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Biomedical subjects

H Lange

Publications and source records attributed to H Lange.

At least 55 records · Page 3Linked to original sources

Severe coagulopathy after a bite of a green bush viper (Atheris squamiger): case report and biochemical analysis of the venom.

A 34 year old male bitten by an adult Atheris squamiger snake developed symptoms of nausea, vomiting, diarrhea which were followed by drowsiness and impaired breathing. Local hemorrhage, edema and pain at the bite-site occurred, but no systemic bleeding or hemorrhagic diathesis developed. All clinical and laboratory parameters were in the normal range except for afibrinogenemia, thrombocytopenia and slight proteinuria. Replacement therapy (fibrinogen and platelet concentrates) and treatment of shock stabilized the patient within 2d and coagulation returned to normal. Atheris squamiger venom was subjected to biochemical and biological analysis. The LD50 of the venom was 5 mg/kg (mice, s.c.). It produced local hemorrhage corresponding to about 25% of the activity of puff adder venom (Bitis arietans). In vitro the venom had a fibrinogen-converting activity, it did not activate purified prothrombin but very likely contained a F V and Ca2+-dependent prothrombin activator. The venom exhibited strong platelet-aggregating activity, which was not inhibited by protease inhibitors and by EDTA or EGTA. The venom also aggregated acetylsalicylic acid treated platelets indicating, that the arachidonic acid pathway was not essential for activation. Rat serum rapidly inhibited the platelet-aggregating activity of the venom; human serum, however, had only a partial inhibitory effect. Preliminary experiments showed that platelet-aggregating activity may be separated from fibrinogen-converting activity by anion-exchange chromatography.

Adult↗

Biocompatibility differences with respect to the dialyzer sterilization method.

The impact of the method of sterilization (steam vs. ethylene oxide, ETO) on indices of biocompatibility is investigated using polysulfone membranes. Eight patients were treated with a random choice of the high-flux membranes F60S (steam) and F60 (ETO) and the low-flux membrane F6 (ETO). Blood samples were taken prior to and 5, 15, 30, 60, and 180 min after the start of hemodialysis. White blood cell count, platelet count, and plasma concentrations of polymorphonuclear neutrophil elastase, complements C3a and C5a, and beta2-microglobulin were determined. The dialysis procedure was associated with a significant decrease in white blood cell count and beta2-microglobulin level and a significant increase in polymorphonuclear neutrophil elastase and complement C3a and C5a levels. However, the steam-sterilized F60S membrane had a significantly lower impact on the biocompatibility indices than the ETO-sterilized F60 and F6 membranes (p < 0.05 or p < 0.001 for the individual markers). We conclude that using steam instead of ETO for sterilization may improve the biocompatibility of membranes.

Adult↗

Persistent long-term changes in lymphocyte subsets induced by polyclonal antibodies.

BACKGROUND: Clinicians are well aware of the short-term effects of immunosuppression by mono- or polyclonal antibodies. Little is known about long-term changes induced by these therapies. METHODS: Forty-three renal allograft recipients were selected according to their initial postoperative immunosuppression: (1) BI group=basic immunosuppression with steroids and cyclosporine, n=16; (2) ATG group=basic immunosuppression plus polyclonal antibody antithymocyte globulin (ATG), n=11; and (3) OKT3 group=basic immunosuppression plus monoclonal antibody OKT3, n=16 patients. At intervals of 6 months, the following parameters were measured prospectively: lymphocyte surface antigens (HLA-DR, CD3, CD4, CD8, CD16, CD19, CD56, and CD57); serum and urine neopterin; serum amyloid A; and indirect and direct tests for herpes viruses. RESULTS: The mean period of observation was 58.4 months. The most significant differences between the groups occurred for CD4+ and CD8+ T cells. The ratios of CD4+ to CD8+ cells (n=278 measurements) were significantly and persistently lower in the ATG group (P<0.001, Brown-Mood test). Five years after transplantation, the ATG group had a CD4+ to CD8+ cell ratio of x=0.6 versus x=1.7 in the OKT3 group and x=2.0 in the BI group. This inversion was due to a persistent depletion of the CD4+ cells and an increased regeneration of the CD8+ cells, in particular of the CD8+brightCD57+ subpopulation. Extent and duration of CD4+ depletion correlated with the cumulative ATG dose (r=0.7, P<0.05, Spearman rank correlation test). CONCLUSION: Therapy with polyclonal antibody ATG induces dose-dependent long-term changes in T-cell lymphocyte subsets, which persist over a period of years.

Adult↗

[Warning signals in acute abdominal disorders. Lactate is the best marker of mesenteric ischemia].

An increased plasma lactate concentration (PLC) is a recognized danger signal often found in cases of shock, septicaemia, hepatic and renal failure, and diabetic ketoacidosis. In 120 patients with abdominal complaints, we found the PLC to be above normal limits in 96 per cent (24/25) of the mesenteric ischaemia subgroup, in all 20 of the general bacterial peritonitis subgroup, in 30 per cent (6/20) of the acute pancreatitis subgroup, and in about half of the 25 cases of intestinal obstruction. In all other abdominal conditions represented (n = 30), comprising various inflammatory or infectious abdominal diseases, the PLC was within the normal range. In patients with abdominal complaints, an increased PLC usually indicates the needs of emergency surgery. In the present series, the PLC manifested a sensitivity of 96 per cent and a specificity of 38 per cent as a marker of mesenteric ischaemia, and was also found to be a useful aid in the diagnosis of bowel obstruction and general bacterial peritonitis.

Abdomen, Acute↗

Prospective evaluation of pretransplant blood transfusions in cadaver kidney recipients.

BACKGROUND: A beneficial effect of pretransplant transfusions on graft survival was demonstrated in the early 1970s. In the mid-1980s, however, retrospective studies showed that transfusions had lost their graft-protective effect in the cyclosporine era. During the last 10 years, deliberate transfusion pretreatment of transplant patients has been discontinued. METHODS: Within a collaborative project of 14 transplant centers, prospective recipients of cadaver kidney grafts were randomized to receive either three pretransplant transfusions or transplants without transfusions. RESULTS; The graft survival rate was significantly higher in the 205 transfusion recipients than in the 218 patients who did not receive transfusions (at 1 year: 90+/-2% vs. 82+/-3%, P=0.020; at 5 years: 79+/-3% vs. 70+/-4%, P=0.025). Cox regression analysis showed that this effect was independent of age, gender, underlying disease, prophylaxis with antilymphocyte antibodies, and preformed lymphocytotoxins. CONCLUSIONS; Transfusion pretreatment improves the outcome of cadaver kidney transplants even with the use of modern immunosuppressive regimens.

Blood Transfusion↗

Pancreas-specific protein (PASP), serum amyloid A (SAA), and neopterin (NEOP) in the diagnosis of rejection after simultaneous pancreas and kidney transplantation.

A reliable, noninvasive indicator of pancreatic allograft rejection is urgently needed. In this study, serum (S), plasma (P), and urine (U) levels of pancreas-specific protein (P-PASP, U-PASP), neopterin (S-NEOP, U-NEOP), amylase (U-AMYL), and amyloid A (SAA) were measured daily in ten type I diabetic patients following simultaneous pancreas and kidney transplantation (SPK). Rejection episodes occurred in three isolated pancreas, nine isolated kidney, and five simultaneous pancreas and kidney transplants. In the case of the eight pancreas rejections, SAA was the rejection marker with the highest diagnostic accuracy (94%). Using P-PASP and U-PASP, an accuracy of 81% and 79%, respectively, was achieved. During viral infections, U-NEOP levels increased to a maximum level of 1904 mumol/mol creatinine, whereas during bacterial infections, SAA levels increased to a maximum value of 43 mg/dl. SAA, measured for the first time in SPK, appears to be a valuable rejection parameter. In combination with U-NEOP and U-AMYL, a differential diagnosis between rejection, bacterial infection, and viral infection was possible. Neither U-PASP nor P-PASP monitoring led to a significant improvement in the results.

Acute Disease↗

[Fatal chronic oxalosis after sublethal ethylene glycol poisoning].

A 36-year-old man known as chronic alcohol abuser presently suffered from arthralgia and showed bilateral petriefied kidneys by sonography and computed tomography. Because of an unclear renal failure a kidney biopsy was performed and presented typical chronic renal oxalosis with massive oxalate crystal deposits, tubular atrophy and interstitital fibrosis. Since the man had never shown signs of hyperoxaluria in his life before, a secondary oxalosis was supposed. The subsequently prompted exploration established a three to four times abuse of rocket fuel with cola lemonade 12 years before during the patient's army time as a marine soldier. Such fuels contain ethylene glycol (glysantin) as antifreeze commonly known to cause in toxic doses acute renal tubular necrosis with hyperoxaluria. The presented case, however, suggests a rare sublethal ethylene glycol poisoning with initial renal tubular damage, oxalate crystal deposition and subsequent chronic interstitial oxalate nephritis with tubular atrophy, interstitial fibrosis and chronic renal failure. Undergoing chronic hemodialysis, the patient died 5 months after the kidney biopsy diagnosis by acute heart failure. At autopsy, progressed chronic renal oxalosis could be confirmed. Decompensated oxalate cardiomyopathy with disseminated myocardial oxalate crystal deposits caused acute heart failure promoted by myocardial hypertrophy in renal hypertension.

Adult↗

Detection of renal allograft rejection by complement components C5A and TCC in plasma and urine.

Allograft rejection is associated with complement activation. Yet inconsistent results were obtained in evaluating plasma levels of complement factors or activation products as rejection markers. Therefore the human anaphylatoxin C5a and the soluble terminal complement complex (TCC) were measured by daily enzyme immunoassays on plasma (P) and urine (U) samples from 28 patients undergoing renal transplantation over a mean postoperative period of 25.8 days. The complement levels were evaluated longitudinally (cutoff of 100% increase on the previous day's level) during periods of rejection, stable graft function, acute tubular necrosis, and cytomegalovirus disease. Regarding the detection of 13 acute rejection episodes, U-C5a showed a diagnostic accuracy of 81% (sensitivity of 85%, specificity of 77%), P-C5a one of 62%, and P-TCC one of only 30%. The U-C5a increment (mean rise of 379%) preceded the clinical diagnosis of rejection by an average of 1.6 days. Cytomegalovirus diseases (n = 4) were associated with high P-C5a levels (mean increase of 251% by the time of the first detection of viral DNA). In contrast, resumption of kidney function after acute tubular necrosis (n = 10 periods) was heralded by marked peaks of U-C5a (x = 43.7 microg/l). U-TCC was not detected in any clinical setting. In conclusion, as opposed to P-TCC, U-TCC, and P-C5a, the anaphylatoxin C5a, measured daily in urine, might have potential as an early and reliable marker for acute renal allograft rejection.

Adult↗

Impact of profile haemodialysis on intra-/extracellular fluid shifts and the release of vasoactive hormones in elderly patients on regular dialysis treatment.

In 15 patients with end-stage renal failure and proven coronary heart disease, profile haemodialysis with decreasing ultrafiltration rate and hyperionic, decreasing dialysate solute concentration was compared with conventional, extracorporeal bicarbonate haemodialysis (Na+D = 138 mmol/l). Body fluid distribution and the release of vasoactive hormones (plasma renin activity, aldosterone, norepinephrine, epinephrine, and atrial natriuretic peptide) were investigated. Haemodialysis with constant ultrafiltration rate and constant dialysate composition (A) was followed by two dialysis profiles: decreasing ultrafiltration rate (B) and additional hyperionic, decreasing dialysate sodium concentration (C). In all 15 patients, the dialysis procedures (A) - (C) were used for 2 weeks each with six sessions, the last being taken for investigation. Body fluid distribution was calculated. In patients with serum sodium above 136 mmol/l, the conventional dialysis (A) as well as the Uf profile (B) showed a net fluid shift from extracellular volume (ECV) to intracellular volume (ICV). Using the profile with hyperionic, decreasing Na+D (C), the reverse fluid shift with decreasing ICV was achieved not only in those with serum Na+ <136 mmol/l, but also in those with serum Na+ > or = 136 mmol/l. The release of vasoactive hormones decreased already at profile haemodialysis (B) compared with (A) and was further reduced in (C). These results would suggest, profile dialyses B and C to have less impact on the cardiovascular system in elderly patients assuming higher patient comfort compared with the standard dialysis procedure. A higher benefit was obtained in C compared with B, presumably due to the additional prevention of the ICV shift and plasma volume depletion in patients with initial serum sodium > or = 136 mmol/l using transiently hyperionic Na+D. These results show that in elderly patients, hyperionic profile haemodialysis (Na+D > Na+S) had less impact on cardiovascular regulation than conventional bicarbonate dialysis.

Aged↗

Correlation between immune maturation and idiotypic network recognition.

The maturation of T-dependent humoral immune responses is mediated by somatic mutations. Antigen selection is one mechanism for the activation of B cell clones which express antibodies with progressively increased affinity and which are derived as somatic variants from germ-line-encoded genes. However, the emergence of B cell clones secreting rather low-affinity antibodies and the shift to alternative germ-line V region gene combinations during secondary and tertiary responses cannot be explained by antigen selection. It has been considered that idiotypic suppression may favor this clonal shift. Such an involvement would require that idiotypic recognition in the syngeneic host must be highly restricted to private idiotopes of each clone sequentially activated during immune maturation. To test this possibility, we produced 19 syngeneic anti-idiotypic antibodies to the germ-line-encoded major Ox1 idiotype (IgM-IdOx1 H11.5) of the anti-2-phenyl-oxazolone (phOx) immune response in BALB/c mice. The fine specificity of these anti-IdOx1 was tested with a set of anti-phOx monoclonal antibodies, representing the first steps of maturation. About half of the anti-IdOx1 showed almost no reactivity with the IdOx1 after the switch to IgG and none of the anti-IdOx1 reacted with anti-phOx antibodies which carried a glycine or histidine instead of arginine as the middle amino acid of the D region. These observations suggest a strong correlation between immune maturation and the idiotypic network. A model is presented in which idiotypic suppression may function as a driving force for diversification and maturation of the antigen-induced immune response.

Animals↗

The anaphylatoxin C5a, a new parameter in the diagnosis of renal allograft rejection.

In the underlying study the diagnostic value of the anaphylatoxin C5a was evaluated in kidney transplantation. In 49 transplant patients the following parameters were measured daily for a mean period of 25.1 days: plasma C5a [P-C5a], urine C5a [U-C5a], serum amyloid A [SAA], serum neopterin [S-NEOP] and urine neopterin [U-NEOP]. Sensitivity, specificity and day of first significant parameter increase (exceeding a cut-off level of > 50%) were evaluated retrospectively during 30 periods of rejection and 30 periods of stable graft function. U-C5a was the parameter with the highest sensitivity (84%) and specificity (84%), increasing in the mean 1.3 days before clinical diagnosis of rejection. Sensitivity and specificity of the other markers was lower: SAA 77% and 77%, U-NEOP 68% and 65%, S-NEOP 45% and 77%, and P-C5a 45% and 48%, respectively. During four instances of cytomegalovirus disease extremely high U-NEOP (> or = 1520 +/- 518 mumol/mol creatinine) and slightly increased P-C5a levels (> or = 1.5 +/- 1.4 ng/ml) occurred. Elevated urinary excretion of C5a seems to be a reliable and early marker of renal allograft rejection. In combination with SAA and U-NEOP, the daily assessment of U-C5a differentiates between viral infection and allograft rejection.

Adult↗

Assessment of metabolic liver function and hepatic blood flow during cardiopulmonary bypass.

A modified monoethylglycinexylidide (MEGX) test was performed in 14 patients undergoing myocardial revascularization to evaluate liver function during cardiopulmonary bypass (CPB). MEGX is the principal metabolite of lidocaine. Different studies have shown a decrease in MEGX formation in patients with impaired liver function. Following a low-dose bolus application of 0.3 mg/kgBW lidocaine MEGX concentrations were measured in five-minute intervals for half an hour. This was done once before and once during CPB. Arterial and hepatic vein blood samples were obtained in order to avoid the effects of hemodilution by CPB priming. Hepatic blood was calculated using the indocyanine green (ICG) infusion extraction technique. MEGX formation during CPB decreased. After the 10 and 15 minutes measurement points the mean arterio-hepatic venous concentrations were 61 +/- 7.2 micrograms/L and 63 +/- 7.3 micrograms/L respectively in comparison to pre-CPB values of 36 +/- 5.8 micrograms/L and 42 +/- 5.1 micrograms/L. Hepatic blood flow increased insignificantly from a mean of 835 +/- 54 ml/min prior to CPB to 913 +/- 83 ml/min during CPB. As a result the MEGX clearance calculated 15 minutes after administration of lidocaine bolus application did not differ significantly before (51.2 +/- 6.4 micrograms/min) and during CPB (40.2 +/- 5.7 micrograms/min). In conclusion, a decrease in MEGX formation was found during CPB. However, due to increased hepatic blood flow there was no significant change in MEGX clearance before and during CPB.

Adult↗

Loss of disgust. Perception of faces and emotions in Huntington's disease.

Face perception and emotion recognition were investigated in a group of people with Huntington's disease and matched controls. In conventional tasks intended to explore the perception of age, sex, unfamiliar face identity (Benton test) and gaze direction from the face, the Huntington's disease group showed a borderline impairment of gaze direction perception and were significantly impaired on unfamiliar face matching. With a separate set of tasks using computerinterpolated ('morphed') facial images, people with Huntington's disease were markedly impaired at discriminating anger from fear, but experienced less difficulty with continua varying from male to female, between familiar identities, and from happiness to sadness. In a further test of recognition of facial expressions of basic emotions from the Ekman and Friesen (1976) series, interpolated images were created for six continua that lay around the perimeter of an emotion hexagon (happiness-surprise; surprise-fear; fear-sadness; sadness-disgust; disgust-anger; anger-happiness). In deciding which emotion these morphed images were most like, people with Huntington's disease again showed deficits in the recognition of anger and fear, and an especially severe problem with disgust, which was recognized only at chance level. A follow-up study with tests of facially and vocally expressed emotions confirmed that the recognition of disgust was markedly poor for the Huntington's disease group, still being no better than chance level. Questionnaires were also used to examine self-assessed emotion, but did not show such striking problems. Taken together, these data reveal severe impairments of emotion recognition in Huntington's disease, and show that the recognition of some emotions is more impaired than others. The possibility that certain basic emotions may have dedicated neural substrates needs to be seriously considered: among these, disgust is a prime candidate.

Adult↗

Induction of a non-oscillating, long-lasting humoral immune response to an internal network antigen.

B lymphocyte antigen receptors form an internal idiotypic network which is also connected by idiotypic interactions with the T lymphocyte compartment. Idiotypic-anti-idiotypic activation of lymphocytes has mainly been measured at the cellular level while the kinetics of primary anti-idiotypic humoral responses has so far not been determined. Here, we describe the induction of an anti-idiotypic immune response to the major idiotype (IdOx1) of the primary immune response in BALB/c mice to the hapten 2-phenyl-t-oxazolone coupled to chicken serum albumin. A primary anti-idiotypic humoral response could be induced with the phOx-binding and IdOx1-expressing, germline-encoded antibody H11.5 (mu, kappa) coupled to keyhole limpet hemocyanin. Compared to that of conventional antigens, the anti-idiotypic response showed a lag phase of 3 weeks. When the anti-IdOx1 serum titers had declined to background levels, a secondary anti-IdOx1 response could be induced even with soluble H11.5. This response showed as fast an increase as conventional antigens, but the antibody plateau did not exceed that of the primary response. During this secondary anti-IdOx1 response and probably to a small extent also during the primary response, the mice developed an idiotypically non-related IgM-anti-phOx response. In contrast, soluble H11.5 - either passively injected or transiently expressed during the early primary anti-hapten response - suppressed the anti-idiotypic response to H11.5 for up to 7 months in the majority of mice, while individual mice exhibited an early release from this suppression at various times. The differences and similarities between external and internal antigen-induced immune responses as well as the implications for idiotypic network regulation are discussed.

Animals↗

Immunotherapy trial for horses in British Columbia with Culicoides (Diptera:Ceratopogonidae) hypersensitivity.

Immunotherapy was used to treat horses in British Columbia for Culicoides hypersensitivity. This is a severe, chronic, recurrent allergic disease of horses that results in severe irritation, large lesions, hair loss and secondary infection in the ventral midline, mane, and proximal region of the tail. A crude Culicoides extract was injected subcutaneously, in increasing doses, into 10 horses that were affected severely by the disease. Weekly doses reduced the clinical signs in 9 of the 10 horses in the 1st yr. Eight horses were treated with a maintenance dose during a 2nd yr. After the 2nd yr, 3 horses were completely free of clinical signs, 3 showed much less severe clinical signs than in untreated years, and 2 showed moderate reduction in clinical signs. Dosage, frequency of injections, and possible future applications of this technique are discussed.

Animals↗