strains, representing 5 distinct biochemical types, which had been originally isolated from foods, were able to produce such levels of histamine in TFIB. No correlation was found between histamine production and other biochemical characteristics or antibiotic resistance. Of the 12 histamine-producing strains, 11 belonged to type 2, which is characterized as indole negative with positive reactions in the urea and Voges-Proskauer tests. However, only 50% of the type 2 strains examined produced high levels of histamine in TFIB. Additionally, the implicated K. pneumoniae strain and one other strain belonged to type 1, which is characterized by positive reactions in the indole, urea, and Voges-Proskauer tests.


Tandem coagulase/thermonuclease agar method for the detection of Staphylococcus aureus.

In optimizing previously reported coagulase agar media to obtain a rapid, reliable, and inexpensive coagulase test agar, variations in plasmas, pH, buffer system, fibrinogen, and fibrinolytic inhibitor were investigated. The agar with the following composition was determined best for the demonstration of coagulase production by Staphylococcus aureus: 25 ml of 15% bovine fibrinogen (fraction I, type I, citrated, Sigma Chemical Co.), 25 ml of rehydrated rabbit plasma (coagulase plasma ethylenediaminetetraacetic acid, Difco), 10.0 mg of soybean trypsin inhibitor (Schwarz/Mann), and 450 ml of brain heart infusion agar (Difco). In additional studies involving 7 different temperatures and 11 heating times, the thermal destruction of microbial nucleases on plate count agar and coagulase test agar was investigated. Heating the plates for 2.5 h at 65 degrees C destroyed all heatlabile nucleases, but not thermonucleases of S. aureus. A tandem agar plate method for the identification of S. aureus was developed. Coagulase and thermonuclease activity of 50 colonies can be detected on a single agar plate. Suspect S. aureus colonies isolated on various selective media are transferred to coagulase test agar, the plates are incubated at 37 degrees C for 18 h, and the coagulase reaction is recorded. The plates are then heated at 65 degrees C for 2.5 h, overlaid with toluidine blue-metachromatic diffusion agar, and reincubated at 37 degrees C for 3 h, and the thermonuclease reaction is recorded. Studies based on 88 enterotoxigenic S. aureus strains and 133 and 48 suspect S. aureus strains isolated from fresh salami mixtures on mannitol salt and tellurite-polymyxin-egg yolk agars, respectively, demonstrated 100% agreement between the tandem agar plate method and standard coagulase and thermonuclease tests. Overall, the tandem agar plate method is a rapid and convenient approach contributing to the identification of S. aureus from foods.


Uneven distribution of aerobic mesophilic bacteria on human skin.

Viable aerobic mesophilic bacteria are not evenly distributed on the skin of the volar forearm. An increase in the size of the area sampled did not result in a proportional increase in the number of the viable aerobic mesophilic bacteria recovered.


Effects of trimeprazine and trimipramine on nocturnal scratching in patients with atopic eczema.

Twelve men with severe and long-standing atopic eczema were admitted to a double-blind trial to establish the effects of trimeprazine tartrate, trimipramine maleate, and placebo on nocturnal scratching. Neither of the drugs altered the likelihood of a scratching bout beginning in wakefulness or in any stage of sleep. However, both drugs, especially trimipramine, made sleep less broken, and the reduced time spent in stage 1 of sleep accounted for a modest reduction in the overall amount of scratching during the night.


In vivo bound pemphigus antibodies in a stillborn infant. Passive intrauterine transfer of pemphigus vulgaris?

Pemphigus vulgaris developed in a 23-year-old woman during the first trimester of pregnancy. In the 33d week she had a stillbirth of a female child who showed extensive skin lesions clinically suggestive of pemphigus. The application of direct immunofluorescence staining to skin tissue sections showed deposition of IgG in the intercellular spaces of the epidermis of both mother and child. Our findings raise the possibility of transplacentar passage of pemphigus antibody, which may have been responsible for the fetal skin lesions.


Localized pemphigoid simulating dyshidrosiform dermatitis.

A patient had a localized, persistent vesicular eruption of the feet that was clinically identical to dyshidrosiform dermatitis. Direct and indirect immunofluorescent studies revealed a bullous pemphigoid (BP) pattern. Antibody blocking experiments showed the patient's circulating basement membrane zone antibody to be identical to that of classical BP. Possible pathogenetic mechanisms of localized BP are discussed.


Bullous eruption of diabetes mellitus.

Bullous eruption of diabetes is a cutaneous sign of diabetes mellitus. Patients with this disorder manifest a sudden onset of intraepidermal or subepidermal bullae, which are primarily confined to the extremities and heal within several weeks without scarring. Our patient had severe diabetes and experienced two episodes of bullae associated with intense, ultraviolet light exposure. Negative immunofluorescence, early disappearance of anchoring filaments and half-desmosomes between cell membrane and basal lamina, and the absence of urinary uroporphyrins separate this entity from certain similar-appearing conditions. Cation imbalance, precipitated by renal failure, could be a possible causal factor.


Beaded fluorescence pattern of FTA-ABS test associated with malignancy.

A beaded pattern of immunofluorescence (IF) occasionally occurs in routine FTA-ABS testing. This phenomenon strongly correlates with false-positive reactions in patients with SLE. We report on this IF finding in association with carcinoma of the colon.


Polymorphic pemphigoid.

We describe 20 patients with a chronic polymorphic eruption; they shared clinical, histopathological, and therapeutic features of both dermatitis herpetiformis and bullous pemphigoid (BP). In 14 of these 20 cases, direct and indirect immunofluorescence studies corresponded to BP. The remaining six patients showed IgA deposits in a linear pattern at the basement membrane zone, and two of these six showed IgA pemphigoid antibodies in their sera as well. No significant clinical and histological differences were detected in the patients, in connection with the immunological findings. Furthermore, one patient's condition, which was studied by repeated immunofluorescence examinations, changed from a linear IgA pattern and a negative indirect test to a linear IgG pattern and a positive reaction for IgG pemphigoid antibodies. We concluded that these cases constitute a polymorphic variant of BP.


Correlation of antibodies in skin and serum with disease severity in pemphigus.

Direct and indirect immunofluorescence (IF) testing was performed on 63 patients with active or inactive pemphigus in order to determine the reliability of these tests for diagnosis and for monitoring disease severity. Direct IF was positive in 58 of 63 patients with pemphigus. The five patients with negative direct IF had been free of lesions for more than a year. Thus, the direct IF test is a reliable diagnostic procedure that shows positive findings early in the disease. Indirect IF is inferior to direct IF as a diagnostic test because it may be negative in early cases, as observed in four patients. Furthermore, indirect IF, contrary to claims, is not reliable for evaluating the status of the disease. Thus, in patients with lesions and receiving treatment, 41% of the determinations showed a negative titer; whereas in patients free of lesions, 45% of the determinations showed a positive titer. In particular, seven patients without lesions and without treatment for more than a year had a positive titer.


Pemphigoid vegetans.

A 24-year-old woman had massive purulent and verrucous vegetations with fissuring in the groin and axillae. She also had scaling, crusted, bullous, and purulent lesions on the scalp, face, axillae, umbilicus, groin, and hands. Biopsy specimens of skin for histopathologic examinations and direct immunofluorescent study showed typical bullous pemphigoid, and serial serum samples tested by indirect immunofluorescent study confirmed the diagnosis. A basement membrane antibody was presented on four occasions at titers of 320, 1,280, 169, and 320. The differential diagnosis included dermatitis vegetans and pemphigus vegetans. An appropriate term for this manifestation of bullous pemphigoid is "pemphigoid vegetans."


Childhood asthma. A controlled trial of family psychotherapy.

In an attempt to evaluate the effectiveness of family psychotherapy as an adjunct conventional treatment in childhood asthma, children with moderate to severe asthma were randomly allocated to a control group or to an experimental group; the latter group received 6 hours of family treatment during a 4-month period, and both groups had standard medical treatment. While there was no significant difference between the two groups on three parameters, the experimental group were significantly better in day-wheeze score and thoracic gas volume. These results suggest that family treatment in selected cases may have a place in the overall management of childhood asthma, and that more research with larger numbers of children is necessary.


Hepatic dysfunction in childhood malaria.

Hepatic function of 80 children aged under 3 years with Plasmodium vivax malaria were studied during the acute attack and 6 weeks after antimalarial treatment. Raised levels of serum aspartate transaminase (serum AST; SGOT), serum alanine transaminase (serum ALT; SGPT), and alkaline phosphatase were observed in 68%, 39% and 46% of cases respectively. AST levels were higher than ALT ones and the mean level of both enzymes was much higher in patients with hepatomegaly. The hepatic dysfunction which these observations reflect is transient, as these enzymes were found to be at their normal levels 6 weeks after treatment. A transient derangement of liver function is thus a common feature of childhood malaria, and hepatic dysfunction takes place to a significant degree even in P. vivax malaria.


A controlled trial of cyclophosphamide and azathioprine in Nigerian children with the nephrotic syndrome and poorly selective proteinuria.

In a controlled trial, symptomatic treatment alone, or 12 weeks of cyclophosphamide or azathioprine were compared in Nigerian children with nephrotic syndrome (mainly quartan malarial nephropathy) and poorly selective proteinuria. Full remission in 2 patients in each of the two groups treated with drugs, and diminution of proteinuria in most patients in the cyclophosphamide group showed possible evidence of benefit. Infections during treatment were significantly more common in the drug-treated groups but were controllable. Mortality from renal failure in the 2nd year after treatment was significantly greater in the azathioprine-treated group than in the other two, suggesting that the drug may have exacerbated the nephritis. The 5-year survival rate was similar in the cyclophosphamide and the control group.


A clinical comparison of beclomethasone dipropionate delivered by pressurised aerosol and as a powder from a rotahaler.

14 children with severe asthma were studied for 2 months in a double-blind cross-over trial to compare the efficacy of beclomethasone dipropionate delivered as an aerosol and as a powder from a rotahaler. Inhalation via the aerosol was satisfactory in 13 patients, each of whom used the rotahaler correctly. Younger children preferred to use the rotahaler. Comparison of daily symptoms, twice daily peak expiratory flow rate (PEFR), and use of salbutamol during the 2 months of the trial showed that control of asthma was equally good, irrespective of the device used to deliver active beclomethasone.


A thermographic and clinical comparison of three intra-articular steroid preparations in rheumatoid arthritis.

We have compared three intra-articular steroid preparations in a double blind study on 30 patients with rheumatoid arthritis and bilateral synovitis of the knees. One knee was injected with 1.0 ml of either prednisolone t-butyl acetate, methyl prednisolone acetate, or triamcinolone hexacetonide, and the patients were followed up for 6 weeks with regular clinical and thermographic assessments. Thermographic improvement was seen with all 3 drugs but was greatest initially and longest lasting with triamcinolone. No significant systemic improvement was seen with any drug after a single injection, though all 3 steroid preparations suppressed endogenous cortisol.


Reticulum cell sarcoma in azathioprine-treated systemic lupus erythematosus.

The development of a reticulum cell sarcoma in the lung of a patient with systemic lupus erythematosus treated with azathioprine for 18 months is described. This possible hazard of immunosuppressive therapy is discussed in relation to patients with SLE.


Neurological complications of anticoagulation therapy: a neurologist's review.

Anticoagulant-induced bleeding may involve the brain, spinal cord, or peripheral nerves. It may occur with either coumarin or heparin anticoagulants, in the absence of trauma, and while prothrombin times, clotting times, or partial thromboplastin times are in accepted therapeutic ranges. Bleeding involving the brain occurs usually as a subdural hematoma, with intracerebral or subarachnoid hemorrhages occurring less frequently. There may be diagnostic problems in the recognition of these anticoagulant-related subdural hematomas. The spinal cord involvement usually appears in the form of an extradural hematoma. This condition can progress rapidly, and prompt recognition of its presence, localization with myelography, and laminectomy for surgical evacuation are necessary. The peripheral nerve most frequently compressed is the femoral nerve, due to bleeding into the iliacus muscle. Other nerves can be involved, and surgical evacuation may be necessary at times.


Asymptomatic bilious ascites following percutaneous liver biopsy.

Asymptomatic bile leakage developed in a woman following percutaneous liver biopsy. The case is remarkable because features of cholestasis were not present at the time of biopsy, the bile leak occurred through the needle tract in the liver, billous ascites occurred without signs of acute peritonitis, and the complication was the initial manifestation of extrahepatic biliary obstruction due to encasement of the common bile duct by histiocytic lymphoma.


Apparent cure of intracranial Nocardia asteroides infection by minocycline.

Currently preferred therapy for CNS Nocardia infection is high-dose sulfonamide coupled with surgical drainage. Neither of these could be used in our patient; this led to therapy with minocycline alone. Several months after completion of minocycline therapy, the patient apparently is cured. His favorable outcome probably resulted from a combination of susceptibility of the organism to minocycline coupled with good CNS penetration of the agent resulting in CNS levels of drug 16 to 22 times higher than the Nocardia inhibitory concentration.


Arrhythmogenic effects of orally administered bronchodilators.

The respiratory and circulatory effects of orally administered ephedrine sulfate, 25 mg, aminophylline, 400 mg, terbutaline sulfate, 5 mg, and placebo were evaluated in 20 patients with ventricular arrhythmia by a double-blind crossover method. The bronchodilator effect of terbutaline was similar to that of aminophylline over four hours but superior to ephedrine at the fourth hour. Both terbutaline and ephedrine exhibited chronotropic effects, with the effect of terbutaline greater than that of ephedrine at the fourth hour. The effect of aminophylline on heart rate did not differ from placebo. Only terbutaline was associated with an increase in ventricular ectopic beats. Ventricular tachycardia occurred in three patients treated with terbutaline and in one patient with ephedrine. There were no significant changes in blood pressure. Orally administered terbutaline should not be regarded as safer than orally administered ephedrine or aminophylline in patients with arrhythmias.


Acute leukemia and immunosupressive drug use: a review of patients undergoing immunosuppressive therapy for non-neoplastic diseases.

We have reviewed 61 reported cases of acute leukemia developing in patients who had previously received immunosuppressive agents for non-neoplastic disorders. In three patients the diagnosis of acute leukemia was made less than six months after the first exposure to immunosuppressive drugs and was, therefore, considered coincidental. Among the remaining 58 patients, most diagnoses were of myeloblastic or myelomonocytic leukemia. The underlying diagnoses in most of the 58 patients were rheumatoid arthritis or renal disease or renal transplant. Thirty patients had received alkylating agents exclusively, 10 had received antimetabolites only, while the remaining 18 patients had received multiple therapeutic modalities including antimetabolites, alkylating agents, and/or radiation. Most patients had also received large amounts of corticosteroids. Although we do not have the overall denominator of population at risk, the relatively high proportion of patients who had received alkylating agents before developing acute leukemia doses suggest a causal relationship, and one might, therefore, hesitate before using such drugs in non-life-threatening diseases.


[Plasma vasopressin in premature infants on mechanical ventilation].

A systematic study has been undertaken to improve the understanding of water regulation in premature babies who are artificially ventilated. Thirty nine premature babies, 16 normal (Group N, GA 31.4 weeks, B/W 1622 g) and 23 with respiratory distress syndrome who were ventilated with or without continuous positive pressure (Group V, GA 31 weeks, BW 1505 g) have been studied. Plasma osmolalities were the same in both groups (284 and 282 mosM/Kg H2O) but there were significant differences (p less than 0.001) between the urine osmolalities N = 150.6 +/- 19.6 V = 294 +/- 25.9 mosM/Kg H2O) and the plasma ADH levels of the two groups (N = 2.9 +/- 0.4 pg/ml, V = 12.2 +/- 2.4 pg/ml). There was a significant correlation between the urine osmolality and the plasma ADH level but not between plasma osmolality and the plasma ADH level. Several hypotheses can be proposed but none are satisfactory.


Psychiatric disorders in two African villages.

Adults in two small Ugandan villages were interviewed, using a standard psychiatric examination and standard methods of case identification and diagnosis. Twenty percent had disorders just above threshold level, and a further 5% had more definite disorders. Most of these conditions were depressive, but hypomanic and anxiety states were also represented. A survey of women in southeast London found only half this frequency of disorders. Further studies are required to confirm these results.


Treatment of secondary depression in schizophrenia. A double-blind, placebo-controlled trial of amitriptyline added to perphenazine.

The combination of antidepressants and neuroleptics has been widely recommended and commonly used clinically for the schizophrenic patient who becomes depressed. However, the value of the combination for these patients has not been clearly demonstrated. This report presents results of a double-blind, randomized, placebo-controlled clinical trial designed to evaluate the combination of perphenazine and amitriptyline hydrochloride with that of perphenazine alone in the treatment of 35 ambulatory chronic schizophrenic patients in whom depressive symptoms developed. Results showed that the addition of amitriptyline to perphenazine, when compared with perphenazine alone, was more effective in reducing symptoms of depression after four months of treatment, but less effective in reducing thought disorder. The study concludes that the value of adding an antidepressant to the usual neuroleptic in the treatment of secondary depression in schizophrenia should be reviewed.


Distribution and frequency of gastrin cells in the digestive tract of the Japanese quail.

The gastrin cells of the Japanese quail were studied histologically and immunocytochemically. Cells reacting with antiserum to gastrin (gastrin cells) were demonstrated by the peroxidase-labelled antibody method and showed brownish cytoplasm. They also were stained argyrophil by the Grimelius' silver method. Gastrin cells were found in the epithelium of the pyloric region and small intestine and not in any other regions. They were the most numerous in the pyloric region (382.14 +/- 12.77/1.25mm2), next in the ileum (3.79 +/- 1.24/1.25mm2) and duodenum (2.93 +/- 0.62/1.25mm2), and the least in the jejunum (0.93 +/- 0.62/1.25mm2). Remarkable concentration of gastrin cells in the pyloric region has thus been demonstrated.


Angiotensin-like immunoreactivity in the rat submaxillary gland.

Rat salivary glands were examined by an indirect immunofluorescence technique using anti-angiotensin II antiserum. Cells reacting with the antiserum were found in the convoluted granular tubules of the submaxillary gland. In view of the previous reports that renin was isolated from the rat submaxillary gland and that cells with a renin-like immunoreactivity were demonstrated in the convoluted granular tubules of the gland, the present study suggests that a set of substances forming the renin-angiotensin system may be present in this gland.


Enhancement of cardiac allografts in rats at the major AbG locus. I. Synergistic effect of specific and non-specific immunosuppression.

Investigations of the specific and nonspecific immunosupression of heart transplants in rats are presented. Pretreatment of the Wistar recipient of the August heart with donor strain cellular antigen and anti-donor hyperimmune serum 11 and 10 days before transplantation caused enhancement of the heart graft in this strain combination differing in the major AgB histocompatibility locus. Combination of that protocol with non-specific immunosuppression, i.e. ATS treatment caused synergistic effect. Heart grafts in animal treated with that full protocol of biological immunosuppression survived for 50.8 days.


Active enhancement of dog kidney allografts using ALG and donor platelets.

The results of the studies indicate that platelets can be used as donor specific antigen in protocols of "biological suppression". Administration of donor specific platelets 10 days after transplantation to unmatched mongrel dogs treated for a brief period with ALG resulted in a marked prolongation of kidney allograft survival. Acute rejection of a second kidney from an indifferent donor suggests that a state of specific unresponsiveness was achieved by recipients pretreatment with ALG and donor antigen challenge.


Heterotopically induced bone marrow. I. Cellular composition of bone marrow derived from the heterotopic ossicles induced in mice by xenogeneic epithelia of human amnion and dog's transitional epithelium.

Following heterotopic osteogenesis by implantation of xenogeneic epithelia (FL and WISH cell line, transitional epithelium of dog) in mice a biogenesis of hemopoietic tissue among induced ossicles is observed. Precursors and mature forms of all types of blood cells are found in the induced bone marrow. The concentration of lymphocytes in the induced bone marrow is higher, and that of erythropoietic cells lower as compared with orthotopic femur bone marrow. The yield of myeloid cells varied from 0.14 to 3.61 x 10(6) cells per induced bone-containing nodule.


Heterotopically induced bone marrow. The concentration of hemopoietic stem cells in the induced bone marrow and its ability to repopulate lethally irradiated recipients.

Bone marrow induced in mice by xenogeneic epithelia of human amnion established cell line and of dog transitional epithelium seems to contain hemopoietic stem cells in the same concentration as orthotopic bone marrow. The induced bone marrow is able to protect lethally irradiated syngeneic recipients when used in the same doses as orthotopic one.


Attempts of bone induction by xenogeneic epithelial cells in sublethally and lethally irradiated mice. Preliminary report.

Contrary to non-irradiated mice, no heterotopic bone formation was observed in sublethally (700 R) irradiated animals. In animals lethally irradiated (850 R) and protected with syngeneic bone marrow, a bone induction can be observed. The induction is weaker and infrequent when inducing cells are administered 2 weeks after irradiation and repopulation, and a cortisone was given at the time of epithelial cell grafting, than when the inducing cells were given immediately after irradiation and repopulation, and no cortisone was administered.


Immunogenicity of fresh and preserved cortical and cancellous allogeneic bone grafts as tested by modified migration inhibition test in mice.

Mice were grafted with allogeneic compact and cancellous bone. The bone used was fresh and preserved by either lyophilization or deep freezing. Preserved grafts were radiosterilized by a dose of 3.3 MRads. The immunization of recipients was assessed by a modified migration inhibition test based on migration of cells from three-dimensional clot culture. Both preservation methods seem to change bone immunogenicity and enhancement of migration instead of inhibition occurring in the case of fresh bone was noted.


Preserved bone in clinical transplantation.

Results of treatment by preserved bone transplantation in 552 patients are presented. Analysis is based on the activity of the Central Tissue Bank in Warsaw. Radiation-sterilization of lyophilized bone allografts is a routine method used in this bank. After long term observation of patients, the importance of age and diagnosis for clinical results of bone transplantation are discussed.


Biological and biochemical characteristics of serum fraction effluent from xenografts and inhibiting leukocyte migration.

Serum effluent from the hyperacutely rejected rabbit-to-dog liver graft strongly inhibits migration of peripheral blood leukocytes. Fractionation of this serum on DEAE-Sephadex A-50 revealed the most active fraction to be that containing IgG. This finding supports our view that immune complexes formed during the hyperacute rejection of xenografts are mainly responsible for the inhibition of migration of peripheral blood leukocytes.


Preparation of immune sera against carcinoembryonic antigen (CEA).

CEA antigen obtained by the Wrocław team and CEA standard antigen from Chester Beatty Cancer Research Institute, London were used for immunization of goats. Two immunization methods were adopted: one with decreasing antigen doses beginning from 500 microgram and the other with equal, small doses of 10 microgram. Anti-goat IgG1 + IgG2 immune serum was obtained by immunizing a horse with 10 mg of the antigen with complete Freund's adjuvant. Anti-CEA immune sera obtained after immunization with small doses were highly active; in the RIA test they showed half maximum CEA binding at 1:40,000 and 1:80,000 dilutions. Likewise, the anti IgG1 and IgG2 serum from the horse proved to be highly active.


Immunochemical studies on free lipid A from Proteus mirabilis 1959.

The chemical composition and serological activity of free lipid A from Proteus were studied. Only two fatty acids: myristic acid and 3-hydroxymyristic acid were detected. When calculated for glucosamine disaccharide unit, 2 moles of ester-linked and 1 mole of amide-linked fatty acid are present. Amino group of glucosaminyl residue is substituted by 3-hydroxymyristic acid. The occurence of an uncommon (4-aminoarabinose) substituent, attached outside the backbone, was noticed. The results of serological investigation indicate the great similarity between antigenic determinants of Proteus lipid A and Salmonella-type of lipid.


Study of antibody dependent cellular cytotoxicity (ADCC). II. ADCC activity in renal graft recipients and acute accelerated graft rejection.

ADCC activity in 27 cadaver renal allograft recipients was studied. All the patients were given standard immunosuppressive treatment. Significant positive correlation between high ADCC activity during first 5 days after grafting and accelerated rjection crisis was found. The high positive ADCC test may signalize the possibility of acute accelerated rejection of renal allograft.


Interferon induction in mice by uniform salt forms of Shigella sonnei lipopolysaccharide and its components.

Interferon-inducing capacity of uniform salts of Shigella sonnei lipopolysaccharide (LPS), its polysaccharide component and lipid A were compared. Low-molecular-weight triethylamine and ethanolamine salt forms of the lipopolysaccharide were most active in interferon production. It was confirmed that lipid part of LPS is responsible for interferon-inducing activity.


Detection of circulating immune complexes in patients with glomerulonephritis.

143 patients were evaluated clinically on the basis of the renal biopsy. Three methods for detecting circulating immune complexes (CIC) were employed: complement consumption test, inhibition of erythrocyte antibody IgG-EA rosette forming test and optical density of 4% PEG precipitated sera. CIC were present in the sera of all patients with acute poststreptococcal glomerulonephritis (2 weeks after streptococcal infection of the throat). In a group of patients with chronic glomerulonephritis the highest values in positive results were observed in lupus nephritis, chronic proliferative glomerulonephritis and chronic submicroscopic glomerulonephritis. These results were compared with levels of total hemolytic complement, C3, C4 components and serum immunoglobulins (IgA, IgG, IgM).


Immune processes induced by dysentery bacilli in mice.

Studies on immune reactions induced by dysentery bacilli revealed that mice immunized orally or intravenously develop the specific general resistance against reinfection with the microorganisms. Antibodies circulating against bacilli were the indicators of humoral immune response and the activated T lymphocyte detected in the spleen of immunized mice were the indicators of the cell mediated immunity.


Studies on virulence of Shigella flexneri.

The antigenic structure and some biological properties were compared in virulent S. flexneri strains of differences in: 1) antigenic composition; 2) biochemical activity; 3) sensitivity to a set of Shigella phages and 4) susceptibility to phagocytosis. The only difference found concerned the LD50 for mice; it was 10 to 100 times larger for avirulent than for virulent strains of S. flexneri. The toxic products of the strains were also compared. The lipopolisaccharide and free endotoxin purified from virulent and avirulent variants behaved similarly when tested for: LD50, pyrogenicity and the local Shwartzman reaction. A striking difference was demonstrated in the ultrastructure of lipopolisaccharide and free endotoxin isolated from virulent and avirulent variant of S. flexneri 3a.


The protective function of cell-mediated immunity in syphilis.

Experimental evidence has been obtained to show that the cell-mediated response in syphilis is protective. The use of chemical immunosuppressors (cyclophosphamide, 5-fluorouracil) resulted in the abolition of the cell-mediated response measured by the macrophage migration inhibition test (MMI test), and was accompanied by an enhancement in the severity of the lesions during the course of experimental syphilis in the rabbit. Successful adoptive transfer of resistance to syphilitic infection from immune donor rabbits to normal recipient rabbits employing lymph node lymphocytes was accomplished.


Immunologic phenomena in herpes gestationis.

Immunofluorescence studies were performed in 12 cases of herpes gestations. Direct IF staining (performed in 10 of them) revealed a highly characteristic pattern, notably 1) Constantly BMZ deposits of complement component C3, 2) In most biopsy specimens also C4 and C5, 3) Deposits of C4, C5, properdin and IgG variable in different specimens of given patients. About half of the specimens examined contained properdin and about one third stained for IgG, 4) Findings of IgM, IgA, IgD and IgE were consistently negative, 5) Serum findings of BMZ antibodies in given cases were variable. In two cases circulating BMZ antibodies were detected in one of the samples examined. On the base of these findings it seems that HG is related to BP.


Subepidermal bullous disease of childhood with linear IgA deposits.

It has been shown that a group of bullous diseases of children with overlapping symptoms of dermatitis herpetiformis (DH) and bullous pemphigoid (BP), characterized by linear IgA deposits in the unchanged skin, should be regarded as a nosological entity. From the practical point of view it seems justified to set apart this group because of differences in treatment.


Crithidium luciliae immunofluorescence test (CL test) a simple and reliable method for detecting anti-native DNA antibodies.

Antibodies directed against native DNA using Crithidium lucillae as an antigen substrate were demonstrated in 39 of 72 cases of systemic lupus erythematosus (SLE) with active lesions whereas results were negative in 42 cases of SLE during remission and in 69 cases of other collagenoses, and in 20 healthy subjects. A clearcut correlation with the peripheral type of fluorescence of anti-nuclear antibodies (ANA) was found in the routine method of immunofluorescence on the monkey esophagus. Renal lesions were present in almost all cases of SLE with positive results of the test for Crithidium luciliae. The new technique of detecting antibodies against native DNA is simple and creates new diagnostic and prognostic possibilities in SLE.


Cellular immunity in asbestosis.

A highly statistically significant correlation was found between asbestosis and impaired responsiveness in skin reaction to intermediate and second strength tuberculin and SK-SD. Considering ANA incidence these antibodies were found with higher frequency in asbestos workers who lacked a cutaneous response to the recall antigens. In asbestosis cases peripheral blood lymphocyte profiles are also abnormal demonstrating low proportions of E-RFC. Moreover, MIF test results showed the impairment of this cytokine generation when lymphocytes were stimulated with SK-SD, PPD and PHA in asbestosis cases. The lymphocyte transformation study documents an impaired response mainly to a lower dose of PHA and ConA in asbestosis cases and in asbestos workers with ANA.


Short time and prolonged low dose X radiation in human immunity.

In 172 X-ray technicians and 178 controls the occurrence of autoantibodies and serum immunoglobulin levels were determined. A slight and non-significant prevelance of autoantibodies was found in X-ray exposed women with extended employment. IgM levels tend to be higher in this group. X-ray technicians had lower proportions of E-RFC. Moreover, MIF generation is slightly impaired in X-ray exposed people. Peripheral blood lymphocyte profiles were determined in patients before and after X-ray examinations. Significant drops in EAC-RFC were found in these people at 1 and 3 hrs after exposure. Such changes were not revealed in the control group. LIF was measured before and 3 hrs after X-ray exposure in patients, who underwent a digestive tract examination, the coefficients of correlation between the LIF results were weaker as compared with the control results.


The influence of aminoguanidine derivatives on the process of humoral and cellular immunogenesis.

The influence of six aminoguanidine derivatives on the process of humoral and cellular immunogenesis was examined. The obtained results can be presented in the following items: 1. Strong action inhibiting the primary humoral response was found in mice of Balb/c strain where the decrease of PFC number in spleen was from 34.8% to 96.7%; only the second preparation (D-mannose-ylidene-aminoguanidine) (HCl) caused a significant increase of PFC number and thus, on the contrary, exerted the action stimulating the humoral immunological response. 2. Among the examined preparations only three (third, fourth and fifth) showed the action inhibiting MIF production (the decrease within 30-50%) and only these three preparations caused a clear prolongation of allograft survival in the pattern: Balb/c-recipient, C3H-skin graft donor. 3. The clear decrease of the number of lymphocytes in peripheral blood was found (within 40-60%) as a result of administering aminoguanidine derivatives. 4. Synergism was not found to occur when administering jointly ALS and aminoguanidine derivatives, with the aim of prolonging allograft survival or inhibiting MIF production.


Lymphokine-supressing cells in patients after kidney transplantation.

Streptococcal antigens elicit Leukocyte Migration Inhibitory Factor (LMIF) production by sensitive human lymphocytes in vitro leading to an inhibition of leukocyte migration in agarose plates. When mononuclear cells isolated from peripheral blood of healthy donors are added to the assay system, no significant alteration of LMIF generation occurs. Likewise, cells from patients with kidney allografts obtained during an uneventful postoperative course did not influence lymphokine synthesis. Conversely, cells isolated from patients undergoing acute graft rejection abolished SKSD-induced LMIF production by normal lymphocytes. These results support our earlier report of the existence of lymphokine-suppressing cells in man and suggest that they may play yet poorly defined role in certain immunopathologic situations.


In vitro proliferation of hematopoietic stem cells circulating in blood of patients with kidney allografts.

The in vitro formation of lymphoid (L-CFU) and myeloid (GM-CFU) colonies derived from progenitor cells circulating in blood of patients bearing kidney allografts was studied upon a stimulation with PHA and Colony Stimulating Factor. In patients undergoing acute rejection a marked reduction of L-CFU and GM-CFU was found. Chronic rejection was associated with moderate impairment of GM-CFU proliferation, while patients with stable graft function had moderately reduced L-CFU progenitors with normal level of GM-CFU cells.


Neutrophil functions in renal transplant recipients.

Neutrophils obtained from peripheral blood of renal allograft recipients were studied for their ability to kill Gram-positive and Gram-negative bacteria as well as to enhance intracellular metabolism measured by the reduction of NBT salts. In addition, the influence of sera these patients on normal cells was investigated. At the same time, these cells were also tested for candidacidal activity. The data derived from these studies indicate that phagocytic cells from these patients are impaired with respect to their capacity to fight the pathogenic microorganisms as well as their sera do not promote normal killing of microorganisms, while the NBT reaction is not changed significantly. Large doses of steroids and rejection crises do not appear to affect dramatically these functions, while an ATG therapy abolishes neutrophil killing ability.


Lymphocyte dependent antibody (LDA) test in renal transplanted patients.

Using LDA test the presence of antibodies in patients prior to and post renal transplantation was studied. The relationship between the results of LDA test and graft rejection episodes, the treatment with large doses of prednisolone and CDC test performed simultaneously were analized. No correlation between results of LDA test prior to transplantation or its response to prednisolone treatment and acute rejection crises was found. The value of LDA test in predicting rejection episodes was not confirmed. LDA test detects antibodies 10 times more frequently than CDC test. The presence of cytotoxic antibodies CDC was not always connected with the presence of LDA and vice versa.