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Biomedical subjects

K Wilhelm

Publications and source records attributed to K Wilhelm.

At least 37 records · Page 2Linked to original sources

Model-based optimization of viral capsid protein production in fed-batch culture of recombinant Escherichia coli.

An optimized fed-batch cultivation process for the production of the polyoma virus capsid protein VP1 in recombinant Escherichia coli BL21 bacteria is presented. The optimization procedure maximizing the amount of desired protein is based on a mathematical model. The model distinguishes an initial cell growth phase from a protein production phase initiated by inducer injection. A new approach to model the target protein formation rate was elaborated, where product formation is primarily dependent on the specific biomass growth rate. Lower growth rates led to higher specific protein concentrations. The model was identified from a series of fed-batch experiments designed for parameter identification purposes and possesses good prediction quality. Then the model was used to determine optimal open-loop control profiles by manipulating the substrate feed rates in both phases as well as the induction time. Feed-rate optimization has been solved using Pontryagin's maximum principle. The solution was validated experimentally. A significant improvement of the process performance index was achieved.

Journal Article↗

Local intra-arterial thrombolysis in the carotid territory: does recanalization depend on the thromboembolus type?

Little is known about whether recanalization of carotid territory occlusions by local intra-arterial thrombolysis (LIT) depends on the type of the occluding thromboembolus. We retrospectively analysed the records of 62 patients with thromboembolic occlusions of the intracranial internal carotid artery (ICA) bifurcation or the middle cerebral artery who were undergoing LIT with urokinase within 6 h of symptom onset. We determined the influence of thromboembolus type (according to the TOAST criteria), thromboembolus location, leptomeningeal collaterals, time interval from onset of symptoms to onset of thrombolysis, and patient's age on recanalization. The thromboembolus type was atherosclerotic in six patients, cardioembolic in 29, of other determined etiology in four, and of undetermined etiology in 23 patients. Thirty-three (53%) thromboembolic occlusions were recanalized. The thromboembolus location but not the TOAST stroke type nor other parameters affected recanalization. In the TOAST group of patients with cardioembolic occlusions recanalization occurred significantly less frequently when transoesophageal echocardiography showed cardiac thrombus. The present study underlines the thromboembolus location as being the most important parameter affecting recanalization. The fact that thromboembolic occlusions originating from cardiac thrombi had a lower likelihood of being resolved by thrombolysis indicates the thromboembolus type as another parameter affecting recanalization.

Carotid Artery Thrombosis↗

Gender differences in depression risk and coping factors in a clinical sample.

OBJECTIVE: To examine gender differences in depression risk and coping factors in a clinical sample of patients with a diagnosis of DSM-IV major depression. METHOD: Patients were assessed for substance use and abuse, family history of psychiatric disorder, interpersonal depressogenic factors and lifetime history of anxiety disorders. Trait anxiety, coping styles when depressed, parental bonding, marital features and personality style were also measured. Patients were reassessed at 12-month follow-up. RESULTS: There were few gender differences in experience of depression (either in duration, type or severity prior to treatment) in a group with established episodes of major depression but women reported more emotional arousability when depressed. Women reported higher rates of dysfunctional parenting and childhood sexual abuse, and rated their partners as less caring and as more likely to be a depressogenic stressor. Men were more likely to have a generalized anxiety disorder at assessment, to use recreational drugs prior to presentation. Men were rated as having a more rigid personality style and 'Cluster A' personality traits both at assessment and follow-up. CONCLUSION: There were few gender differences in severity or course of established episodes of major depression. Gender differences were related to levels of arousal, anxiety disorders, and repertoires for dealing with depression, rather than depressive symptoms per se.

Adaptation, Psychological↗

[Scapho-lunate ligament reconstruction with Mitek suture anchors. Initial clinical results].

The scapholunate dissociation is an often misjudged lesion of carpal ligaments as clinical and radiological signs often don't allow a clear interpretation. Apart from chronical courses with increasing arthrosis the consequences are limited and more difficult operations. The application of Mitek suture anchors is a new and simple supplement to large-scale operative reconstructions of ligaments or partial arthrodesis. Of nine reconstructions of the scapholunate interosseous ligament using this anchor method so far only one relaps occurred.

Adult↗

Early and late onset depression in old age: different aetiologies, same phenomenology.

BACKGROUND: Phenomenological differences between older patients with early onset (EO; onset of first major depressive episode before 60 years) and late onset (LO) depression have been inconsistent but, if real, may reflect differences in aetiology. We aimed to compare aetiological factors, phenomenology and cognitive function in older patients with depression by age of onset. METHODS: Subjects were all patients > or =60 years old (n=73) from 407 consecutive attenders to a Mood Disorders Unit, diagnosed with DSM-III-R Major Depressive Episode, at or close to the nadir of their episode. Putative risk factors were assessed by structured interview. Psychological morbidity and depressive symptoms were assessed by the 21-item Hamilton Rating Scale for Depression, CORE rating of psychomotor disturbance, Newcastle Endogeneity Scale, Zung Depression Scale and General Health Questionnaire. Cognition was assessed by tests of memory, attention, executive function and motor speed. RESULTS: Personality abnormalities, a family history of psychiatric illness and dysfunctional past maternal relationships were significantly more common in EO depression. The two age of onset groups were essentially similar in terms of depressive sub-type and severity, phenomenology, history of previous episode, and in neuropsychological performance. LIMITATIONS: Use of self-report data, moderate sample size, sample not age-matched, tertiary referral patients. CONCLUSIONS: EO and LO depression are similar phenotypically, but differ aetiologically. The pursuit of mechanisms which predispose depressive episodes may be heuristically more valuable than further investigation of individual depressive features in distinguishing early from late onset depression.

Aged↗

The differential impact of age on the phenomenology of melancholia.

BACKGROUND: We pursue an observation that age may influence the clinical features of melancholia and, in particular, psychomotor disturbance. METHODS: Two large clinical databases were amalgamated allowing the clinical features of 124 depressed subjects meeting DSM-III-R and clinical criteria for melancholia to be contrasted with 218 subjects diagnosed as having a non-melancholic depression by both criteria sets. Psychomotor disturbance was assessed by the CORE measure and by seven classical endogeneity symptoms of melancholia which, when summed, created a ENDOG score. RESULTS: There was no impact of age on ENDOG scores in either the melancholics or non-melancholics. In the melancholics, increasing age was associated with increasing CORE scores and with agitation scale scores in particular. In a set of discriminant function analyses seeking to identify the comparative utility of a set of predictors of melancholic (versus non-melancholic) groups, age was significant, and while CORE and ENDOG scores were individual predictors, their combined entry established that the CORE score alone made the ENDOG score redundant, and that the addition of age then made little impact. CONCLUSIONS: Melancholia appears to have a later age of onset than non-melancholic depression, while its phenotypic expression appears to change with age, with psychomotor disturbance being more distinct in older subjects. Such an effect may have a number of clinical implications, including possible differential effects of varying antidepressant treatments.

Adult↗

Late-onset depression: genetic, vascular and clinical contributions.

BACKGROUND: Neuropsychiatric research needs to examine the relationships between aetiological, genotypic and clinical risk factors and behavioural phenotypes. These relationships can now be examined in older patients with depressive disorders. METHODS: Key behavioural features, clinical and vascular risk factors and putative genotypes for late-onset neurodegenerative disorders and/or vascular disease were recorded in 78 older patients with depression (mean age = 549 years, S.D. = 14.1) and 22 healthy control subjects (mean age = 55.5 years, S.D. = 9.6). RESULTS: Two or more vascular risks were more common in older patients (65% v. 26% of control subjects, P < 0.01), and in patients with late-onset disorders (82% v. 57% in patients with early-onset disorders, P < 0.05). Patients with late-onset depression had a higher prevalence of the homozygous or heterozygous forms of the C677T mutation of the methylenetetrahydrofolate reductase enzyme (MTHFR)(74% v. 48% in patients with early-onset disorders, P < 0.05). In a multivariate model, only presence of the MTHFR gene mutation predicted late-onset depression (odds ratio = 3.8, 95% CI = 1.1-12.9). Neither apolipoprotein E epsilon 4 or epsilon 2 was associated with depression, late-onset depression, cognitive impairment, or psychomotor change. Patients with apolipoprotein E epsilon 4 were less likely to have psychotic forms of depression. CONCLUSIONS: Patients with late-onset depression had an increased rate of the C677T MTHFR gene mutation and other vascular risk factors. This suggests that a proportion of these patients may have genetically-determined and/or other vascular aetiologies. Patients at risk of these disorders may be assisted by currently-available preventative strategies.

Adult↗

Depression and smoking: examining correlates in a subset of depressed patients.

OBJECTIVE: The objective of this study was to examine for associations between depression and cigarette smoking. METHOD: A sample of 92 depressed smokers was compared with a control sample of depressed non-smokers, matched for age, gender and diagnostic variables. Comparisons were made across a range of demographic, depression, family history, developmental factors, anxiety and personality style variables, as well as use of alcohol and illicit drugs. RESULTS: We failed to find any difference between smokers and non-smokers in history or severity of depression. Cigarette smokers were distinguished principally by greater exposure to aversive experiences in childhood, disordered personality function, greater use of illicit drugs, anxiolytics and alcohol. Logistic regression identified dysfunctional personality 'domains', physical violence in childhood, long-term anxiolytic use and illicit drug use as the most significant predictor set. CONCLUSIONS: Results favour a model of cigarette smoking and depression as linked by shared early deprivational variables, rather than cigarette smoking causing depression or the converse.

Adult↗

[Obstruction of surgical portosystemic shunts in the early postoperative phase: interventional treatment by angioplasty with stent implantation].

PURPOSE: Recurrent variceal bleeding in patients treated with surgical porto-systemic shunting is most often due to shunt stenoses or occlusion. Radiological interventional procedures are a possible method of therapy and our experience herein is described in this report. PATIENTS AND METHODS: From 1997 to 1999 54 patients with recurrent variceal bleeding were treated with a surgical porto-systemic shunt procedure. Of these early shunt occlusion occurred in 5 patients, which was treated with percutaneous transcatheter techniques. RESULTS: In only one patient was PTA alone sufficient to reestablish shunt patency, in four patient stent placement was necessary in addition. In the follow-up period 1 patient died 26 month after intervention with (autopsy-proven) patent shunt, in one patient shunt reocclusion occurred after 11 months and in 3 patients the shunt is still patent. CONCLUSIONS: PTA, if necessary in combination with stent placement, is an attractive alternative method of therapy in case of an early surgical porto-systemic shunt occlusion.

Adult↗

Oxygen radical generation by emigrated, intra-abdominal, and circulating PMNLs during human secondary peritonitis.

The purpose of the study was to characterize oxygen radical generation by emigrated, intraabdominal and circulating polymorphonuclear leukocytes (ePMNLs and cPMNLs) during peritonitis, as well as to assess any differences between oxygen radical production in patients with low Mannheim peritonitis index (MPI < 26, group 1) or high Mannheim peritonitis index (MPI > or = 26, group 2). Lucigenin-enhanced chemiluminescence was used to determine spontaneous and stimulated (FMLP, PMA, and A23 187) oxygen radical generation by ePMNLs and cPMNLs. In group 1 spontaneous and stimulated oxygen radical generation by emigrated PMNLs was markedly enhanced compared to circulating PMNLs (e.g., spontaneous oxygen radical generation: 30.3 +/- 11.8 cpm/cPMNLs versus 107 +/- 46 cpm/ePMNLs, P < 0.05) . In group 2 oxygen radical generation by cPMNLs markedly increased within 48 h after diagnosis of peritonitis and surgery, contrary to radical generation by ePMNLs (e.g., A23 187-stimulated oxygen radical generation 993.7 +/- 350 cpm/cPMNLs versus 285.6 +/- 77 cpm/ePMNLs, P < 0.05. In conclusion, cPMNLs and ePMNLs exhibit marked polymorphism in their capacity to generate oxygen radicals in response to secondary peritonitis. Severe peritonitis (MPI - 26) was associated with a strong increase in oxygen radical generation by cPMNLs without a parallel activity being manifest by ePMNLs.

Abdomen↗

Assessing the comparative effectiveness of antidepressant therapies: a prospective clinical practice study.

BACKGROUND: Although efficacy studies suggest equal potency among antidepressant treatments, their effectiveness in clinical practice appears more variable, particularly in that the newer antidepressants may be less effective in either more severe depression or the melancholic subtype of depression. We pursue some factors that may impact the effectiveness of antidepressant treatments in a clinical sample. METHOD: A sample of 182 patients with DSM-IV major depressive disorder was assessed at baseline and 12 months later to establish treatments provided, identify patients who had recovered from the index episode, and quantify likely treatment determinants. Four systems for distinguishing patients with melancholic and non-melancholic depression were examined to assess for differential effects of the antidepressant strategies across those subtypes. RESULTS: Multimodal therapy (commonly, psychotherapy combined with an antidepressant drug) and patients' frequent attribution of recovery to spontaneous improvement made for difficulty in disentangling recovery determinants. After excluding a spontaneous improvement component, electroconvulsive therapy (ECT) and the irreversible monoamine oxidase inhibitors (MAOIs) appeared to be the most effective therapies across the sample, while the reversible inhibitor of monoamine oxidase-A (RIMA) appeared to be the least effective. The distinct gradient of suggested effectiveness of various strategies appeared to be contributed to principally by the varied effectiveness of alternate treatments across the melancholic subtype, whereby ECT, tricyclic antidepressants, and MAOIs were the most effective, and the selective serotonin reuptake inhibitors (SSRIs), RIMAs, and antipsychotic drugs were much less effective. For the nonmelancholic disorders, the effectiveness of SSRIs appeared to be comparable with that of older antidepressants. CONCLUSION: Although most patients received a physical treatment, they commonly judged psychotherapy and spontaneous improvement to be influential in their recovery. Reasons for such attributions are worthy of clarifying studies. Despite patients' concerns about the side effects and stigma of ECT as well as the side effects associated with the older antidepressants, these therapies were rated as more helpful by patients-and were more strongly associated with recovery-than the newer antidepressant drugs. Such overall results are compatible with an earlier study undertaken by us involving an independent sample and retrospective data. The overall gradient is clarified by studying depressive subtypes, allowing an important conclusion. Although the newer and older antidepressant drugs may be of similar effectiveness in nonmelancholic depression, the newer agents appear comparatively inferior for the treatment of melancholia, findings that have clinical implications and perhaps inform us about the pathogenesis of melancholia.

Adult↗

Indicators of suicide over 10 years in a specialist mood disorders unit sample.

BACKGROUND: There are few firm data to guide the clinician in identifying individual depressed patients who may be at high risk for completing suicide. In particular, there have been few prospective studies of well-characterized depressed patients to determine indicators of such future events. METHOD: Eight hundred thirteen patients with a major depressive episode (DSM-III, DSM-III-R, or DSM-IV criteria) were assessed in detail in a specialist Mood Disorders Unit (MDU) over a 10-year period. Follow-up at the end of that period (mean = 5.1 years) confirmed that 31 patients (3.8%) had completed suicide. The suicide completers were compared on a broad range of clinical and demographic variables obtained at baseline with (1) the total remaining depressed sample, (2) 31 age- and sex-matched subjects who were confirmed to be alive and had never attempted suicide, and (3) 24 age- and sex-matched living subjects who had made at least 1 suicide attempt. RESULTS: The most consistent finding, across all 3 comparisons, was that the suicide completers were more likely to have been inpatients at the time of the index MDU assessment. Other characteristics of completers were a greater number of prior admissions for depression, being older and in a relationship, and being male and married or female and single. Somewhat paradoxically, suicide completers also evidenced fewer previous suicide attempts and less suicidal ideation compared with living subjects who had attempted suicide at the time of index assessment. CONCLUSION: Overall, we were able to find few predictors of later suicide in this sample. Those who completed suicide demonstrated evidence of more severe illness over a lifetime (for example, having more admissions). but revealed less suicidal ideation at the time of the index MDU assessment. While these features were statistically significant, they are of limited usefulness in predicting suicide in an individual patient.

Adult↗

The clinical features of bipolar depression: a comparison with matched major depressive disorder patients.

BACKGROUND: Despite a resurgence of interest in the treatment of bipolar depression, there have been few controlled studies of the clinical characteristics of this condition. Identification of any distinctive clinical "signatures" of bipolar depression would be helpful in determining treatment options in the clinical setting. METHOD: From a cohort of 270 inpatients and outpatients assessed in detail during a DSM-IV major depressive episode, 39 bipolar I disorder patients were identified and closely matched with 39 major depressive disorder patients for gender, age, and the presence or absence of DSM-IV melancholic subtype. Patients were compared on a broad range of parameters including the Hamilton Rating Scale for Depression (depression severity), 54 depressive symptoms, the Newcastle Endogenous Depression Diagnostic Index, 3 family history items, 2 physical health items, the CORE scale (psychomotor disturbance), and 5 history items. RESULTS: Although the bipolar patients were no more severely depressed than the major depressive disorder controls, they were more likely to demonstrate psychomotor-retarded melancholic and atypical depressive features and to have had previous episodes of psychotic depression. These findings were largely duplicated even when the population was confined to those with DSM-IV melancholia. CONCLUSION: The clinical admixture of psychomotor-retarded melancholic signs and symptoms, "atypical" features, and (less frequently) psychosis may provide a "bipolar signature" in clinical scenarios when there is uncertainty concerning the polarity of a depressive presentation.

Adult↗

[Distal radius fracture. Surgery or plaster cast?]].

Fractures of the distal radius are most commonly seen in women in the sixth and seventh decade of life. These fractures range in severity from simple, stable non-dislocated metaphyseal transverse fractures of the distal radius to complex, intra-articular fractures of the wrist with involvement of the carpus. This means that individual consideration of the appropriate therapeutic approach that needs to be adopted is required. A decisive role for surgical treatment is played by the anatomical angles at the radiocarpal articular surface, and the congruence of the distal radio-ulnar joint. If care is not taken to establish proper anatomical relationships, persistent problems must be expected.

Casts, Surgical↗

[Mycobacterium avium infection presenting as a mass in the right lung].

BACKGROUND: The diagnostic procedure of pulmonary masses in patients with AIDS is presented. CASE REPORT: A 39-year-old patient with AIDS was admitted to hospital because of a non-productive cough and radiologic evidence of mediastinal and right hilar masses suggestive of lymphoma associated with pneumonia of the right lower lobe. Bronchoscopy revealed a stenosis of the right lower lobe bronchus with small endobronchial lesions. Biopsies showed granulomatous inflammation, but no microorganisms were detected. Chest pain with dyspnea developed and was relieved by evacuation of pus during mediastinoscopy. The diagnosis of Mycobacterium avium infection was established via culture of sputum and bronchoalveolar lavage fluid and via mediastinoscopy. The patient was commenced on a 3-drug regimen with rifabutin, ethambutol and clarithromycin and has remained asymptomatic now for over 9 months. CONCLUSION: Mycobacterium avium infection needs to be included in the differential diagnosis of patients with AIDS presenting with mediastinal and hilar masses. When procedures such as bronchoscopy and chest CT-scans are non-diagnostic, mediastinoscopy may become necessary in order to establish the diagnosis.

AIDS-Related Opportunistic Infections↗