Biomedical subjects
Publications and source records attributed to M Weiss.
This is a case report of an unusual cause of Potter sequence. Autopsy showed lethal pulmonary hypoplasia in association with a transverse vaginal septum, hydrocolpos, and a secondary obstructive uropathy.
Diabetic neuropathy is thought to comprise a reversible metabolic and an irreversible structural component of neuronal abnormality. To study whether cardiac sympathetic dysinnervation in poorly controlled longer-term Type 1 Diabetes Mellitus (DM) without myocardial perfusion abnormalities is partially reversible with improved metabolic control, 123-I-metaiodobenzylguanidine (123-I-MIBG) scintigraphy (myocardial uptake score 1-6) was performed in 11 Type 1 DM patients (HbA1c 12.0 +/- 1.8%, duration of diabetes 10 +/- 4 yrs) one year after initial assessment. During follow-up, all patients had been treated with intensive insulin therapy and at one year, HbAlc had fallen to 8.4 +/- 1.4% (p < 0.01). The global myocardial 123-I-MIBG uptake score had improved in 5 patients at one year, remained unchanged in 5 patients, and deteriorated in 1 patient. Cardiac sympathetic dysinnervation (123-I-MIBG myocardial uptake (MU) score >2), initially observed in 10 patients, was detectable in 8 patients at follow-up. Myocardial uptake scores of the anterior, lateral, posterior, septal and apical region had improved in 6, 6, 6, 7 and 6 patients, but the mean changes of these scores did not reach significance. In patients with substantial improvement of metabolic control (HbAlc 7.3 +/- 0.6% at one year, mean HbA1c of months 2-12: 7.8%, n = 6), global myocardial uptake had improved from 4.3 +/- 1.0 to 3.2 +/- 1.0 (p < 0.05). Respectively, myocardial uptake score of the anterior, posterior and septal region had ameliorated: 3.8 +/- 1.3 vs 2.3 +/- 0.8 (p < 0.05), 4.0 +/- 1.7 vs 2.5 +/- 1.0 (p < 0.05), 4.3 +/- 1.2 vs 3.2 +/- 1.5 (p < 0.05). In conclusion, cardiac sympathetic dysinnervation in poorly controlled longer-term Type 1 DM patients is dominated by irreversible neuronal abnormalities. Substantial metabolic improvement, however, partially restores cardiac sympathetic dysinnervation, indicating the presence of a reversible component of cardiac sympathetic dysfunction in longer-term Type 1 DM.
A laparoscopic technique for splenopexy of a wandering spleen using an absorbable mesh in an adult woman is described for the first time. This patient was referred to surgery because of recurrent biliary colic secondary to cholecystolithiasis. The wandering spleen had been diagnosed at least 4 years earlier, but a conservative approach had been adopted for a symptomless patient. Laparoscopic cholecystectomy was performed concomitantly with splenopexy. Laparoscopic splenopexy seems a feasible and safe procedure, especially when performed by experienced laparoscopic surgeons.
X-linked lymphoproliferative disease (XLP) is a primary immunodeficiency, which most often manifests itself after Epstein-Barr virus (EBV) infection. The main clinical phenotypes include fulminant or fatal infectious mononucleosis, dysgammaglobulinaemia and malignant lymphoma. We have recently cloned the SH2D1A gene, which has been shown to be mutated in approximately 70% of XLP patients. Now we report five novel SH2D1A mutations in patients from five unrelated XLP families. No mutations were found in another three XLP families. In three boys with early onset non-Hodgkin lymphoma (NHL) from two unrelated families a deletion of SH2D1A exon 1 and a splice site mutation were found, respectively. These patients did not show any laboratory or clinical signs of a previous EBV infection. A fourth EBV-uninfected and unrelated boy with a stop mutation in the SH2D1A gene shows only signs of dysgammaglobulinaemia. Development of dysgamma-globulinaemia and lymphoma without evidence of prior EBV infection in four of our patients suggests that EBV is unrelated to these phenotypes, in contrast to fulminant or fatal infectious mononucleosis. The role of SH2D1A as a putative tumour suppressor gene remains to be investigated.
BACKGROUND: Morphine is metabolized to two major metabolites, morphine-3-glucuronide and morphine-6-glucuronide (M6G). Under the conditions of long-term oral morphine administration, the accumulation of M6G may contribute to the analgesic effects, but it may also cause respiratory depression. METHODS: Five healthy male volunteers (ages 25-34 yr) received 90 mg MST (morphine sulfate 5H2O sustained-released tablet, equivalent to 67.8 mg oral morphine). Multiple plasma and urine samples were taken for as long as 14 and 36 h, respectively. Individual pharmacokinetics after intravenous administration of morphine and M6G were available from a previous investigation. A new model that considers the M6G-plasma profile as a sum of the input from the first-pass metabolism of morphine and the input from systemically available morphine was applied to the plasma concentration versus time curves of M6G. The concentrations of M6G at the effect site after long-term morphine administration were simulated. RESULTS: The fraction of morphine absorbed from the gut was 82+/-14%. Of this, 42+/-8% passed through the liver, resulting in an oral bioavailability of morphine of 34+/-9%. Of the total amount of M6G, 71+/-7% was formed during the first-pass metabolism, and 29+/-7% was formed by metabolism of systemic morphine. After 36 h, the amounts of M6G and morphine excreted in the urine were 92+/-17% and 9+/-3%, respectively. Simulation of effect-site concentrations of M6G indicated that after multiple oral dosing of morphine in patients with normal liver and renal function, M6G might reach concentrations two times greater than that of morphine. CONCLUSIONS: M6G may contribute to the analgesic and side effects seen with long-term morphine treatment. The current model of morphine and M6G pharmacokinetics after oral administration of morphine may serve as a pharmacokinetic basis for experiments evaluating the analgesic contribution of M6G with long-term oral dosing of morphine.
BACKGROUND: The insertion of a chest drain into the pleural space is a common procedure used for treatment in various intrathoracic abnormalities. Recently, a new technique for chest-tube insertion for pleural cavity drainage, using the disposable endoscopic trocar-cannula, was described for the treatment of some pathologic conditions. METHODS: In a prospective study, we used this technique in the treatment of patients with chest trauma, spontaneous and iatrogenic pneumothorax, and various kinds of pleural effusion. RESULTS: One hundred twelve patients were treated by using the endoscopic trocar-cannula for tube insertion into the pleural cavity. Among them, 39 patients were treated after blunt and penetrating chest trauma. Most cannulae were of 10 to 11 mm in diameter, which enabled the insertion of large-bore drain tubes. In five trauma patients, chest-tube insertion was done successfully without antecedent chest x-ray films. The complication rate was 0.89% for intrapulmonary positioning of a chest tube in a patient who had previous ipsilateral thoracic surgery. CONCLUSION: The use of endoscopic trocar-cannulae for chest-tube insertion is a safe, simple, and effective technique for management of trauma and other diverse intrathoracic abnormalities. Its use outside the hospital should be further studied.
The influence of increased training on the sympathoadrenergic system was investigated. Moderately trained male subjects (n = 15) increased their training within 10 wk by 60%; eight of the subjects increased their training volume, and seven increased their training intensity. Before and after the training, an exhaustive treadmill exercise was carried out. Acute treadmill exercise increased beta-adrenergic receptor number on mononuclear lymphocytes, isoproternol-stimulated cAMP production, and plasma catecholamine concentration. The increase of receptor number can at least partially be explained by a changed lymphocyte composition at rest and after exercise. After training, the exercise-induced increase of beta-adrenergic receptor number was significantly blunted, and the exercise-induced increase of the isoproternol-stimulated cAMP production per beta-receptor was enhanced. Subjects who experienced increased symptoms of physical discomfort and/or mood changes showed an enhanced cAMP production after training. These findings point to an altered regulation of the receptor and postreceptor mechanisms as an effect of a 10-wk period of hard training.
The RATEMA project is an international cooperation between the University of Ulm in Germany and the Urals Research Centre for Radiation Medicine in Chelyabinsk, Russia. For one year we conducted weekly conferences between the two sites, based on a satellite link with a 384 kbit/s connection. During the videoconferences the physicians on both sides--experts in radiation medicine--discussed the health status of Russian patients who had been chronically exposed to ionizing radiation in the South Urals region. The German partners presented patients with comparable haematological and oncological diseases. The project has shown the advantages and difficulties of working in an international and interdisciplinary environment. The experience gained has been very valuable for planning new projects with similar tasks. The results and the contents of the RATEMA database are the basis for education and research for physicians involved in the management of radiation victims.
BACKGROUND: Neonatal sepsis is a common and life-threatening disorder, particularly among preterm infants. Early initiation of antibiotic therapy is frequently delayed because the first clinical signs of sepsis are non-specific and there are no reliable early laboratory indicators. We investigated the time course of expression and the prognostic power of the early inflammatory mediators interleukin-1 receptor antagonist (IL-1ra), interleukin-6 (IL-6), and circulating intercellular adhesion molecule-1 (cICAM-1) before clinical diagnosis of sepsis. METHODS: In a prospective multicentre study, we monitored 182 very-low-birthweight infants in six intensive-care units for occurrence of sepsis. During routine or clinically indicated blood sampling, an additional sample was collected for measurement of IL-1ra, IL-6, cICAM-1, and C-reactive protein (CRP). Infants were grouped into those with proven sepsis, no infection, or unclassified. The mean study duration was 34 days. Whenever sepsis occurred, a study period of 10 days was defined: day 0 was the day of clinical diagnosis of sepsis; days -4 to -1 were the 4 days before diagnosis; days +1 to +5 were the 5 days after. We compared the concentrations of the immune mediators during the 10-day study period with group-specific baseline values from before day -4. FINDINGS: 101 infants were included in the analysis: 21 with proven sepsis, 20 with no infection, and 60 unclassified. We excluded 57 because of incomplete datasets and 24 who had early-onset sepsis. IL-1ra and IL-6 increased significantly 2 days before diagnosis of sepsis; maximum median increases within the study period were 15-fold for IL-1ra and 12-fold for IL-6. The diagnostic sensitivities of IL-1ra, IL-6, and CRP concentrations on day 0 of diagnosis were 93%, 86%, and 43%, respectively; corresponding values on day -1 were 64%, 57%, and 18%. The specificities of IL-1ra, IL-6, and CRP concentrations were 92%, 83%, and 93%. cICAM-1 had a specificity of only 64%. INTERPRETATION: IL-1ra and IL-6 are superior to cICAM-1 and CRP as predictors of sepsis 1 or more days before clinical diagnosis. Ad-hoc measurement of these cytokines could allow earlier initiation of antibiotic therapy with corresponding improvement in outcome in very-low-birthweight infants with sepsis.
We study the sorption of colloids on equally charged surfaces. Our focus is on the time scale from hours to weeks, where adsorption is not an irreversible process but interplays with (spontaneous) desorption. Using model calculations, we show how the desorption kinetics is influenced by readsorption, a potential barrier, a secondary potential minimum, local variation of the potential, and bond aging. In the experimental part we present results of in situ observation of the sorption kinetics of polystyrene latex particles onto a glass surface. Combining the evanescent field method with video microscopy, we were able to identify the particle arrival and departure times individually and therefrom determine the adhesion time distribution function. The nonexponentiality of this function can be explained by a gamma distribution of the potential depth at the binding sites as well as by logarithmic bond aging. Copyright 1998 Academic Press.
In our present work we present the determination of bovine lactoferrin in whey concentrates as they are typically produced by milk and cheese industry after production of cheese. Due to the high total protein content the analysis of whey concentrate samples is difficult and even not possible by using capillary zone electrophoresis with UV detection. To enhance the detection sensitivity we applied a more promising approach by using affinity interactions in combination with laser-induced fluorescence detection. By mixing fluoresceine isothiocyanate (FITC)-conjugated polyanionic lipopolysaccharide with the mostly positively charged lactoferrin we found a significant migration time shift which is clearly dependent on the concentration of the added protein. In the second approach we developed an immunoassay using FITC-conjugated specific antibody against bovine lactoferrin. The results of the immunoassay measurements were compared with data obtained by standard enzyme-linked immunosorbent assay analysis.
To study the viscoelastic behavior of antibody films on a surface acoustic wave device, we have measured the influence of multiple layers of antibodies onto the propagation of the wave. Attenuation and sound velocity variation caused by up to 20 layers have been measured. The results can be interpreted with the propagation of a viscously damped Love wave in a film with an extremely low velocity of sound. From our results, we conclude that, for the one- or two-layer films normally used in acoustic wave immunosensing, a pure mass effect is dominant. For thick films, a saturation of the sensor response is observed.
We describe a new cystatin in both mice and humans, which we termed leukocystatin. This protein has all the features of a Class II secreted inhibitory cystatin but contains lysine residues in the normally hydrophobic binding regions. As determined by cDNA library Southern blots, this cystatin is expressed selectively in hematopoietic cells, although fine details of the distribution among these cell types differ between the human and mouse mRNAs. In addition, we have determined the genomic organization of mouse leukocystatin, and we found that in contrast to most cystatins, the leukocystatin gene contains three introns. The recombinant proteins corresponding to these cystatins were expressed in Escherichia coli as N-terminal glutathione S-transferase or FLAGTM fusions, and studies showed that they inhibited papain and cathepsin L but with affinities lower than other cystatins. The unique features of leukocystatin suggests that this cystatin plays a role in immune regulation through inhibition of a unique target in the hematopoietic system.
HISTORY AND CLINICAL FINDINGS: A medical examination, undertaken in an apparently healthy 30-year-old man because of his occupational exposure to chemicals, revealed haematuria and proteinuria. Physical examination was unremarkable except for oral hair-leukoplakia and swelling of the cervical, supraclavicular, axillary and inguinal lymph nodes. INVESTIGATIONS: Examination of the urine demonstrated selective glomerular proteins (1.5 g/24 h) and dysmorphic erythrocytes. SGOT and SGPT activities were raised (73 and 129 IU/l, respectively). Active hepatitis B virus (HBV) and human immunodeficiency virus (HIV-1) infections were demonstrated virologically. The CD4+ count in blood was reduced to 200 cells/microliter. Renal biopsy showed an IgA nephropathy. TREATMENT AND COURSE: Antiretroviral treatment with zidovudine and lamivudine were started. SGOT and SGPT activities and HIV load fell steadily, while CD4+ cell count rose markedly. Renal functions have remained stable during the past 6 months. CONCLUSION: Signs of glomerular damage are not unusual in systemic diseases, tumors or infections (Hepatitis B and HIV in this case) and they may be the first manifestations of the underlying disease.
Fast and reproducible separation and determination of amino acids serves the economical and reliable characterization and quantification of peptides and proteins as well as the identification of proteins by amino acid composition analysis on a large-scale. A prerequisite of a successful compositional analysis is a complete hydrolysis of the peptides and proteins and a quantitative recovery of the residues in the hydrolyzate. We investigated the effect of different acid-hydrolysis methods on the compositional analysis of known proteins in solution and after blotting onto polyvinylidene difluoride membranes and worked out the conditions for the processing of large numbers of samples. The reliability of each method was studied by introducing the analysis data into the AACompIdent software and deducing the protein identification scores. All acid-hydrolysis methods delivered reliable analysis data. The most accurate data were provided by conventional, thermal hydrolysis of proteins in solution in the presence of methanesulfonic acid, closely followed by hydrolysis with hydrochloric acid and microwave radiation-dependent hydrolysis with hydrochloric or methanesulfonic acid, respectively. For blotted proteins, conventional hydrolysis delivered more accurate analysis data in comparison with the microwave radiation-induced hydrolysis. The extraction of the residues from the membrane hydrolyzate was a critical step for unambiguous protein identification. Microwave radiation-induced hydrolysis was responsible for a higher degree of racemization of the residues.
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Chemokines are key molecules in directing leukocyte migration toward sites of inflammation. We have previously cloned a putative CC chemokine receptor gene, TER1, whose expression is restricted to lymphoid tissues and cell lines. Recently, this receptor has been shown to signal in response to the human CC chemokine I-309 and thus it has been renamed CCR8 according to the current nomenclature. In the present study, we report the identification of the CC chemokines thymus and activation-regulated cytokine (TARC) and macrophage inflammatory protein-1 beta (MIP-1 beta) as CCR8 ligands, as they induce chemotaxis in CCR8 Jurkat stable transfectants. Furthermore, we have generated a polyclonal antiserum that is able to recognize the CCR8 molecule in transfectant lysates. The pattern of CCR8 mRNA expression and the functional effects exerted by its ligand suggest that the triggering of this receptor may regulate multiple functions including activation, migration and proliferation of lymphoid cells.
The enterohepatic circulation of thyroxine (T4) and triiodothyronine (T3) is higher in thyrotoxicosis. Bile-salt sequestrants bind iodothyronines and thereby increase their fecal excretion. We, therefore, evaluated the effect of colestipol-hydrochloride administration on clinical and biochemical indices of patients with hyperthyroidism. In a prospective, controlled trial, ninety-two adult volunteers with Graves' disease, toxic autonomous nodule or toxic multinodular goiter were randomly assigned into the following treatment protocols: Group 1, 30 mg of methimazole (MMI) and 20 g of colestipol-hydrochloride (COL) daily; Group 2, 30 mg of MMI daily; and Group 3, 15 mg of MMI 20 g of COL daily. The patients were further classified into Group A, severe hyperthyroidism (baseline levels of total T3 (TT3) > or =5 nmol/l) and Group B, mild to moderate thyrotoxicosis (baseline levels of TT-3<5 nmol/l). Crook's clinical index, serum free T4 (FT4), TT3 and thyroid stimulating hormone (TSH) levels were determined before (WO), following one week (W1) and two weeks (W2) of treatment. Serum TT3 level decreased (mean+/-SE) at W1 by 40.8+/-2.6% of WO in Group1 and by 29.2+/-2.4% in Group 2 (p<0.001), and down further to 47.8+/-3.0% at W2 in Group 1, and 40.6+/-2.8% in Group 2 (p=0.01). Serum FT4 level decreased (mean+/-SE) from WO to W1 by 31.7+/-2.7% in Group 1 and by 16.2+/-3.1% in Group 2 (p=0.005), and down to 49.1+/-2.8% of WO at W2 in Group 1 and to 38.7+/-3.5% in Group 2 (p=0.07). In sub groups B COL was not effective in reducing thyroid hormone levels nor in ameliorating the clinical status of the patients. However, in Group A3 COL lowered FT4 (p=0.001) and TT3 (p=0.05) levels as compared to group A2. At W2 the clinical hyperthyroidism score improved faster in Group A1 (p<0.001) and Group A3 (p=0.012) as compared to the control Group A2. In conclusion, COL is an effective and well tolerated adjunctive agent in the treatment of hyperthyroidism. Its main effect is in severe cases of thyrotoxicosis, and in the first phase of treatment. As adjunctive COL treatment in hyperthyroidism allows reducing MMI dosage it may decrease the rate of dose dependent MMI side effects.