Complementary scanning electron microscopy: technical notes and applications.

This report introduces practical techniques and applications of complementary scanning electron microscopy (SEM). To identify the complementary structures at high magnification, we first made a montage pair of low magnification micrographs as a guide map. Consulting the map, we took complementary micrographs at high magnification. When taking a picture at high magnification, we drew the outline of the most prominent structures on a transparent plastic plate attached to the cathode-ray tube of a SEM. Then another picture of the complementary structures was taken after adjusting the complementary structures to the reverse image of the plastic plate. We performed three applications of the complementary SEM: 1) complementary observation of the epithelial underside and lamina propria of the rat urinary bladder; 2) complementary observation of the fractured Golgi apparatus; and 3) evaluation of specimen drying methods. After proper digestion of the rat urinary bladder using strong alkali, the epithelium was detached from the underlying lamina propria. On the basal side of the epithelium, the meshwork of grooves were visible. The observation of the corresponding lamina propria confirmed that the grooves were occupied by blood capillaries located in the uppermost part of the lamina propria. The complementary observation of the Golgi apparatus was useful for understanding its three-dimensional architecture. The observation on both complementary fractured surfaces of the Golgi apparatus from the mouse lacrimal gland demonstrated the continuity of the Golgi stacks. It was also effective for observing both the cis and trans side of the same Golgi stack. Complementary SEM was also useful for evaluating the specimen drying method.(ABSTRACT TRUNCATED AT 250 WORDS)


Preparation of human chromosomes for high resolution scanning electron microscopy.

The addition of ethidium bromide during the last 2.5-3 h of lymphocyte culturing restricted chromosome contraction and preserved the banding structure in scanning electron microscopy. Treatment of the chromosomes with trypsin and use of impregnation with osmium tetroxide and thiocarbohydrazide resulted in a structural preservation of high resolution quality.


Human fibroblast intracellular network prepared with digitonin for field emission scanning electron microscopy.

Results obtained by extracting human fibroblast cells for the study of cytoskeletal structures are compared. Cells grown in culture were treated with digitonin in contrast to other methods of detergent preparation using Triton and Saponin. The three dimensional intracellular network which resulted from digitonin treatment was found to be similar in appearance to the structures observed by high voltage transmission electron microscopy of untreated cells described as a microtrabecular lattice by Porter and Tucker (1981). Our results, obtained by high resolution, field emission scanning electron microscopy indicate that the microtrabecular lattice may indeed be one conformation of a dynamic cytoskeleton.


Intussusceptive microvascular growth: a common alternative to capillary sprouting.

Intussusceptive capillary growth represents a new principle for microvascular growth as described in the lungs of growing rats. According to this concept, the capillary network expands by the formation of slender transcapillary tissue pillars, which give rise to new vascular meshes. The process was first observed in Mercox casts of the lung microvasculature, which revealed the existence of multiple tiny holes with diameters around 1.5 microns. Consecutive transmission electron microscopic investigation of serial sections demonstrated that the holes corresponded to slender tissue pillars (Burri and Tarek, 1990). The corrosion cast technique thus appears to be an adequate screening method for intussusceptive growth. In the present investigation, Mercox casts of various vascular systems, namely, those of the eye, submandibular gland, heart, liver, stomach, small and large intestine, trachea, kidney, uterus and ovary were prepared from rats aged between 4 and 9 weeks in order to screen them for the existence of the typical tiny holes representing tissue pillars. In all organs investigated, these structures were observed in various locations to a variable degree. They were mainly encountered within dilated vascular segments or at triple or quadruple branching points of the circulation. Even in capillary networks with a three-dimensional arrangement could these pillars be detected. Intussusception thus appears to be a principle of growth appertaining to many vascular systems.


Three-dimensional architecture of pericytes with special reference to their topographical relationship to microvascular beds.

Microvascular beds and pericytes in the submandibular gland, thyroid gland and heart were studied by combined scanning electron microscopy and chemical digestion. The submandibular gland had a relatively loose network of blood capillaries, the thyroid gland possessed a close-meshed network of capillaries, and those in the myocardium ran parallel to the long axis of myocardial cells. The thyroid gland exhibited the largest numbers of pericytes. Three types of pericytes could be distinguished by their shape and localization. Type I pericytes, which were confined to true capillaries, had a fusiform or polygonal cell body, a few long, slender longitudinal processes (primary ones) and short, fine circumferential processes (secondary ones). Type II pericytes, which were found in the arterial side of myocardial capillaries, were characterized by large, circumferential band-like processes completely encircling the vessel. Type III pericytes, which were seen on the venous side of thyroid and myocardial capillaries, had a flattened cell body and short, irregular processes. Type II and III pericytes appear to show an intermediate or transitional form between smooth muscle cells and typical pericytes (Type I). Judging from the configuration of pericytes suggests that these are related to functions such as contraction as well as mechanical support.


Three-dimensional ultrastructure of the autonomic nerve terminals in the lamina propria mucosae of the rat large intestine.

The three-dimensional ultrastructure of the autonomic nerve terminals in the lamina propria mucosae of the rat large intestine was studied by scanning electron microscopy using the KOH-collagenase digestion method as well as by transmission electron microscopy. Observations showed unmyelinated nerves in the lamina propria mucosae as well developed just above the muscularis mucosae and forming a two-dimensional irregular network by anastomosing with one another. Each nerve in the network consisted of axons and Schwann cells. The axons were about 0.1 micron in diameter and had local swellings (about 0.2-0.5 microns diameter) along their course. Transmission electron microscopy revealed the presence of synaptic vesicles in these varicosities. Although some of the axons left the Schwann cell processes to run separately, most of them twined around or were embedded in the Schwann cell bodies or processes. Blind ends of axons were only occasionally observed in the nerve network. These findings suggest that the network of the unmyelinated nerves itself represents a terminal apparatus acting upon the muscular and glandular cells.


Changes in size and shape of smooth muscle cells from the portal vein of spontaneously hypertensive rats: an ultrastructural analysis.

The portal vein was investigated in male spontaneously hypertensive rats (SHR), from Wistar-Kyoto (WKY) and Wistar strains, in animal 16-20 weeks old. In SHR, the inner circular smooth muscle was unchanged, but the outer longitudinal layer showed marked alterations in shape and size, readily observed in three-dimensional micrographs using scanning electron microscopy. The cells in both Wistar and WKY were elongate and tubular with little variation along their lengths and with a relatively smooth sarcolemma. This applied to both the inner and outer layers of smooth muscle. In contrast, the smooth muscle cells from SHR in the outer layer varied considerably in thickness along their lengths, and had very irregular outlines with numerous pits or depressions of varying sizes. In addition, the cells frequently had major forks or branches. The vasa vasorum running through the muscle layer, fibroblasts and nerve bundles were also identified. Sectioned material (transmission electron microscopy) showed a change in shape and hypertrophy of the smooth muscle cells from the portal vein of SHR, and also demonstrated a significant increase in paracellular connective tissue in the outer layer of smooth muscle. Such major morphological alterations in the outer layer of smooth muscle in the portal vein from SHR could have profound effects on functional studies.


Inadequate vasculature in solid tumours: consequences for cancer research strategies.

In the last decade, since we first postulated that antiproliferating endothelial therapy was a promising new approach to therapy, there have been remarkable developments. Vascular effects have been recognized from completely unrelated and unexpected agents, including hyperthermia, photodynamic therapy, misonidazole, tumour necrosis factor, FAA, interferon and interleukins. These vascular effects may coexist with direct cytotoxicity to the tumour cells or they may explain all of the antitumour activity. In order to benefit from such vascular effects, we need to monitor them, understand their mechanisms of action and ensure that the clinical scheduling is optimized to give the greatest therapeutic advantage. The biologist must re-evaluate the validity of his or her tumour models and the clinician must question whether drugs targeted at tumour cells should be sought or whether it would be more productive to target the nutrient supply through the neovasculature. The molecular biology approaches of oncogene expression in tumour cells and growth factor dependency must be weighed against angiogenesis, the pathophysiology of the tumour mass and its supporting normal stromal elements. Since this is a highly complex field there will be many fascinating years of work elucidating tumour versus normal vascular differences. In the meantime, we need to ensure that we do not reject useful therapeutic agents by inappropriate scheduling based on a misunderstanding of their mode of action, or by the use of inappropriate models for testing potential anticancer agents.


Antitumor effect of a Coliolus preparation, PSK: induction of macrophage chemotactic factor (MCF) in spleens of tumor bearing mice.

The effect of administration of PSK (Polysaccharide Kureha), a Coliolus preparation, in Meth-A solid tumors was analyzed in BALB/c mice. Spleen cells prepared from normal, non-treated Meth-A bearing, PSK-treated normal and PSK-treated tumor bearing mice were examined for induction of macrophage chemotatic factor (MCF). Only spleen cells from the latter mice produced MCF after 48 hrs of cultivation in the presence of Meth-A cells or concanavalin A (Con A). MCF-producing cells were indicated to be Lyt-1 positive, L3T4 positive and Lyt-2 negative cells in the negative elimination assay. There were no differences in the production of other cytokines including interleukin-2, interferon and tumor necrosing factor, spleen cells obtained other different groups of mice. The antitumor effect of either crude or purified MCF (molecular weight 100,000) was examined by daily consecutive intratumoral injections into Meth-A tumor tissues, and a significant inhibitory effect was detected.


Systemic IL-1 and adjuvant treatment of an experimental tumor. II. Immune status during primary tumor challenge.

In this investigation, systemic administration of interleukin-1 (IL-1) and local adjuvant therapy were shown to modify immunological parameters associated with the lymphatics draining the site of experimental tumor inoculation. These immunological parameters were shown to be modified early (within 7 days) following tumor inoculation and within the time period of IL-1 administration. IL-1 induced a marked increase in the number of lymphocytes within the brachial and axillary lymph nodes associated with the tumor inoculation site. This increase was characterized by an overall augmentation in the number of CD8+ and CD4+ lymphocytes. In vitro, these lymph node cells showed enhanced proliferation in response to interleukin-2 (IL-2) when compared to non-IL-1 treated animals, and were capable of mounting a potentially greater cytotoxic response for both NK sensitive and NK resistant tumor targets. Without IL-1 administration, temporal and sequential lymph node cellular changes were observed, but were diminished and delayed when compared to the IL-1 treated animals. By adoptive transfer of tumor resistance, lymph node cells from IL-1 treated animals were demonstrated to be tumor-protective in vivo. These results demonstrate that systemic IL-1 induces regional changes in the lymphatics of mice undergoing primary tumor challenge with adjuvant therapy and that these changes result in tumor protection for the host.


Interferon-alpha, interferon-gamma and sizofiran in the adjuvant therapy in ovarian cancer--a preliminary trial.

The study included 24 cases of negative second-look laparotomy (SLL) after operation on ovarian cancer. 12 cases were treated with sizofiran and recombinant interferon-gamma before and after SLL and then with human lymphoblastoid interferon-alpha. The remaining 12 cases (controls) were followed up without any drug therapy after SLL. There were no recurrences in the treated group, but in 3 cases of the control group. Also significant difference in survival was noted in the treated group.


Lymphocyte responses to food antigens in food sensitive patients with allergic tension-fatigue syndrome.

Scores of radioallergosorbent test (RAST) for cow's milk or buckwheat flour and proliferative responses of peripheral blood mononuclear cells (PBMCs) to bovine serum albumin and beta-lactoglobulin or buckwheat flour were measured in cow's milk or buckwheat flour sensitive patients with allergic tension-fatigue syndrome. In all 3 cow's milk sensitive patients with allergic tension-fatigue syndrome, RAST scores for cow's milk were negative or slightly positive, but PBMCs well responded to bovine serum albumin and beta-lactoglobulin, but not to ovalbumin. In a buckwheat flour sensitive patient with allergic tension-fatigue syndrome, RAST scores for buckwheat flour were negative, but PBMCs well responded to buckwheat flour, but not to ovalbumin, bovine serum albumin and beta-lactoglobulin. Conversely, in cow's milk or buckwheat flour sensitive patients with immediate allergic symptoms, RAST scores for offending foods were positive although PBMCs did not respond to offending food antigens. These results suggest that proliferative responses of PBMCs to food antigens are very useful for detection of offending foods in allergic tension-fatigue syndrome.


Effect of pyridoxine on tumor necrosis factor activities in vitro.

Clinical trials with tumor necrosis factor (TNF) as an antitumor agent have so far given rather disappointing results. In this study we show that the naturally occurring vitamin B6 compound, pyridoxine, enhances TNF-induced cytolysis of three subclones of a mouse fibrosarcoma cell line (WEHI 164). The degree of pyridoxine-induced enhancement of TNF cytotoxicity seems to be dependent on the cells sensitivity to TNF, as the enhancement was much more pronounced in the relatively TNF resistant subclone act-R(cl.12)-WEHI 164, than in the very TNF sensitive subclone WEHI 164 clone 13. Furthermore, our study shows that pyridoxine, in contrast to its enhancing effect on TNF-induced cytotoxicity, rather inhibits TNF-induced growth of human FS-4 fibroblasts. Pyridoxine also enhances lymphotoxin (LT)-induced tumor cell killing and inhibits LT-induced fibroblast growth. Pyridoxine is a relatively non-toxic agent in vivo. Our results suggest that a combination of TNF and pyridoxine may be more efficient than TNF alone, in the treatment of cancer patients.


Frozen-thawed human blood monocytes respond reproducibly to activation stimuli: implications for screening of BRMs.

The purpose of this study was to identify the optimal freezing conditions for human blood monocytes to allow their recovery and use for in vitro screening of activation stimuli. Human monocytes separated from buffy coats of healthy blood donors were suspended at a density of 1 x 10(7) cells/ml in freezing medium consisting of 70% medium: 20% fetal bovine serum: 10% DMSO frozen in a stepdown freezer, and stored at -180 degrees C. Monocytes were thawed at different times up to 4 months later. Viability was > 90%. Fresh monocytes from different donors and frozen monocytes thawed at different times were incubated with different concentrations of lipopolysaccharide, muramyl tripeptide, muramyl dipeptide, or lipopeptide. Tumoricidal activity and IL-1 production of fresh monocytes varied greatly among the 5 different preparations. In contrast, the frozen monocytes (thawed at different times) produced uniform levels of antitumor activity and IL-1 production. These results show that monocytes recovered from frozen storage maintain their ability to respond to activation stimuli in a uniform and reproducible manner. Thus, the use of frozen-thawed monocytes is recommended for screening of macrophage-activating agents.


A comparison of ketoprofen SR and sulindac in the elderly with rheumatoid arthritis.

The elderly (age > 65 years) are more vulnerable to side-effects induced by non-steroidal anti-inflammatory drugs (NSAIDs). We therefore performed a double-blind comparative study of ketoprofen SR and sulindac in patients with active rheumatoid arthritis, 65 years of age or older. Sulindac was chosen because of its possible renal sparing effects, and ketoprofen SR because of its short half life and sustained release delivery system. Eighty patients were entered. More patients withdrew from the study due to side-effects in the sulindac group; both treatment groups had a high incidence of side-effects during this study and during previous exposure to other NSAIDs, demonstrating that the elderly are susceptible to side-effects from NSAIDs.


Tolerance and long-term efficacy of a fixed combination of atenolol and nifedipine in the treatment of angina pectoris. Stuart Clinical Research Group.

To monitor the tolerance and long-term efficacy of a low-dose fixed combination of 50 mg atenolol and 20 mg nifedipine (slow release formulation) in patients with stable angina pectoris, 157 patients received treatment twice daily in a multi-centre, open-label fashion for periods up to 12 months following a four week run-in period on atenolol 50 mg twice daily. A total of 122 patients completed the study and had data from all treatment visits. In these patients the median number of weekly anginal attacks was halved, compared to the run-in period on atenolol alone following one month's fixed combination treatment, and this benefit was maintained throughout the 12-month study period. In addition, GTN consumption similarly declined on the fixed combination in comparison with the run-in period. Treatment with the fixed combination was not associated with any long-term increase in the frequency of reported side-effects or adverse biochemical changes compared to run-in. The fixed combination of atenolol 50 mg and nifedipine 20 mg reduced anginal frequency and GTN consumption compared to atenolol alone without causing any increase in adverse effects.


The role of early surgery following myocardial infarction. European Coronary Surgery Bypass Group.

This co-operative study was a prospective randomised study to evaluate the role of coronary bypass surgery following acute myocardial infarction. The criterion for entry was an early positive exercise tolerance test. All patients who satisfied the clinical criteria of acute myocardial infarction but who were excluded had information on survival obtained after two years. A total of 4658 patients were assessed, with 3334 (71%) having a modified exercise test. This test was positive in 728 patients, of whom 598 then underwent coronary angiography. Three hundred and forty-eight patients were randomised (surgery 168, continuing medical treatment 180). At two years the survival in the medical group was 96% and in the surgical group was 93%. At five years the corresponding figures were 88% and 91%. Sub group analyses in terms of age, ejection fraction and extent of vessel disease failed to show any significant differences between those randomised to medicine or surgery. A positive exercise test early after infarction does help to delineate those more likely to require intervention, but a negative exercise test is not an indication for complacency.


A critical appraisal of in-patient neurological services in a subregional centre.

A computer database was established for the medical audit of admissions to the North Manchester General Hospital neurology unit. Over a six-month period, 277 patients completed 300 hospital stays. A higher proportion of patients were admitted from the North Manchester District compared with the peripheral districts served by the unit, suggesting that more neurology in these areas was performed by general physicians. This supports claims for an increase in the number of neurologists to improve the quality of service at district level. The introduction of a programmed investigation unit, closed at weekends, would allow financial savings since 60% of cases did not require a bed at the weekend. It would also allow more efficient pre-booking of investigations. The diagnostic yields from routine B12 and folate levels, syphilis serology, thyroid function tests, chest radiography and electrocardiography were low and should be replaced by more selective investigations. Savings might also be made by performing the 38% of myelograms restricted to the lumbar region in the out-patient department. The introduction of out-patient magnetic resonance imaging will make significant savings by obviating the need for many of the inpatient myelograms which were required in 55 patients. The simple and relatively inexpensive technology used in this study provided medical staff with valuable information on which to base changes in practice and evaluate their consequences.


Randomised cross-over comparison of five inhaler systems for bronchodilator therapy.

The pharmacological efficacy of beta-2 agonists such as bronchodilators is well established, yet many patients fail to obtain optimum benefit from conventional metered-dose inhalers. This is usually because of difficulty in achieving adequate co-ordination between activation of the aerosol and inhalation. To some extent this problem can be alleviated by detailed personal instruction and re-instruction, but the medical or paramedical staff needed to do this may be unavailable and in any case their time is expensive. To increase the benefit obtained from bronchodilators, therefore, pharmaceutical companies have produced a variety of devices, eg, large-volume (750 ml) spacers (Nebuhaler, Volumatic) which enclose a cloud of aerosol, obviating the need for actuation-inhalation co-ordination, and breath actuated dry-power inhalers with (Rotahaler, Diskhaler) or without (Turbohaler) carrier powders. Subsequent compliance with treatment is dependent upon the acceptability of the inhaler device to the patient.


Razoxane for Crohn's colitis and non-specific proctitis.

Oral razoxane 125 mg daily brought active Crohn's disease into remission when used alone and mainly on an out-patient basis in all nine patients studied. Remissions took several months to achieve, but no relapses have occurred on treatment and no surgery has been necessary in any of the patients. In the two patients with active non-specific proctitis, oral razoxane 125 mg daily rapidly controlled the condition. Apart from mild bone marrow toxicity in one patient, no other acute toxicity has occurred and no long-term side-effects have been observed.


Genital herpes: audit of cases referred by general practitioners to a department of genito-urinary medicine.

An audit was carried out of all cases of genital herpes referred by a general practitioner to a department of genito-urinary medicine from 1987-1990. Attention was paid as to whether or not the diagnosis had been made correctly and what drugs, if any, the patient had been prescribed. A total of 196 patients (78 men, 118 women) were eligible for study. GPs correctly diagnosed herpes in 32/78 (41%) of the men. Among the 46 who were not diagnosed, 12 were prescribed antibacterial drugs, three were prescribed antifungal cream, two were prescribed a combination of the above and three received miscellaneous non-antiviral agents. GPs correctly diagnosed 56/118 (47%) of the women. Sixty-two women were not diagnosed, of whom 17 were prescribed anti-bacterial drugs, 21 were prescribed antifungal cream, seven were prescribed a combination of these and six received miscellaneous non-antiviral agents. GPs appeared to have difficulty in diagnosing genital herpes in these patients, with the result of prescription of inappropriate and expensive medications.


The aetiology and pathogenesis of vaginal candidosis: an update.

The aetiology and pathogenesis of the condition of vaginal candidosis is discussed in brief. The causative organism, the incidence and source of infection and various host and pathogen factors related to the disease state are dealt with. An update of current work relating to the cause of the recurrent condition is presented.


The incompetent cervix--a review.

Repeated midtrimester pregnancy loss due to incompetence of the cervical os has long been recognised as a treatable condition, but the aetiology, diagnosis and management of this condition remain controversial. Some women have clinically obvious cervical incompetence and may benefit from a cerclage operation, but criteria for early diagnosis are not universally agreed upon. Universal agreement on the aetiology and diagnostic criteria is a prerequisite for determining which women may benefit from surgical management.


Infarction of the tongue in Wegener's granulomatosis.

Wegener's granulomatosis is a form of systemic vasculitis. Untreated, it has a 90% two year mortality, but complete remission can be obtained in 93% of patients following treatment with cyclophosphamide (usually in combination with steroids). There is early and major involvement of the respiratory tract. Renal involvement adversely affects prognosis.


Wolff-Parkinson-White syndrome mimicking myocardial infarction on ECG--exploitation by a heroin addict.

Wolff-Parkinson-White (WPW) syndrome produces several electrocardiographic features, including mimicking the changes of myocardial infarction. A case is described of an astonishingly well-informed heroin addict, who himself had WPW syndrome and who exploited his condition attempting to obtain opiates from hospital.


Covert toxocariasis--a cause of recurrent abdominal pain in childhood.

Toxocariasis, usually caused by Toxocara canis, is a zoonosis acquired by ingestion of worms which inhabit the gut of young canines. Domestic pets, such as dogs, become infected from soil in public parks and playgrounds which are often heavily contaminated. Although toxocariasis is often regarded as having two principal, though uncommon, manifestations--visceral larva migrans (VLM) and ocular toxocariasis (OT)--recent studies have suggested otherwise. A third, more common, condition, termed 'covert toxocariasis', describes patients in whom positive toxocara serology is associated with a number of systemic and localised symptoms and signs (notably abdominal pain) but not VLM or OT. A quarter of patients with covert toxocariasis have no eosinophilia and, although symptoms regress after treatment, they may persist for months or years. We report a 13-year-old girl with recurrent abdominal pain who, despite positive toxocara serology, was extensively investigated for other abdominal pathology.


Intrahepatic bilomas--a possible complication of cholecystectomy?

Biloma(s) were initially defined as encapsulated extrahepatic collection(s) of bile. Subsequently the definition was expanded to include abnormal intrahepatic bile collection(s) located outside bile ducts. Most descriptions are of subhepatic or subphrenic collections (extrahepatic bilomas), following surgical procedures involving the biliary system or trauma. We report a case of intrahepatic collections of very large amounts of bile, apparently following cholecystectomy.


Splenic abscess: is conservation applicable?

A rare occurrence of salmonella abscess in a congenital cyst of the spleen is presented. Although splenectomy was curative, the role of splenic salvage is discussed. Percutaneous drainage is curative in about 70% of cases and may be the treatment of choice in solitary thick-walled abscesses. It should be remembered, however, that residual or regenerated splenic tissue is no absolute guarantee against sepsis. The treatment of splenic abscess should be individualised.


Sterno-costo-clavicular hyperostosis.

Sterno-costo-clavicular hyperostosis (SCCH) is a condition of unknown aetiology in which a chronic inflammatory osteitis affects predominantly the medical clavicle, sternum and distal tibia and femur, sometimes associated with skin disease. We report on two patients with the typical bony lesions of SCCH and no associated skin disease.


Severe orthostatic hypotension in carcinoma of the pancreas.

Autonomic dysfunction has been described in patients with advanced forms of cancer. We report a case of severe orthostatic hypotension in a patient with carcinoma of the pancreas in whom there was no clinical evidence of autonomic failure to account for the severity of the hypotension. Despite normal circulating levels of nor-adrenalin and an appropriate rise in the erect position, the vascular system appeared unresponsive. We suggest that in this patient the orthostatic hypotension was due to a paraneoplastic complication of the pancreatic tumour.


Antigen presenting cells and the immunogenetics of autoimmune diabetes in NOD mice.

Genetically-controlled defects in the development and function of antigen presenting cells may explain why NOD mice exhibit an impaired ability to induce tolerance and/or activate immunoregulatory T cells. These defects provide understanding for why diabetogenesis in NOD mice is so sensitive to immunomodulatory changes mediated through the environment. Although the unique MHC haplotype of NOD mice is clearly a major contributor to diabetes susceptibility, evidence for a complex interaction between MHC loci and many other polygenetic factors is reviewed.


Linkage between T cell receptor genes and susceptibility to multiple sclerosis: a complex issue.

Susceptibility to Multiple Sclerosis (MS) and to other autoimmune diseases has been linked to genes encoded within the HLA complex. More recent evidence indicates linkage between MS and genes encoded within or closely linked to the T cell receptor (TCR) beta chain gene complex. However, not all available data are concordant. Discrepancies are most likely rooted in the complex nature of TCR and MHC genes and interactions of their products in initiating and sustaining autoimmune responses. An evaluation of linkage of TCR and MHC genes to autoimmune disease processes must take into account the nature of polymorphism in the gene complexes, the complexity of autoimmune diseases along with the multigenic nature of genetic predisposition. These factors create a situation in which simple genetic linkage may be the exception rather than the rule. The present report reviews data concerning TCR and MS linkage and enumerates the complexities that arise in evaluating results from such studies.


The immunogenetics of susceptibility and resistance to murine experimental allergic orchitis.

The results of both clinical and experimental studies suggest that immunologic mechanisms may be significant in the pathogenesis of idiopathic infertility. We have defined and preliminarily characterized a number of immunoregulatory genes which control the phenotypic expression of infertility associated with autoimmune disease of the testis. Our studies utilizing the murine model of experimental allergic orchitis have clearly demonstrated that both classical (class II antigens) and nonclassical major histocompatibility complex-linked immune response genes play a central role in controlling disease susceptibility. We have mapped one nonclassical immune response gene, orchitis susceptibility gene-1 (Orch-1), to an interval of ca. 100 kilobases within the H-2S-H-2D region. In addition, immunogenetic analyses have identified two immune suppression genes, Orch-2 and Orch-3, which control active immunoregulatory mechanisms governing the phenotypic expression of disease resistance. The genetic control of autoimmune infertility in this model therefore appears to be polygenic.


Genetic variability in tumor necrosis factor production: relevance to predisposition to autoimmune disease.

Rather than being involved merely in the effector arm of inflammatory processes that contribute to autoimmune organ destruction, a primary involvement of TNF may be in some of the more basic mechanisms that occur in autoimmune disease. In this review, data are presented on TNF-alpha that suggest the involvement of this cytokine in the genetic predisposition to autoimmune diseases such as lupus nephritis.


A clinical evaluation of root resorption by formocresol treatment in 120 cases of pulpotomy in permanent molars.

The effect of a formocresol pulpotomy of a 120 permanent molar showed external and internal resorption on distal root in lower molar, and palatal root in the upper molar. In this study 33.3% were male and 66.7% were female. The age distribution of patients was 16 to 20 years of age and 21 to 25 years of age. The rate of resorption for chronic pulpitis was more than acute pulpitis. The success of formocresol pulpotomy treatment at the end of the 10th year for acute pulpitis was 92.26% in contrast to 84% for chronic pulpitis.


Immunogenetic aspects of clinical and experimental uveitis.

Genetic association of some immune-mediated human uveitic diseases with histocompatibility antigens, ethnic origin, familial background, or gender have suggested the presence a hereditary component in susceptibility. Experimental autoimmune uveoretinitis (EAU) can be induced in inbred rodents by immunization with evolutionarily conserved retinal proteins, and mimics many features of human uveitis. Susceptibility to EAU is genetically controlled, and the model is being used to study mechanisms that might affect susceptibility to ocular autoimmune disease. EAU expression in mice and in rats requires the presence of both a susceptible MHC haplotype and a "permissive" genetic background. MHC control of susceptibility in H-2k mice was tentatively mapped to the I-A subregion (HLA-DR equivalent), implicating epitope recognition as a major mechanism in susceptibility. In contrast, expression of the I-Ek gene product (HLA-DQ equivalent) appeared to have an ameliorating effect on disease. Susceptible H-2 haplotypes exhibited highest disease scores on the B10 background, and disease was reduced, or even absent, on some other (nonpermissive) backgrounds. Factors which may determine "permissiveness" or "nonpermissiveness" of a particular genetic background, as studied in mice and rats, may include regulation of responses to lymphokines, hypothalamic-adrenal-pituitary axis hormones, mast cell/vascular effects, and possibly the T cell repertoire. The data are interpreted to suggest that, in individuals susceptible to uveitis by virtue of their MHC, the final expression of disease will be determined by the genetic background. These results might help to explain why only a minority of individuals with a susceptible HLA type develop uveitis, as well as the variable incidence of disease in HLA-identical populations of different ethnic backgrounds.


The prevalence of congenitally missing teeth in class I, II, III malocclusions.

A total of 1619 patients, 502 males and 1117 females, ranging in age from 6.5 to 32 years old were examined. The study used a full set of radiographs, panographs, lateral cephalogram and study models to find the highest prevalence of congenitally missing teeth in class II malocclusion patients and a significant amount of missing maxillary teeth in Class III malocclusion patients.


The effect of inferior alveolar neurotomy on mandibular growth in the rat.

To assess the role of possible growth alterations on the mandible, an investigation was undertaken to analyze the effect of bilateral sectioning the inferior alveolar nerve on mandibular growth in 21 day-old Charles River strain rats. The experimental group (n = 26) was subjected to bilateral resection of the inferior alveolar nerve, while 34 animals of comparative age were sham operated and served as controls. At 111 days maturity, the following alterations in the size and shape of the mandible were observed in the experimental animals: 1) the coronoid process in the experimental group was longer, slightly thinner and more curved, 2) antegonial notching was more pronounced. Mandibular length increased from 14 mm to 20.9 mm in control animals, while in the experimental animals, the length of the mandible was 19.6 mm. Thus, the length of the mandible in experimental group was 1.3 mm on the average shorter than the control group (p < 0.0001) and the difference between the two groups was highly statistically significant. The average 1.6 mm difference between the mandibular height of control and experimental animals indicated that the experimental mandibular ramus was approximately 0.5 mm shorter than in control animals. The difference in ramus height between the groups was statistically significant (p < 0.003), but the difference in intercondylar width between control and experimental groups (p < 0.31) was not statistically significant. The corpus height between control and experimental groups was statistically significant (p < 0.0001). Incisor overjet increased from 1.3 mm in control group to 3.2 mm in experimental group (p < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)


Resin adhesion to the ground primary enamel: influence of etching times and thermal cycling test.

The purpose of this study was to investigate the influence of etching times and thermal cycling on resin adhesion on ground primary enamel. Two hundred bovine mandibular primary incisors were used. Materials used in this study were 40% phospholic acid gel, Photo Bond and Photo Clearfil A (Kuraray Co., Kurashiki, Japan) in PCA groups and 37% phospholic acid gel, Scotch Bond and Silux (3M Co., St. Paul, MN) in the Silux groups. The etching times were 0, 10, 20, 30 and 60 seconds. Shear bond strengths were tested. After the shear bond strength test, the test surfaces of the enamel and the resin specimens were observed using the SEM. The etching times that showed the highest bond strengths were 30 seconds both in the PCA non-thermal cycled group (80.10 +/- 13.01 MPa) and the PCA thermal cycled group (78.99 +/- 10.93 MPa), 20 seconds in the Silux non-thermal cycled group (76.77 +/- 12.99 MPa) and 60 seconds in the Silux thermal cycled group (63.61 +/- 19.64 MPa). The influence of thermal cycling test to the enamel-resin adhesion is relatively slight both in the PCA group and the Silux group.


Clinical application of visible light-cured fluoride-releasing sealant to non-etched enamel surface of partially erupted permanent molars.

A visible light-cured fluoride-releasing sealant was applied to non-etched enamel surfaces of partially erupted permanent molars. A scanning electron microscope was used to find an effective procedure to clean pits and fissures of the occlusal surfaces prior to application of the sealant. This procedure proved clinically acceptable and effective for prevention of dental caries immediately after eruption of permanent molars.


Chronic disseminated histiocytosis X: a case report.

A case of chronic disseminated histiocytosis X (Hand-Schuller-Christian Disease) of the mandible is presented. Multi-modal approach to management is discussed.


Prader-Willi syndrome: report of a case with special emphasis on oral problems.

A case with Prader-Willi syndrome (P.W.S.) is reported. The patient manifests: obesity, hypogonadism, hypotonia, mental retardation, small hands and feet, prominent forehead, bitemporal narrowing, strabismus, hypoplastic teeth, generalized caries and thick, sticky saliva. The patient is presented at two different ages (10 and 14), and the development of the characteristics of the syndrome is described. Emphasis is given to the oral findings especially to the generalized caries, that led to an almost complete destruction of the teeth. The role of the dentist is considered to be important for the control of the dental problem of this syndrome.


Predictors of condom use in sexually active adolescents.

Unprotected sexual intercourse places a substantial number of adolescents at risk for sexually transmitted disease (STD) and human immunodeficiency virus (HIV) infection. While the most effective means of preventing STD/HIV infection among sexually active adolescents is consistent condom use, little is known about the factors that influence their consistent use among adolescents. This study of adolescents (n = 1049, mean age = 16.2 years) found that of the 266 teens who recently became sexually active, only 29% reported using condoms consistently. Consistent condom use was more frequent in males, those with little history of risk behavior and those with stronger intentions to use condoms in the future. Fear and anxiety of HIV, attitudes about risks other than HIV, and other safe behavior intentions were not significantly related to consistent condom use. Although intentions and recent behavior were significantly related, a different group of factors was found to predict intention to use condoms (e.g., perception of condom use by friends, general impulsive attitudes). Identifying and understanding the factors that influence adolescent sexual behavior and intentions is important for developing maximally effective HIV education/prevention programs.


Substance abuse among sexually abused adolescents and their families.

The concurrence of substance abuse and history of sexual abuse among adolescents has prompted this study of substance abuse patterns among families of adolescents who report incest or extrafamilial sexual abuse. A total of 3,179 ninth-grade students in a rural midwestern state completed a survey that included questions about individual and family substance abuse. Adolescents who had been sexually abused were more likely to report substance abuse for themselves as well as for members of their immediate families. They were also more likely to report that they used substances because of family problems, school problems, and because they were sad, lonely, or angry. Adolescents reporting a parent with an alcohol or a drug problem were more likely to use cigarettes, marijuana, alcohol, or "speed." Adolescents experiencing extrafamilial abuse reported more alcohol abuse and more alcohol-related problems than those who experienced incest. There were similar reports of parental and familial alcohol and drug problems among these experiencing incest and those experiencing extrafamilial abuse. Those with drug-abusing parents, however, were most likely to report some kind of sexual abuse history.


A descriptive study of trauma, alcohol, and alcoholism in young adults.

Young adults, 18-20 years of age, admitted to a trauma center via the emergency department, were studied to determine if they had been drinking prior to their injury event. The prevalence of self-reported chronic alcohol problems was examined using the short Michigan Alcohol Screening Test (SMAST). Of the 319 subjects, 131 (41%) tested positive for alcohol, including about one-half of those with intentional injuries and 38% with unintentional injuries. Approximately 22% had blood alcohol concentrations of 100 mg/dL or more, indicating they were legally intoxicated at the time of their injury. Of study subjects who completed the SMAST, 49% attained scores suggesting potential or probable alcoholism, and 20% had already sought some type of treatment, despite their young age. Health-care practices and policies related to these findings include routine screening of trauma patients for alcohol abuse and integration of chemical dependency intervention services with trauma care.


Patterns of teen exposure to a community-based violence prevention project.

This paper describes the implementation of a community-based youth violence prevention project that utilized an educational curriculum and a mass media campaign. The extent of penetration of the intervention into target areas and the degree of contamination of control areas are assessed, and the most frequently contacted forms of educational outreach are identified. Two sources of data, provider interviews and a random digit dialed telephone survey, were used to track the source and extent of teens' exposure to the intervention. Agency provider data revealed that 40% of the 92 contacted agencies actually conducted violence prevention education, reaching 22% of the target area teens. Approximately one-half of the surveyed teens reported some exposure to the program, with 13% of the teens in target areas reporting participation in interactive educational activities associated with the project. The most common source of exposure was the media campaign. Most teens report a single exposure, usually to the media campaign, although 29% report contact with more than one form of violence prevention education. While the project did not achieve community saturation, the data show that the community-based model of intervention for violence prevention is feasible and effective in reaching teenagers. This research highlights some difficulties in evaluating prevention programs, including reconciling community ownership with project identification, the ethics of curtailing services for control purposes, and factors influencing recall of participation.


Psychosocial and economic factors associated with infant feeding intentions of adolescent mothers.

The infant feeding intentions of 64 primiparous, adolescent females, ages 14-18 years, were studied to assess factors which differentiated those who chose breastfeeding from those who did not. The study population consisted of 43 Hispanic, 9 black, 7 non-Hispanic white, and 5 Filipino or Southeast Asian subjects interviewed after delivery. Among the Hispanics, 31 primarily spoke Spanish, and 12 primarily spoke English. A total of 72% intended to breastfeed, and 22% planned to exclusively formula feed. Those teens who intended to breastfeed were significantly older, more often married, more likely to be Hispanic and Spanish speaking, and less likely to have been in school during the pregnancy. In addition, teens were more likely to choose breastfeeding if they had been breastfed themselves or exposed to other women who breastfed. These data suggest that the younger, non-Hispanic, single teen who is enrolled in school and lacking exposure to breastfeeding is the most in need of breastfeeding-promotion programs.


Transition program from pediatric to adult care for cystic fibrosis patients.

A survey of adolescents and young adults with cystic fibrosis (CF) attending an adult CF center was conducted to evaluate a transition program as a means of transferring care from pediatric to adult setting. A total of 40 patients completed a self-administered questionnaire of whom 13 (32.5%) went through the transition program, and 21 (52.5%) received their care at the University of Michigan Cystic Fibrosis Center. Fourteen patients (35.0%) were cared for at other pediatric CF centers, and five (12.5%) were first diagnosed as adults. All those in the transition program approved of having the visit with the internal medicine physician in the pediatric clinic. Most thought that the transition program made the change from pediatric to adult care easier. All patients were comfortable leaving the pediatric clinic after the transition period. Of the 40 patients, 17 (42%) recommended that other patients go through the transition program, although 9 of these 17 patients did not themselves go through the transition program. Twenty-six patients (65%) preferred the adult program. These findings suggest that adolescents with CF should be encouraged to transfer their medical care to an adult CF Center once they have reached an agreed-upon age. This process should be smooth and should occur as part of the regular CF care. This is possible through a well-structured and well-organized transition program with committed pediatric and adult staff.


Labeling relaxation procedures: impact on adolescent's self-report of effectiveness.

Adolescents are being taught relaxation techniques by health-care professionals with increased frequency. The present study examined the effect, on self-reported relaxation, of labeling passive relaxation techniques as "hypnotic relaxation" or as "relaxation training." Subjects were 64 adolescent college students who scored above the 50th percentile, from a subject pool of 189 potential subjects, on the Spielberger Trait Anxiety Inventory. A two by two by two factorial design was utilized with sex, label (hypnotic relaxation versus relaxation training) and relaxation technique (hypnotic induction versus autogenic training) as the independent variables. Under the guise of an investigation of the physiologic correlates of relaxation, subjects were assigned at random to one of four groups. Manipulations of label and relaxation technique were presented on tape via an intercom system. The dependent variable, perceived degree of relaxation, was obtained using a form presented as a "double check" of the accuracy of the physiologic monitoring equipment to which subjects seemingly were attached. Results indicate that the label attached to relaxation techniques can have a significant effect on an individual's subjective report of relaxation depending on the subject's sex.


Laparoscopic cholecystectomy in teenagers.

The positive experience with laparoscopic cholecystectomy (LC) in the adult surgical community encouraged us to perform LC in our last nine adolescent patients requiring cholecystectomy. There were no operative or postoperative complications, and the average hospital stay was less than 3 days. All the teenagers resumed their normal activities 1 week after surgery and were pleased with the small operative scars. Once the technique has been mastered and adequate experience gained with the new instrumentation, laparoscopic cholecystectomy would seem to offer many advantages in the teenage patient.


Health profile of pregnant adolescents among selected tribal populations in Rajasthan, India.

Among primitive tribal communities in India, girls are traditionally married immediately after attaining menarche. In the present study all adolescent girls in the second and third trimesters of pregnancy from 15 randomly selected villages of 4 tribal development blocks of Udaipur district (South Rajasthan State, India) were studied. The data were analyzed with reference to parity, anthropometry, anemia, and other dietary deficiencies. A total of 54 adolescent girls (13-19 years of age) were included in the present study. Of these, 59% (n = 32) were found to be primigravidas, 30% (n = 20) were pregnant for the second time, and 2 girls were pregnant for the third time. A majority were illiterate (n = 46), and almost all of them were found to be suffering from moderate-to-severe anaemia (n = 51). Similarly, a large majority (n = 46) had a body mass index (BMI) less than normal and body weight less than 42 kg. Two of the pregnant girls were also found to be suffering from pellagra, while approximately one-third of the girls had vitamin A deficiency. Only 2 had ever practiced family planning, consisting of some herbal preparations given to them by the folk doctor. Of the study participants, 19 girls (35.0%) were in the third trimester of pregnancy; of these, 7 had evidence of malpresentation or cephalopelvic disproportion. This study highlights the health profile and needs of pregnant adolescents among tribal populations in a drought-affected area in India.


Pregnant again? Psychosocial predictors of short-interval repeat pregnancy among adolescent mothers in Mexico City.

Which adolescent mothers are most likely to become pregnant soon after their first delivery? This study identifies and explores selected background, pregnancy, and postpartum predictors of short-interval repeat pregnancy among urban Mexican adolescents who were single when they conceived their first pregnancy. Of 137 adolescents followed until their second postpartum year, 26 had short-interval repeat pregnancies. These pregnancies were most likely to occur if the teenager was married or in consensual union by 5 months postpartum, was not using an IUD, and had a mother who had been an adolescent mother. Being married or in consensual union postpartum was, in turn, predicted by positive reactions of the adolescent and her partner during the first pregnancy. Nonuse of IUD was more likely if the adolescent had left school prior to pregnancy, did not receive support from her partner during the first pregnancy, and had not obtained an IUD before hospital discharge after first delivery. Adolescents whose mothers had been teen mothers came from more disadvantaged families.


Asthma prevalence and management in Australian adolescents: results from three community surveys.

Three population surveys of asthma, conducted as part of a community-based asthma education program in southwestern Sydney, Australia, illustrate the relationship between health behaviors and asthma morbidity. The first survey was carried out in five secondary schools (n = 2514, 52% participation rate); the second survey, in eight schools (n = 4550, 82% participation rate); and, the third survey was conducted among patients who attended 38 general practices in the region (n = 633 adolescents, 72% participation rate). The prevalence of diagnosed asthma in Australian adolescents across all three studies was 16.5% (95% CI, 15.7%-17.3%). Asthma prevalence declined in males, but increased in females from ages 12-15 years. It was noted that smoking prevalence was similar in asthmatic adolescents, compared with nonasthmatics, and that the adoption of smoking occurred at similar ages. Further, behavioral self-management of asthma was infrequent in this group, with low levels of preventive practice and preventive medication use. We present a conceptual model of the barriers to optimal asthma management among asthmatic adolescents. The results of these surveys have led to community-wide efforts to improve asthma management and decrease smoking prevalence among these adolescents.


Pulmonary embolus in an adolescent on oral contraceptives.

Deep venous thrombosis with pulmonary embolus is a rare complication of oral contraceptives, which generally occurs in adult women and becomes more common with increasing age. These complications are believed to be less common with low dose oral contraceptives than with the higher dose forms. This is a case report of a deep venous thrombosis presenting with a life-threatening pulmonary embolus in an adolescent on low dose triphasic oral contraceptives.


How can CRNAs receive third party reimbursement as recognized providers of anesthesia service?

To remain professionally viable, CRNAs must receive fair and adequate reimbursement for services rendered. Denial of payment by third party insurers can result in frustration, loss of income, and potential negative impact on the right to practice. The insurance industry and other health care organizations categorically and conditionally deny reimbursement for a variety of reasons. Categorical denial is the greatest threat to practice. Conditional denial can usually be resolved. When discussing issues with insurers it is important to deal with those in a position to make or influence policy. It is important for individuals and their respective state associations to be familiar with pertinent insurance laws and regulations because they identify practitioner rights and claims that can be made against the insurer. Any categorical denial should be brought to the state association's attention and investigated for possible illegal action.


Comparison of low-dose sufentanil and fentanyl in balanced intravenous anesthesia for orthotopic cardiac transplantation.

A retrospective review was made of the records of 118 patients who received orthotopic heart transplant. Anesthetic techniques, drugs, dosage, hemodynamic profiles, intubation time, and intensive care unit stay were evaluated. The efficacy of sufentanil was compared to fentanyl in a balanced anesthetic when given in lower doses. Patients were given adequate anesthesia with total opioid doses of sufentanil, 6.5 +/- 2.9 micrograms.kg-1, or fentanyl, 58.9 +/- 24.9 micrograms.kg-1. Midazolam was used in all patients (mean dose 7.6 +/- 3.8 mg). There were no differences between the groups in complications, requirements for inotropic support, or time to extubation. A significantly higher pulmonary artery pressure was noted in patients who received sufentanil, but not fentanyl, pretransplant. The pulmonary artery pressures were not significantly elevated posttransplant. This review indicated that patients can be safely anesthetized with either combination of drug in lower doses than previously recommended.


Association of coagulation tests with blood use during liver transplantation.

This study is a retrospective review of 263 adult patients who underwent either their first or their second orthotopic liver transplantation between March 1985 and January 1992. Activated partial thromboplastin time (APTT) and prothrombin time (PT) were analyzed for correlation with the amount of blood transfused 70 minutes after reperfusion. The data were analyzed to estimate correlation between variables using Spearman's rank correlation coefficient. A P value less than .05 was considered significant. Data analysis demonstrated a positive association between APTT and blood transfusion in all disease states, with the exception of patients who had retransplantation. A positive association existed between PT and the amount of blood transfused in patients with alcoholic liver disease, primary biliary cirrhosis, and primary sclerosing cholangitis.


Mivacurium chloride.

This brief review summarizes the major research to date involving the clinical use of mivacurium in adults and children. The principle focal points are the pharmacokinetic and pharmacodynamic characteristics of the drug and the side effects that have been commonly observed with its clinical use. Comparisons and contrasts with vecuronium, atracurium, and succinylcholine are made. Particular attention is focused on dosages, infusion rates, recovery characteristics, and individual patient variability.


Craniofacial applications for the Medpor porous polyethylene flexblock implant.

We describe use of flexblock, a newly designed Medpor porous polyethylene implant. This implant is ideally suited for repair of small to medium-sized cranial defects and correction of contour deformities. Medpor is used for a wide variety of maxillofacial procedures, and its properties make it an excellent choice for the cranium. It is a highly stable and somewhat flexible porous alloplast that has been shown to exhibit rapid soft-tissue and bone ingrowth. Flexblock, which was designed as an onlay for calvarial bone graft donor sites, has a smooth exterior surface and a series of conical ridges on its undersurface that enable easy bending, good contour adaptability, and suitable strength. We used the Medpor flexblock implant in 12 patients over 2 years for correction of contour deformities, cranial defects, and reconstruction of the supraorbital rim. There were no complications. Larger cranial defects and complex reconstructions can be performed using customized Medpor implants. The properties of Medpor and the flexblock design make this implant an excellent alternative to the existing methods of cranioplasty and cranial contour correction.


Solitary calvarial plasmacytoma.

One patient with a solitary plasmacytoma of the frontal bone was treated with complete surgical resection. To reconstruct the large calvarial defect, a split-thickness calvarial graft was harvested from the parietal area and secured in place with miniplates. Solitary plasmacytomas of the calvaria are not common. Clinical presentation, diagnostic criteria, therapeutic approaches, and prognosis are discussed.


Reconstruction of a large congenital cranioorbital defect with a species-specific demineralized bone implant.

Bone grafting is one of the most common operative procedures in craniofacial surgery today. Almost all surgical defects have to be closed with a graft, and all stabilized segments require bone grafts for stabilization prior to fixation. In certain circumstances, however, lack of availability of large grafts necessitates the use of bone substitutes. In the patient presented, a large defect--which is larger than a critical size defect--did not close on its own, even though neonates have a very high potential for forming bone around the dura. The defect was closed with demineralized bone implantation and showed complete filling of the defect through the bone induction principle.


Demineralized perforated bone implants in craniofacial surgery.

Between July 1990 and September 1991, demineralized perforated allogeneic bone implants (Pacific Coast Tissue Bank, Los Angeles, CA) were placed in 72 patients. Because many patients received more than one implant, a total of 248 implants were used in 80 procedures. The technology of processing demineralized bone implants is described in detail. All patients were operated on by one surgeon (K.E.S.) at the Humana Craniofacial Institute in Dallas, Texas. Forty-one patients had craniofacial deformities, 16 had secondary deformities following cleft lip and palate repair, 8 had bony defects following removal of tumors, and 10 had various skeletal deformities following trauma. Of the 72 patients, 6 had two surgical procedures during which additional implants were inserted. Implants placed in the cranial vault and the maxillary complex, including alveolar grafts, were inlay grafts, whereas implants placed in the orbital, nasal, paranasal, temporal, and malar areas were onlay grafts used for contouring, augmentation, or both. Complications were limited to delayed wound healing in 6 patients. According to our observations, demineralized perforated bone implants represent an encouraging alternative to autogenous bone grafting. Further clinical and experimental studies are necessary to obtain more information about this material.


Demineralized bone matrix polydioxanone composite as a substitute for bone graft: a comparative study in rats.

Demineralized bone matrix (DBM) has been successfully used as a substitute for bone grafting. Autogenous bone grafts (ABG) may cause donor site morbidity and undergo significant resorption. DBM may overcome these problems but is mechanically unstable when originally placed. We explored using a slowly resorbable template, polydioxanone (PDS), in combination with DBM and compared it to ABG in a rat 9 x 9 mm cranial defect model. After both 1 and 3 months, histologically and biochemically well-formed bone was present in ABG/PDS and DBM/PDS-treated defects, but not in control defects (PDS alone). Mechanical push-out tests using a servohydraulic testing frame were conducted. Maximum load before failure of DBM/PDS increased from 65% at 1 month to 100% of that of intact skull at 3 months. In contrast, ABG/PDS was 50% as strong as DBM/PDS and not significantly stronger than PDS alone. ABG/DBM did not significantly increase in strength from 1 to 3 months. We conclude that DBM/PDS is better than ABG/PDS in treating cranial defects in the rat model, and that an absorbable osteoinductive bone substitute with superior mechanical advantage is possible without the disadvantages of ABG.


An in utero model of craniosynostosis.

To define better the pathophysiology of craniosynostosis, we developed an in utero model in rabbits. Premature fusion of the sutures was achieved by osteoinduction using demineralized bone matrix (DBM). Thirty-six fetuses from 18 time-dated pregnant rabbits underwent coronal strip craniectomies and implantation of DBM at 25 days of gestation (term = 31 days). Seventeen (47%) survived vaginal delivery and 10 (28%) survived for long-term follow-up. Surviving, operated animals demonstrated bony fusion across the coronal sutures presumably due to osteoinduction by the DBM. Coronal computed tomographic scans with sagittal reconstructions revealed that experimental animals had taller and wider skulls than nonoperated control animals. We conclude that employing DBM to create craniosynostosis in the fetal rabbit is technically feasible. Such a model may be used to more clearly define the pathophysiology of craniosynostosis and to evaluate methods of treatment.


Bending mechanics of bone grafts: an experimental study.

We compare the mechanical properties of rib and cranial grafts subjected to bending stresses and analyze the modification of those properties following miniplate fixation. Standardized side-paired rib and cranial bone samples were harvested from human cadavers. Twenty bone specimens were divided into four study groups, comprising rib and cranial grafts, with and without miniplate reinforcement. Bone segments were subjected to measured stresses in an Instrom unit with simultaneous strain recording. The stress/strain curves were analyzed to determine the modulus of elasticity, failure points, and elastic properties. Experimental findings and clinical implications are discussed.


Trigonocephaly.

Trigonocephaly has been described either as an isolated anomaly or as part of the clinical spectrum of some well-known syndromes. Treatment, complications, and prognosis are closely related to the manifestations of the associated anomalies. We report on the main types of syndromes with trigonocephaly and the management of this condition.


Lower-third facial injuries: management and complications.

I report 1,110 patients with lower-third facial injuries isolated from 1,608 patients with different types of facial injuries. Mixed injuries (bone and soft tissue) were most common (72%; n = 805). The most common site of fracture was the body of the mandible (26.12%; n = 290). One hundred sixty-three patients underwent soft-tissue and bony reconstruction with a local soft-tissue flap or an iliac bone graft, or both. Three procedures failed because of gingival tearing. Other treatments ranged from conservative treatment to different types of closed or open reduction. Postinjury and postsurgery complications were many and involved soft tissue, nerves, tongue, and bones. The follow-up period ranged from 3 months to 3 years.


Fixture design and overload influence marginal bone loss and fixture success in the Brånemark system.

It has been documented that the long-term clinical outcome of the Brånemark system is very favourable. However, failures do occur before and after loading. This study examined the differences in marginal bone loss between standard and self-tapping fixtures and attempted to explain excessive marginal bone loss or loss of osseointegration during the first 3 years of loading. Marginal bone loss (scored on long cone radiographs) and fixture failure rate were compared for different fixture designs. For standard fixtures, in comparison with self-tapping fixtures, the failure rate was clearly higher before as well as after loading. However, for successful fixtures no difference in marginal bone loss was observed. For the conical fixtures an increased marginal bone loss around the smooth part was observed. The effect of fixture overload, marginal bone height and loss of osseointegration was examined in 69 patients with 1 and 15 patients with 2 fixed full prostheses, and in 9 patients with an overdenture in the upper jaw. Excessive marginal bone loss (more than 1 mm) after the first year of loading and/or fixture loss correlated well with the presence of overload due to a lack of anterior contact, the presence of parafunctional activity and osseointegrated full fixed prostheses in both jaws.


Putative periodontal pathogens on titanium implants and teeth in experimental gingivitis and periodontitis in beagle dogs.

The microflora around titanium implants and teeth in 4 beagle dogs was analyzed in order to follow the longitudinal development from healthy conditions to experimental gingivitis and periodontitis. A 2-month plaque control program was performed to establish healthy conditions on titanium implants and control teeth (baseline, day 0). Subgingival bacterial samples and radiographs were obtained. The plaque control was ceased and all measurements were repeated on day 21 (gingivitis). A new period of plaque control was initiated to re-establish healthy conditions (day 49). A cotton ligature was placed subgingivally around the implants and the control teeth to induce tissue breakdown. The ligatures were removed on day 91. The study was completed with registrations on day 121 (periodontitis). No significant microbiological difference was found between titanium implants and teeth in healthy conditions and in gingivitis and periodontitis. The mean total viable count increased 10 times on implants as well as on teeth. Streptococci were dominating at baseline: 40.2% on implants and 60.6% on teeth and decreased in gingivitis to 11.7% and 5.4%. When periodontitis had developed, the proportion of streptococci was < 1%. At baseline few Porphyromonas gingivalis and Prevotella intermedia were detected. They increased at gingivitis to 37.4% and 21.0%; when periodontitis developed, they comprised about 25.0%. Microbial colonization and establishment on titanium implants with healthy gingiva, experimental gingivitis and periodontitis follow the same pattern as on teeth.


Evaluation of different methods to clean titanium abutments. A scanning electron microscopic study.

The cleaning effectiveness of different treatment methods for titanium abutments was evaluated using scanning electron microscopy (SEM). In the mandible of 4 beagle dogs, 25 titanium abutments were installed (modum Brånemark). After 16 weeks of plaque accumulation, mineralized deposits had formed on 23 abutments. Each of these abutments was subjected to one of the following treatment methods: scaling with (1) metal, (2) plastic, or (3) ultrasonic instruments; (4) air-polishing, (5) weekly rubber cup polishing or (6) daily brushing with a conventional toothbrush. Fourteen abutments were removed immediately after treatment. On 9 abutments, the scaling procedures and air-polishing were repeated after another 16 weeks of plaque accumulation. The abutments were prepared for SEM, and each of them was viewed and photographed at 3 different magnifications. The photomicrographs were evaluated by 3 examiners who, guided by reference pictures, gave each abutment a "cleanliness" score, ranking from 0 to 5. Regular rubber cup polishing and regular brushing resulted in the highest surface cleanliness, while the air-polishing procedure showed the lowest cleanliness score. None of the 3 scaling methods created a cleanliness score better than 3. The 3 scaling methods were considered equal in their cleaning effectiveness. No differences could be observed between surfaces treated 1 x or 2 x. Taken the present findings and those of other studies concerning the effects of scaling on the surface roughness and biocompatibility into consideration, it was concluded that plastic scalers may be the instruments of choice for debridement of titanium implant surfaces.


Mechanical resistance of cemented post and core buildups for ITI-Bonefit implants.

In order to improve the prosthetic versatility of the ITI-Bonefit implant system, a clinical technique was tested whereby a custom made post and core buildup was cemented into implants. Specially designed threaded and serrated posts were machined in precious metal. After the posts were seated into the threaded channel of the implants, cores were built using autopolymerizing resin. Those were then cast and cemented into the implants. For the remainder of the procedure, the buildups were treated like natural abutments using conventional prosthodontic techniques. Mechanical tests were performed to assess the clinical viability of these buildups. The ultimate tensile strength of annealed posts lies in the 700-800 N range. By comparison, the pull-out resistance of posts cemented into natural roots ranged between 108 and 177 N, and the maximum pull-out resistance of manufactured abutments is about 1040 N. When the resistance against lateral forces was tested, the cemented build-ups ranged between 981 and 1128 N, whereas natural teeth fractured between 206 and 903 N depending on the diameter of the root. Manufactured abutments failed at stress levels of about 1020 N. Considering these favorable results, we conclude that the technique described above can be applied clinically for further investigation. Additionally, we suggest some modifications in implant design that would enhance the versatility of the system.


Healing-in of root analogue titanium implants placed in extraction sockets. An experimental study in the beagle dog.

The aim of these animal experiments was to characterize and evaluate the healing-in of root analogue titanium implants fitting with high precision to the alveolar wall. Four beagle dogs were used in the study. The roots of the 3rd and 4th mandibular premolars in both quadrants of 3 dogs and in 1 quadrant of 1 dog (dog 4) were extracted after hemisection. Each root was machine-copied to 1 titanium analogue. In dog 4, however, 2 titanium analogues were fabricated from each of the 4 extracted roots. This enabled insertion of analogues also into the contralateral sockets obtained by extraction of the corresponding roots immediately before implant installation, which was undertaken 2 weeks after the first extractions. Thus, in all, 32 analogues were implanted in their respective (or contralateral) sockets following ridge incision and elevation of mucoperiosteal flaps. The analogues were carefully covered by the repositioned flaps. In dog 4, 2 analogues from the immediate sockets and 2 from the 2-week sockets were surgically exposed and supplied with titanium crowns after a healing period of 2 months. The healing after implantation was evaluated by clinical, radiographic and histological measures after 2, 12 or 36 months. Two analogues (6%) were lost due to early (during the 1st week) exposure to the oral cavity. Another 2 analogues (6%) were, although not exposed, encapsulated by soft tissue and were easily removed with a surgical forceps. Twenty-eight analogues (88%) were healed-in by contact between bone and implant (osseointegration).(ABSTRACT TRUNCATED AT 250 WORDS)


Osseous healing of experimentally created defects in the calvaria of rabbits using guided bone regeneration. A pilot study.

The aim of this study was to test whether healing of extensive transosseous defects in the calvaria can successfully be achieved using guided bone regeneration. The results demonstrated complete osseous bridging of the skull defect in the test specimen. In the control specimen, fibrous connective tissue occupied the area of the skull defect.


Long-standing plaque and gingivitis at implants and teeth in the dog.

The experiment was performed to evaluate the effects of long-standing plaque on the gingiva and peri-implant mucosa. 5 beagle dogs were used in the study. The mandibular right premolars were extracted. 3 months later, 3 titanium fixtures were installed and after another 3 months, abutment connection was performed. Plaque control, in the implant as well as the contralateral tooth regions, was maintained during a 4-month period prior to the start of the main experiment. On Day 0, the teeth and implant sections were examined with respect to plaque and gingivitis. The plaque control program was terminated. The animals were subsequently fed a diet which allowed gross plaque accumulation. After 90 days of undisturbed plaque formation, the dogs were re-examined and biopsies harvested from implants and contralateral teeth. On day 90, all teeth and implants had accumulated large amounts of plaque. The soft tissue at implants and teeth bled on gentle probing. The histological examination of the gingiva and the peri-implant mucosa revealed: (i) both tissues contained an inflammatory cell infiltrate; ICT, (ii) the apical extension of ICT was more pronounced in the peri-implant mucosa than in the gingiva and (iii) the composition of the 2 lesions had many features in common.


Group sequential distribution-free methods for the analysis of multivariate observations.

Many studies involve the collection of multivariate observations, such as repeated measures, on two groups of subjects who are recruited over time, i.e., with staggered entry of subjects. Various marginal distribution-free multivariate methods have been proposed for the analyses of such multivariate observations where some measures may be missing at random. Using the multivariate U statistic of Wei and Johnson (1985, Biometrika 72, 359-364), we describe the group sequential analysis of such a study where the multivariate observations are observed sequentially--both within and among subjects. We describe a multivariate generalization of the Hodges and Lehmann (1963, Annals of Mathematical Statistics 34, 598-611) estimator of a location shift that can be obtained via the multivariate U statistic with the Mann-Whitney-Wilcoxon kernel. We then describe large-sample group sequential interval estimators and tests based on an aggregate estimate of the location shift combined over all of the repeated measures. We also describe how the same steps could be employed to perform a group sequential analysis based on any one of the variety of marginal multivariate methods that have been proposed. These methods are applied to a real-life example.


Two-sample nonparametric estimation and confidence intervals under truncation.

We consider point estimates and confidence intervals for the difference in location or scale between two populations when the observations are subject to truncation. We suggest procedures analogous to those for the complete-sample case. A rigorous justification is presented to support the proposed confidence interval procedure. Finally, some simulations verify the properties of the estimators and confidence intervals. We illustrate the procedure using data on tumor size.


Nonparametric estimation and testing in a cure model.

Nonparametric generalized maximum likelihood product limit point estimators and confidence intervals are given for a cure model with random censorship. One-, two-, and K-sample likelihood ratio tests for inference on the cure rates are developed. In the two-sample case its power is compared to the power of several alternatives, including the log-rank and Gray and Tsiatis (1989, Biometrics 45, 899-904) tests. Implications for the use of the likelihood ratio test in a clinical trial designed to compare cure rates are discussed.


Estimation of completeness and adjustment of age-specific and age-standardized incidence rates.

This note discusses the use of capture-mark-recapture methods and log-linear, linear, product models for incomplete tables (Espeland, 1986, Communications in Statistics--Simulation and Computing 15, 405-424) to estimate completeness of reporting in a disease registry and to estimate incompleteness-adjusted incidence rates. The method had several desirable features, including the ability to handle complex experimental designs, to incorporate auxiliary data (that may be related to the likelihood of reporting), to test the contribution of model terms, and to generate point estimates and associated standard errors.


A hypothesis for the local control of osteoclast function by Ca2+, nitric oxide and free radicals.

Several important conclusions have recently emerged from in vitro studies on the resorptive cell of bone, the osteoclast. First, it has been established that osteoclast function is modulated locally, by changes in the local concentration of Ca2+ caused by hydroxyapatite dissolution. It is thought that activation by Ca2+ of a surface membrane Ca2+ receptor mediates these effects, hence providing a feedback control. Second, a number of molecules produced locally by the endothelial cell, with which the osteoclast is in intimate contact, have been found to affect bone resorption profoundly. For instance, the autocoid nitric oxide strongly inhibits bone resorption. Finally, reactive oxygen species have been found to aid bone resorption and enhance osteoclastic activity directly. Here, we will attempt to integrate these control mechanisms into a unified hypothesis for the local control of bone resorption.


Lysis of erythrocytes by Trichomonas vaginalis.

The in vitro hemolytic activity of 4 isolates of Trichomonas vaginalis was investigated. Repetitive hemolysis assays of any one isolate showed cyclical fluctuations in hemolytic activity, varying over 24 hr of continuous culture. Maximal hemolytic activity was detected using trichomonads in the lag phase of the growth cycle. Investigations showed that hemolysis was a contact-dependent phenomenon and microscopic investigation of samples showed a significant correlation between hemolysis and attachment of erythrocytes to the trichomonad surface. Quantitative data from cytoadherence assays using [51Cr]-labeled erythrocytes were consistent with these observations. It is suggested that hemolytic activity is dependent upon adherence of red blood cells to the surface of T. vaginalis.


ph-dependent hydrophobicity profile of hemagglutinin of influenza virus and its possible relevance in virus fusion.

The hydropathy profile of hemagglutinin (HA) subunits HA1 and HA2 of influenza virus X31 and A/PR 8/34 is analyzed at different pH. At neutral pH (7.4) pronounced hydrophobic sequences of HA correspond to the N-terminus and the transmembrane spanning sequence of HA2. At pH 5.0 where influenza virus is known to fuse with biological membranes several hydrophobic sequences in the ectodomain exist which are comparable in both the hydrophobicity and length of the N-terminus of HA2. It is suggested that these hydrophobic stretches are important for the fusion complex, in addition to the N-terminal site of HA2.


Carboxyterminal telopeptide of type I collagen, ICTP, as a marker of matrix degradation in neonatal mouse calvarial bones, in vitro.

Bone resorption, in vitro, is often measured as the release of prelabelled 45Ca from neonatal mouse calvarial bones, or from fetal rat long bones. In this report we describe a technique to measure the breakdown of bone-matrix, in vitro. We also describe a new way to dissect neonatal mouse calvarial bones, in order to obtain large amounts of bone samples. Twelve bone fragments were dissected out from each mouse calvaria and were thereafter cultured in CMRL 1066 culture medium in serum-free conditions in 0.5 cm2 multiwell culture dishes. Matrix degradation after treatment with parathyroid hormone was assessed by measuring the amount of carboxyterminal telopeptide of type I collagen (ICTP) by RIA. The data on matrix degradation was compared to the release of prelabelled 45Ca from neonatal mouse calvarial bones. We found that the dose-responses for parathyroid hormone-induced release of prelabelled 45Ca and ICTP were identical. RIA-analysis of the ICTP-release is an easy and accurate method to measure degradation of bone-matrix, in vitro. Furthermore, the new dissection technique, described in this report, makes it easy to obtain large amounts of bone samples and thus to perform extensive experiments, e.g. dose-responses for agents that enhance bone resorption.


Inhibitors such as staurosporine, H-7 or polymyxin B cannot be used in skeletal muscle to prove the role of protein kinase C on insulin action.

The precise role of protein kinase C in insulin action in skeletal muscle is not well defined. Based on the fact that inhibitors of protein kinase C block some insulin effects, it has been concluded that some of the biological actions of insulin are mediated via protein kinase C. In this study, we present evidence that inhibitors of protein kinase C such as staurosporine, H-7 or polymyxin B cannot be used to ascertain the role of protein kinase C in skeletal muscle. This is based on the following experimental evidences: a) staurosporine, H-7 and polymyxin B markedly block in muscle the effect of insulin on System A transport activity; however, this effect of insulin is not mimicked in muscle by TPA-induced stimulation of protein kinase C, b) H-7 and polymyxin B block insulin action on System A transport activity in an additive manner to the inhibitory effect of phorbol esters, c) staurosporine, H-7 and polymyxin B block the effect of insulin on lactate production, a process that is activated by insulin and TPA in an additive fashion, and d) staurosporine completely blocks the tyrosine kinase activity of insulin receptors partially purified from rat skeletal muscle.


Effect of HDL1 infusion on biliary secretion in perfused rat liver.

The effects of HDL1 lipoprotein infusion on biliary lipid secretion were studied in the in vitro model of rat perfused liver. A strong increase in bile flow was observed during and after lipoprotein infusion. This caused a significant rise in cholesterol, phospholipid and bile salt secretions. However, only the percentage of cholesterol increased with respect to the other bile lipids. The changes observed in the cholesterol/phospholipid molar ratio values of liver membrane subfractions (i.e., liver plasma membrane, mitochondria plus lysosomes and microsomes) isolated from the perfused rat liver after HDL1 administration were not significant.


[The dynamics of somatosensory and visual evoked potentials as a correlate of reversible states of altered consciousness].

Somatosensory and visual evoked potentials (EPs) of the brain of 17 sensitive subjects (extrasenses) and 12 ordinary healthy subjects were studied. It was found that during extrasensory activity (direct impact, meditation) in comparison to rest values, the amplitude of intermediate and late components of visual and somatosensory EPs of both hemispheres and early components of somatosensory EPs of ipsilateral in relation to stimulation hemisphere diminished 2-4--fold. There was a recovery of these components after discontinuation of extrasensory activity. It is shown that ordinary subjects could not change their EPs when they tried their best to decrease EPs. It is shown that ordinary subjects could not change their EPs when they tried their best to decrease EPs. It is suggested that the ability of extrasenses for reversible changes of their mind by direct adjustment of the activity of the ascending nonspecific systems of the brain and by alterations of interhemispheric relations forms the basis of extrasensory activity.


[The role of the liver macrophage system in decreasing the immune complex level of the blood during adaptation to periodic hypoxia].

It has been established that adaptation to intermittent hypoxia in altitude chamber considerably increases the capacity of hepatic macrophagal systems (MFS) to uptake Indian ink particles from the blood as well as immunoglobulin labelled with fluorescein isothiocyanate. There is simultaneous catabolism of labelled albumin in hepatic MFS. It has been suggested that the increased C3b-component of complement system in blood observed in adaptation to hypoxia plays a substantial role in the activation of hepatic MFS. The role of hepatic MFS activation in reducing the number of circulating immune complexes is emphasized as well as its role in therapeutic effect of adaptation in allergic diseases.


[The effect of the delta sleep-inducing peptide on the development of toxic brain edema-swelling].

Antiedematic effects of the drugs are connected with their action on the mediator systems. DSIP has a wide range of modulatory effects on the brain mediator systems. DSIP antiedematic effect was studied on the toxic brain edema-swelling (BES) model. Physical characteristics of the nervous tissue such as thickness and wetness were used as evaluation criteria. According to the findings, the doses of 75-100 micrograms/kg DSIP were optimal. It is suggested that DSIP effect on BES is multicomponent and rather complicated. Inhibition of serotonin, noradrenaline and histamine systems and activation of GABA-ergic system by DSIP act as a possible antiedematic mechanism.


[The effect of negatively charged liposomes on thrombocyte aggregation induced by ADP].

The incubation of platelet-rich plasma of rats with liposomes has changed cell functional activity. Lipid composition of liposomes modulated the ability of the platelets to respond to ADP. Vesicles, containing phosphatidylserine, phosphatidylinositol or stearylamine inhibited the aggregation by 70, 30 and 40%, respectively. The inhibition of aggregation by phosphatidylserine-containing liposomes was of linear and dose-dependent character. The maximal inhibition was reported at 10-min incubation of liposomes with platelets. The impairment of platelets aggregation can be explained by interactions of liposomes with plasma coagulation factors and blocking the receptors on the platelets membranes.


[The effect of synthetic enkephalins on prostaglandin synthesis and lipid peroxidation in the isolated heart during the activation of free-radical processes].

The system Fe(2+)-ascorbate was used for lipid peroxidation (LPO) activation in isolated heart tissue. The stimulation of free radical processes in the myocardium caused a rise in the level of LPO products and a significant lowering of that of prostacyclin. Intravenous injection of synthetic analogues of enkephalins before LPO activation inhibited LPO and resulted in prostacyclin synthesis normalization. The addition of peptides under study into perfusion solution led to a decrease in LPO primary products level and in thromboxane synthesis.


[The surface activity of vasopressin and its interaction with artificial and biological membranes].

It was determined that vasopressin has surface active properties and in nanomolic concentrations is capable to incorporate in lipoprotein monolayers which are formed from myocytes plasma membranes. By means of pH-metric and fluorescent analysis it was shown that vasopressin interacts with other membrane structures which have no specific receptors--phosphatidylcholinic liposomes and vesicles of sarcoplasmic reticulum of skeletal muscles causing increasing permeability of phospholipid bilayer for Ca2+ ions.


[Biologically active substances from the skin that influence the proliferation and differentiation of cultured human keratinocytes].

Three fractions of biologically active substances of human skin varying in molecular weight (F1 > 15 kD, F2 1.4-15 kD, F3 < 1.4 kD) were tested in primary and regenerating cultures of human epidermal keratinocytes. F1 and F3 caused stimulation of keratinocyte proliferation, F2 inhibited proliferation and enhanced terminal differentiation of epidermal cells.


[The effect of natural and synthetic antioxidant polyhydroxynaphthoquinones on cholesterol metabolism in cultured rabbit hepatocytes].

Primary cultures of rabbit hepatocytes were used to examine the effect of natural and synthetic antioxidants--polyhydroxynaphthoquinones (PHNQ) and alpha-tocopherol on cholesterol and bile acid synthesis. Histochrome, one of the PHNQ, slightly decreased cholesterol synthesis at concentrations 10-100 microM, whereas alpha-tocopherol stimulated cholesterol synthesis. After administration of histochrome or alpha-tocopherol into culture medium a significant stimulation of bile acid synthesis in dose-dependent manner was observed. The increase of bile acid secretion by histochrome in the presence of physiological concentration of HDL2 was found as well. Since histochrome in contrast to alpha-tocopherol enhanced accumulation of [14C] cholesterol of HDL2 in the hepatocytes, it was concluded that histochrome stimulated bile acid synthesis as a result of increased input of HDL2 cholesterol into hepatocytes. These data suggest that histochrome may exhibit a hypocholesterolemic effect by stimulation of bile acid synthesis and inhibition of cholesterol synthesis.


[The effect of ultrahigh-frequency electromagnetic radiation on learning and memory processes].

Low-intensity electromagnetic field (12.6 cm, 2375 MHz, power density 1 mW/cm2) produced retrograde amnesia in the rat passive avoidance test. No effect was registered of microwave irradiation on the open field behavior and the pain sensitivity. Functional activity of the m-cholinergic receptors decreased, but their number increased in the brain cortex. It is suggested that cholinergic system plays an important role in the effects of electromagnetic field on memory processes.


[The immunochemical detection of apoprotein dissociation from particles of very low-density lipoproteins in human blood plasma].

The dissociation of very-low-density lipoprotein (VLDL) apoproteins was studied using immunochemical approaches. The analysis of monospecific antibody binding to apo E, C-II and C-III on VLDL surface showed low apoprotein accessibility for the antibodies while the accessibility of apo C-II and C-III in solution was complete. Lipoprotein preparation dilution resulted in increasing of apo E and C-II accessibility. It was suggested that apoprotein dissociation led to apoprotein cluster dissolving on VLDL surface and higher antigen determinant accessibility. The findings confirmed previous theoretical analysis of apoprotein dissociation.


[The effect of nitroglycerin, nitrosorbide and nitroprusside on the intracellular content of Ca2+ ions in human lymphocytes].

We used Fura-2 fluorometry to observe the effects of nitroglycerin (NG), isosorbide--2,5--dinitrate (ISDN) and sodium nitroprusside (NP) on basal and mitogen-induced (Con A, 25 micrograms/ml) cytoplasmic Ca++level ([Ca++]) in human blood lymphocytes. It is shown that nitrates dose-dependently decrease Con-A-induced increase in [Ca++]i. When compared for the effect on calcium metabolism, NP appeared most potent (IC50 = 4.1 x 10(-7) M). The drug action was not reported when the cells were exposed to Ca(++)-free solution. 120-min preincubation with 10(-4) M NG led to complete abolishment of the ISDN and NG effects. The results suggest that human lymphocytes may be used as an experimental model of nitrates action and mechanisms underlying tolerance to them.


[The effect of hydrocortisone on the alkaline proteinase activity in the target organs of rats].

The effect of hydrocortisone on the thymus and liver proteinases activity in the alkaline pH range was studied on rats. It is shown that the alkaline proteinases are activated in the thymus and inhibited in the liver of hormone-treated animals. Possible relationship between the effect of glucocorticoids on protein metabolism and alkaline proteinases activity is suggested.


[The effect of cyclosporin A on the islet cells of mice].

The action of immunosuppressive agent ciclosporin A on the insular apparatus was studied with an original method of cytochemical zinc detection in experiments on mice. The drug was found to lower zinc levels in pancreatic beta-cells. In ciclosporin A pretreatment the sensitivity of mice to zinc-binding diabetogenic agent enhanced.


[The effect of MPTP on the neuronal uptake of monoamines].

The results of kinetic analysis of synaptosomal uptake of dopamine, noradrenaline, adrenaline and serotonin showed the presence of their own carrier systems with high or low affinity for each monoamine. The low affinity system of the uptake of monoamines by nerve endings differs from extraneuronal one by higher affinity. MPTP noncompetitively inhibits the system of highly effective uptake of the studied monoamines by nerve endings, competitively inhibiting synaptosomal uptake with low affinity of noradrenaline, adrenaline and noncompetitively serotonin and dopamine. The constant values of inhibition showed that MPTP most strongly blocks the system of synaptosomal uptake of low affinity serotonin and approximately 2-times weaker affects its system of high affinity. Carrier systems of high affinity of dopamine, adrenaline and noradrenaline block MPTP 150-500 times weaker than that of serotonin, and as for low affinity--in 2000-4000 times. It may be supposed that synaptosomal uptake of low affinity serotonin is most perceptible to the effect of MPTP and is of a particular importance in the development of Parkinson's disease symptoms.


[The effect of amiridin on the MPTP-induced Parkinson-like syndrome in monkeys].

Development of behavioral disturbances was investigated during N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration (0,2 mg/kg, i/m, at 48 h. intervals, total dose 11.2-13.2 mg/kg) in experiments on two monkeys Macaca rhesus. MPTP induced the complex of symptoms, which are typical for idiopathic Parkinson's disease. Administration of amiridine (0,25-0,4 mg/kg) to MPTP-treated monkeys caused gradual decline of Parkinson syndrome. Mechanisms of action of amiridine are discussed.


[The protective role of estradiol under extreme conditions].

It has been demonstrated that estradiol increases the resistance of the animals to hemorrhagic shock. Apparently, it is accounted for by its positive effect on cardiovascular system (by stimulation of myocardial contractility, stabilization of ATP and CF pools, inhibition of lipid peroxidation and lysosomal enzymes, etc.).


[The effect of ubiquinone-10 on the development of D-galactosamine-induced hepatitis in rats].

It has been shown that prophylactic administration of ubiquinone protects rats liver from the toxic damage by D-galactosamine both on ultrastructural and on cell levels. Ubiquinone administration prevents necrosis in hepatocytes and preserves their ability for compensatory reactions expressed in activation of protein-synthesis regulating structures in the cell. Ubiquinone decreases hyperfermentemia and hyperbilirubinemia as well as prevents the decrease in liver protein content caused by galactosamine. Ubiquinone exerts an antioxidant effect, blocking the induction of lipid peroxidation both in intact and hepatic rats.