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Biomedical subjects

F Schneider

Publications and source records attributed to F Schneider.

At least 91 records · Page 5Linked to original sources

Variant human immunodeficiency virus type 1 proteases and response to combination therapy including a protease inhibitor.

The objective of this observational study was to assess the genetic variability in the human immunodeficiency virus (HIV) protease gene from HIV type 1 (HIV-1)-positive (clade B), protease inhibitor-naïve patients and to evaluate its association with the subsequent effectiveness of a protease inhibitor-containing triple-drug regimen. The protease gene was sequenced from plasma-derived virus from 116 protease inhibitor-naïve patients. The virological response to a triple-drug regimen containing indinavir, ritonavir, or saquinavir was evaluated every 3 months for as long as 2 years (n = 40). A total of 36 different amino acid substitutions compared to the reference sequence (HIV-1 HXB2) were detected. No substitutions at the active site similar to the primary resistance mutations were found. The most frequent substitutions (prevalence, >10%) at baseline were located at codons 15, 13, 12, 62, 36, 64, 41, 35, 3, 93, 77, 63, and 37 (in ascending order of frequency). The mean number of polymorphisms was 4.2. A relatively poorer response to therapy was associated with a high number of baseline polymorphisms and, to a lesser extent, with the presence of I93L at baseline in comparison with the wild-type virus. A71V/T was slightly associated with a poorer response to first-line ritonavir-based therapy. In summary, within clade B viruses, protease gene natural polymorphisms are common. There is evidence suggesting that treatment response is associated with this genetic background, but most of the specific contributors could not be firmly identified. I93L, occurring in about 30% of untreated patients, may play a role, as A71V/T possibly does in ritonavir-treated patients.

Adult↗

Comparison of DNA sequencing and a line probe assay for detection of human immunodeficiency virus type 1 drug resistance mutations in patients failing highly active antiretroviral therapy.

The resistance of human immunodeficiency virus type 1 (HIV-1) to drugs is a major cause of antiretroviral treatment failure. We have compared direct sequencing to a line probe assay (LiPA) for the detection of drug resistance-related mutations in 197 clinical samples, and we have investigated the sequential appearance of mutations under drug pressure. For 26 patients with virological failure despite the use of two nucleoside analogues and one protease inhibitor (indinavir [n = 6], ritonavir [n = 10], and saquinavir [n = 10]), genotypic resistance assays were carried out retrospectively every 3 months for up to 2 years by using direct sequencing (TruGene; Visible Genetics) and a LiPA for detection of mutations in the reverse transcriptase (INNO-LiPA HIV-1 RT; Innogenetics) and the protease (INNO-LiPA HIV Protease, prototype version; Innogenetics) genes. Comparison of the results from both assays found rare major discrepancies (<1% of codons analyzed). INNO-LiPA detected more wild-type-mutant mixtures than sequencing but suffered from a high rate of codon hybridization failures for the reverse transcriptase. LiPA detected earlier and more frequently than sequencing the transient mixed virus population that contained I84V, which appears before V82A in the protease sequence. Mutations M461, G48V, and L90M were often transient and drug pressure related. In conclusion, direct sequencing and LiPAs give concordant results for most clinical isolates. LiPAs are more sensitive for the detection of mixed virus populations. Mutation I84V appears in minor populations in the early steps of the pathways of resistance to indinavir and ritonavir. The fact that some mutations can be found only transiently and in minor virus populations highlights the importance of a low detection limit for resistance assays.

Acquired Immunodeficiency Syndrome↗

Subjective ratings of pain correlate with subcortical-limbic blood flow: an fMRI study.

Studies investigating the cerebral representations of pain using functional imaging techniques failed to elucidate the affective aspects of pain. This investigation used functional magnetic resonance imaging to measure pain-related changes in cerebral activity during painful stimulation with a strong affective component. Vascular pain was induced via balloon dilatation of a dorsal foot vein of healthy volunteers. The subjects rated their perceived pain uninterruptedly during imaging, allowing cerebral activity to be correlated with both stimulus function (boxcar) and, more importantly, subjective ratings reflecting individual pain experience. The findings indicated signal increases in subcortical-limbic regions, particularly in the amygdala. This region is suggested to be involved in the affective dimension of pain.

Affect↗

Subcortical correlates of craving in recently abstinent alcoholic patients.

OBJECTIVE: This study investigated functional cerebral correlates of craving in alcoholic patients and examined the state/trait characteristics of the regional cerebral network implicated in craving. METHOD: Functional magnetic resonance imaging (fMRI) was used to map cerebral response elicited by ethanol odor in 10 male patients with alcohol dependence who had undergone detoxification and 10 matched nonpatients. After 3 weeks, during which the patients underwent standardized behavioral therapy with psychopharmacological intervention, all subjects were studied a second time with fMRI to evaluate the effects of therapy on the functional cerebral correlates of craving. RESULTS: In the alcoholic patients, cue-induced craving before treatment elicited activation primarily in the subcortical-limbic region of the right amygdala/hippocampal area and in the cerebellum. After treatment, activation was found in the superior temporal sulcus, while subcortical or cerebellar participation was no longer present. Comparison subjects showed no comparable amygdala or cerebellar activation during ethanol stimulation and demonstrated no change in activation pattern between measurements. CONCLUSIONS: This investigation points to state-dependent neurobiological correlates of cue-induced craving in alcoholic patients and suggests that these correlates can be influenced by therapeutic interventions. The presence of emotional aspects of craving is suggested by amygdala activation.

Adult↗

Effects of exogenous somatotropin during early gestation on maternal performance, fetal growth, and compositional traits in pigs.

The objective of this study was to determine the effects of maternal treatment with porcine somatotropin (pST) during early gestation on embryonic survival, fetal development, and internal environment for fetal growth. Sixty-two crossbred gilts received daily injections of either 3 mL of a placebo (control, n = 31) or 6 mg of pST (n = 31) from d 10 to 27 of gestation. Representative gilts were slaughtered on d 28, 37, and 62 of gestation. The remaining gilts were allowed to farrow. It was found that embryonic survival was not influenced by pST treatment (P > 0.10). However, pST affected the growth and composition of the maternal (endometrium) and fetal (chorion) parts of the placenta. Thus, endometrial RNA concentration tended to be increased by pST at d 37 (P = 0.15), and it was increased at d 62 (P < 0.05) of gestation, which is indicative of increased capacity for protein synthesis. At birth, placental chorion weight (P < 0.10) and contents of DM and protein (P < 0.05) were increased due to pST treatment, but no effects were detectable up to d 62 of gestation. Maternal pST treatment was effective at increasing nutrient supply to the embryo as suggested from elevated glucose concentrations in amniotic and allantoic fluids (P < 0.05) at d 28 of gestation. With regard to prenatal growth, embryonic DNA concentration was slightly elevated at d 28 (P < 0.10), but pST did not induce any changes in average embryonic, fetal, or neonatal weights. However, within litters, the birth weights of piglets in the 25% lowest weight group (LW) were increased by pST treatment vs control LW pigs (1,241+/-55 vs 1,099+/-59 g, P < 0.10). Thirty-eight neonates from 15 litters divided among the three weight groups were examined for body composition. The weight of the intestinal tract was increased above average after maternal pST treatment (P < 0.01). Additionally, the amounts of tissues such as bone (P = 0.12) and s.c. fat (P = 0.06), and of protein, fat (P = 0.10), and ash (P < 0.05) were increased, whereas the relative body composition remained unchanged by pST (P > 0.10). On average, muscle protein concentration was elevated due to pST (P < 0.01), and, in LW piglets, plasma IGF-I concentration was increased (P < 0.10). The results suggest that maternal somatotropin is a critical factor in early pregnancy capable of influencing placental nutrient transfer and placental growth. It thereby selectively improves the growth conditions for the smaller littermates.

Allantois↗

Mitral valve repair versus mitral valve replacement.

Over the past 40 years mitral valve surgery has changed dramatically. After initial enthusiasm with the introduction of valve prostheses in the 1960s, a renewed interest in repair techniques began in the 1970s with the introduction of annuloplasty rings. These repair techniques revealed that the integrity of the subvalvular apparatus plays an important role in left ventricular function. When considering the major series comparing early and late results of mitral valve repair versus prosthetic mitral valve replacement, operative mortality rate is lower for patients with mitral valve repair. Long-term results also show a superior survival rate after mitral valve reconstruction. In addition, several problems can occur with the prosthetic valve, such as thromboembolism and endocarditis. All of these factors favor valve repair over replacement. The success of mitral valve repair depends on many factors: etiology of the mitral valve disease and the resultant pathomorphology of the valve, patient's circumstances such as age or contraindication for anticoagulation, and the experience of the surgeon. The decision whether to repair or replace the mitral valve depends on these factors. Data in the literature and in large collective databases reflect the advantages of mitral valve repair, with over 75% of current mitral valve surgeries being repairs. In the past 5 years the exposure of the mitral valve through a right lateral minithoracotomy using video assistance has developed into a widespread technique. This approach allows complex mitral valve repair as well as mitral valve replacement even with biological stentless prostheses, with decreased morbidity. The addition of radiofrequency ablation for restoration of sinus rhythm enhances the outcome after mitral valve surgery, and can also be easily performed through a minithoracotomy technique.

Follow-Up Studies↗

[Perioperative cortical stimulation of language fields under local anesthesia in preparation to excision of tumors of the dominant hemisphere].

OBJECTIVES: The aim of this study is to demonstrate the accuracy of direct cortical stimulation of language areas preparatory to the removal of infiltrating tumors of dominant hemisphere. MATERIAL AND METHODS: From June 1998 to March 2000 we included in our study 15 patients, aged from 30 to 75 years, harboring gliomas (14 high grades and 1 low grade) close to language-specific cortex. All patients had slight inaugural phasic troubles. They underwent craniotomy under local anesthesia for cortical stimulation language mapping, in conjunction with electrocorticography to identify the after-discharge threshold. Stimulation mapping covered the entire macroscopically tumor involved area, extending up to 3 cm away from the margins of the lesion, without searching to identify systematically the language areas. Therefore, the lesion was removed as completely as possible, respecting a security margin of at least 1 cm from the recognized language sites. RESULTS: We identified from 1 to 6 language sites for 14 of our patients, in different locations. A radical removal was achieved for all high grade gliomas, while the low grade was only partially removed. A patient died on the 16th postoperative day from pulmonary embolism; 2 patients deteriorated from peri- or immediate postoperative complications; 9 showed a transient neurological worsening that receded by the 2nd postoperative month, while 3 did not present any postoperative aggravation. At a follow-up of 1 month to 2 years (mean 8 months), 6 patients died and the 9 survivors maintain a good life quality. CONCLUSIONS: Cortical stimulation for language mapping is an accurate technique that allows the surgical morbidity of lesions in proximity to language areas to decrease and become comparable to the surgical morbidity for lesions in non eloquent areas.

Adult↗

Baseline HIV type 1 genotypic resistance to a newly added nucleoside analog is predictive of virologic failure of the new therapy.

We evaluated the predictive value of baseline HIV-1 genotypic resistance mutations for failure of a nucleoside reverse transcriptase inhibitor (NRTI) containing therapy. The change in therapy of 88 HIV-1-infected patients was analyzed retrospectively, relating the genotypic resistance profile at baseline to the evolution of viral load and CD4+ T cell counts. Genotypic resistance at baseline and at 6 months was evaluated with the LiPA HIV-1 RT, which detects mutations at codons 41, 69, 70, 74, 184, and 215. At 1 to 3 months after change in therapy, patients without preexisting resistance mutations to the new drug (group S) had a significantly better evolution in viral load (reduction of 0.37 log(10)) compared with patients with known preexisting resistance mutation(s) (group R) (increase of 0.08 log(10)). This difference was particularly striking for patients with the baseline M184V mutation and whose treatment was modified by the addition of lamivudine. After 6 months the median difference in viral load evolution between the two groups increased to 0.61 log(10): the viral load of patients of group S was still 0.18 log(10) below baseline while patients of group R had an increase of 0.43 log(10) in viral load above baseline. Changes in CD4+ T cell counts were not significantly different. The evolution in viral load in HIV-1-infected patients with and without baseline resistance mutation(s) toward a newly added NRTI is significantly different at 1-3 months and at 6 months after changing or adding one NRTI.

CD4 Lymphocyte Count↗

Emotional processing in schizophrenia across cultures: standardized measures of discrimination and experience.

Schizophrenia appears quite similar across a range of cultures. However, variability has been noted, and understanding the variant and invariant features of the disorder is necessary for elucidating its biological and environmental basis. Evidence of prominent emotion processing deficits in schizophrenia, including perceptual and experiential aspects, led us to extend the paradigm of standardized measures cross-culturally. We assessed performance of American, German, and Indian patients with schizophrenia and healthy controls on standardized emotion discrimination and experience (mood induction) procedures using happy, sad, and neutral facial expressions of Caucasian actors. Participants were 80 Americans (40 patients; 40 controls), 48 Germans (24 patients; 24 controls), and 58 Indians (29 patients; 29 controls). Face discrimination performance was impaired across patient groups, but was most impaired in those of Indian origin. Lower performance was also found in Indian controls, relative to their American and German counterparts. Mood induction produced weaker effects in all patient groups relative to their respective controls. The results supported the feasibility of cross-cultural comparisons and also emphasized the importance of poser ethnic background for facial affect identification, while poser ethnicity was less consequential for mood induction effects. Emotion processing deficits in schizophrenia may add to the clinical burden, and merit further examination.

Adult↗

A DNA-binding domain swap converts the invertase gin into a resolvase.

DNA resolvases and invertases are closely related, yet catalyze recombination within two distinct nucleoprotein structures termed synaptosomes and invertasomes, respectively. Different protein-protein and protein-DNA interactions guide the assembly of each type of recombinogenic complex, as well as the subsequent activation of DNA strand exchange. Here we show that invertase Gin catalyzes factor for inversion stimulation dependent inversion on isolated copies of sites I from ISXc5 res, which is typically utilized by the corresponding resolvase. The concomitant binding of Gin to sites I and III in res, however, inhibits recombination. A chimeric recombinase, composed of the catalytic domain of Gin and the DNA-binding domain of ISXc5 resolvase, recombines two res with high efficiency. Gin must therefore contain residues proficient for both synaptosome formation and activation of strand exchange. Surprisingly, this chimera is unable to assemble a productive invertasome; a result which implies a role for the C-terminal domain in invertasome formation that goes beyond DNA binding.

Base Sequence↗

Gender differences in regional cerebral activity during sadness.

Functional magnetic resonance imaging and echo-planar-imaging were used to investigate affect related gender differences in regional cerebral activity. The experiment was conducted using a standardized mood induction procedure. Blood-oxygen-level-dependent effect was measured in 13 male and 13 female healthy subjects, during both moods of happiness and sadness, respectively. Parallel to earlier neuroimaging findings, our results show brain activity in the amygdala of males during negative affect. Females failed to demonstrate a similar activation pattern despite matched subjective ratings of negative affect to males. Results point to differential regional cerebral correlates of emotional experience in males and females, which is suggestive of a more focal and subcortical processing of sadness in men.

Adult↗

[Delirium after vascular surgery interventions. Intermediate-term results of a prospective study].

INTRODUCTION: Postoperative delirium is a common psychic disturbance occurring acutely after various surgical procedures and typically presenting with a fluctuating course. These patients' recovery takes longer. In this study we analyze the incidence of postoperative delirium in patients undergoing vascular surgery and try to identify risk factors for its development. METHODS: Patients undergoing elective arterial operations were included. Their medical history, the specific vascular diagnosis and operation performed, the medication and laboratory data were monitored. Additionally the patients were preoperatively interviewed by a psychiatrist. Intraoperatively the drugs, infusions, possible transfusions, blood gases and pressures were monitored, as were the times of surgery and anesthesia. Postoperatively patients were seen daily by the psychiatrist and the surgeon for at least 7 days. Postoperative delirium was diagnosed according to DSM IV criteria, and mild, moderate and severe delirium were distinguished. RESULTS: Fifty-four patients entered the study. Twenty-one (38.9%) developed postoperative delirium (11 mild, 2 moderate, 8 severe). Patients with aortic operations developed delirium more frequently than those with non-aortic procedures(55.5 vs 22.2%, n = 27 each). Some preexisting diseases (hearing disturbance) increased the probability of postoperative delirium, while age was not identified as a risk factor. General psychopathological and depressive disturbances increased the likelihood of postoperative delirium. Patients who had a severe intraoperative course developed postoperative delirium more frequently. This was not seen in the absolute time of surgery or anesthesia nor in the intraoperative development of blood pressure or intraarterial gases, which did not differ between patients with and without postoperative delirium. More reliable parameters were an increased intraoperative need for crystalloid volume, intra- or postoperatively decreased hemoglobin values (Hb < 10 g/dl) and the development of acidosis that had to be treated. Patients with delirium had serious complications more often (8/21 = 38.1% vs 6/33 = 18.2%) and needed Intensive Care treatment longer (2.7 vs 2.1 days, only aortic surgery 3.2 vs 2.4 days). CONCLUSIONS: Postoperative delirium after vascular surgery is frequent. Patients undergoing aortic surgery, with specific concomitant medical disease, psychopathological disturbances and a severe intraoperative course, are at risk of developing postoperative delirium.

Aged↗

[External quality assurance of inpatient treatment in schizophrenia. results of a multicenter study].

Due to legal regulations, external quality assurance is mandatory in Germany. Supported by the German Health Ministry (BMG), we present the results of a multicenter study in four hospitals with different structures on 1042 inpatients with the tracer diagnosis of schizophrenia (ICD 10). We defined disease-specific indicators of structure, process, and outcome quality, developed an assessment instrument, and implemented a feedback system for quality comparison. The resulting quality profiles are useful as a starting point for internal quality management.

Acute Disease↗

Neurological complications and pleural lavage with a fibrinolytic agent. A two-case report.

We report on an unusual, albeit potentially severe, complication of the performance of a pleural lavage with streptokinase in two patients demonstrating parapneumonic pleural effusion. During the time they underwent repeated pleural lavages with saline and streptokinase, they suddenly demonstrated focal neurological signs. As a result of early diagnosis and emergency hyperbaric oxygenation, both patients recovered without delayed sequelae. Air embolism is a potentially severe complication which can occur during pleural lavage. Whether streptokinase increases the risk of opening a latent vascular breach cannot be definitely established, but clinicians should be aware of this risk. In this context, the onset of acute focal neurological signs should suggest the possibility of air embolism and lead to the transfer of the patient close to a hyperbaric facility within a few hours.

Adult↗

Genetic variability of measles viruses circulating in the Benelux.

In Europe measles incidence remains high and in some parts the disease is likely to be still endemic due to insufficient vaccination. Luxembourg experienced an outbreak with at least 110 cases in 1996, and cases continued to be reported throughout 1997. We used molecular epidemiology to investigate this apparent endemicity. On the basis of their N gene sequences, the isolates were assigned to the typical European C2 and D6 genotypes. Sequence diversity within the outbreak was 0.2%. The nucleotide distance between the C2-viruses of the outbreak and the other C2 isolates was at least three or four times higher, suggesting an independent origin of the latter viruses. Similarly, the four D6 viruses found in Luxembourg were thought to be of at least two or three origins. Thus, we propose here to use intra-outbreak sequence diversity to differentiate between sporadic endemic cases and a "pseudo-outbreak" of multiple unrelated imported cases.

Belgium↗

Cerebral microemboli during minimally invasive and conventional mitral valve operations.

BACKGROUND: Intraoperative cerebral microembolism may cause postoperative neurologic damage. The aim of this study was to determine the frequency of cerebral microembolic signals (MES) during minimally invasive surgery (MIS) and conventional (conv.) mitral valve operations and to determine the association of MES with various stages of the operation. METHODS: Intraoperative computer-aided transcranial Doppler measurements were performed to detect cerebral microemboli in 21 patients undergoing MIS and in 14 patients undergoing conv. mitral valve operation. We calculated the mean embolic rate for three time periods: P1, start of the operation until aortic clamping; P2, aortic clamping until clamp removal; and P3, declamping until end of surgery. RESULTS: There was no significant difference in the total number of detected cerebral MES between both patient groups (MIS 1,014+/-753, conv. 937+/-519; NS). In both groups, the highest number of MES were detected during the third time period when the heart regained effective ejection (MIS 875+/-746, conv. 680+/-462; p > 0.5). CONCLUSIONS: Transcranial Doppler was useful to detect cerebral microemboli in MIS and conv. mitral valve operation. We found no increased risk of cerebral microembolism during the minimally invasive method compared with the conventional technique.

Cardiopulmonary Bypass↗