Studies on endogenous formation of N-nitroso compounds in the guinea pig supplemented with proline or thioproline and sodium nitrate. The endogenous formation of N-nitrosoproline (NPRO) and N-nitrosothioproline (NTPRO, N-nitrosothiazolidine-4-carboxylic acid) was studied by monitoring their excretion in the urine of guinea pigs given oral doses of 10 mg proline or thioproline after supplementation with 34 mg (0.4 mmol) sodium nitrate. In order to estimate the conversion of nitrate to nitrite, the animals were also supplemented with 3.5 mg (0.05 mmol) sodium nitrite instead of sodium nitrate. In animals fed commercial diets, the excretion of NPRO and NTPRO under supplementation with sodium nitrate was 2.0 micrograms and 28.7 micrograms/animal/day, respectively, whereas the excretion under supplementation with sodium nitrite was 0.7 micrograms and 13.3 micrograms/animal/day, respectively. The higher excretion of NTPRO than NPRO in each case shows that thioproline is more effective for nitrite trapping than proline. The animals supplemented with nitrate excreted more than twice the amounts of NPRO or NTPRO than those supplemented with nitrite. It is assumed, therefore, that more than 0.1 mmol nitrate is reduced to nitrite and takes part in the endogenous nitrosation of the guinea pig. When various concentrations of L-ascorbic acid (AsA), known to inhibit the formation of N-nitroso compounds, were also administered orally to animals immediately after supplementation with sodium nitrate, the NPRO excretion decreased with increasing AsA concentration. These data indicate that the guinea pig, which is unable to synthesize AsA as well as humans, may be an appropriate animal model for evaluation of the endogenous nitrosation ability of humans ingesting nitrate.


Effects of phenolic smoke condensates and their components on hepatic drug metabolizing systems. Treatment of food with wood smoke is a long-established method of preservation and flavouring food. Recently, hardwood smoke condensates, purified of polycyclic hydrocarbons, have become of importance for direct flavouring of sausage-meat. The acute toxicity of the purified phenolic fraction in mice after intraperitoneal administration was therefore investigated. The LD50 was found to be 940 mg/kg body weight, which is about three times the LD50 of phenol (about 300 mg/kg). Only high concentrations of phenols or smoke condensate fractions are able to damage cytochrome P-450 by conversion to cytochrome P-420, whereas lower concentrations exhibit inhibitory effects on monooxygenase activity. Inductive properties of the phenolic fractions could not be demonstrated. Concentrations in vivo of free phenolic compounds do not reach inhibitory levels, since the hexobarbital-induced sleeping-time and 14CO2-exhalation after administration of p-[methoxy-14C] acetanilide are not altered. It is concluded that the phenolic compound intake with food regularly treated with smoke condensate fractions is below a toxicologically relevant level.


A 4-week feeding study of ground red chilli (Capsicum annuum) in male B6C3F1 mice. The toxicity of red chilli was examined in male B6C3F1 mice fed a commercial meal diet mixed with ground Capsicum annuum (Linn.) at levels of 0.5, 1.0, 2.5, 5.0, 7.5 and 10% by weight. Mice were offered control or test diets ad lib. starting at 6 wk of age. Food consumption was measured daily and individual body weights recorded weekly for the 4-wk feeding period. General health, body weight and food intake were apparently not adversely affected at any level of pepper consumption. Histopathological evaluation revealed slight glycogen depletion and anisocytosis of hepatocytes in the 10% group. However, other organs did not reveal any lesions attributable to the chilli exposure. It appears that red chilli is relatively non-toxic at the doses tested in male B6C3F1 mice.


A novel pharmacological approach for paraquat poisoning in rat and A549 cell line using ambroxol, a lung surfactant synthesis inducer. Paraquat (PQ) is a widely used herbicide that causes acute adult respiratory distress syndrome (ARDS) and chronic lung damage (diffuse fibrosis). One of the earliest biochemical effects induced by PQ is damage to type II pneumocytes with consequent depletion of surfactant. With the aim of counteracting the toxic effects of PQ, a series of investigations were performed into the possible protective effect of the drug ambroxol, which induces the synthesis of surfactant in lung alveolar type II cells. The number of survivors and survival time of rats treated ip with 35 mg PQ/kg was significantly increased by 3 days of ambroxol pretreatment and by ambroxol treatment 30 min or 2 hr after PQ. Total phospholipid content in lung and bronchoalveolar lavage fluid (BALF) was significantly reduced 30 hr after treatment with PQ alone. The association of ambroxol with PQ significantly antagonized this reduction. In BALF the ratio between palmitic acid and stearic acid concentrations was significantly lower in animals treated with PQ alone but was returned to normal by the association with ambroxol. The cell line A549, exposed in vitro to PQ concentrations from 0.5 x 10(-4) to 2 x 10(-3) M, showed a significant dose-dependent loss of viability. Cells pretreated with ambroxol (10 mg/ml) were more resistant to PQ and their viability started to decrease significantly only from a PQ concentration of 0.8 x 10(-3) M. Membrane microviscosity was measured on the same cells. Cells treated with PQ alone showed a reduction of membrane microviscosity, which was significantly counteracted by ambroxol pretreatment. The curves of modification of membrane microviscosity of cells treated with PQ and with ambroxol plus PQ paralleled those of cell viability, indicating that the stimulation of surfactant synthesis in vitro may be a prerequisite for counteracting some of the early effects of PQ.


Comparison of the partition coefficient and skin penetration of a marine algal toxin (lyngbyatoxin A). Lyngbyatoxin A is produced by marine algae, and causes local cutaneous toxicity in swimmers. The purpose of this research was (1) to determine the partition coefficient of lyngbyatoxin A in octanol/water and (2) to use methods in vitro to measure the penetration and distribution of lyngbyatoxin A in guinea pig and human skin. Discs of excised guinea pig and human skin were mounted in diffusion chambers that exposed the epidermal surface to air and bathed the dermis with HEPES-buffered Hanks' balanced salt solution with gentamicin sulphate. The epidermal surfaces were dosed with 26 micrograms lyngbyatoxin A/cm2 dissolved in 13 microliters dimethyl sulphoxide/cm2. The diffusion chambers were incubated at 36 degrees C for varying periods (1.0-24 hr). HPLC was used to quantify lyngbyatoxin A. Skin penetration was calculated by summing the amount of lyngbyatoxin A recovered from the dermis and receptor fluid. The mean partition coefficient for lyngbyatoxin A was 1.53. Penetration of lyngbyatoxin A (expressed as a percentage of dose, n = 3) in guinea pig and human skin was 23 and 6.2 (respectively) after 1 hr of topical exposure. The amount of lyngbyatoxin A in the dermis and receptor fluid did not change significantly over time.


Embryotoxicity study of propenoic acid, 3-(4-methoxyphenyl)-3-methylbutylester in the Wistar rat. 3-(4-methoxyphenyl)-3-methylbutylester, propenoic acid (MPMBE; CAS no. 71617-10-2), a UVB-light filter used for sun protection of the skin, was administered once daily by intragastric gavage to pregnant Wistar rats on days 6-15 of gestation. Doses of 0.25 ml/kg/day (study group: D0.25), 0.75 ml/kg/day (D0.75) and 2.25 ml MPMBE/kg/day (D2.25) were applied. A positive control group (Pos) received 15 mg (all trans) retinoic acid/kg/day. MPMBE revealed some toxic effects in the dams of the group receiving the highest dose (D2.25): marked loss of body weight, polydipsia, reduced food consumption and intensified loss and thinning of hair. Only thinning or partial loss of hair without any other harmful effects was seen in the dams of group D0.75. An increase in embryonic deaths was striking in group D2.25; the living foetuses revealed signs of retarded development, but no major external or internal anomalies as signs of teratogenicity. This study was not able to present any teratogenic effects induced by MPMBE in the offspring, even at very high oral doses (> 2 g/kg/day) that caused substantial toxicity in the dams. In conclusion, concerning embryotoxicity an oral dose of 250 mg/kg/day MPMBE is regarded as a safe no-observed-effect level, whereas even 750 mg/kg/day MPMBE--following acknowledged rules--can be judged as a borderline no-observed-adverse-effect level.


Guidelines for safety evaluation of cosmetics ingredients in the EC countries. The Scientific Committee on Cosmetology (SCC) of the Commission of the European Communities was established in 1978 to assist the Commission in the application of the 76/768 Directive, which regulates the production and marketing of cosmetics products. The Committee has been asked to update the general guidelines, defined in 1982, for testing cosmetics ingredients with the aim of ensuring consumers' safety. In the present paper the full document approved by the SCC in October 1990 is reported. This new document is based on the experience of the Committee over the last 10 years, during which more than 400 cosmetics ingredients have been evaluated. The document also highlights the need to proceed to define standard methods to be used to assess dermal absorption and phototoxicity--areas in which international guidelines have not yet been approved. The document also includes some comments made by the author in order to explain better the position of the Committee in relation to certain items.


Great toe metatarsophalangeal joint arthrodesis: a user-friendly technique. Thirty-four feet (23 patients) were treated with a metatarsophalangeal (MP) joint fusion of the hallux using five threaded 0.062-in K wires for fixation. Operations were done for the following diagnoses: rheumatoid arthritis (26 procedures), hallux rigidus (1), salvage of previous bunionectomies (3), hallux valgus with absent toe, bilateral fusion (2), severe hallux valgus with chronic MP joint synovitis (1), and congenital hallux varus (1). The ages ranged from 17 to 73 years, with an average of 55 years. Follow-up was available on 31 of the fusions by questionnaire and telephone contact, with an average follow-up of 24 months and a minimum of 1 year. The successful arthrodesis rate was 97%. In 9% of the procedures (three cases), the patients were dissatisfied: This was due to pain under the first metatarsal head in two cases and to impingement between the first and second toes in a third case. In 91% of the fusions (29 of 32 patient responses), the patients stated that they would have the surgery if they had to choose again. Patients indicated "complete satisfaction" in 15 fusions and "satisfaction with reservations" in 14. Patients felt that their ability to wear desired shoes was improved in 48% of the procedures, was unchanged by the fusions in 26%, and was worse than before the operation in 26%. Based on this study and review of the literature, a recommendation is made for fusing the rheumatoid hallux with 25 degrees to 30 degrees of valgus and 10 degrees of extension. In general, selection of toe position for fusion is based on reducing stress on the hallux interphalangeal joint and accommodating the position of the second toe. The multiple pin fixation technique gives a high incidence of fusion, it is easy to perform, and it is adaptable to the varying requirements for toe position.


Chevron osteotomy for hallux valgus.

Chevron osteotomy for hallux valgus. A retrospective study of the Chevron osteotomy procedure for hallux valgus was carried out on 112 patients (168 feet) with an average age of 39.7 years (range 19 to 61 years). The average follow-up was 4.4 years (range 13 months to 7.5 years). The preoperative diagnosis was symptomatic hallux valgus. The average preoperative intermetatarsal 1-2 angle was 15.5 degrees (range 11 degrees to 18 degrees) and the hallux valgus angle was 28.1 degrees (range 21 degrees to 42 degrees). The operation was effective in improving symptoms, cosmesis, and function and in decreasing the deformity.


Ankle arthroscopy: review and long-term results. Ankle arthroscopy has evolved over the past decade as a diagnostic and an operative modality. Forty ankle arthroscopies were performed by the senior author (G.J.S.) for osteochondral fractures, chronic sprains unresponsive to conservative treatment, posttraumatic osteoarthritis, adhesions, locking, instability, synovitis, and ankle disability of undetermined cause. Thirty cases with at least 24 months of follow-up were reviewed. Complications occurred in two patients: reflex sympathetic dystrophy and a fibular fracture. Postoperatively, the patients were rated clinically as having 13% excellent, 60% good, 17% fair, and 10% poor results. However, 95% of the patients stated that they would undergo the same operation again if needed. Results were significantly better in those patients who had chondral or osteochondral defects as the diagnosis, and in noncompensation cases.


The use of ultrasonography in the foot and ankle. Ultrasonography of the soft tissue has achieved an increasing importance in the last years. Since sonography of the shoulder, knee, muscles, and tendons has become a routine method, there is less application of ultrasound in foot and ankle pathology. Since 1985, ultrasonography has been the routine examination technique in the Trauma Department of Hannover Medical School, Hannover, Germany. We now have a series of more than 4000 sonographic examinations. This paper gives a comprehensive overview of the possibilities in application and technique of ultrasonography in foot and ankle disorders. The sonographic patterns of the pathological changes of the main structures are described.


Collateral ligament reconstruction of the unstable metatarsophalangeal joint: an in vitro study. Anatomic reconstruction of the collateral ligaments of the lesser metatarsophalangeal joints is proposed for certain cases of metatarsophalangeal instability. The suggested reconstruction involves replication of the attachments of the collateral ligaments. As an example of such a reconstruction, the interosseous tendon was used in this study as a graft for anatomic replacement of the collateral ligaments. The tendon was left attached distally where its attachments include the volar plate and proximal phalanx, thereby resembling the distal attachment of the collateral ligament. The proximal portion of the tendon was inserted into the metatarsal head, replicating the attachment of the collateral ligament at that location. Preliminary testing of such a reconstruction shows that it can re-establish stability caused by loss of the collateral ligaments. Such a procedure may be applicable in select cases of crossover toe deformity and straight vertical instability.


The morbid anatomy of congenital deficiency of the tibia and its relevance to treatment. Two specimens obtained from a 5-month-old boy with bilateral type 1a congenital tibial deficiency were dissected to describe their morbid anatomy. Examination revealed a rigid equinovarus deformity, absence of a tibial remnant, an abnormal saddle-shaped talus, and several tarsal coalitions. Observation of the arterial pattern during surgery supported the previously reported finding that persistence of an immature arterial structure is inherent in this condition. Knowledge of potential structural anomalies is essential during the planning of an amputation or of a knee or an ankle reconstruction. Anatomic abnormalities may affect the design of soft-tissue flaps in an amputation and plantigrade positioning and foot biomechanics in reconstructive procedures.


Radiological assessment of a modified anterior drawer test of the ankle. Chronic ankle instability is a common complication of ankle sprain. The clinical assessment of ankle instability is usually incomplete and difficult to interpret. Recently, more attention has been paid to the value of the anterior drawer test of the ankle. We assessed the accuracy of a modification of the anterior drawer test, comparing it with radiological stress view of the ankle in 25 patients with recurrent ankle sprain. The radiological examinations were performed by a TELOS instrument and included lateral and anteroposterior stress views. We found that the modified anterior drawer test correlated with the posterior opening of the tibiotalar joint and with the lateral tilt of the talus. We conclude that a slightly positive modified anterior drawer test may indicate injury to the anterior talofibular ligament. A significant movement of the ankle elicited by the modified anterior drawer test may indicate combined injury to anterior talofibular and calcaneofibular ligaments.


Ankle fracture classification systems: a case for integration of the Lauge-Hansen and AO-Danis-Weber schemes. The two dominant classification systems for ankle fractures in use are the Lauge-Hansen and AO-Danis-Weber schemes. Each has certain advantages and disadvantages. Because of basic similarities, integration of these systems into one scheme involving three basic patterns with appropriate staging appears to be reasonable. This integration is based upon combining the pronation-abduction and pronation-external rotation injuries in Lauge-Hansen's scheme into one pronation-abduction-external rotation pattern. The resultant system would appear attractive in terms of combining relative simplicity with completeness.


Triple arthrodesis through a single lateral approach: a cadaveric experiment. Using a single lateral approach, triple arthrodesis was performed on six cadaveric feet. An attempt was made to obliterate the talocalcaneal, talonavicular, and calcaneocuboid joints. The limbs were subsequently disarticulated to allow for an inspection of the talonavicular, talocalcaneal, and calcaneocuboid joints. An estimate of cartilage and subchondral bone removed from each articular surface was made by a single observer (J.V.B.) by direct visual inspection. Results were as follows: calcaneocuboid joint, 90% of cartilage removed; talocalcaneal joint, 80% of cartilage removed; talonavicular joint, 38% of cartilage removed. Failures at the talonavicular joint were attributed to a poor appreciation of the anatomy of the talar head and poor observation. Complications involved in obliteration of the talonavicular joint from a single lateral approach included: inadvertent division of the talar neck; inadvertent division of the talar head; removal of excessive bone stock; medial skin punctures; and creation of an iatrogenic cut through the talar dome. Therefore, a triple arthrodesis through a single lateral approach, as described by Ryerson, Hoke, and Campbell, cannot be recommended. The talonavicular joint should be approached through an auxiliary medial incision, as recommended by Cracchiolo. This paper documents the experience of a beginner with this operation, and demonstrates the value of using the anatomy laboratory.


The dynamics of peroneus brevis tendon splits: a proposed mechanism, technique of diagnosis, and classification of injury. The etiology of peroneus brevis splits is unclear. Because longitudinal splits in the peroneus brevis tendon do not necessarily effect the integrity or strength of the tendon, it is difficult to ascertain whether or not injury to the peroneus brevis tendon is present. Recent clinical, anatomic, and histologic reports have suggested that the split develops from prolonged mechanical attrition within the fibular groove as a result of ankle trauma with resultant lateral ankle instability and incompetency of the superior peroneal retinaculum with resultant subluxation of the peroneal tendons. This cascade of events may result in splitting of the peroneus brevis tendon. The purpose of this paper was to report the investigation of the mechanism by which peroneus brevis splits develop, to describe a technique of diagnosis, and to propose a classification of injury. Peroneus brevis splits are the result of a dynamic mechanical insult at the fibular groove. Laxity of the superior peroneal retinaculum combined with peroneus longus mechanical compression causes the peroneus brevis to splay out and eventually split over the sharp posterior edge of the fibula. Anatomic factors, such as a shallow fibular groove (congenital convex groove) or the presence of an anomalous low-lying peroneus brevis muscle belly or peroneus quartus tendon, may also play a role in this mechanism by interfering with the competence of the superior peroneal retinaculum.


Traumatic subluxation/dislocation of the peroneal tendons. Traumatic subluxation/dislocation of the peroneal tendons has been reported following a variety of sports-related activities. The peroneal musculature contracts reflexively during the injury and overcomes the restraining soft tissue. The tendons can then dislocate anteriorly from behind the distal fibula. Some patients have anatomical variations of the posterolateral ankle that predispose them to injury. If the physician is unaware of the injury, the diagnosis may be missed in the acute setting and can develop into a chronic, disabling condition. Treatment of the acute injury is controversial because advocates exist for both conservative and surgical therapies. The chronic, painful lesion should be treated operatively. A tremendous number of surgical procedures have been described for the treatment of chronic tendon dislocations. Choice of a surgical procedure depends upon the anatomy of the peroneal groove and the retinaculum, and the nature of the damage to the area.


[The spiral CT imaging technic--the initial experience for orthodontic examinations]. Within the course of the rapid development of CT technology, a new imaging technique, spiral computed tomography, is presently undergoing clinical testing. This procedure is based on a complete investigation of large volumes. In order to determine the suitability of this technique for the diagnostic evaluation of orthodontic problems, 25 patients were investigated. The most important advantage of this volumetric CT technique proved to be the capability of permitting complete recording of the object with only one scan, the extremely short examination time, and the associated reduction in radiation exposure, coupled with mostly improved image quality. These advantages, together with a discussion of various recording parameters and possible applications, are illustrated on the basis of typical cases. For orthodontic problems, the recording of small volumes provides the best three-dimensional surface reconstruction available at present.


[The initial morphological state in the basally pneumatized maxillary sinus--a radiological-histological study in man]. Twenty human autopsy specimens of the lateral maxilla with radiologically diagnosed extended basal maxillary sinus were prepared either in the horizontal, sagittal or transversal plane. Generally the cortical bone of the maxillary sinus showed a thickness up to 1000 microns. In areas with root contact histological findings could be described as follow: reduction of thickness, bone perforations, bone perforations combined with apical and or lateral root resorptions and root resorptions without bone perforations. These morphological findings could not be verified by X-ray examination.


[The testing of the toxicity of the plastics used in orthodontics]. Eighteen bracket adhesives and one to three differently coloured samples of the plastic materials Orthocryl and Wil-o-dont used for removable appliances were tested for toxicity in vitro by cell culture using both L-929 mouse fibroblasts and human keratinocytes. The results differed from product to product. Some adhesives were moderately and some slightly toxic, while others were non-toxic. After 30 days of washing in PBS, none of the adhesives showed any toxicity. Orthocryl was not toxic regardless of colour, while the possible toxicity of Wil-o-dont could be a problem.


[The deactivation behavior and effectiveness of different orthodontic leveling arches--a dynamic analysis of the force systems]. Using the orthodontic measuring and simulation system (OMSS), the deactivation behaviour of diverse orthodontic levelling arches was investigated. The vertical forces and uprighting moments, as also the levelling effectiveness for initial malalignments of tooth 21 (1 mm and 2 mm infraocclusion, 20 degrees angulation) were measured, with the influence of various ligatures used in clinical practice being taken into account. The results may be summarized as follows: In the case of a large vertical offset (infraocclusion) the vertical forces can attain values of up to 3.8 N, depending on the type of levelling arch used. On deactivation, we can observe a sharp decrease in force caused by the frictional resistance between bracket and arch wire, which has to be overcome by the wire. The loss of desired force caused by friction may be as much as 50%, and is determined by the arch wire, bracket and mode of ligation. A smaller vertical offset (infraocclusion) (1 mm) is associated with extrusive forces of 0.2 N--0.8 N. Using looped levelling arches made of 0.016" standard steel wire, there is no frictional loss of orthodontic force, so that the highest vertical forces (more than 3.0 N) are observed with these arch wires. With an initial angulation of the tooth of about 20 degrees, uprighting moments of between 3.0 Nmm and 33.0 Nmm are measured, the looped arches again generating the highest moments. To ensure adequate uprighting moments in a combination of vertical offset (infraocclusion) and angulation, very high extrusive forces must be accepted. As a dynamic analysis of the tooth movement with the OMSS shows, the use of a specific arch wire results in a typical levelling defect. There is no general correlation between extrusive force or uprighting moment and the levelling effectiveness of an orthodontic arch. It is not possible to recommend a particular levelling arch.


[A pseudoelastic NiTi uprighting spring for the molars--its design, biomechanical testing and clinical use]. Uprighting inclined molars is one of the most common problems encountered in pre-restorative orthodontics. To prevent occlusal trauma, an intrusive force has to be applied to the molar in addition to the uprighting moment. Owing to their construction, current mechanical devices for uprighting either to not meet this requirement, or are difficult to adjust when in place. For this reason, an improved uprighting spring is described which utilizes the properties specific to super-elastic (pseudo-elastic) NiTi alloys. The most important property of super-elastic wires is the fact that they produce constant forces or moments within a specific deformation range. In order to utilize this useful property, certain design criteria have to be met. Recent measurements have shown that a super-elastic wire (Sentalloy, 0.016'' x 0.022'') having a length of 10 mm generates a constant moment of 7 to 8 Nmm within a bending angle of 50 degrees to 180 degrees. On the basis of these results, a table that permits the determination of the proper wire length needed to provide a constant moment within a given range of bending angles is proposed. The superelastic uprighting spring described here comprises an NiTi wire segment having a length of 7 mm and a mesial and distal steel wire segment. In the active state, the spring generates an uprighting moment of 8 Nmm and an intrusive force of 0.6 N. Numerical analysis using the finite element program, SOLF/MESY, and biomechanical testing with the orthodontic measuring and simulation system (OMSS) have shown that this force system remains stable throughout the entire uprighting process. The clinical application of the spring is demonstrated in a specific case.


[The tensile strength of bracket adhesives depending on the adhesive layer thickness--an in-vitro study]. The purpose of this study was to determine the influence of the thickness of the adhesive layer between bracket base and enamel surface on tensile bond strength. Stainless steel brackets with retentive net bases were bonded to bovine incisors with adhesive layers varying in thickness from a minimum of 0.0 mm to a maximum of 0.8 mm. Eight different orthodontic adhesives were investigated; in order to simulate the procedure of indirect bonding, combinations of two different adhesives were also tested. It was found that the highly filled composites provided greatest bond strength. Increasing the thickness of the adhesive layer had no significant influence on tensile bond strength. In the case of light-cured composites, maximum tensile bond strength was achieved at a thickness of the adhesive layer of 0.2 mm. This is probably due to better penetration of light at this thickness. In the case of chemically curing no-mix adhesives, it was impossible to produce effective adhesive layers thicker than 0.2 mm, presumably because curing at the primer paste interface becomes a problem at greater thickness. The influence of cement thickness on tensile bond strength was basically identical whether brackets were bonded with one or two adhesives. Thus, an additional adhesive-adhesive interface has no influence on bond strength. If adhesive layer thickness of more than 0.2 mm are required, a chemically cured, highly filled paste-paste system should be used.


[The correction of fanned-out incisors--an important orthodontic contribution to aesthetic dentistry]. Account has to be taken of the increased aesthetic awareness of the adult patient by all sub-specialties of dentistry. Here, orthodontics often plays the role of a central link between periodontics and prosthetics. Taking pathological migration of the incisors as an example, the pathogenesis, therapeutic procedures and orthodontic possibilities for the restoration of normal dentofacial aesthetics are demonstrated and discussed.


[Ventricular function in hypertrophic cardiomyopathy. Systolic and diastolic ventricular function]. BASIC CONSIDERATION: Hypertrophic cardiomyopathy is defined as a primary myocardial disease associated with a hypertrophic non-dilated left ventricle with no other heart or systemic disease that might lead to hypertrophy of the left ventricle. The leading symptoms are effort-associated angina and dyspnea, rapid fatigue, dizziness and syncope. The hemodynamic situation is characterized by a hyperdynamic systole and impaired diastole and left-ventricular filling. In the obstructive form, hypertrophy of the basal septum and an anteriorly moving mitral valve during systole result in an end-systolic reduction in the cross-section of the outflow tract associated with considerable intraventricular pressure gradients. Disturbances in the myocardial calcium metabolism are presently suspected to be causally involved in the diastolic function impairment.


[Hypertrophic obstructive cardiomyopathy: surgical therapy]. Surgical treatment of hypertrophic obstructive cardiomyopathy (HOCM), which may present in a typical (subaortic) or atypical (mid-ventricular) form, is indicated only after prior long-term drug treatment. The results obtained in 353 patients presenting with a symptomatic form of HOCM operated on between 1963 and 30 June 1991 are reported. The operative procedure took the form of transaortic subvalvular myectomy (TSM) as described by Morrow, modified by extending the myectomy. The patients comprised 210 males and 143 females aged between 6 and 76 years (average age 41.7 years). With few exceptions, all patients were in clinical stage III or IV (NYHA). The overall hospital mortality rate was 4.8% (n = 17); for TSM alone 3.1% (n = 8 out of 261 patients), for combination surgery with additional surgical measures 9.8% (n = 9 out of 92 patients). Among the last 194 patients (since 1984), the mortality rate was 2.06% (n = 4). To date, follow-up show an improvement in the symptoms and physical performance, and an annual mortality rate of about 1.8-4% among patients treated with drugs, and a post-operative mortality of about 1.1%, so that in HOCM patients with symptoms despite prior drug treatment, surgery can be recommended.


[Adult children of alcoholics. A new diagnostic group with reference to general practice and clinical aspects]. FUNDAMENTAL CONSIDERATIONS: Adult children of alcoholics have, in recent years, become identified as a specific group with often characteristic patterns of health disorders. Those involved have a three- to four-fold greater risk of developing a dependence themselves than the general population. They are more likely to marry partners who are also dependent and have an above-average propensity toward separation and divorce. Most members of this group have adopted a specific role within the family they come from: for example that of the whipping boy, family hero or fool. Of therapeutic importance is the recognition of one's own involvement through parent dependence and to develop an awareness of specific areas of disorder, for example, in a partnership, self-identity crises, emotional blockades and the risk of becoming dependent oneself. Therapists with experience of habit-forming disorders and social family work can develop specific activities within the general practice, psychosocial counseling centers, and even in detoxication services. The new self-help groups of adult children of alcoholics are very helpful.


[Amaurosis fugax].

[Amaurosis fugax]. Presentation of the etiology, diagnosis, possible complications and treatment of amaurosis fugax. amaurosis fugax is a transient monocular loss of vision, usually affecting the entire visual field. Amaurosis fugax is caused by transient retinal ischemia resulting from embolism, hemodynamic insufficiency or ocular vascular disease. In view of the high complication rate (annual blindness rate 1%, annual risk of an ischemic insult 2%, myocardial infarction 30%, and an 18% mortality rate), an immediate search for the underlying causes is mandatory. Diagnostic evaluation should include ophthalmological, neurological and cardiovascular investigations. Management of amaurosis fugax comprises, in the first instance, treatment of the underlying disease and administration of anti-platelet agents. In cases in which stenosis of extracranial vessels presents, endarterectomy may sometimes be considered.


[Echocardiography findings in hypertrophic cardiomyopathies. Diagnostic value of different echocardiography procedures]. In the present paper, the contribution of TM 2D and Doppler echocardiography to the non-invasive diagnostic evaluation of hypertrophic cardiomyopathies is discussed. The selective use of various echocardiographic possibilities for the representation (visualization) of typical morphological and functional changes in hypertrophic myocardial diseases is described.


[Compulsory admission of psychiatric patients in a national and international comparison--incidence and factors of influence]. The frequency of compulsory admissions of psychiatric patients is very variable if compared nationally and internationally. In the old Laender of West Germany, between 2.8% (Bremen) and 44.8% (West Berlin) of all psychiatric admissions were compulsory. The range is even broader, if one compares different western countries: while in Denmark the frequency of compulsory admissions is about 5% of all admissions, it is 50-93% in Switzerland. In this paper the reasons for this wide variation are analysed, making a distinction between "true" and "artificial" differences in frequency. Artificial differences are mainly due to insufficient representativity and comparability of the populations studied. True differences on the other hand are mainly a consequence of the differing legislation in the individual countries and of regional differences in administrative regulations, but also of the situation of mental health care. Apart from analysing these patient-independent factors influencing compulsory admission, the characteristics of patients are studied which are associated with a higher risk of compulsory admission. The relation of these patient characteristics with the factors "danger to oneself or others", which are the prerequisites of compulsory admission in most countries, is discussed.


[Physical therapy and speech therapy in Parkinson syndrome--a status assessment]. 74 inpatients and outpatients (mean age 71.9 years) with idiopathic Parkinson's disease, a vascular pseudo-parkinsonian syndrome or a Parkinson-associated dementia were analysed by present-state clinical rating with regard to use and needs of physical and speech therapy. 55% of the patients had physical therapy whatsoever, 32% of them on a daily schedule. 58% of patients without everyday physical therapy indicated to do less physical therapy than one year ago or that they have quite any exercise. This item showed significant correlations with: age of disease onset over 70 years, Hoehn-Yahr stage of 3 and over, activities of daily living according to Schwab-England of less than 60%, diagnosis of vascular pseudoparkinsonian syndrome or Parkinson-associated dementia, more frequent use of community support services for the ambulatory elderly. Only 8% of the patients had ever had speech therapy. Using both ratings of complaints and clinical findings, about 30% of patients had moderate to severe impairment of speech, 80% of these had also considerable memory disturbances. The study suggests that the need for physical therapy might be derived more from patient's assessment of reduced daytime motor activities than from a scaled item rating of an external observer. Use and continuity of physical and speech therapy in Parkinsonism seems to be limited largely by cognitive disturbances and social variables. Speech therapy appears to be useful only for a subgroup of Parkinsonian patients.


[Relations of model and drug-induced psychoses to schizophrenic diseases]. From the clinical point of view, substance-induced psychosis can be rather similar to schizophrenia. However, the question whether phenomenological resemblances represent similar underlying causal mechanisms is unsolved. Whereas the interest in experimentally induced psychosis was purely academic until the mid-1960s, the widespread use of "recreational" drugs provided this research with an important practical impact. With respect to a given case the differential diagnosis between schizophrenia and drug-induced psychosis it is often problematic. The differences in psychopathology refer to the disturbances of experience in general (Ichstörungen), the character of the hallucinations and the quality and quantity of the alterations of consciousness. Contrary to the sharp distinctions which used to be drawn between schizophrenia and drug-induced psychotic states, we hold that these states are rather similar, and may even represent a common underlying pathology. Hence, the renewed interest in the study on experimentally induced psychotic states using advanced methodology seems justified.


[Recent trends in pharmacotherapy of aggressive behavior in psychiatric patients]. Patients with recurrent pathologic aggressive behavior constitute a severe problem for psychiatric institutions. Besides of being dangerous towards others, these patients themselves suffer from a variety of negative consequences, such as the danger of long-term hospitalisation etc. Therefore, pharmacologic treatment in addition to psychotherapeutic and social interventions is not only ethically justified but mostly inevitable. This kind of combined treatment as a rather common procedure in psychiatric institutions leads time and again to fairly high doses of neuroleptics but not to satisfactory results. This article gives an overview of studies on the advantages and drawbacks of alternative substances: Benzodiazepines, beta-blockers, lithium salts, amine precursors and antiepileptics. Differential indications are described.


Chondromalacic changes of the patella in rabbits. Malalignments of the patellofemoral joints were artificially made in eleven rabbits using four different methods in order to generate chondromalacia of the patella. Chondromalacic changes and the location similar to the chondromalacia of the human body were generated in one joint of the patching group. According to the results of our investigation, the most reasonable etiological factor of the chondromalacia is thought to be the expansion of the medial retinaculum and capsule of the knee joint, and chondromalacia patellae may not be a precursor of osteoarthritic changes.


The measurement of muscle strength in the hip joint expressed by the octagonal diagram. For grasping hip joint function objectively and planning an adequate program for individual use in rehabilitation during and after the treatment for hip joint impairments, the octagonal diagram of the correct distribution of the hip joint muscle strength will be useful. The muscle strength was measured in the eight directions using the Cybex-II on the U.B.X.T. table not only on the peak torque but also on the maximum work and the maximum work/sec in eighty healthy subjects, forty of each male and female. No difference of the muscle strength between the dominant and the non-dominant legs of both male and female has shown. In the percentage of the values of the muscle strength, there are differences between the peak torque, the maximum work value and the maximum work/sec. The data obtained from this investigation will be available to judge the degree of hip joint impairment, and to make a better therapeutic program for the patients.


[Two cases of blind pouch syndrome].

[Two cases of blind pouch syndrome]. Case 1. A 39-yr-old male was presented with anemia. Initial blood examination showed remarkable iron deficiency anemia. Small bowel X-ray and abdominal CT examination revealed a dilated tract at the end of the ileum. Surgical operation was done. The surgical specimen showed side to side anastomosis which was reconstructed at the operation for rt. inguinal herniation 46 days after his birth. The oral side of the tract was remarkably dilated. Case 2. A 50-yr-old male was presented with dizziness. He had anemia and clubbed fingers. A small bowel X-ray examination was done and it showed side to side anastomosis in the middle of the small intestine. Surgical operation was performed. The surgical specimen showed side to side anastomosis about 2 m 20 cm from the Treitz' ligament, which was reconstructed during the operation for ileus when he was 10 years old. The blind portion was remarkably dilated. In both case, the anemia was improved after the operation.


[A case of idiopathic hemochromatosis associated with gastric cancer]. A 76-year-old male was admitted to our hospital because of general fatigue in June 1987. He had received total gastrectomy against gastric carcinoma two years previously. The examinations revealed the elevation of GOT, GPT and gamma-GTP, and increased CT number of the liver. Specimen of the liver biopsy showed deposition of iron and slight fibrosis. He was diagnosed as idiopathic hemochromatosis. He was given deferoxamine, and his elevated GOT, GPT and gamma-GTP were normalized. Idiopathic hemochromatosis is frequently associated with various malignancies including hepatic carcinoma. However, only a few cases of idiopathic hemochromatosis associated with gastric carcinoma have been reported.


Role of asynchronous activation of the ventricular fibres by an ectopic pacemaker in the accidents, especially fibrillation, caused by Ic antiarrhythmic drugs. Class Ic antiarrhythmic drugs, which are known to slow down conduction in the ventricular muscle, are likely to impair synchrony in activity of the ventricular fibres. Asynchronous activation was first investigated between an ischaemic and a normal area by the simultaneous recording in anaesthetized, open-chest pigs of two left ventricular monophasic action potentials (MAPs) under ventricular pacing at a high rate of 180 beats.min-1. Asynchronous activation was then investigated in the intact myocardium according to the distance separating the recording from the pacing electrode. Furthermore, mechanical effects of left ventricular systole were observed by recording dP/dt(max) and mean arterial blood pressure during the pacing periods. Ischaemia was produced by transient complete occlusion of the left anterior descending coronary artery near its origin; as a result, activation time reached 85 ms in the ischaemic area under flecainide administered iv in a 2.5 mg.kg-1 dose instead of approximately 60 ms in the normal area for fibres equi-distant from the pacing electrode. Similar delays in activation were observed in the intact myocardium, depending on whether the explored region was close to or far from the pacing electrode. In the latter case, the difference in activation time may become markedly greater if the distance or the dose of flecainide are increased. This difference, which possibly exceeds one-third of the MAP duration (practically unchanged by flecainide), may account for the occurrence of fibrillation or the sudden loss of systole mechanical efficacy.


CRL41405: a drug with a new pharmacological profile on pancreatic exocrine secretion in the rat. The recently described compound CRL41405 displays central effects suggesting possible antidepressive and awakening properties. In order to further analyze the pharmacology of this compound, its effects were studied on basal and stimulated pancreatic secretion in anaesthetized rats. CRL41405 alone (7-20 mg/kg, sc) had no effect on basal pancreatic secretion. Larger doses (67-200 mg/kg) increased basal secretion through the stimulation of cholinergic muscarinic receptors, the effect being antagonized by atropine. CRL41405 (20 mg/kg) suppressed the 2-deoxyglucose-induced (but not the acetylcholine-induced) stimulation of pancreatic secretion through an alpha-2 adrenoceptor inhibitory mechanism that was blocked by idazoxan (0.3 mg/kg, sc). In addition, a beta adrenoceptor mediated stimulation of sodium and bicarbonate excretion (blocked by propranolol) was evidenced when the alpha-2 inhibition was suppressed by idazoxan. Under alpha-2 adrenoceptor blockade, water and electrolyte stimulation by CRL41405 could be demonstrated on basal, 2-deoxyglucose-induced and acetylcholine-induced pancreatic secretion. This original profile makes CRL41405 a unique drug in pancreatic pharmacology.


Differential effects of cromakalim on pancreatic vascular resistance and insulin secretion in vitro. The effects of the potassium channel opener cromakalim on vascular resistance and insulin output were investigated in vitro within the same experimental preparation, the isolated rat pancreas perfused at a constant pressure with a physiological solution containing 8.3 mM glucose. Cromakalim induced a clear and concentration-dependent dilatory response of pancreatic vessels; the concentration-response curve obtained in the range of 10(-8) - 10(-5) M had a sigmoidal shape with a linear part between 10(-7) and 10(-6) M. Cromakalim did not inhibit insulin release at these concentrations. These results differ from those obtained with diazoxide, which has been previously shown both to inhibit insulin secretion and induce vasodilatation of the pancreatic vascular bed in a similar range of concentrations (10(-6) - 10(-5) M). The data presented provide evidence for a selective effect of cromakalim on pancreatic vascular resistance. Our present and previous results support the view that cromakalim is effective on K+ channels of vascular smooth muscle that differ from the ATP-sensitive K+ channel opened by diazoxide in insulin-secreting B-cells.


Could saliva stand for plasma in theophylline monitoring in asthmatic children? Still a controversial problem. Theophylline determination in saliva was proposed several years ago as a convenient and non-invasive alternative to monitoring plasma in children and adults. Published data demonstrated that theophylline saliva concentration linearly correlates plasma concentration. However, the variability found in interindividual serum/saliva ratios and the wide scattering among the data points precluded the clinical use of saliva for theophylline monitoring. The purpose of this study was to compare different standardized methods for obtaining stimulated saliva intending to reduce the variability in plasma/saliva ratios and to determine the most reliable one. A group of 150 ambulatory chronic asthmatic 4.5 to 20.83 (10 +/- 3.7; M +/- SD) year-old patients receiving theophylline 6.85 +/- 1.88 mg/kg every 12 h as slow release preparations for 4 to 100 days was studied. One ml venous blood and salivary specimens were simultaneously collected 5.15 +/- 0.36 h after the morning maintenance dose. In a subgroup of 75 patients, saliva was collected using first a new device called salivette, immediately followed by the collection of an expectorated sample 30 s after citric acid crystals stimulation. In the other patients saliva was collected using citric acid containing salivette. Theophylline concentration was determined using HPLC. For all types of saliva collection, salivary and plasma theophylline concentrations correlated significantly. However whichever method was used, based on the -2 to +2 SD interval, a large range of plasma theophylline was predicted from a single salivary theophylline concentration. Despite a further standardization of the sampling of saliva, saliva theophylline could not accurately predict plasma concentration.


Endoscopic retrograde cholangiopancreatography in childhood. ERCP was performed in 19 children and adolescents aged 4 to 16 years. In 13 children the examination was done under general anesthesia, in 6 cases with the usual premedication using dolsin and atropine. Indications for examination were unclear abdominal pain with occasional amylase elevation, in 3 patients status after an abdominal injury. In 16 patients the examination clarified the complaints by detecting organic disease of the gallbladder or the pancreas. ERCP is an important procedure in the event of uncertain diagnosis in children and adolescents and, if the indication is correct, and the technique good, is well tolerated by the patients.


Cholecystectomy by minilaparotomy without muscle section: a short-stay procedure. The aim of this prospective study was to assess the results of cholecystectomy performed by an incision characterized by its small size and absence of muscle section, to minimize postoperative discomfort, and shorten hospital stay. Surgical access was via a transverse division of the linea alba extending 1.5-2 cm on the rectus sheath, on both sides, without section of muscle. One hundred and ninety-one patients were operated on. Only 1 (0.5%) peroperative complication (injury of cystic artery) and 4 (2%) benign postoperative complications occurred. The mean postoperative hospital stay was 4.4 +/- 1.7 days (range 2 to 12); for the 90 patients operated on in 1989-1990 it was 3.3 +/- 1.7 days (range 2 to 12). Long-term results were assessed in 113 patients. Only 1 (0.6%) complication occurred, namely migration of a retained common duct stone. Neither incisional hernias nor a need for reoperation occurred. The cosmetic results were assessed by the patients themselves as very good in 95 (84.1%) cases and good in 16 (14.2%) cases.


Percutaneous transhepatic biliary drainage in patients with malignant biliary obstruction of the hepatic confluence. Despite many studies on percutaneous transhepatic biliary drainage (PTBD), there are no satisfactory reports of PTBD for malignant obstruction of the hepatic confluence. In this study, the results of PTBD using the direct anterior approach under fluoroscopic guidance are described in 16 patients with malignant biliary obstruction of the hepatic confluence. A total of forty-two drainage catheters were placed in the 16 patients: one catheter was placed in three patients; two catheters in six; three catheters in four; four catheters in two; seven catheters in one. PTBD was successful in 100% of the cases with no mortality or critical complications, and the biliary decompression effect of PTBD was highly satisfactory. Nine patients underwent histologically curative hepatectomies. Two of the nine resected cases died of postoperative hepatic failure, but the postoperative course in the others was satisfactory. The authors stress that selective biliary drainage for each isolated segmental duct is mandatory for advanced malignant obstruction of the hepatic confluence.


Management of postoperative bile leakage with endoscopic sphincterotomy (EST) and a naso-biliary drain (NBD). Between July 1987 and December 1990, 13 patients with postoperative bile leakage were treated with endoscopic sphincterotomy and a naso-biliary drain. All the leaks healed in two weeks, except for one (intrahepatic) that needed two months to heal in association with percutaneous management. The non-surgical treatment of bile leakage is the preferred approach on account of the superior safety, efficacy and cost-effectiveness as compared with surgical repair, which is associated with significant morbidity, mortality and costs. The treatment of choice has to be endoscopic, which is much easier and safer than the transhepatic approach, especially in the non-dilated duct, while another advantage over radiology includes the possibility for rapid definitive treatment of distal obstruction (e.g. residual stones). A leak from an extrahepatic duct heals rapidly, while a leak from an intrahepatic duct takes longer to heal and sometimes needs associated percutaneous drainage. Finally, the authors propose treating an extrahepatic bile leak merely with naso-biliary drainage without cutting the papilla, and an intrahepatic bile leak with endoscopic sphincterotomy, nasobiliary drainage and a bilio-duodenal endoprosthesis.


Critical evaluation of the anastomoses in large bowel surgery: experience gained in 533 cases. We critically examined the morbidity and mortality of manual and stapled colorectal anastomosis in a retrospective study of 533 patients who underwent colorectal resection for neoplastic and non-neoplastic disease. The clinically detected anastomotic dehiscence rate was 4.5%, and the mortality rate 1.8%. The extraperitoneal site of the anastomosis after rectal anterior resection with stapled anastomosis and surgery for cancer showed a statistically significant predisposition to anastomotic dehiscence. Age, emergency surgical intervention, curative versus palliative resection, the location of the anastomosed intestinal segments, type of anastomosis and presence of a protective colostomy did not appear to be statistically significant factors for anastomotic dehiscence. While the stapler may offer an advantage in the individual case, the low incidence of morbidity and mortality for manual anastomosis in this study reaffirms the soundness and importance of the manual colorectal anastomosis in the surgeon's technical armamentarium.


Experimental model with bilioenteric anastomosis in rats--technique and significance. A simple technique of hepaticojejunostomy in rats is introduced in this paper and its suitability for use as an experimental model was evaluated histologically. Hepaticojejunostomy was performed as follows; the stump of the supra-pancreatic common bile duct (CBD), detached from adjacent tissue, was introduced into the jejunal lumen using the outer catheter previously inserted into the jejunum, and the jejunal wall close to the implantation site of the CBD was fixed to the porta hepatitis with a suture. Among 40 rats in which hepaticojejunostomy was performed, the postoperative mortality rate was 17.5%. The remaining experimental animals (33 rats, 82.5%) survived for the duration of this study. The rats were sacrificed at 3, 5, 8, and 12 months after surgery, and liver function tests, macroscopic and histological studies of the biliary tract were carried out. No signs of cholangitis or liver abscess were noted in any experimental animals during this period. The median values of liver function tests were within normal limits in almost all of the experimental rats. The anastomotic stoma was also patent, and free drainage of bile was noted, but the bile duct proximal to the site of anastomosis was generally macroscopically dilated. Histologically, epithelial hyperplasia and fibrous thickening of the wall accompanied by inflammatory cell infiltration were noted in the rats sacrificed at 3 and 5 months postoperatively. Marked hyperplasia of mucous glands, goblet cell metaplasia and atypical epithelium were usually seen in the rats killed at 8 months and 12 months after surgery.(ABSTRACT TRUNCATED AT 250 WORDS)


A new liver and soft tissue biopsy instrument. A new liver biopsy instrument taking the form of a suction biopsy syringe with two pistons and a Menghini needle, is described. A vacuum is first created, and the whole procedure is effected by a continuous uninterrupted movement into the liver and instantaneous withdrawal. The syringe is held in one hand. The procedure is very simple and requires minimal training. A total of 118 biopsies have been performed. The specimens were suitable for histopathological examination. Pain was minimal and there were no complications.


Hepatic encephalopathy secondary to a large-caliber porto-hepatic venous shunt. A case report. A case of hepatic encephalopathy secondary to a large-caliber porto-hepatic venous shunt in a 61-year-old woman with gastric cancer is reported. Mild confusion, flapping tremor and hyperammonemia were noted preoperatively. Abdominal ultrasonography showed a large-caliber porto-hepatic venous shunt in the left lateral segment of the liver. Percutaneous transhepatic portography and superior mesenteric angiography were confirmatory. Intraoperative portal scintigraphy was performed before and after temporary shunt occlusion to measure the intrahepatic shunt rate, which decreased markedly after occlusion. Portal pressure was also measured, and increased only slightly after occlusion. Left lateral hepatic segmentectomy, and subtotal gastrectomy with splenectomy were performed. Hepatic encephalopathy resolved postoperatively. The shunt was thought to be acquired. The relevant reports on large-caliber porto-hepatic venous shunts in the literature are reviewed.


Primary sarcoma of the liver in the adult. Report of five surgically treated patients. During the 5-year period between 1988 and 1989, five patients with primary sarcomas of the liver underwent surgery. Since the patients presented in an early stage of the tumor, all the sarcomas were resectable, in three cases with wide margins (R-0 resection). Five histological types were detected: malignant hemangiopericytoma, malignant fibrous histiocytoma, hemangiosarcoma, rhabdomyosarcoma, and embryonal sarcoma. Two patients with high-grade sarcomas received adjuvant chemotherapy. The follow-up was favorable in three patients with R-0 resections (two had adjuvant chemotherapy). They were still alive, with no evidence of disease 30, 46, and 63 months after the diagnosis. The two other patients had to be reoperated on for local recurrences. Both died of their tumor disease, 30 and 35 months after the initial diagnosis. Extensive chemotherapy in one of these cases failed to arrest tumor progression. Hence, liver resection with wide margins is a very important measure in such cases.


Immunotherapy of chronic active viral hepatitis B with propionibacterium granulosum KP-45 (a 5-year follow-up report). In the period 1982 to 1984, 14 HBS-AG-positive patients with chronic active hepatitis B were treated monthly with a cell wall preparation (5 or 10 mg) of Propionibacterium granulosum KP-45 (PG), intravenously administered for a period of 6 to 10 months. All 14 patients were monitored by serological and biochemical tests as well as liver biopsy two, three and five years after completing immunotherapy with PG. During this period the patients received neither a specific antiviral, corticosteroid or interferon therapy, nor PG. Re-appearance of HBSAG or HBeAG was never seen in patients who were already free from the antigens one year after completing PG immunotherapy. During the 5-year follow-up, spontaneous improvement in serological and morphological (liver biopsy) parameters of chronic virus B hepatitis occurred in six patients. Five years after completion of PG immunotherapy, only four of the 14 patients showed trace amounts of serum HBSAG (carriers), and in two low levels of anti-HBeAG were present, while the whole group showed a decreasing tendency and serum anti-HBc was still detectable in six patients. HBeAG- and DNA-polymerase-positivity was absent in all patients. Microscopic examination of liver biopsies 5 years after PG immunotherapy showed mild symptoms of chronic hepatitis with inflammatory infiltration, non-active cirrhosis, but without massive periportal and/or multilobular necrosis and trace amounts of HBsAG and HBcAG in hepatocytes only in the four carriers. The remaining 10 patients were free of symptoms of active hepatitis and/or active cirrhosis, but all the patients had moderate to intensive fibrosis in their liver biopsies.


Hyperbilirubinemia, jaundice and anergy. A prospective study of delayed hypersensitivity response was carried out in jaundiced patients. One hundred and seventy-seven subjects were studied. Fifty-nine were controls and one hundred and eighteen were patients with hepato-pancreato-biliary pathology and biliary tract obstruction. A multitest technique was used to evaluate the delayed hypersensitivity response, classifying the subjects into one of three groups: immunocompetent, relatively anergic and anergic. In the control group 76.3 per cent of the subjects were immunocompetent as opposed to 16.1 per cent of the patients (p less than 0.0001). Twenty-four per cent of the control subjects and eighty-four per cent of the patients presented anergy or relative anergy (p less than 0.0001). Among the patients no difference could be found in the index of anergy between malignant and benign pathology. We have found, moreover, that patients with a mean bilirubin level of 12 mg/dl showed a change in the delayed hypersensitivity response, with development of anergy or relative anergy.


Indications and results of hepaticojejunostomy in benign strictures of the biliary tract. The postoperative and late results of 99 patients with benign strictures of the biliary tract are presented. Patients were classified according to Bismuth into 24 cases with lesion type I, 36 cases with type II, 35 cases with type III and 4 patients with type IV. All were submitted to hepaticojejunostomy with a long Roux-en-Y loop. The etiology of the strictures varied according to the type of stricture. In patients of type I, inflammatory and iatrogenic causes were observed. Among type II and III patients, previous cholecytocholedochal fistulas were the main cause, together with accidental section or ligature of the common bile duct. Operative mortality was absent in strictures of types I and II, while it was around 25% in cases of types III and IV. At late control, the best results were seen among patients with strictures of types I and II. We believe that the main factor determining the early and late outcome of these cases with benign strictures is the location of the stricture and the quality of the proximal duct.


A comparison between antipyrine and aminopyrine blood clearances. The purpose of this study was to investigate the relationship between two quantitative liver functions, that is, antipyrine blood clearance and aminopyrine blood clearance, in normal subjects and in patients with liver cirrhosis. The mean blood clearances of antipyrine and aminopyrine in cirrhotic patients (0.220 +/- 0.085 ml/min/kg and 1.13 +/- 0.56 ml/min/kg; n = 64) was 50% and 38% of that of normal subjects (0.440 +/- 0.110 ml/min/kg and 2.95 +/- 0.59 ml/min/kg; n = 11). While no significant correlation was demonstrated between these two values in normal subjects (n = 11, r = -0.107, p greater than 0.10), a strong positive correlation was observed between antipyrine and aminopyrine blood clearances in cirrhotic patients (n = 64, r = 0.846, p less than 0.001). These results suggest that both antipyrine and aminopyrine blood clearances may be valuable indicators for assessing the total hepatic functioning mass in cirrhotics.


Surgery in cholangitis: bacteriology and choice of antibiotic. Owing the frequent occurrence of intrahepatic stones in orientals, cholangitis presents a real problem. Surgery and antimicrobial drug therapy are the main forms of treatment. A retrospective study of choledochotomy, including biliary tract surgery, performed between July 1987 and June 1990, was conducted. Cases with negative common duct exploration during cholecystectomy were excluded. Among 186 cases, 128 (68%) had positive bile growth, which was defined as cholangitis. Sepsis-related complications occurred in 51 patients (27.4%), including 3 surgical deaths, 30 wound infections, and 18 others. The complication rate was higher in the cholangitis group than in the negative group (37.5% vs. 5.2%). However, if peri-operative antibiotics were effective against the cultured bacteria species, the complication rate was 16.9%; if not, the complication rate was 85.3%. For the different-generation cephalosporins used in the peri-operative period, the complication rates were 32.2%, 20.8%, and 27.6% each for 1st, 2nd, and 3rd generation cephalosporins, with no statistically significant differences. In microbiological study, polymicrobial infection was the rule. On average, 2.3 species were grown from each specimen. Enterococcus proved the most important species with a 54% culture rate. E. coli and Pseudomonas were important gram-negative bacilli, with culture rates of 46.1% and 39.1%, respectively. Anaerobic species were cultured in 12.3% of the patients. For good coverage of cholangitis prior to operation, the proper antibiotic should have potency against gram-positive Enterococcus, gram-negative bacilli, especially Pseudomonas and E. coli, and anaerobic species, especially Bacteroides.


Amikacin once daily plus metronidazole versus amikacin twice daily plus metronidazole in colorectal surgery. Amikacin administered once a day plus metronidazole is compared with amikacin given twice a day plus metronidazole in colorectal surgery (prophylactic or therapeutic antibiotic treatment). A total of 325 patients were studied in this randomized multicenter trial. The results of this trial suggest that a single daily dose of amikacin is equally as effective in combating infectious postoperative complications as twice a day administration. The side effects were similar, with the exception of renal effects, which were somewhat more pronounced in once a day amikacin administration. Nevertheless, all the renal function alterations were transient and we observed no definitive renal insufficiency.


The impact of early or late diagnosis on patient survival in gastric cancer in Greece. The purpose of this study was to investigate the reasons for delayed diagnosis of gastric cancer in the Greek population and correlate survival with early or late diagnosis. We studied 100 patients with gastric cancer proven at endoscopy. Early diagnosis (less than 3 months from the onset of symptoms) was established in 28 patients (28%), while the diagnosis was late (greater than 3 months) in 72 patients (72%). The reasons for late diagnosis were: 1. delayed consultation on the part of the patient, 2. incorrect medical diagnosis at a) initial evaluation, b) radiological evaluation and, as a result, c) failure to refer for endoscopy and biopsy. Patient survival correlated well with tumor resectability, irrespective of early or late diagnosis. In patients with early diagnosis and resectable tumor survival was 9.9 +/- 4.8 months (mean +/- SD) whereas with non-resectable tumor 4.8 +/- 4.0 months (p less than 0.01). In patients with late diagnosis, survival in resectable tumor was 13.5 +/- 11.7 months compared with 8.5 +/- 6.9 months in non-resectable tumor. No correlation was noted between survival and anatomic location of tumor or degree of histologic differentiation. Early diagnosis of gastric cancer is associated with a higher degree of resectability and therefore of better survival.


Chief cell mass after short-term ranitidine treatment for duodenal ulcer. The chief cell mass and the parietal cell mass were evaluated in endoscopically obtained biopsy specimens of fundic mucosa from 15 duodenal ulcer patients before and after ranitidine treatment. Patients were given ranitidine, 300 mg/day, for 8 weeks. Chief cell mass and parietal cell mass were expressed respectively by a "zymogenous index" (ZI) and a "parietal index" (PI), obtained by multiplying the number of cells per mm2 by the thickness of the glandular layer. From the results of this study it would appear that, in patients with duodenal ulcer, treatment with ranitidine at a dose of 300 mg/day for 8 weeks results in a significant increase in parietal cell mass and a decrease in chief cess mass.


Major bacterial infections following liver transplantation: a prospective study. The incidence and characteristics of major bacterial infections were studied prospectively in 50 consecutive adult patients who underwent liver transplantation (LT). All patients received the same protocol of immunosuppression, bowel decontamination, antibiotics prophylaxis, and follow-up. Thirty-two patients (64%) had at least one episode of major bacterial infection. One death was directly related to a bacterial infection, accounting for 13% of postoperative mortality. The most critical period for infection was the first 2 months after surgery, when 69% of the infections occurred. The most frequent clinical presentations were bacteremia, pneumonia and abdominal abscesses. Eighty percent of the bacteremias had an identifiable source, the most frequent being intravascular catheters. Gram-positive microorganisms (69%) predominated over gram-negative rods (26%) and anaerobes (5%). The use of selective bowel decontamination (SBD) with norfloxacin may explain this predominance. Major bacterial infections are an important source of morbidity and mortality after LT. Efforts to prevent these infections and to determine their source and specific treatment, will improve the management and the outcome of these patients in the future.


Gastric acid secretion and plasma gastrin during short-term treatment with omeprazole and ranitidine in duodenal ulcer patients. The aim of this study was to evaluate changes in peptic acid secretion, and in fasting and meal-stimulated plasma gastrin levels after a 7-day course of omeprazole 30 mg/day or ranitidine 300 mg/day, administered in accordance with a randomized, double-blind, double-dummy protocol. Ten duodenal ulcer patients were studied. Their acid and pepsin output was determined prior to and after treatment. Plasma gastrin levels were also determined under basal conditions on day 7 of treatment, and 24 hours after the last administration of the drug. With regard to acid output, omeprazole resulted in a 98% reduction in BAO and an 80% reduction in PAO, both significantly greater than those achieved with ranitidine (BAO 50%, PAO 25%). No significant changes in pepsin secretion were observed. The increase in fasting plasma gastrin observed after ranitidine and omeprazole was 86% and 242%, respectively, on day 7, and 13% and 103% twenty-four hours after final dose. Increases in meal-stimulated plasma gastrin were, respectively, 126% and 125% on day 7 and 8 after omeprazole, whereas the increase with ranitidine was 62% only on day 7 of treatment, with subsequent normalization. In addition to confirming the well-known effect of omeprazole on the physiology of gastric secretion, our data show that administration of therapeutic doses of traditional H2-antagonists is accompanied by a secondary hypergastrinemia, which is rapidly reversible after discontinuation of therapy.


Cholesterol polyp of the gallbladder showing rapid growth and atypical changes--a case report. We report on a case of resected cholesterol polyp with typical ultrasonic findings that became atypical, with a 40% increase in diameter, over a period of about 10 months. The resected specimen revealed a black polyp with a large-nodular appearance. The pathological diagnosis was cholesterol polyp with marked glandular proliferation, and the glandular cavity showed cystic dilatations filled with dark brown fluid. It is suspected that the aggregation of large numbers of these dilated glands explained the black color, the rapid growth, and the development leading to the atypical ultrasonic findings.


[Effect of pretreatment with N-methyl-N-nitrosourea or streptozotocin on the cytotoxicity and the induction of sister chromatid exchanges in human and rodent brain tumor cells treated with chloroethylnitrosourea]. Effects of pretreatment with N-methyl-N-nitrosourea (MNU) or streptozotocin (STZ) on cytotoxicity and induction of sister chromatid exchanges (SCE) in human and rodent brain tumor cells treated with 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) or 1-(2-chloroethyl)-1-nitrosourea (CNU) were investigated. 9L-2 and SF-188 cells were more resistant to the cytotoxic effects of chloroethylnitrosourea than 9L and SF-126 cells. SF-295 cells were more resistant to the cytotoxic effects than SF-126, but more sensitive than SF-188 cells. Pretreatment of 9L-2 cells with MNU or STZ resulted in a dose-dependent increase in cytotoxicity and SCE induction by BCNU. Treatment with 1mM MNU or 1.5mM STZ completely reversed the cellular resistance of 9L-2 cells to BCNU but did not potentiate either cytotoxicity or SCE induction in 9L cells. Pretreatment of SF-188 and SF-295 cells with MNU or STZ resulted in a dose-dependent increase in cytotoxicity and SCE induction by CNU. Treatment with 500 microM MNU or 1.5mM STZ for SF-188 cells, and with 250 microM MNU or 1.5mM STZ for SF-295 cells completely reversed the cellular resistance to CNU. These results are consistent with the hypothesis that pretreatment with MNU or STZ inhibits O6-alkylguanine-DNA-alkyltransferase (O6-AT) and inhibition of the enzyme allows the formation of DNA interstrand cross-links resulting in increase in cytotoxicity and induction of SCE in resistant cells treated with chloroethylnitrosourea. In this regard, O6-AT plays an important role in determining the cytotoxicity and induction of SCE by chloroethylnitrosourea in both rodent and human brain tumor cells.


Studies on mitochondrial and microsomal phospholipids and phospholipase A2 in heart from rats subjected to prolonged exercise. Alterations in phospholipids and phospholipase A2 activity produced in cardiac mitochondria and microsomes by prolonged exercise and the effect of quinacrine on these changes have been studied in two types of experiment done on rats subjected to prolonged swimming exercise. In Experiment I, rats swam for 0.5, 1.5 or 3 h carrying a weight representing 3% of body weight. At the end of exercise or after varying recovery periods, the hearts were removed, mitochondria and microsomes were isolated and phospholipid constituents, cholesterol and phospholipase A2 (PLA2) determined. The phosphatidylethanolamine (PE) and phosphatidylcholine (PC) levels in mitochondria were progressively reduced by exercise for 0.5, 1.5, and 3 h as compared with control rats (the rats which trained to swim with loading for 4 days and took rest for 1 night). After recovery periods of 6 and 12 h, levels were partially restored, but after 24 and 48 h they decreased slightly below the control values. By 120-240 h, PE and PC levels recovered to slightly higher values than control. In microsomes, PE and PC levels were also decreased at the end of exercise for 0.5, 1.5, or 3 h, but over recovery periods of 6 to 48 h, they gradually increased and stabilized. In Experiment II designed to study the cause of the exercise-induced decrease in PE and PC, intravenous quinacrine was used to inhibit PLA2. PE and PC in exercised rats injected with saline (ES group) were markedly decreased after prolonged exercise when compared with control rats injected with saline (CS group). In exercise rats injected with quinacrine (EQ group), PC was significantly decreased when compared with the CS group while PE was slightly decreased but was not significantly different. Total activity (TA) and specific activity (SA) of PLA2 in mitochondria did not differ significantly in the three groups. In microsomes, TA in the ES group was significantly increased compared with the CS group while that in EQ group was slightly increased but was not significantly different. SA was unchanged in three groups. These results suggest that quinacrine can partially prevent the decrease of phospholipid and partially inhibit the activity of PLA2 after prolonged exercise. RCR in ES group increased significantly after prolonged exercise while RCR in EQ group tended to increase. ADP/O ratio was not significantly different in all groups.


[In vitro and in vivo immunobiological responses of glioblastoma to human natural tumor necrosis factor-alpha]. Biological effects of human natural tumor necrosis factor-alpha (TNF) on glioblastoma cells in vitro and on glioma patients were investigated. TNF treatment on glioblastoma cells, even at a high dose (256 U/ml), exhibited no remarkable cytocidal activity in MTT assay, but at lower doses significantly inhibited colony forming and DNA synthesis. TNF at a low dose (10 U/ml) stimulated production of prostaglandin E2, Mn-superoxide dismutase, interleukin (IL)-6 and IL-8 by glioblastoma cells. These results indicated that the direct effect of TNF on human glioblastoma cells is rather antiproliferative than cytotoxic and is to modulate their metabolic pathways. In an early Phase I clinical trial, TNF was administered intracranially to six patients bearing glioblastoma. In this trial, the author studied in vivo immunological responses in the cerebrospinal fluid and regional fluid after the regional TNF injections. TNF in these body fluids were detected with a half life of several hours. There occurred a substantial number of leukocyte migration after the TNF administration. Neutrophils appeared first peaking at 8 to 12 hours, and then CD4+CD8-T cells and CD11b+CD13+CD14+ monocytes followed. IL-8 activity in the cerebrospinal fluid simultaneously corresponded to peak of the neutrophil migration. Increases in IL-6, IL-1 beta and prostaglandin E2 levels in the cerebrospinal fluid, regional fluid or both occurred peaking at 8 to 12 hours after TNA infection. Neither IL-2 nor interferons was detected. In conclusion, TNF may act as an antineoplastic agent by its direct cytostatic effects and indirectly through immune modulatory effects.


[The effect of oxygen free radical scavenger on endothelial cell at ischemic and reperfusion injury]. Although a lot of investigations indicated that free radical scavengers, such as superoxide dismutase (SOD) and catalase, reduced ischemia-reperfusion injury, the precise mechanism including the sites of action are still controversial. The purposes of this study were to investigate the sites of action of SOD and catalase by assessing postischemic cardiac and endothelial cell function. Wistar rats (450-550g) were used as support animals to establish blood perfused circuit. A peristaltic pump controlled the femoral arterial supply at 3.0 ml/min and the venous return to the jugular vein with gravity. Hearts (n = 8/group) from the Wistar rats were perfused (Langendorff model) and paced at 350 beats/min. After assessing baseline functions, hearts were rendered ischemia at 37.5 degrees C for 20 min. Then hearts were reperfused for 35 min, at the end of which left ventricular functions were re-assessed. One group of hearts received a continuous infusion of SOD and catalase during the period of 10 min before ischemia to 20 min after the onset of reperfusion. Left ventricular functions were measured with a left intraventricular balloon. The end-diastolic pressure was fixed at 10 mmHg, which was equivalent to the normal left ventricular end-diastolic pressure. The mean postischemic recovery of the left ventricular end-systolic pressure was increased from 55 +/- 3% in the control group to 67 +/- 2% in the SOD and catalase group (P less than 0.05). Similarly, the postischemic compliance was increased from 1.28 +/- 0.12 (microliters/mmHg) in the control group to 1.61 +/- 0.11 (microliters/mmHg) in the SOD and catalase group (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)


[Sulfolipids and glycolipid sulfotransferases in a human renal cell carcinoma cell line]. A cell line (SMKT-R3) established from renal cell carcinoma was characterized by sulfolipids and glycolipid sulfotransferases. It was found by analyzing glycolipids extracted from SMKT-R3 cells that sulfolipids constituted a large part of acidic glycolipids. When SMKT-R3 cells were metabolically labeled with sodium [35S]sulfate, the incorporation of the radioactivity was detected in accordance with SM4, SM3 and SM2, which were major sulpholipids found in the cells, by autoradiography of thin layer chromatogram of the acidic glycolipid extracts from the cells. Markedly high activity level of glycolipid sulfotransferases toward GalCer and LacCer as substrates was observed in SMKT-R3 cells. Effects of 12-0-tetradecanoylphorbol-13-acetate (TPA) and a protein kinase C inhibitor on glycolipid sulfotransferases were investigated in SMKT-R3 cells. The treatment with TPA caused a dose- and a time-dependent reduction of the enzymes activities. Similarly, H-7 and staurosporine, which are inhibitors of protein kinase C, reduced the glycolipid sulfotransferase activities. These results indicate that the glycolipid sulfotransferase activities are mediated by protein kinase C in SMKT-R3 cells. On the other hand, the treatment of SMKT-R3 cells with epidermal growth factor (EGF) was associated with the increase of the glycolipid sulfotransferase activities in a dose-dependent manner. However, this effect of EGF was counteracted by the pretreatment with TPA or H-7. These findings suggest that EGF induces the glycolipid sulfotransferase activities through protein kinase C.


[Establishment and characterization of human lung squamous-carcinoma sublines resistant to cis-diamminedichloroplatinum (II)]. I have established human lung squamous-carcinoma cell lines resistant to cis-Diamminedichloroplatinum (II) (CDDP), designated PC10-B3 and PC10-E5, from the original cell line PC10, by a stepwise increment of CDDP concentration. An MMT assay revealed that PC10-B3 was 11.4-fold, and PC10-E5 was 19.9-fold more resistant to CDDP than PC10, respectively. PC10-B3 was cross-resistant to CBDCA and 254-S, but not to doxorubicin and etoposide. The level of intracellular platinum accumulation was reduced by about 5 to 8-fold in PC10-B3 when compared with PC10. A two-dimensional gel electrophoresis was used to analyse the relative amount of proteins as between PC10 and its CDDP resistant sublines. The protein spot MW50 kD, pI5.3 was markedly reduced, and the spot MW50kD, pI4.9 was increased in PC10-B3 and PC10-E5 when compared to PC10. The spot MW58kD, pI5.8 newly appeared only in PC10-E5. I collected the most dramatically changed spot, MW50kD, pI5.3 (50kD-5.3), and processed it to determine its peptide sequence. I found that 50kD-5.3 was identical to 50kD, type I keratin (K14). Moreover, a retinoic acid-mediated K14 reduction was concomitant with a 4.0-fold transient increase in CDDP resistance in PC10. Taken together, the reduced intracellular platinum accumulation and the marked decrease of K14 imply that they are important factors in contributing to CDDP resistance in PC10-B3.


[Analysis of acute graft-vs-host like reaction in [B6-lpr----B6] spleen chimera mice]. The lpr autoimmune mice develop massive lymphadenopathy and autoimmune disease. Transfer of lpr autoimmune disease to normal mice by bone marrow transplantation did not succeed, but caused a severe wasting syndrome like graft-vs-host (GvH) disease (lpr-GvH). We previously demonstrated that the transfer of B6-lpr spleen cells to B6 mice ([B6-lpr----B6] chimera) caused acute GvH-like disease accompanied by remarkable CD8+ T cell expansion, and that chimera spleen cells had suppressive activity on mitogen responses of spleen cells from normal mice. In this paper, I studied strain difference of acute lpr-GvH disease and mechanism of suppressive activity further. [B6-lpr----B6] chimera spleen contained more than 70% of CD8+ cells. However, [MRL-lpr----MRL-(+)] chimera and [C3H-lpr----C3H] chimera contained less than 20% of CD8+ cells. Both B220+ DN T cells and CD 8+ T cells were requisite for expansion of CD8+ T cell in the chimera spleen. Mixed chimera experiments using CD8+ T cells from B6-lpr-Thy1.1 mice and B220+ DN T cells from B6-lpr mice showed that CD8+ but not B220+ DN T cells were direct precursors of expanding CD8+ T cells. The mechanism of suppressive activity on Con A responses was different from that on LPS responses. A cell-to-cell interaction was essential for suppression of Con A response without involvement of CD8- cells, while suppression of LPS responses was mainly exhibited by soluble factors. Suppression of LPS responses was abrogated by the presence of anti-IFN-gamma monoclonal antibody, suggesting that those factors contain IFN-gamma. These data suggest that CD8+ T cells from B6-lpr mice were activated by unidentified antigen(s) which were expressed by B6 but not B6-lpr cells, and that IFN-gamma and/or unknown inflammatory factors secreted by the CD8+ T cells induced pathological outcome indistinguishable from GvH reaction in B6 recipient mice.


[Biochemical study on steroid sulfatase and its clinical application to the obstetrics and gynecology]. Steroid sulfatase desulfates a number of 3 beta-hydroxysteroid sulfates, converting inactive steroid hormone to the active form. I have developed an enzyme-linked immunosorbent assay (ELISA) using polyclonal antibody against the sulfatase which was purified from human placenta to measure an amount of the enzyme protein in sera of gynecologic cancer patients. By this method, it was found that the serum steroid sulfatase level is significantly elevated in patients with endometrial carcinoma (p less than 0.05) and ovarian carcinoma (p less than 0.01) as compared to that of normal women. Steroid sulfatase deficiency, X-linked ichthyosis (XLI) is an inherited skin disorder. The sulfatase gene and the enzyme protein were examined in patients with XLI. When the first and last (exon 10) exons of the sulfatase gene were amplified by PCR using patients' genomic DNA as templates, no product was detected in all six cases examined. In addition, neither mRNA of the sulfatase nor the enzyme protein was detected in a patient with XLI. These observations suggest that most Japanese XLI patients are caused by an extensive deletion of the steroid sulfatase gene.


[Synergism between transcription factors NF-IL6 and NF-kappa B in IL-6 gene regulation]. NF-IL6 and NF-kappa B are nuclear proteins supposed to play an important role in the regulation of acute-phase protein synthesis and inflammatory response against infection and tissue injury as a host defence mechanism. In addition the promoter region of the interleukin-6 (IL-6) gene has a NF-kappa B binding motif as well as a NF-IL6 binding site. Considering of these facts, we come to investigate that there may be a synergistic effect between NF-IL6 and NF-kappa B in the regulation of IL-6 gene expression. In order to study it, some combinations of expression vectors NF-IL6 cDNA, NF-kappa B (p50/p65) cDNA and reporter plasmid K18-CAT which contains human IL-6 promoter linked to the chloramphenicol acetyltransferase (CAT) gene, were transfected into Jurkat cells and the CAT activities were examined. Co-transfection of NF-IL6 and NF-kappa B (p50/p65) cDNA revealed a dramatic increase of acetylated [14C] chloramphenicol, and its CAT activity reached to 40%. Then, co-transfection of NF-IL6 and NF-kappa B subunit p65 alone showed a high level of CAT activity, too. When 5' deletion mutant reporter plasmid K9-CAT lacking the NF-IL6 binding site was used, co-transfection of NF-IL6 and NF-kappa B (p50/p65) showed low level of CAT activity. These results indicate that there is a synergistic effect between NF-IL6 and NF-kappa B (p50/p65) in IL-6 gene regulation. Among two subunits of NF-kappa B (p50/p65), p65 seems to play an important role rather than p50 does in synergism between NF-IL6 and NF-kappa B. Besides, this synergistic function comes to work only when NF-IL6 binds to its binding site of IL-6 promoter region.


[Analysis of polymorphism at the human class I MHC locus, HLA-G]. HLA-G is one of the non-classical HLA class I gene and its expression has been identified in cytotrophoblasts and in some choriocarcinoma cell lines. It encodes apparently non-polymorphic antigen and is considered to play an important role in the fetomaternal immune system. However, the monomorphism of the HLA-G gene has not been established firmly. In order to examine the polymorphism of the HLA-G locus, a clone 7.0E was isolated from a genomic library using a probe derived from 3' untranslated region of HLA-G (Orr). Additionally, PCR/SSCP analysis of the HLA-G 3' untranslated region was carried on 35 DNA samples of unrelated individuals taking advantage of the fact that HLA-G (Orr) and 7.0E differed in 14bp length in the amplified fragments. The nucleotide sequence of 7.0E was homologous to HLA-G (Orr), but the sequence was more closely related to a cDNA sequence of BeWo-G7 which has been cloned from mRNA of BeWo cells. Among these 3 clones no amino acid substitution was found in the coding region, Thus, 7.0E should represent a genomic clone of BeWoG7. PCR/SSCP analysis showed that 33 out of 35 samples (94%) contained 7.0E gene, 29 contained HLA-G (Orr) gene (83%). Two samples (6%) contained only HLA-G (Orr), and 6 samples contained only 7.0E (17%). Among 29 DNA samples containing HLA-G (Orr), 3 samples showed the shift in electrophoretic mobility in HLA-G (Orr), suggesting minor sequence differences in HLA-G alleles. From these results it is concluded that HLA-G antigen is monomorphic, but there are several alleles recognizable by DNA sequence and/or SSCP analysis.


[Identification of molecular species in porcine luteal glutathione S-transferase and its hormonal regulation by hypophyseal gonadotropins]. The glutathione S-transferase (GST) was purified to homogenous state from cytosol fraction of porcine corpora lutea. Present studies showed that the final enzyme preparation was consisted of a single molecular species of GST 1-1 (ligandin), which has been identified from its enzymatic properties, amino acid sequences and immunological reactivity. Furthermore, it has been suggested that the ovarian GST involves in the steroidogenesis, especially in the step of progesterone synthesis, from the following results. 1) The final enzyme preparation has a significant delta 5-3-ketosteroid isomerase activity. 2) GST activity in the cultured porcine granulosa cells was remarkably increased in the luteinizing process, which was induced by an addition of hypophyseal gonadotropins such as FSH and LH to the culture system. 3) Changes of GST activity induced by FSH and LH were closely associated with progesterone production. 4) The GST localized in the luteal cells and theca interna, but not in the granulosa cells, which has been revealed by an immunohistochemical staining using anti-luteal GST antibodies.


[A cardiodynamic study on cardio-assistive effect of the assist device: evaluation on left ventricular dehematizing system]. Of late years, assist artificial heart device has been more and more investigated with subsequent reports being made of its clinical application. Dehematization of left ventricular assist device (LVAD) is divided into two systems, i.e., left atrial dehematization and left ventricular dehematization according to the location of the canula's tip. At present in our country, the former system is being adopted for the majority of LVADs and is generally regarded as preferably acceptable. However, because of low survival rate of LVAD in spite of its comparatively good rate of break-away, not a few cases appear to exist beyond the limit of the former system's effects. Then, compared with the left atrial dehematizing system, LVAD according to the left ventricular dehematizing system was examined for its cardio-assistive effect both blood circulatorily and cardiodynamically. A pneumatically-driven diaphragm type pump was implanted between the left ventricular apex and the descending aorta of a dog and was driven by ECG-synchronous counterpulsation method with heart rate versus pump beating number ratios of 1:1, 2:1 and 4:1 and fixed beating number method with beating number of 60 and 80 beats/min (bpm). In order to measure the left ventricular diameter and myocardial length, 7 pairs of ultrasonic sonomicrometers were embedded intra-left ventriculomurally. Ischemia was prepared by ligating the left anterior descending coronary artery (LAD). Bulk mechanical work and regional mechanical work were calculated from these dimensions and the left ventricular pressure. The following results were obtained: 1) In all driving modes but that of 4:1, compared with non-driven pumping, heart rate, peak left ventricular pressure, mean left atrial pressure and total peripheral resistance showed low values, and mean aortic pressure and total blood flow showed high values. Moreover, in the above driving modes, total bypass was obtained. 2) In the above driving modes, bulk and regional mechanical works were practically null with a de-loading effect of 100% or so being obtained. 3) Compared with the left atrial dehematizing system, peak left ventricular pressure showed remarkably low value with increases in mean aortic pressure and total blood flow, and with remarkable decreases in bulk and regional mechanical works. 4) In driving modes of 2:1, 1:1, I60 and I80, little difference in the effect according to the driving mode was noted.(ABSTRACT TRUNCATED AT 400 WORDS)


[Effects of a non-ionic low osmolar contrast medium on thyroidal radioiodine uptake in rats]. Recently non ionic low osmolar contrast media (NILOCM) have been widely used in radiographic contrast studies. These new agents have a great advantage over conventional ionic high osmolar contrast media (IHOCM) in low chemical toxicity and good X-ray absorption. However, their effects on thyroid function, especially on thyroidal radioiodine uptake (TRIU), are still unknown and it is not clear how long NILOCM interfere with TRIU. Therefore, the extent of the interference with TRIU caused by previous NILOCM injection was examined using rat thyroid. Male WKA rats were divided into four groups and fed under different dietary conditions, A) routine diet for rats; B) low iodine diet (LID) for 1 week, C) LID for 2 weeks, and D) LID for 8 weeks. Iopamidol was used as NILOCM, and iothalmate, one of IHOCM, was also employed for comparative study. After feeding, some rats in each group were injected with 300 mgI/kg. b.w. of iopamidol or iothalmate. The remaining rats in each group received saline injection as the control. At day 1, 2, 3, 7, and 14 following injection, I-131 was administered intravenously and a 24 hour TRIU (% dose/mg tissue) was measured in each group. Thyroidal iodine content (TIC: micrograms I/mg tissue) at day 1, 7, and 14 was also measured in group A, C, and D. Until day 3, severe suppression on TRIU was observed in all groups, and TIC elevated at day 1 in iothalmate-injected rats. In iopamidol-injected rats, TRIU and TIC recovered after then, and reached the same levels as those in control rats until day 14 except for group D. However, TRIU was still significantly lower and TIC levels in group D was higher at day 14 in iothalmate-injected rats. It is concluded that iopamidol has less effects on TRIU and TIC with a shorter period of recovery than iothalmate. This results maybe beneficial to the patients who were injected NILOCM prior to radioiodine scintigraphy.


[A clinical study on non-verbal psychotherapy in childhood and adolescence: a proposed classification and psychopathological considerations]. The author examined the therapeutic sequence of 37 child and adolescent cases of neurotic disorder in whom the non-verbal approach was successively taken for more than 6 months. The cases could be classified into two types, according to their choice of non-verbal methods: "simple type" cases, who chose only one method at all their therapeutic sessions and "mixed type" cases, who took various combinations of non-verbal methods during the period of psychotherapy. In "simple type" cases, premorbid character was usually introverted and emotionally stable. As for their family situations, their fathers were rather asthenic and their mothers often lacked emotional communication in child-rearing. Patients showed one or only few clinical symptoms. The therapeutic relationship with them was superficially calm and stable, and it was often difficult to deepen the emotional commitment further. In "mixed type" cases, on the other hand, premorbid character was emotionally often unstable. Their fathers tended to be away from home, and mothers were conspicuously overprotective and meddlesome. Their clinical symptoms were varied. In the therapeutic sessions, they often became dependent on therapists and, at the same time, ambivalent and unstable in certain conditions, showing dissatisfactions and reacting strongly against their therapists. The characteristics of these two types can be observed in relation to other clinical disorders. Regarding the development of interpersonal relationship and personality, it can be seen that the two types is derived from the different quality of the "sense of basic trust" of each patient acquired in early childhood. Based on the above findings, the author discussed a few psychopathological issues on his proposed classification.