[The early axial traction of the cervical spine after anaesthesia with intubation and extreme reclination of the head]. / Die frühe axiale HWS-Traktion bei Gelenkfunktionsstörungen nach extremer Kopfreklination in Intubationsnarkose.

OBJECTIVE: Patients who have an operation under general anaesthesia with muscle relaxation often complain about neck pain if the head needs to be placed in extreme reclination to facilitate surgical access. Patients complain about vertigo, light muscle tenseness but also about severe joint blockages in the neck region. Due to this complication the standard practise in some hospitals is to refer these patients routinely to a physiotherapist postoperatively. This study investigated the influence of an axial traction - a treatment which can easily be learned by anaesthesiologists - on blockages of the cervical spine in those patients. METHODS: In two randomised groups (n = 15 each) of preoperative inconspicuous patients the following directions of motion were investigated: Ante- and retroflexion of C0/1, side inclination C0/1, side nodding and side movement C2/3 to C6/T1, dorsal movement C5/Th2. The examinations took place at the preoperative anaesthetic round, shortly before extubation, two hours after extubation and the next day. Additionally the patients were asked about their discomfort. An axial traction of the cervical spine was performed in one group after extubation. The number of new blockages and the subjective discomfort of the patients was compared with the Chi-Square test. RESULTS: An axial traction of the cervical spine reduces the frequency and the intensity of symptoms significantly. CONCLUSION: It was investigated whether an axial traction of the cervical spine - a treatment that can easily be learned by anaesthesiologists - could improve patients' comfort. The study showed that an axial traction of the cervical spine immediately after extubation reduces the frequency and intensity of symptoms significantly. This treatment is highly effective, not very time consuming and, if done correctly, without any risk for the patient. By using this treatment routinely, additional expenses for physiotherapeutic interventions could be reduced.

Cellular and humoral immune response in progressive multifocal leukoencephalopathy.

Progressive multifocal leukoencephalopathy (PML) is a fatal, demyelinating disease caused by JC virus (JCV) in patients with severe immunosuppression. We studied the JCV-specific cellular and humoral immune response in 7 healthy donors (HD), 6 human immunodeficiency virus-1 (HIV-1)-infected patients without PML (HIV), 4 HIV-1-negative patients with PML (PML), and 8 HIV-1-positive patients with PML (HIV/PML). As antigens, recombinant virus-like particles of the major structural protein VP1 (VP1-VLP) of JCV, tetanus toxoid (TT), or the mitogen phytohemagglutinin (PHA) were used. Proliferation of peripheral blood mononuclear cells (PBMC) after stimulation with the VP1-VLP was significantly suppressed in PML and HIV/PML patients compared to HD. After antigen stimulation the production of interferon-gamma (IFN-gamma) was reduced in PML, in HIV/PML, and in HIV patients. The production of interleukin-10 (IL-10), however, was elevated in HIV/PML patients. Neither proliferation nor cytokine production correlated with the presence of JCV DNA in PBMC. The immunoglobulin G serum antibody titer to the VP1-VLP was slightly elevated in HIV, elevated in PML, and highly elevated in HIV/PML patients compared to HD. The development of PML appears to coincide with a general impairment of the Th1-type T-helper cell function of cell-mediated immunity.

C1 inhibitor prevents capillary leakage after thermal trauma.

OBJECTIVE: In burned patients, activation of the complement and clotting systems is suggested to play an important role in the development of the capillary leak syndrome and inflammatory tissue destruction. In an animal model of thermal trauma, the possible protective effect of C1 inhibitor (C1Inh), a major control protein of both the complement and clotting systems, was investigated. DESIGN: Prospective, controlled study. SETTING: Animal model. SUBJECTS: Healthy pigs weighing 30 kg. INTERVENTIONS: Pigs were scalded for 25 secs with 75 degrees C hot water to achieve a 30% total body surface deep partial-thickness burn. The treatment group (n = 8) received C1Inh concentrate at an initial dose of 100 units/kg body weight immediately after thermal trauma, followed by three further applications every 12 hrs. Two control groups included animals that were either scalded (n = 8) or not scalded (n = 7) and treated with lactated Ringer's solution. MEASUREMENTS: Before and at various time points after trauma blood samples were analyzed for complement activation (APH50, CH50, SC5b-9, C3). Continuous monitoring of hemodynamic variables was performed and postmortem histologic examination of specimens from lung, heart, liver, kidney, stomach, duodenum, jejunum, ileum, and colon was carried out. Aseptically collected mesenteric lymph nodes were pooled and screened for bacterial translocation. For evaluation of the burn wound, biopsies from defined scalded and not scalded areas were taken daily. As a measure for edema formation, the weight of the animals was recorded every 2 hrs. RESULTS: After C1Inh treatment, which led to a significantly reduced complement activation, the clinical outcome was clearly improved, as indicated by vital signs and as demonstrated by reduced edema formation. Treated animals presented a diminished bacterial translocation. Pathologic alterations were clearly diminished in the burned skin, in shock-related organs, and in the intestines. CONCLUSION: Application of C1Inh appears to be an effective means to prevent capillary leakage and inflammatory tissue destruction after thermal trauma.

Packaging of small molecules into VP1-virus-like particles of the human polyomavirus JC virus.

Recombinantly expressed VP1-virus-like particles (VP1-VLP) of human polyomavirus JC virus (JCV) were described recently as a new DNA transporter system. It was shown that DNA molecules could be packaged into VP1-VLP during a controlled chemical reassociation/dissociation process. In the present study VP1-VLP were studied as carriers for pharmaceutical substances. Propidium iodide (PI) was packaged into VP1-VLP as a reporter molecule. The PI-containing VP1-VLP could be detected directly by flow cytometry. The fluorescence intensity of the VP1-VLP depended strongly on the initial PI concentration. This packaging method is easy to handle and applicable to viruses and VP1-VLP which can be dissociated and reassociated chemically.

Combination anesthesia with ketamine and pentobarbital: a long-term porcine model.

Anesthesia of the pig poses great problems for experimental animal-based research and particularly in shock research. In this study, five mechanically ventilated domestic pigs were given long-term anesthesia with a combination of ketamine plus pentobarbital. Circulatory parameters were recorded every 2 h via an arterial catheter placed in the right common carotid artery, a Swan-Gans thermodilution catheter (7F), that was placed in the pulmonary artery of the right middle-lobe in a wedge position through the external jugular vein, and another catheter in the internal jugular vein for measuring central venous pressure. Moreover, body weight, blood gases, pH, blood cells, electrolytes and serum enzymes were measured. Further serum traits as total protein and glucose and pathological alterations in different organs were recorded. The animals were observed for a period of 96 h and then killed painlessly. It was shown that pigs can survive 96-h anesthesia with the combination of ketamine and pentobarbital. Optimum, carefully controlled anesthesia did not impair the integrity of the regulatory mechanisms of circulation.

Molecular cloning and expression of major structural protein VP1 of the human polyomavirus JC virus: formation of virus-like particles useful for immunological and therapeutic studies.

The major structural viral protein, VP1, of the human polyomavirus JC virus (JCV), the causative agent of progressive multifocal leukoencephalopathy (PML), was expressed by using recombinant baculoviruses. Recombinant VP1 formed virus-like particles (VLP) with the typical morphology of empty JCV capsids. Purified VP1 VLP bind to SVG, B, and T cells, as well as to monkey kidney cells. After binding, VP1 VLP were also internalized with high efficiency and transported to the nucleus. Immunization studies revealed these particles as highly immunogenic when administered with adjuvant, while immunization without adjuvant induced no immune response. VP1 VLP hyperimmune serum inhibits binding to SVG cells and neutralizes natural JCV. Furthermore, the potential of VP1 VLP as an efficient transporter system for gene therapy was demonstrated. Exogenous DNA could be efficiently packaged into VP1 VLP, and the packaged DNA was transferred into COS-7 cells as shown by the expression of a marker gene. Thus, VP1 VLP are useful for PML vaccine development and represent a potential new transporter system for human gene therapy.

The therapeutic effect of C1-inhibitor on gut-derived bacterial translocation after thermal injury.

To test the effects of C1-esterase inhibitor in scald burns on bacterial translocation and intestinal damage, standardized deep partial-thickness burns were inflicted on domestic pigs, scalding 30% of the skin surface for 25 s with 75 degrees C hot water. The animals (n = 17; weight 25-35 kg) were divided into three groups: I) the control group (n = 5) without scald burn; II) the group (n = 6) with scald burn; and III) the group with C1-inhibitor (n = 6): scald burn and treatment with C1-inhibitor (C1-INH; BERINERT, Behring, Marburg, Germany). Parameters measured and compared in this model were activity of complement system, hemodynamics, body weight, pathological organ alterations including intestinal lesions, bacterial translocation, and skin damage. C1-INH administration significantly decreased the plasma levels of the specific soluble membrane attack complex (SC5b-9), bacterial translocation, and the degree of intestinal ischemia in the postburn period compared with untreated animals. Moreover, animals treated with C1-INH exhibited a minor degree of organ alterations including damage of the skin and development of edema. The favorable effects of C1-INH may be explained by the protection of the intestinal and dermal microcirculation in the acute phase of thermal injury.

The influence of the C1-inhibitor BERINERT and the protein-free haemodialysate ACTIHAEMYL20% on the evolution of the depth of scald burns in a porcine model.

Standardized deep partial-thickness burns were inflicted on domestic pigs by scalding 30 per cent of the skin surface for 25 s with 75 degrees C hot water. The animals (n = 18; weight 25-35 kg) were divided into three groups: I, control group (n = 6), Ringer's lactate only; II, haemodialysate group (n = 6), Ringer's lactate and a protein-free haemodialysate of calf-blood (ACTIHAEMYL20%; AH) and III, C1-inhibitor group (n = 6), Ringer's lactate and C1-inhibitor (C1-INH; BERINERT). Skin biopsies were taken at defined time points (4, 28, 52 and 76 h) and investigated histologically. Depth of burn was determined morphometrically after coloration with a modified MTT-staining on frozen sections of the skin biopsies. Fluid therapy with C1-INH decelerated significantly the progression of the burn wound in the postburn-period compared to Ringer's lactate alone. In comparison with C1-INH, the treatment with AH demonstrated a less beneficial influence on the depth of scald burns. The favourable effects of C1-INH are explained by the protection of the dermal microcirculation during the acute phase of thermal injury.

Monoclonal-antibody-mediated apoptosis in adult T-cell leukaemia.

The monoclonal antibody anti-APO-1 recognises a 52 kD cell membrane protein (APO-1) on some lymphoid tumour cell lines and on activated T cells. Binding of anti-APO-1 to cells expressing APO-1 results in programmed cell death, apoptosis, the most common form of death in eukaryotic cells. Expression of the antigen and sensitivity to the induction of cell death by anti-APO-1 were studied in human T-cell lines transformed by human leukaemia virus type 1 (HTLV-I) and in cultured cells from patients with adult T-cell leukaemia (ATL). APO-1 was strongly expressed on both types of cells and incubation of the cells with anti-APO-1 resulted in inhibition of proliferation and apoptosis. Induction of apoptosis may therefore be a possible therapeutic tool in HTLV-I-associated malignant disorders.

[Therapy and therapeutic results in carcinoma-in-situ- of the uterine cervix]. / Therapie und Heilungsergebnisse des Carcinoma in situ colli uteri.

348 cases of carcinoma in situ are reported, which were diagnosed, without exception, by conization from 1966 to 1971. The atypical changes could be removed without leaving any detectable malignant cells in situ in 226 patients (65 per cent). These cases did not need any further therapy. In 45 cases (12,9 per cent) was doubtful if the conization could be performed without leaving malignant cells. In 77 cases (22,1 per cent) the conization was done leaving malignant cells in situ. 49 women of this group had a continued treatment, the vast majority was hysterectomized. All the other cases were strictly controlled. The 5-year healing quotient was 91,7 per cent. 7,1 per cent of the patients have not been heard of again. Only 3 patients (0,9 per cent) suffered a recurrence. They belong, without exception, to the control group in which the carcinoma in situ could not be primarily removed without leaving malignant cells in situ. The significance of an exact method of conization and a careful histotechnical perparation of the specimens in serial sections is especially pointed out. The necessity of a continued treatment by means of hysterectomy with vaginal cuff is stressed in carcinoma in situ which could not be removed without leaving malignant cells in situ.

[Value of suspicious and doubtful cytological findings in gynecologic serial examinations]. / Der Wert der verdächtigen und zweifelhaften zytologischen Befunde bei gynäkologischen Reihenuntersuchungen.

Cytological follow-up and histological results of 2336 patients with Pap III and 10584 with Pap II control of 1973 and 1974 were checked up to May 1976 and compared with new literature. 50% of Pap III became to negatives, 10% of Pap III and 0,82% of Pap II control became positive (Pap IV and Pap V). Up to now histological findings has been resulted in 10% invasive cancers; in 53% carcinomata in situ and severe dysplasia, in 16% moderate and mild dysplasias, and in 5% normal epithelium from repeated Pap III. To avoid to many conizations we have introduced Pap IIID for moderate and mild dysplasia into screening cytology.