Retroviral basis for immunosuppression remains to be proven.
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Biomedical subjects
Publications and source records attributed to P Vogel.
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The time course of thromboxane B2 (TxB2), 6-keto-PGF1 alpha (stable metabolite of prostacyclin), tumor necrosis factor-alpha (TNF alpha), platelet activating factor (PAF), and interleukin-6 (IL-6) formation after three lipopolysaccharide (LPS) infusions was studied in pigs over an 18-hr, period. The Escherichia coli endotoxin W0111:B4 was injected i.v. into 10 of the test group pigs at a dose of 0.5 micrograms/kg over 30 min at 0, 5 and 10 hr of the experiment. Three pigs injected with physiological saline served as controls. At defined time points before and after each LPS administration venous blood was withdrawn (0, 15, 30, 45, 60, 120, 180 min) and plasma levels of TxB2, 6-keto-PGF 1 alpha, PAF, TNF alpha and IL-6 were determined. Pulmonary artery pressure (PAP) and cardiac output (CO) were measured every 15 min. TxB2 and PAF peaked significantly between 30 and 45 min, TNF alpha and 6-keto-PGF 1 alpha between 30 and 60 min, and IL-6 between 120 and 180 min after each LPS injection. The mediators PAF, TNF alpha and TxB2 showed a decreasing three-peak profile whereas 6-keto-PGF1 alpha exhibited an increasing one. IL-6 plasma concentrations increased after each LPS injection. The peak after the third LPS administration, however, was surprisingly low compared to the previous two. The first LPS infusion in our test group led to a significant, sustained rise in mean PAP. After recurrent LPS injections the peak in PAP was not as marked as after the first infusion, indicating the development of a tolerance towards LPS. Initially, CO showed hypodynamic values, whereas the end stage of the experiment was characterized by hyperdynamic CO levels. In conclusion, we believe this porcine model of septic shock to be one of the first large animal models to describe in detail the time-course of various important inflammatory mediators.
The excision of a pilonidal sinus with wound healing by second intention, often results in a long duration of treatment. On the other hand, primary suture after excision has a high rate of abscess formation. In a randomized study we treated 40 patients with excision of pilonidal sinus, insertion of a collagen sponge containing Gentamicin and primary suture (group 1) to prevent this abscess formation. Another 40 patients were treated in the same way but without applying the Gentamicin-collagen sponge (group 2). There had been no significant differences as to the history and duration of the disease, the wound size, the degree of inflammation, the weight of the patients or the amount of hair near the sinus. In group 1 only 7.5% of the patients had a postoperative abscess formation, in contrast to group 2, with an abscess rate of 52.5% and consecutive surgery (p less than 0.001). One year after the operation the recurrence rate was 0 in both groups. Considering the results mentioned, surgical excision of the pilonidal sinus in combination with insertion of a resorbable antibiotic sponge we recommend this therapy.
The most frequent result of a cervical or dorsal spinal cord injury is a transverse lesion with quadriplegia or paraplegia, total loss of bladder and bowel control, breakdown of sympathetic function, and complete loss of sensory function. Partial cord lesion leading to central/anterior/posterior or Brown-Séquard syndromes are rare. Progressive clinical signs of cord damage are only rarely due to sub- or epidural hematoma or edema; in nearly all cases, they point to a persistent instability of the spine.
Despite the fact that human immunodeficiency virus (HIV) is transmitted primarily by sexual contact, the biology of the sexual transmission of HIV is poorly understood. Simian immunodeficiency virus (SIV) can be transmitted to female rhesus macaques by placing cell-free virus into the vaginal canal, and SIV can be isolated from the vaginal secretions of infected rhesus macaques. The authors examined the genital tracts from 16 chronically infected female rhesus macaques and localized SIV-infected cells using in situ hybridization and immunohistochemistry. SIV-infected cells were found in the genital tract of 13 of the 16 animals examined, and in most cases the SIV-infected cells were located in the submucosa of the cervix and vagina. However, SIV-infected cells were also found in the vaginal epithelium. SIV-infected cells were more common in sites of inflammation than in normal areas. These findings suggest that SIV gains access to genital tract secretions from the cervix and vaginal epithelium.
A case of lumbosacral polyradiculitis in an HIV-1-positive man (CDC IIB) leading to a flaccid paraplegia below the level of L4 is reported. A detailed analysis of several cerebrospinal fluid samples led to the suspicion of a bacterial infection. After treatment with antibiotics and tuberculostatic agents the neuropathy improved and the patient has survived for 2 years. In contrast to similar cases that were probably caused by cytomegalovirus in terminal stages of AIDS, it is argued that an unidentified bacterial infection was the cause of the polyradiculitis in the present case.
The nature of anal sinus and anal intramuscular glands is well known, but their origin is still discussed. In the past years a surprising new theory about the invagination of the proctodeum into the hindgut was put forward. Evidence supporting this theory would be the existence of an "anorectal band" and "epithelial debris" in the subanoderm formed during total or partial obliteration of the anal sinuses. To characterize these histological structures, the authors examined 62 autopsy specimens with conventional and special immunohistologic staining methods. In none of the examined specimens could the structures mentioned above be detected. Nearly 90 percent of our specimens contained the well known anal sinuses. In fetuses, neonatal deaths, and children, more than one-half of the anal sinuses were accompanied by anal intramuscular glands penetrating the internal anal sphincter, whereas in adult specimens the anal intramuscular glands were rare. Eight postoperative, idiopathic chronic anal fissures and three postoperative anal fistulas examined with the same staining procedures showed epithelial cells at the base of the fissures or fistulas in two cases (25 percent) and three cases (100 percent), respectively. The results reinforce the theory that anal sinuses and anal intramuscular glands are separate anatomic entities and indicate a new theory of anal development. For idiopathic, chronic anal diseases anal sinuses have little surgical significance. Anal intramuscular glands should be the anatomic correlate of anal fistulas.
Severe trauma favors the susceptibility of patients to infection. It has been shown that proteins or protein fragments are responsible for an endogenous immunodepression. After trauma a coagulopathy accompanied by increased serum levels of fibrinogen degradation products (FDP) is often found. Therefore, we examined whether FDP-D can influence the activity of polymorphonuclear neutrophils (PMN). PMN-activation was measured by two different superoxide-specific methods (Cytochrome-C-test, INT-test). With both methods we found a decrease of PMN activity by FDP-D compared to fibrinogen. Albumin, which was used as a control protein, only influenced PMN activity in unphysiologically high concentrations. The third method used to quantify PMN activity was chemiluminescence, which is a more unspecific method since it is developed not only by oxygen radical species but also by activating the lipoxygenase pathway. In contrast to the superoxide specific tests we found an inhibitory effect of fibrinogen and also serum compared to FDP-D using chemiluminescence.
In hyperfibrinolytic conditions, e.g. in disseminated intravascular coagulation or the adult respiratory distress syndrome, high levels of fibrinogen degradation products (FDPs) D and E are found in human plasma. This study investigates the influence of these fragments on cell attachment of human granulocytes in vitro. While leaving unaffected the adhesion of human umbilical vein endothelial cells (HUVEC) on gelatine-coated glass, both FDP fragments at 50 micrograms/ml inhibited granulocyte attachment to glass as well as to HUVEC monolayers. At the same concentration, the fragments diminished the superoxide release of stimulated granulocytes. These results suggest a modulatory role of pathologically elevated FDPs on the granulocyte function cascade.
The pulmonary and systemic hemodynamic effects of recurrent endotoxemia were studied in pigs over a 48-hr period. Six pigs of the test group were given 0.5 micrograms/kg of an E. coli endotoxin (WO111: B4) over 60 min at the beginning and in the middle (22 hr) of the experiment. Three pigs given the same amount of physiological saline solution served as controls. The hemodynamic response to the first LPS injection was characterized by severe pulmonary hypertension, a significant increase in systemic vascular resistance, and a marked decrease in cardiac output. Circulating TxB2 levels were higher than those of 6-keto-PGF1 alpha levels, so that the first response to LPS is influenced by the vasoconstrictive actions of TxA2. With the second LPS application, the pulmonary response was attenuated, although a significant increase of pulmonary artery pressure and pulmonary vascular resistance occurred. Once again systemic vascular resistance rose and cardiac output decreased, but this time plasma levels of 6-keto-PGF1 alpha were greater than those of TxB2. Toward the end of the experiment, we noted the progressive onset of a hyperdynamic and hypotensive state. Systemic vascular resistant index decreased to 50% of the baseline value. IL-6, a cytokine of systemic importance during the course of septic shock, markedly and significantly peaked after each LPS injection. Circulating plasma levels in response to recurrent endotoxemia are described.
For preoperative staging in lung cancer mediastinoscopy is in competition with X-ray, tomography, and computer-tomography (CT). Many authors certify a high sensitivity and specificity to CT in staging lung cancer preoperatively by measuring the diameter of the hilar and mediastinal lymph nodes. In this study we measured the diameter of 162 lymph nodes from 83 patients postoperatively. In view of staging we found no sufficient correlation between the diameter of the lymph nodes and their infiltration by cancer cells. Even 35.7% of the nodes with a diameter of more than 2 cm were not infiltrated. The data support the opinion that CT alone is not sufficient for preoperative staging in lung cancer.
Functional and organic alterations such as sclerosis of the internal anal sphincter muscle are often discussed as a cause of proctologic diseases. Systematic histopathologic examinations of this muscle are rare, although the internal anal sphincter is of primary significance for the continence of the anal canal and its functional efficiency. The authors believe that the degree of formation of connective tissue in this unstriated muscle depends on the age of the examined specimen. The authors can demonstrate that sclerosis is a physiologic process of aging.
Transthoracic and transesophageal echocardiography was performed in 23 consecutive adult patients with an atrial septal aneurysm. In three patients with a cerebrovascular event the diagnosis was established by the transesophageal approach only. Interatrial shunting on transthoracic imaging with use of echocardiographic contrast imaging or Doppler color mapping, or both, was detected in 7 (41%) of 17 patients. On performing contrast imaging in combination with color flow mapping during transesophageal echocardiography, positive shunting was demonstrated in 15 (83%) of 18 patients. Echocardiographic identification of multiple fenestrations (n = 4) and thrombus within the aneurysm (n = 2) could be achieved for the first time by transesophageal ultrasound application. Cerebrovascular events occurred in 12 (52%) of 23 patients and were regarded as being definitely thromboembolic in 10 (43%); 8 (67%) of the 12 patients had repeated cerebral events. Except for mitral valve prolapse in one patient, no other potential cardiac source of embolism could be identified despite the use of transesophageal echocardiography. A thickening of the aneurysmal membrane greater than or equal to 5 mm was found in 9 (75%) of 12 patients with versus 3 (27%) of 11 patients without a cerebrovascular event (p less than 0.05); this proved to be the only significant difference between the two patient groups. The mechanism of embolization may be both primary thrombus formation within the aneurysm and paradoxic embolization through an interatrial communication as demonstrated by the findings in two patients. It is concluded that atrial septal aneurysm is a cardiac abnormality with thromboembolic potential. In patients with this lesion and a history of an embolic event, long-term anticoagulant therapy is indicated.
Over a period of 3 years, antibody titres against Borrelia burgdorferi in serum were determined for 492 patients with a wide spectrum of neurological diseases. Using the ELISA technique, we found elevated titres against Borrelia burgdorferi in about 20% of these patients. Cranial nerve paresis was often the leading symptom of an acute Neuroborreliosis. In a number of cases the diagnosis was indicated only by an elevated IgG titre in the patient's serum, or a decrease in the titre level following antibiotic treatment. The IgG titres are, however, unsuitable for control of therapy. Non-specific parameters of inflammation such as blood sedimentation rate (BSC), C-reactive protein (CRP), serum-electrophoresis or leucocyte count are also unsuitable in evaluating the therapeutic effect or for confirming the diagnosis. The most important diagnostic criterion is the demonstration of Borrelian antibodies, synthesised locally in cerebrospinal fluid (CSF). A spirochaete index above 2 suggests autochthonous intrathecal antibody production. This procedure corresponds to the determination of intrathecally produced Treponema pallidum antibodies in neurolues from quantitative TPHA values and total IgG in serum and CSF (ITpA Index according to Prange).
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Transoesophageal ultrasound imaging of the spinal canal through an intervertebral disc was successfully achieved in 44 of 50 adults (18 women and 32 men; mean age 56 years, range 22-79) who, for cardiological indications had transoesophageal echocardiography. On average, five (range 1-11), usually sequential, segments were visualized. In 37 patients pulse-synchronous sagittal displacement of the spinal cord was noted, presumably caused by cerebrospinal fluid pulsation. In one woman, with known syringomyelia, the spinal cord cavity was well shown. Real-time demonstration of dynamic events in the spinal canal opens up new possibilities for the diagnosis and follow-up monitoring of spinal diseases.
Nine severely ill patients with a confirmed diagnosis of systemic juvenile rheumatoid arthritis were treated with recombinant gamma-interferon (gamma-IFN) in addition to the therapy they were previously receiving for their disease. Improvements in clinical symptoms were noted in 7 of the patients, and median laboratory values also showed a marked improvement after gamma-IFN treatment. A relapse occurred in 1 patient. The results of this study should stimulate further research on the use of gamma-IFN in systemic juvenile rheumatoid arthritis, particularly in determining the appropriate effective dosage.