Heterozygous familial hypercholesterolemia: a new point-mutation (1372del2) in the LDL-receptor gene which causes severe hypercholesterolemia.
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Arteriosclerosis↗
Biomedical subjects
H Schmidt
Publications and source records attributed to H Schmidt.
[Prevention of joint damage in hemophilic children with early prophylaxis].
Radiological and orthopaedic outcome in severe and moderate haemophilia A and B patients undergoing long-term prophylactic treatment were prospectively investigated focusing on the age of onset of prophylaxis and the number of joint bleedings prior to treatment. We report on 21 patients with severe and moderate haemophilia A and B receiving prophylactic treatment of between 3.1 and 16.1 years duration. Three patient groups were evaluated according to the age at onset of prophylaxis. In group I (n = 8) prophylactic treatment was initiated in the first 2 years of life. Patients of group II (n = 6) received prophylaxis at the age of 3-6 years. Late-onset or secondary prophylactic treatment was started at the age of 6 years and above in 7 patients (group III). All patients received virus-inactivated F VIII or F IX concentrates at dosages of 30-40 IU, in some cases up to 50 IU/kg body weight i.v. three times per week for those with haemophilia A and twice per week for those with haemophilia B. Elbow, knee and ankle joints were investigated at 3-4 yearly intervals according to the radiological and orthopaedic scores recommended by the World Federation of Haemophilia (WFH). The total number of joint bleedings before and after start of prophylaxis were recorded in all patients. In group 17 out of 8 patients had unaffected joints with constant radiological and orthopaedic scores of zero or 1, after a median of 11.25 years of prophylactic treatment. One patient in this group demonstrated mild radiological alterations (score 4). Patients of group II showed neither radiological nor orthopaedic alterations at study entry. Worsening joint scores could be detected despite ongoing prophylaxis after the 3-year interval (median orthopaedic score 4, median radiological score 8). Treatment group III already showed considerable joint damage at study entry with a median radiological score of 11 (0-33) and a median orthopaedic score of 4 (0-11). Despite prophylactic treatment both, orthopaedic (median 8, range 2-12) and radiological scores (median 19.5, range 2-47) deteriorated after 3 years. Prior to onset of prophylaxis no or only one joint bleeding occurred in treatment group I. In group II, a median of 6 joint bleeds (range 1-8) were reported before prophylaxis was started. Patients of group III usually experienced a median of more than 10 joint haemorrhages (range 6-10 or more). Under prophylactic treatment the number of joint bleedings decreased significantly in groups II and III. However, radiological and orthopaedic scores increased as a sign of progressing osteoarthropathic alterations in patients reporting more than 6 joint haemorrhages before onset of prophylaxis whereas no joint alterations could be assessed in patients with no or only one joint bleeding episode prior to prophylaxis. Even a small number of joint bleedings seems to cause irreversible osteoarthropathic alterations leading to haemophilic arthropathy. Once apparent, further progression of joint damage could not be arrested despite of prophylactic treatment (group II and III). In order to prevent haemophilic arthropathy, effective prophylaxis should be started before or at least after the first joint bleeding in severe haemophilia A and B.
Adolescent↗
[Anesthesia for geriatric patients. Pathophysiologic considerations].
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Anesthesia↗
[Digital image archiving--concept of digital image and video documentation in ENT. A contribution to quality assurance].
BACKGROUND: Currently normal or pathologic conditions are documental by color slides, photos or videotape. However, it is more difficult to manage large numbers of images and to recall specific pictures or videos at any time. Digital record archives may be a solution for this problem. MATERIAL AND METHODS: We present a digital video and photographic archive that controls documents with a picture archive software designed for use in ENT examination units. RESULTS: Working on this digital unit we have developed a software program that allows the creation and administration of digital pictures and videos using only one program. To avoid mistakes manual recording of data was reduced to a minimum. Filing is done automatically and similar results can be found via self-explained criteria. Due to the pro-user computer software, less trained persons are not afraid to use the system. Hence, the number of documented diagnoses has increased. Present experience shows that material and videos make it easier to work with patients and clinical confidence is increased. Additionally, the physician is protected indirectly. When many persons work with one system, digital photographic archives increase the clinician's ability to refind documents, even after a period of years. The need for quality assurance in medicine will help find more use for a digital archive in ENT.
Computer Systems↗
[Cardiac chemoreflex sensitivity in relation to various forms of breathing].
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Autonomic Nervous System↗
Streptococcal meningitis: effect of CSF filtration on inflammation and neuronal damage.
The effect of CSF filtration on inflammation and neuronal damage was studied in experimental Streptococcus pneumoniae meningitis. New Zealand white rabbits received either antibiotic therapy alone (ceftriaxone i.v., 20 mg/kg bolus, 10 mg/kg maintenance dose; n = 10) or ceftriaxone plus CSF filtration (n = 11) 12 h after intracisternal infection. Immediately after the onset of antibiotic therapy 300 microliters cisternal CSF was removed, passed through a miniaturized CSF-1 filter at a constant flow of 20 microliters/min, and then reinjected. This procedure was repeated six times at intervals of 20 min. Antibiosis plus CSF filtration caused a transient reduction in CSF bacterial titers and leukocyte counts compared with antibiosis alone (P = 0.04 and 0.02 5 h after initiation of therapy). CSF lipoteichoic acid concentrations were not reduced. The concentration of neuron-specific enolase in CSF and the density of apoptotic neurons in the dentate gyrus were almost equal 12 h after the onset of treatment. Adjuvant CSF filtration accelerated the elimination of viable bacteria from CSF in comparison to antibiotic treatment alone. Parameters of neuronal destruction, however, were not reduced.
Animals↗
Total hepatectomy and liver transplantation for metastatic neuroendocrine tumors of the pancreas - a single center experience with ten patients.
BACKGROUND: Metastatic neuroendocrine pancreatic tumors have a poor prognosis. We have studied retrospectively the efficacy of liver transplantation as ultimate therapy of otherwise untreatable symptomatic neuroendocrine hepatic metastases originating in the pancreas. METHODS: We reviewed our experience of liver transplantation (LTx) for hepatic metastases of neuroendocrine pancreatic tumors in ten patients. The indication for liver grafting was seen in cases of irresectable metastases and when patients were suffering from otherwise untreatable tumor-associated symptoms due to massive hormonal release or large intra-abdominal tumor bulk. RESULTS: In four patients, the primary tumors had been removed before LTx, in five patients simultaneously with LTx and in one case 46 months after grafting. There was no operative mortality. After hepatectomy and LTx, all patients had complete relief of symptoms and all preoperatively increased hormonal levels returned to normal. In nine of ten patients, the transplant procedure had the potential for cure, whereas, in one patient, the primary tumor had remained in situ at LTx and was removed 46 months later by an R2-resection. At present, nine patients are alive with a median follow-up of 33 months (range 13.5 months to 117 months). The one patient in whom the primary tumor was removed after transplantation died due to massive intra-abdominal tumor spread 68 months after LTx. Currently, two patients are without evidence of disease, but one of them after re-operation because of lymph-node metastases 8 months after transplantation. The longest disease-free survival is now more than 7 years. In seven of nine patients, tumor recurred between 1.5 months and 48 months after transplantation. CONCLUSIONS: Patients with otherwise untreatable symptomatic neuroendocrine hepatic metastases of pancreatic origin may benefit from total hepatectomy and liver transplantation with regard to symptomatic relief and long-term survival, despite frequent recurrence of disease. In some patients, liver transplantation may even offer the chance for cure.
Disease-Free Survival↗
Shiga toxins even when different are encoded at identical positions in the genomes of related temperate bacteriophages.
The nucleotide sequence of an 11,142-bp region including the stx2 operon in the genome of the temperate bacteriophage 933W in the EDL933 strain of Escherichia coli O157 was determined and compared to the respective regions derived from other lambdoid bacteriophages. In phage 933W, a region of ORFs interlinked by overlapping start-stop codons (ATGA) was detected preceding the toxin gene. These ORFs show a high degree of sequence identity to genes of the nin region of phage lambda. Immediately downstream of these nin genes we identified an ORF that may code for an anti-terminator similar to the lambda Q protein. It is concluded that toxin expression is directly associated with the initiation of cell lysis. Downstream of the stx2 operon we identified an ORF that is homologous to the holin gene S of bacteriophage PA-2. PCR primers were designed, which, based on a comparison of the phage sequences, appeared to be common to both stx1- and stx2-harbouring phages. However, only seven of the 22 STEC strains investigated from serogroups O157, O26, O103 and O111 yielded the expected PCR amplification product. The data reported here may be useful in developing new strategies for inhibiting the expression of Stx and for developing universal diagnostic primers for use in tracking the origin and evolution of Shiga toxins and the phages that carry them.
Amino Acid Sequence↗
In situ detection of tissue factor within the coronary intima in rat cardiac allograft vasculopathy.
Cardiac allograft vasculopathy is a major cause of morbidity and mortality of cardiac transplant recipients. The underlying cause of this disease remains unclear. Histological studies have implicated accelerated hemostasis and intravascular fibrin deposition in its pathogenesis. In the present study a defined model of this disease in the rat was used to elucidate the implication of tissue factor in the production of the hypercoagulable state observed in cardiac allograft vessels. Tissue factor protein and mRNA expression were studied in rat heart allografts developing allograft vasculopathy resembling human disease. Immunohistochemistry demonstrated tissue-factor-positive cells present in the allograft coronary intima and adventitia. Significant staining for tissue factor was detected in the endothelium lining coronary lesions in cardiac allografts and in interstitial mononuclear cells, respectively. Both transplant coronary endothelial cells and mononuclear cells contained tissue factor mRNA as indicated by oligo-cell reverse transcription polymerase chain reaction after laser-assisted cell picking. In contrast, tissue factor mRNA and protein were not or negligibly detectable within the coronary intima of nontransplanted control hearts. Thus, the present study clearly demonstrates that aberrant tissue factor expression occurs within the coronary intima after cardiac transplantation. Tissue factor, activating downstream coagulation mechanisms, may account for the intravascular clotting abnormalities observed in cardiac allografts and may represent a key factor in transplant atherogenesis.
Animals↗
The structure of specific phobia symptoms among children and adolescents.
Previous research [Frederikson, M., Annas, P., Fisher, H. & Wik, G. (1996). Gender and age differences in the prevalence of specific fears and phobias. Behaviour Research and Therapy, 34, 33-39.] has shown that specific phobia symptoms of adults cluster into three subtypes: animal phobia, blood-injection-injury phobia and environmental-situational phobia. The present study examined whether these specific phobia subtypes can also be found in children. 996 children aged between 7 and 19 years completed a brief questionnaire regarding the frequency with which they experienced specific phobia symptoms. Confirmatory factor analysis was employed to examine the structure of these data. Results showed that childhood specific phobia symptoms indeed cluster into the three subtypes as described by Frederikson et al. and that these subtypes are either intercorrelated or the product of a single higher order factor. This structure appeared to be largely invariant across genders and age groups.
Adolescent↗
Disgust sensitivity, trait anxiety and anxiety disorders symptoms in normal children.
There is evidence to suggest that disgust sensitivity plays a role in the development of small animal fears and phobias. Recently, Phillips, Senior, Fahy, and David (1998) [Phillips, M. L., Senior, C., Fahy, T., & David, A. S. (1998). Disgust: the forgotten emotion of psychiatry. British Journal of Psychiatry, 172, 373-375.] suggested that disgust sensitivity is also involved in various other anxiety-based symptoms (e.g. obsessive-compulsive complaints, social phobia). The present study sought to test this suggestion in a large sample of normal school children (N = 189). Children completed a measure of disgust sensitivity, the trait anxiety version of the Spielberger State-Trait Anxiety Inventory for Children and the Screen for Child Anxiety Related Emotional Disorders, an instrument that measures DSM-defined anxiety disorders symptoms. Disgust sensitivity was indeed found to be correlated with a broad range of anxiety disorders symptoms. However, results also indicated that these correlations were predominantly carried by trait anxiety. That is, when controlling for levels of trait anxiety, only specific phobia symptoms (including animal phobia, blood-injection-injury phobia and situational-environmental phobia) and separation anxiety disorder symptoms were significantly related to disgust sensitivity, although correlations were rather modest. Taken together, these findings cast doubts on the claim that disgust sensitivity is an unique and independent factor that contributes to a broad range of anxiety disorders.
Adolescent↗
Selective targeting of somatostatin receptor 3 to neuronal cilia.
Recently, five members of the somatostatin receptor family have been cloned. However, little is known about their cellular and subcellular localization in the central nervous system. Using specific anti-peptide antisera, we observed somatostatin receptor 3-like immunoreactivity in many brain regions, including the cerebral cortex, hippocampus, hypothalamus, amygdala and cerebellum. In all of these regions (except for the cerebellar cortex), somatostatin receptor 3-like immunoreactivity was selectively targeted to 4-8-microm-long rod-shaped profiles which did not co-localize with axonal or dendritic markers. One immunoreactive profile was always associated with one neuronal cell body. This staining pattern was resistant to colchicine treatment and showed a closely overlapping distribution with somatostatin receptor 3 messenger RNA, suggesting that the receptor protein is not transported over long distances. Electron microscopic analysis revealed that somatostatin receptor 3-like immunoreactivity is localized to the plasma membrane of neuronal cilia which extended into an intercellular pocket and showed a 9+0 filament pattern in their basal body and proximal segments. Thus, somatostatin receptor 3 demonstrates a unique example of a G-protein-coupled receptor not localized to "classical" pre- or postsynaptic sites, but selectively targeted to neuronal cilia. The presence of the somatostatin receptor 3 receptor on neuronal cilia suggests that these presumably non-motile cilia may not merely represent developmental remnants, but rather function as chemical sensors of the immediate milieu.
Amino Acid Sequence↗
Epidemiology and diagnosis of Shiga toxin-producing Escherichia coli infections.
Shiga toxin-producing Escherichia coli (STEC) have been identified as a worldwide cause of serious human gastrointestinal disease and the life-threatening hemolytic uremic syndrome. The most common serotype implicated is E. coli O157: H7, but infections involving various non-O157 serotypes have been found with increasing frequency in many countries. Food-borne outbreaks caused by STEC can affect large numbers of people and cause serious morbidity, making the bacteria one of the most important emerging pathogens. Because there is no specific treatment of the disease currently available, there is an urgent need for effective preventive measures based on a detailed understanding of the epidemiology of STEC infections. Such measures will also be dependent on the availability of rapid, sensitive, and simple procedures for the detection of the pathogens both in human samples and in samples of nonhuman origin such as food. This review summarizes the current knowledge on the epidemiology of STEC infection and presents a survey of laboratory methods currently available for diagnosis of STEC. Special attention is given to new diagnostic procedures for the less readily detectable non-O157 STEC strains and to simple procedures, usually based on commercially available kits, that can be used in routine clinical microbiological laboratories.
Adult↗
Transverse conduction capabilities of the crista terminalis in patients with atrial flutter and atrial fibrillation.
OBJECTIVES: In this study, the transverse conduction capabilities of the crista terminalis (CT) were determined during pacing in sinus rhythm in patients with atrial flutter and atrial fibrillation. BACKGROUND: It has been demonstrated that the CT is a barrier to transverse conduction during typical atrial flutter. Mapping studies in animal models provide evidence that this is functional. The influence of transverse conduction capabilities of the CT on the development of atrial flutter remains unclear. METHODS: The CT was identified by intracardiac echocardiography. The atrial activation at the CT was determined during programmed stimulation with one extrastimulus at five pacing sites anteriorly to the CT in 10 patients with atrial flutter and 10 patients with atrial fibrillation before and after intravenous administration of 2 mg/kg disopyramide. Subsequently, atrial arrhythmias were reinduced. RESULTS: At baseline, pacing with longer coupling intervals resulted in a transverse pulse propagation across the CT. During shorter coupling intervals, split electrograms and a marked alteration of the activation sequence of its second component were found, indicating a functional conduction block. In patients with atrial flutter, the longest coupling interval that resulted in a complete transverse conduction block at the CT was significantly longer than that in patients with atrial fibrillation (285 +/- 49 ms vs. 221 +/- 28 ms; p < 0.05). After disopyramide administration, a transverse conduction block occurred at longer coupling intervals as compared with baseline (287 +/- 68 ms vs. 250 +/- 52 ms; p < 0.05). Subsequently, a sustained atrial arrhythmia was inducible in 15 of 20 patients. This was atrial flutter in three patients with previously documented atrial fibrillation and in eight patients with history of atrial flutter. Mapping revealed a conduction block at the CT in all of these patients. CONCLUSIONS: It was found that the CT provides transverse conduction capabilities and that the conduction block during atrial flutter is functional. Limited transverse conduction capabilities of the CT seem to contribute to the development of atrial flutter.
Aged↗
Influence of epinephrine and norepinephrine on intestinal villous blood flow during endotoxemia.
PURPOSE: The objective of this study was to determine the effects of epinephrine and norepinephrine on mucosal villous blood flow in a normotensive model of endotoxemia. MATERIALS AND METHODS: Thirty-two anesthetized rats were laparotomized, and a jejunal portion was exteriorized and opened by an antimesenteric incision. The jejunal segment was fixed on a plexiglass stage with the mucosal surface upward. Microcirculatory parameters were assessed by intravital videomicroscopy. The animals were randomly assigned to receive one of four treatments: infusion of Escherichia coli lipopolysaccharides (LPS, 2 mg/kg/h) without catecholamine pretreatment (LPS group); or infusion of LPS with epinephrine pretreatment (0.2 microg/kg/min, start 30 minutes before LPS infusion) (E group), or infusion of LPS with norepinephrine pretreatment (0.2 microg/kg/min, start 30 minutes before LPS infusion) (NE group). The control group did not receive either catecholamines or LPS. Mean diameter of central arterioles (D(A)) and mean erythrocyte velocity within the arterioles (V(E)) were measured 30 minutes before and at 0, 60, and 120 minutes after induction of endotoxemia. Mucosal villous blood flow was calculated from D(A) and V(E). RESULTS: LPS infusion alone and norepinephrine plus LPS infusion led to a significant vasoconstriction of central arterioles, which was associated with a similar decrease in mucosal villous blood flow. Epinephrine infusion alone led to a vasodilation and an increase in villous blood flow within the first 30 minutes. After induction of endotoxemia, D(A) returned to baseline values and villous blood flow was as low as in the LPS and the norepinephrine group after 120 minutes. CONCLUSION: In this experimental rat model, the catecholamines epinephrine and norepinephrine in a dosage of 0.2 microg.kg(-1).min(-1) neither diminish nor improve mucosal villous blood flow during the early phase of endotoxemia.
Animals↗
Biochemical modulation of 5-fluorouracil by leucovorin with or without interferon-alpha-2c in patients with advanced colorectal cancer: final results of a randomised phase III study.
5-Fluorouracil (5-FU) remains the mainstay of treatment for advanced colorectal carcinoma, although response rates are generally less than 20%. Improved therapeutic efficacy has been reported using biochemical modulation of 5-FU by leucovorin (LV) or interferon alpha (IFN), the combination of 5-FU/LV frequently considered as standard therapy in metastatic colorectal cancer. In an attempt to enhance the cytotoxicity of 5-FU, a prospective randomised trial was initiated to compare 5-FU/LV with 5-FU/LV plus IFN. Patients were randomised to receive either LV, 100 mg/m2 intravenously (i.v.), followed by 5-FU, 500 mg/m2 as a 1-h i.v. infusion, daily for 4 days, followed by weekly infusions until week 8, or the same regimen of 5-FU/LV plus IFN-alpha-2c, 30 micrograms subcutaneously (s.c.), three times weekly. Cycles were repeated after a 2-week rest period. Among 269 enrolled patients, 219 were available for response and 243 for toxicity. An objective tumour response was observed in 38 of 107 (36%) and 28 of 112 (25%) patients in the treatment arms with and without IFN, respectively (difference not significant). There was no significant difference between the two groups in response duration (median 8.4 versus 12.1 months), time to treatment failure (median 6.5 versus 4.9 months), or overall survival (median 10.0 versus 12.6 months). However, patients in the IFN arm experienced significantly more haematological and gastrointestinal toxicity and more frequent alopecia. In conclusion, the addition of IFN to 5-FU/LV in the schedules and doses used in the study did not provide any clinical benefit over 5-FU/LV alone and cannot be recommended for routine use in the treatment of advanced colorectal cancer.
Adult↗
Intravenous granulocyte colony-stimulating factor increases the release of tumour necrosis factor and interleukin-1beta into the cerebrospinal fluid, but does not inhibit the growth of Streptococcus pneumoniae in experimental meningitis.
Granulocyte colony-stimulating factor (G-CSF) possesses an antimicrobial effect in several animal models of infection. To evaluate a possible effect of G-CSF on the course of pneumococcal meningitis, rabbits infected intracisternally (i.c.) with Streptococcus pneumoniae type 3 (n = 7) received 50 microgram/kg of rhG-CSF intravenously (i.v.) 1 h prior to infection. Seven infected animals served as controls. Uninfected rabbits received 10 microgram of G-CSF (n = 3), 2 microgram G-CSF (n = 3) or saline (n = 3) i.c. G-CSF injected i.c. did not produce cerebrospinal fluid (CSF) leucocytosis. Compared with the control group, i.v. G-CSF given prior to i.c. infection increased the percentage of granulocytes in blood 6 h and 12 h after infection. Twelve hours after infection, CSF tumour necrosis factor (TNF) activity and CSF interleukin (IL)-1beta concentrations were significantly higher in G-CSF-treated animals. G-CSF did not decrease bacterial growth in the subarachnoid space and the CSF leucocyte densities were not influenced. At 24 h after infection, G-CSF did not reduce the CSF concentrations of neurone-specific enolase and the density of apoptotic neurones in the dentate gyrus of the hippocampus. In conclusion, i.v. G-CSF increased the concentration of pro-inflammatory cytokines in the CSF but did not decrease the growth of Streptococcus pneumoniae in the subarachnoid space.
Animals↗
Five-year-survey of invasive aspergillosis in a paediatric cancer centre. Epidemiology, management and long-term survival.
The epidemiology, management, and long-term survival of invasive aspergillosis was assessed in a prospective, 5-year observational study in 346 unselected paediatric cancer patients receiving dose-intensive chemotherapy for newly diagnosed or recurrent malignancies. Invasive aspergillosis occurred exclusively in the context of haematological malignancies, where it accounted for an incidence of 6.8% (n = 13 of 189). The lung was the primary site in 12 cases, and dissemination was present in three of those. Prior to diagnosis, the overwhelming majority of patients had been profoundly neutropenic for at least 14 days (n = 11 of 13) and were receiving systemic antifungal agents (n = 10 of 13). Clinical signs and symptoms were nonspecific but always included fever. All 11 patients who were diagnosed and treated during lifetime for a minimum of 10 days responded to either medical or combined medical and surgical treatment, and seven were cured (64%). Nevertheless, the overall long-term survival was merely 31% after a median follow-up of 5.68 years after diagnosis. Apart from refractory or recurrent cancer, the main obstacles to successful outcome were failure to diagnose IA during lifetime and bleeding complications in patients with established diagnosis. The frequency of invasive aspergillosis of greater than 15% in paediatric patients with acute myeloblastic leukaemia and recurrent leukaemias warrants the systematic investigation of preventive strategies in these highly vulnerable subgroups.
Adolescent↗