Biomedical subjects
Publications and source records attributed to E Schmidt.
In-111 DTPA cisternography confirmed placement and patency of a slow flow, implanted, programmable, intrathecal morphine infusion pump system. Other radiologic methods failed and were impractical.
At discharge from hospital, 36 preterm infants (birthweight < 1,800 g) were randomized to be given either a standard formula or an identical formula enriched with calcium (47 vs. 80 mg/100 ml) and phosphorus (30 vs. 45 mg/100 ml) exclusively until they reached a corrected age of 3 months, thereafter beikost and other formulas were introduced into the diet. Weight, head circumference and radial and body length were measured and radial bone mineral content (BMC) and bone width (BW) determined by single photon absorptiometry at discharge, at 3 and at 6 months of corrected age. Additionally, an X-ray of the wrist was taken and serum alkaline phosphatase activity determined at discharge, and the latter repeated at 3 months. Bone mineral content, bone width, and the individual increments of both parameters were significantly higher in infants fed the enriched formula at 3 months of age, but these differences were less pronounced at 6 months.
BACKGROUND: Some clinicians administer prophylactic antibiotics routinely before laparoscopic cholecystectomy, and the results of some of the studies in the literature support this practice. We conducted a prospective randomized trial to determine whether administration of prophylactic antibiotics is necessary during routine laparoscopic cholecystectomy in low-risk patients. STUDY DESIGN: Two hundred fifty patients without evidence of acute inflammation, common duct stones, or other indications for antibiotics were randomized to receive three perioperative doses of cefazolin or no prophylaxis and followed up for complications up to 30 days postoperatively. The primary end point was the occurrence of a major infectious complication, defined as that causing a systemic response, delaying discharge, or leading to readmission. Minor infectious problems were also noted, defined as those causing local symptoms only. RESULTS: One hundred twenty-eight patients were randomized to receive prophylactic antibiotics (PA group), 122 to receive none (NONE group; two patients in this group were actually given preoperative antibiotics). Only one major complication occurred (in a patient in the NONE group), an abscess in the presence of a bile leak, despite the administration of antibiotics when the leak was discovered several days before infectious problems arose. There were four minor problems: two lower urinary tract infections and one superficial wound infection in a NONE patient and one urinary tract infection in a PA patient (not significant); all were easily managed. The prophylactic antibiotics did not sterilize the bile, and infectious complications were not associated with weight, inflammation found at the time of operation, reported stone or bile spill-age, or conversion to open operation. CONCLUSIONS: Prophylactic antibiotics are not necessary for elective laparoscopic cholecystectomy in low-risk patients.
It is necessary to clamp the renal artery for some time in renal surgery to preserve the organ. Not only the renal parenchyma but also the wall of the clamped renal artery may be damaged due to known ischaemic-reperfusion causes. Regional venous renal hypothermia induced by intracellular solutions (Sacks II, Euro-Collins) could provide protection against damage of the vessel wall caused by reperfusion or clamping in our experiments, in cases of clamping for 30 minutes, probably because it also ensured the cooling of the surface of the vessel wall. Similar vasoprotective effect could be achieved by systematic antioxidant treatment (MTDQ-DS) and regional renal hypothermia given in combination. Harmful effects of 45-minute clamping could be best avoided by applying antioxidant treatment alone. While there were no significant morphological changes in the renal arteries the persistent endothelial damage may trigger further complications like renal ischaemic condition.
It has been well known that reperfusion following ischaemia may cause functional and structural damage to not only the organ involved but also the blood vessels supplying that organ. As in organ-sparing renal surgery it is inevitable to clamp the renal artery for some time, it is expected that reperfusion, following the removing of clamping, causes structural changes in the vessel wall which may result in a decrease in arterial function. In our model experiments on animals, the left renal arteries were atraumatically clamped for 30, 45 and 60 minutes. Simultaneously with clamping, perfusion regional renal venous cooling was applied to some of the animals, together with nephrotomy. In some cases cooling was performed in combination with antioxidant treatment. On the 3rd postoperative day renal arteries from both sides were removed, the right, intact ones serving as control. Noradrenaline dose effect curves characterizing vessel contractility were determined to demonstrate functional changes. It was established that cooling the renal artery for only 30 minutes was enough to rule out the damage due to ischaemia-reperfusion. If clamping lasted for 45 minutes, venous cooling of the kidney in combination with antioxidant treatment was necessary to spare arterial function. Clamping for 60 minutes resulted in irreversible/permanent decrease in contractility even if hypothermia and antioxidant treatment were given simultaneously.
BACKGROUND: Renal angioplasty is an established therapy for treatment of renovascular hypertension. This study was performed to evaluate short- and long-term outcome of this procedure up until 3 years afterwards. PATIENTS AND METHODS: Altogether, 111 renal artery stenosis in 92 patients were dilated. Among these were 31 fibromuscular and 70 arteriosclerotic lesions, 4 transplant artery stenosis and 6 occlusions. RESULTS: The primary success rate for dilatation was approximately 90%. Serious complications occurred in 5 of the patients including 2 fatal myocardial infarctions about 2 weeks after the procedure. Restenosis (altogether 25%) almost exclusively occurred during the first few months after angioplasty (more often in arteriosclerotic lesions than in fibromuscular disease). Successful dilatation resulted in better blood pressure control. In several patients with preexisting chronic renal failure improvement of renal function was observed; in this group, however, restenosis occurred in about 1 third of the patients. CONCLUSIONS: Renal angioplasty is a suitable method for therapy of renovascular hypertension; in patients with preexisting renal failure improvement of renal function may ensue. The decision to treat with angioplasty must be weighted carefully against other established and also newer methods (surgery vs. antihypertensive medication vs. stent implantation) and should be reserved for specialized centers.
Bullous pemphigoid (BP) is an autoimmune subepidermal blistering disease with autoantibodies directed against antigens associated with hemidesmosomes of basal keratinocytes. In addition to autoantibodies and activated complement, cellular mechanisms are crucial for blister formation in this disease. Mononuclear cells, which are the first cells infiltrating BP lesions, mainly belong to CD3, CD4+ T-helper (Th) cells. Elevated concentrations of IL-2, IFN gamma, TNF beta, and IL-5 have been recently demonstrated in BP blister fluid. In this study, we were interested in levels of other Th-type cytokines, including IL-3, IL-4, IL-6, IL-10, and GM-CSF in blister fluid of BP. Cytokines were determined by ELISA or bioassay. Levels in the blister fluid from ten BP patients were compared with those in serum samples taken at the time of blister puncture and with those in suction blister fluid of ten healthy volunteers. In blister fluid of BP, we found significantly elevated concentrations of IL-4, IL-6, and IL-10 relative to both concurrent serum samples and suction blister fluid from controls. No differences were detected for either IL-3 or GM-CSF. Our results suggest that IL-4, IL-6, and IL-10 are released at the site of blister formation in BP.
Psychosocial aspects in phenylketonuric (PKU) patients are reported. In two separate studies patients with PKU differing in age (children versus adolescents), were assessed. The main message of the first prospective study on 58 10-year-old patients is that normally intelligent PKU patients who were treated early and strictly did not show a higher risk for severe emotional and behavioural maladjustment compared with healthy controls at the age of 10 years. The data were obtained in the course of the German PKU Collaborative Study by the "Personality Questionnaire for Children (PFK 9-14)". All patients received nutritional, medical, and psychological counselling every 6 months. In the second retrospective study, 34 early treated, normally intelligent adolescents with PKU (age: mean = 14.6, SD = 2.0, range = 11-18 years) and their mothers were assessed with several psychometric personality inventories and self-developed questionnaires concerning their psychosocial situation and their disease- and diet-specific knowledge. Using the Mannheimer Biographic Inventory (MBI), the Personality Questionnaire for Children (PFK 9-14), and the Freiburger Personality Inventory (FPI) the adolescent patients described their social life and their emotional development as being distinctly restricted. Their knowledge concerning disease and diet was alarmingly poor and the majority had great difficulties in satisfactory dietetic management without parental help. In addition to the burdensome diet, developmental crises like puberty may cause more frequently emotional and behavioural problems in PKU patients.
In a multicentric and interdisciplinary approach the German Collaborative Study of Children Treated for Phenylketonuria (PKU) investigates prospectively the effects of early started strict dietary treatment on the growth and development of 140 patients. The present paper focuses on longitudinal intelligence data from 4, 5 and 9 years of age of 89 patients in relation to the quality of dietary control in comparison to 200 healthy children tested by the same protocol. Cluster analysis of phenylalanine (Phe) levels distinguished a cluster of good dietary control with Phe levels according to the recommendation of maintaining Phe levels below 360 mumol/l, a cluster of poor dietary control with Phe levels greater than 600 mumol/l after the age of 3 years, and a cluster of intermediate control. Intelligence quotients (IQ) and Phe clusters were inversely related with non-significant differences between the clusters good and intermediate. On average, all three clusters scored significantly lower than healthy age peers. Mean IQ scores decreased for patients as well as for healthy children due to different tests used at different measurement occasions. Patients with poor dietary control showed a steeper decrease between 4 and 5 years than patients with better dietary control. Between 5 and 9 years IQ differences between patients and healthy children remained stable. Verbal IQs were higher than performance IQs for patients as well as for healthy children. It is concluded that after early and strict treatment during the pre-school years Phe levels, in the range observed, do not influence IQ development until the age of 9 years. IQ subscale pattern indicate that PKU results in a generalized reduction of IQ instead of disturbing specific abilities. It remains to be investigated whether higher Phe levels are also innocuous and/or may result in late effects.
The effects of short-term and long-term phenylalanine (Phe) levels on sustained attention have been investigated in phenylketonuria (PKU) patients. Two studies, one cross-sectional with 103 patients aged 8.5-9.0 years, the other with 15 adult patients following an interventional design with experimentally manipulated concurrent Phe levels are reported. The effects of concurrent Phe levels separated from long-term Phe control on sustained attention and calculation speed in simple addition tasks were investigated. Children with low concurrent Phe levels performed significantly better than children with high concurrent Phe levels when long-term dietary control was good but not when long-term control was poor. Adult PKU patients with high concurrent Phe levels showed significantly longer reaction times and lower speed in calculation than a healthy control group. Deficits were partly reversible by lowering the concurrent Phe level over a period of 4-5 weeks. The results demonstrated the impact of concurrent Phe level on neuropsychological functioning in childhood as well as in adulthood.
Bullous pemphigoid (BP) is an autoimmune subepidermal blistering disease. In addition to autoantibodies, complement activation and inflammatory cells are necessary for lesion formation. In this study, we investigated the potential involvement of IL-1, secreted by various inflammatory and non-inflammatory cells, in BP lesions. We determined IL-1 alpha IL-1 beta and IL-1 receptor antagonist in both blister fluid and concurrent serum samples of 10 BP patients by ELISAs. For comparison, we assayed experimentally generated suction blisters from 10 healthy volunteers. IL-1 beta levels were significantly elevated in BP blisters, whereas levels of IL-1 alpha were decreased relative to those in controls. In concurrent serum samples, no IL-1 alpha or IL-1 beta were detected in patients or controls. Levels of IL-1 receptor antagonist were significantly higher in BP blisters in relation to both concurrent sera and suction blisters. Our data indicate the release of IL-1 beta, IL-1 receptor antagonist, and to a lesser extent, of IL-1 alpha, at the site of blister formation in BP and support the notion that cell-mediated immune mechanisms may contribute to blister formation in this disease.
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Twenty-four untreated adolescent and adult patients with non-PKU hyperphenylalaninemia (HPA) (serum Phe levels < 600 mumol/L) and 24 healthy controls matched for age, sex, and IQ were investigated for simple motor reaction time and sustained attention, which are prolonged in patients with mild or classical phenylketonuria (PKU). Patients with HPA were of normal intelligence and did not differ significantly from healthy controls in their test results. For HPA patients, reaction times and sustained attention were not significantly influenced by serum phenylalanine concentrations. We conclude that dietary treatment is not necessary in patients with non-PKU HPA.
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Certain aminoacyl-tRNA synthetases discriminate between closely similar amino acids by hydrolytic editing reactions in the presence of their cognate tRNA. An example is the class I isoleucyl-tRNA synthetase. We recently showed that a mutation which eliminates discrimination between isoleucine (Ile) and valine (Val) in the initial amino acid binding and activation steps had little effect on the hydrolytic editing of activated valine in the presence of isoleucine tRNA (tRNA(Ile)). The results showed that initial amino acid binding and discrimination are functionally independent of tRNA-dependent amino acid discrimination. In this work, we cross-linked (to isoleucyl-tRNA synthetase) a reactive analog of valine misacylated onto tRNA(Ile). Mutation of specific residues within a peptide segment identified by the cross-linking analysis severely affected discrimination of Val-tRNA(Ile) versus Ile-tRNA(Ile). The mutationally sensitive residues are part of an insertion into the catalytic domain and are themselves completely conserved among all known prokaryotic and eukaryotic sequences of the enzyme.
As the final electron acceptor in the respiratory chain of eukaryotic and many prokaryotic organisms, cytochrome c oxidase (EC 1.9.3.1) catalyzes the reduction of oxygen to water and generates a proton gradient. To test for proton pathways through the oxidase, site-directed mutagenesis was applied to subunit I of the Rhodobacter sphaeroides enzyme. Mutants were characterized in three highly conserved regions of the peptide, comprising possible proton loading, unloading, and transfer sites: an interior loop between helices II and III (Asp132Asn/Ala), an exterior loop between helices IX and X (His411Ala, Asp412Asn, Thr413Asn, Tyr414Phe), and the predicted transmembrane helix VIII (Thr352Ala, Pro358Ala, Thr359Ala, Lys362Met). Most of the mutants had lower activity than wild type, but only mutants at residue 132 lost proton pumping while retaining electron transfer activity. Although electron transfer was substantially inhibited, no major structural alteration appears to have occurred in D132 mutants, since resonance Raman and visible absorbance spectra were normal. However, lower CO binding (70-85% of wild type) suggests some minor change to the binuclear center. In addition, the activity of the reconstituted Asp132 mutants was inhibited rather than stimulated by ionophores or uncoupler. The inhibition was not observed with the purified enzyme and a direct pH effect was ruled out, suggesting an altered response to the electrical or pH gradient. The results support an important role for the conserved II-III loop in the proton pumping process and are consistent with the possibility of involvement of residues in helix VIII and the IX-X loop.
The mitogen activated protein (MAP) kinase pathway of eukaryotes is stimulated by many growth factors and is required for the integration of multiple cellular signals. In order to study the function of MAP kinases during plant ovule development we have synthesized a Petunia hybrida ovule-specific cDNA library and screened for MAP protein kinase-related sequences using a DNA probe obtained by PCR. A full-length cDNA clone was identified (PMEK for Petunia hybrida MAP/ERK-related protein kinase) and shown to encode a protein related to the family of MAP/ERK protein kinases. Southern blot analysis showed that PMEK is a member of a small multigene family in P. hybrida. The cDNA codes for a protein (PMEK1) of 44.4 kDa with an overall sequence identity of 44% to the products of the mammalian ERK/MAP kinase gene, and the budding yeast KSS1 and FUS3 genes. PMEK1 displays 96 and 80% identity respectively with the tobacco NTF3 and Arabidopsis ATMPK1 kinases, and only 50% to the more distantly related plant MAP kinase MsERK1 from alfalfa. The two phosphorylation sites found in the loop between subdomain VII and VIII in all the other MAP kinases are also present in PMEK1. RNA gel blot and RT-PCR analyses demonstrated that PMEK1 is expressed in vegetative organs and preferentially accumulated in female reproductive organs of P. hybrida. In situ hybridization experiments showed that in the reproductive organs PMEK1 is expressed only in the ovary and not in the stamen.
BACKGROUND/AIMS: Anti-liver-kidney microsomal (LKM) autoantibodies occur in a proportion of patients with chronic hepatitis C and D infections. Because of different immunofluorescence patterns, antibodies in hepatitis C and D were termed LKM-1 and LKM-3, respectively. The aim of the present study was to evaluate the different specificities of LKM-1 and LKM-3 antibodies. METHODS: Forty-nine samples of LKM-1 sera and 16 samples of LKM-3 sera were studied for reactivity against rat and human liver microsomal proteins by immunofluorescence, enzyme-linked immunosorbent assay, and Western blot. RESULTS: Thirty-four percent of the LKM-1 sera reacted with 50-kilodalton cytochrome P4502D6 in Western blot. In addition, a proportion of the sera recognized either a 59- or 70-kilodalton antigen, and 45% of the sera did not react in Western blot. Recently, the major LKM-3 antigen was identified as an autoepitope expressed on uridine diphosphate-glucuronosyltransferases (UGT). Seven LKM-3-positive sera reacted with recombinant rabbit family one UGT. None of the anti-LKM-1-positive hepatitis C sera reacted with UGT. Antibody reactivity against liver microsomal proteins in enzyme-linked immunosorbent assay ended when antigens were pretreated with sodium dodecyl sulfate, confirming that antibodies recognize conformational epitopes. CONCLUSIONS: LKM-1 antibodies in hepatitis C are more heterogeneous and react with different antigens compared with LKM-3 antibodies in hepatitis D.