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PubMed1990

Defecography in patients with anorectal disorders. Which findings are clinically relevant?

To evaluate the results and clinical impact of defecography in patients with anorectal disorders, 100 results of defecographic examinations from 92 patients were reviewed. The defecographic results were screened for the anorectal angle, defined both at rest and during straining, perineal descent, and abnormalities of the rectal configuration during straining. Anal manometry, saline infusion test, rectal capacity measurement, and anal electromyography (EMG) were also performed. There was a significant difference (P less than 0.001) both at rest (22 degrees) and during straining (12 degrees) between the two anorectal angle measurements. Incontinent patients had a larger anorectal angle, both at rest and during straining, than continent patients (P less than 0.04), but with a large overlap. The anorectal angle was not influenced by gender or age. An abnormal rectal configuration was found in 62 defecographic examinations. From the 8 patients with rectopexy performed for a large rectocele or intussusception, incontinent patients with an intussusception had the best results. In four patients, anal EMG showed an increased activity of the external sphincter during straining. Two of these four patients had abnormal defecograhic results. No correlations were found between anorectal angle and the other function tests. In conclusion, the anorectal angle lacks clinical relevance. In patients with defecation problems, defecography may be indicated whenever other investigations (physical examination, anal manometry, anal EMG) have excluded local pathology or a spastic pelvic floor syndrome. In these situations, defecography could detect an intussusception, which could easily be treated with rectopexy.

Aged↗

PubMed2002

[Molecular pathologic diagnosis in solid tumors. What is clinically relevant?].

There are only a few clinically relevant applications of molecular pathology assays in solid tumors. Among the findings which may influence therapy decisions are the amplification of Her-2/new in breast cancer and specific translocations in sarcomas. Mutation analyses of p53 may be helpful for only a very few cases, e.g. for confirming high grade dysplasia in the upper gastrointestinal tract or for diagnosing malignant soft tissue tumors in isolated cases. Microsatellite analyses are important for HNPCC screening or distinguishing tissue specimens of questionable identity. Other applications of molecular pathology assays such as detection of minimal residual disease or tumor cell dissemination and FISH analysis of urine and effusion specimens, may be increasingly applied in the future.

Biomarkers, Tumor↗

PubMed1988

Single hemorrhage: a clinically relevant canine model of hemorrhagic shock.

Clinically encountered hemorrhagic shock is usually caused by a single, rapid hemorrhage secondary to trauma. Experimental models of shock, however, have utilized anesthetic agents and hemorrhage protocols which may compromise the clinical relevance of their findings. This report characterizes the response of conscious, splenectomized dogs to a single hemorrhage of varying rates and volumes, uncomplicated by the presence of anesthetic agents. The duration of a 40 ml kg-1 hemorrhage affected the magnitude of blood pressure recovery, but did not alter the decompensating drop in blood pressure. The shortest hemorrhage duration was chosen for further study, as the blood pressure profile for this hemorrhage duration demonstrated most clearly the recovery, plateau, and decompensation phases. Increasing the hemorrhage volume to 43 ml kg-1 caused a reproducible decrease in the magnitude of the blood pressure recovery, the time to decompensation, and the time to death. Splenectomized dogs, then, demonstrate a reproducible response to a fixed-volume hemorrhage, making chronically instrumented conscious dogs a good animal model with which to study the progression of hypovolemic shock.

Animals↗

PubMed1992

[Ultrasound diagnosis of lumbar intervertebral disk displacement--a clinically relevant method?].

UNLABELLED: In a prospective clinical study, 102 patients suffering from low back pain were examined by ultrasound. In all patients the segments L3/4, L4/5, and L5/S1 were evaluated. We analysed a total of 306 lumbar disc segments. Ultrasound evaluation was transabdominally performed by using a 3,5 MHz scanner. The results of the ultrasound documentation were compared to MRI or if the patient was operated on with the intraoperative findings. In 25 disc the dorsal border of the disc could not be demonstrated by ultrasound. The statistical analysis resulted in the following values: [table: see text] Comparing these results with the results of other imaging modalities like myelography, CT, or MRI, ultrasound scores are significantly inferior. CLINICAL RELEVANCE: With the present technique ultrasound does not seem to be of diagnostic value for patients with herniated disk.

Adolescent↗

PubMed1994

Management of clinically relevant bleeding following endoscopic sphincterotomy.

We report here on our experience of clinically relevant bleeding after endoscopic sphincterotomy (ES). Relevant bleeding was defined by the occurrence of (a) hematemesis or melena and (b) at least a two-point drop in hemoglobin, with no other bleeding source on endoscopy. These two criteria were met in 16 patients between 1983 and 1992. They represented 0.65% of all ES procedures performed during this period. Bleeding occurred immediately after ES in five cases, and was delayed in 11 cases from one to eight days (mean two days). Patients were retrospectively classified into three groups according to the severity of bleeding and subsequent clinical management. In six cases (group 1), bleeding developed slowly without shock and stopped spontaneously. In five cases (group 2), bleeding developed rapidly with melena and a drop in hemoglobin, but without shock. These patients were successfully managed with sclerotherapy without any further complications. The five patients in Group 3 had brisk bleeding with hematemesis and shock. Endoscopic hemostasis could not be performed; emergency arteriography disclosed active bleeding in four patients, and embolization of the gastroduodenal artery was performed. Bleeding stopped in all patients. Billroth II anastomosis appeared to be the only factor associated with an increased risk of clinically relevant bleeding. It was possible to control bleeding following ES using endoscopic or angiographic hemostasis, surgery being avoided in all cases.

Adult↗

PubMed1998

Clinically relevant concentrations of ethanol attenuate primed neutrophil bactericidal activity.

BACKGROUND: Acute alcohol intoxication is associated with an increased risk of infection in the injured patient. The impact of clinically relevant levels of ethanol (ETOH) on neutrophil (PMN) bactericidal activity remains ill-defined. PMN priming optimizes microbicidal activity by enhancing oxygen radical production, degranulation, and adhesion molecule up-regulation. We hypothesized that clinically relevant levels of ETOH attenuate these primed PMN responses critical to eradicate infection. METHODS: After incubation with ETOH (0-1.0%), isolated human PMNs were primed with beta-acetyl-gamma-O-alkyl and activated with N-formyl-methionyl-leucyl-phenylalanine. Superoxide generation was measured by cytochrome c reduction, elastase release was measured by cleavage of methoxysuccinyl-ala-ala-pro-val-p-nitroanilide, and CD11b was measured by fluorescent monoclonal antibody staining. Bactericidal activity was assessed by Staphylococcus aureus killing. RESULTS: ETOH attenuated superoxide production dose-dependently with significance at 0.3% ETOH. Elastase release was attenuated starting at 0.2% ETOH, and CD11b expression was reduced starting at 0.4% ETOH. S. aureus killing was impaired dose-dependently with significance at 0.3% ETOH. CONCLUSION: Clinically relevant concentrations of ETOH attenuate PMN functions critical in host defense against invading pathogens. These results provide direct in vitro evidence consistent with previous in vivo data that acute alcohol intoxication is important in the pathogenesis of trauma-related infections.

Alcoholic Intoxication↗

PubMed2006

Effect of oral administration of clinically relevant doses of dexamethasone on regulation of cytochrome P450 subfamilies in hepatic microsomes from dogs and rats.

OBJECTIVE: To evaluate the effect of oral administration of dexamethasone (DEX) at clinically relevant doses on metabolic activities of cytochrome P450 (CYP) isoenzymes in dogs and rats. ANIMALS: 15 healthy 1-year-old male Beagles and 20 healthy 10-week-old male Wistar rats. PROCEDURE: Hepatic microsomes were harvested from dogs treated orally with DEX at 2.5 and 7.5 mg for 5 days and from rats treated orally with DEX at 0.75, 6, and 48 mg/kg for 5 days. 7-ethoxyresorufin, tolbutamide, bufuralol, and midazolam were used as CYP1A, CYP2C, CYP2D, and CYP3A substrates, respectively. Concentrations of metabolites formed by CYPs were measured by use of high-performance liquid chromatography, except for the resorufin concentrations measured by use of a fluorometric method. Reaction velocity-substrate concentration data were analyzed to obtain maximum reaction velocity (Vmax) and Michaelis-Menten constant (Km). RESULTS: Values of Vmax for midazolam 4-hydroxylation were significantly decreased by treatment with DEX at 2.5 and 7.5 mg in dogs, although values of Km were not affected. Values of Vmax for bufuralol 1'-hydroxylation were also decreased by treatment with DEX. In rats, values of Vmax for midazolam 4- hydroxylation were significantly decreased by treatment with DEX at 0.75 and 6 mg/kg but significantly increased at 48 mg/kg. Other reactions were not affected by treatment with DEX. CONCLUSIONS AND CLINICAL RELEVANCE: Our results indicate that DEX downregulates the CYP3A subfamily when administered at clinically relevant doses to dogs. The effect of downregulation of CYP3A in dogs treated with DEX should be considered to avoid adverse effects from coadministration of drugs.

Administration, Oral↗

PubMed2006

The measurement and clinical relevance of brain atrophy in multiple sclerosis.

Brain atrophy has emerged as a clinically relevant component of disease progression in multiple sclerosis. Progressive loss of brain tissue bulk can be detected in vivo in a sensitive and reproducible manner by MRI. Clinical studies have shown that brain atrophy begins early in the disease course. The increasing amount of data linking brain atrophy to clinical impairments suggest that irreversible tissue destruction is an important determinant of disease progression to a greater extent than can be explained by conventional lesion assessments. In this review, we will summarise the proposed mechanisms contributing to brain atrophy in patients with multiple sclerosis. We will critically discuss the wide range of MRI-based methods used to quantify regional and whole-brain-volume loss. Based on a review of current information, we will summarise the rate of atrophy among phenotypes for multiple sclerosis, the clinical relevance of brain atrophy, and the effect of disease-modifying treatments on its progression.

Atrophy↗

PubMed2002

Anal sphincter complex: reinterpreted morphology and its clinical relevance.

PURPOSE: Recent clinical studies on the anal sphincter complex have criticized the lack of reliable morphologic concepts. The purpose of this study was to determine the anatomy and histology of the anal sphincter complex with the help of undisturbed anatomic preparations. METHODS: The anal sphincter complex was studied in axial, sagittal, and coronal sections of human fetal, newborn, and adult pelves. RESULTS: The anal canal was surrounded by the internal sphincter, the longitudinal muscle layer, and an external sphincter that turned in to become continuous with the internal sphincter and with it to enclose the longitudinal muscle bundles. The classical tripartite subdivision of the external sphincter was not confirmed. The external sphincter seems not to be a complete circle in certain planes, neither in the male nor in the female. Sexual differences of the ventral part of the external sphincter were already present in fetuses. Large lamellated corpuscles were embedded within the interlacing smooth and striated muscles. Branches of the pudendal nerve innervated them. CONCLUSION: Our anatomic and histologic findings highly correlate with the results of magnetic resonance imaging and endosonography as well as with the physiologic findings. Furthermore, they are of great clinical importance for the understanding of sphincter defects during vaginal delivery and for anorectal operations in the adult as well as in the child.

Adult↗

PubMed1991

[Regression of coronary atherosclerosis: possible--and clinically relevant?].

Several recent clinical trials have shown that in male patients with stable coronary heart disease, progression of atherosclerosis can be delayed even in short time. The interventions to bring about less progression and even a regression of coronary artery lesions mainly consisted in lowering high lipid levels, either with drugs, partial ileal bypass surgery or comprehensive lifestyle changes. The results of trials using calcium antagonists were less consistent and failed to show clear-cut slowing or prevention of progression. Some questions, however, arise and are discussed: i.e. the shortcomings of quantitative angiography to assess the extent of atherosclerotic lesions and the clinical importance of the observed changes in luminal diameter, which tended to be small. Despite these intriguing issues, the reported studies provided the additional information that the angiographically demonstrated benefits were paralleled by a reduction of clinical vascular events and an improvement of the short-term clinical outcome.

Coronary Angiography↗

PubMed1989

Neonatal therapeutic drug monitoring--its clinical relevance.

The potential clinical usefulness of therapeutic drug monitoring (TDM) in neonates is discussed. The personnel performing neonatal TDM must be knowledgeable in the many clinical, analytical, and pharmacokinetic variables used for measuring drug concentrations to formulate rational, individualized dosing regimens. Examples of variables and their effects on TDM interpretations are given and some gaps in our knowledge are presented. The theoretical promise of neonatal TDM is contrasted with the practical realities.

Humans↗

PubMed2006

Clinical relevance of rehabilitation programs for Parkinson's disease. I: Non-symptom-specific therapeutic approaches.

The idiopathic Parkinson syndrome (IPS) affects multiple structures of the central nervous system and exhibits a broad variety of clinical symptoms that are only partially treatable by pharmacological treatment. Therefore, non-pharmacological approaches are highly warranted. The aim of this study was to identify, categorize and rate studies on rehabilitative therapeutic approaches for IPS regarding not only study design and statistics, but also clinical relevance. For reasons of homogeneity, only studies applying a rehabilitative program targeting three or more symptoms were included and studies treating isolated symptoms were excluded. Study design and statistics were rated by using an established rating system. To evaluate clinical relevance a rating system was developed considering effectiveness, everyday life relevance, long-term effect, therapy frequency and setting, duration of the therapy units, effects on quality of life, and assessment. Applying this rating system to 17 studies, we found four studies with a Level I of statistical quality and four studies with high clinically relevant information. This novel method of analysing may help to gain valuable data from studies that may lack strong methodology, and may help to promote further research.

Data Collection↗

PubMed2005

The clinical relevance of sensitization to pollen-related fruits and vegetables in unselected pollen-sensitized adults.

BACKGROUND: Previous studies have described cross-reactivity between fresh fruits, vegetables and pollen. However, no data demonstrates the clinical relevance of sensitization to pollen-related fruits and vegetables in unselected pollen-sensitized adults with and without symptoms in the pollen season. OBJECTIVE: The aim of this study was to estimate the clinical relevance of sensitization to pollen-related fruits and vegetables in unselected pollen-sensitized adults and to examine the diagnostic value of skin-prick test (SPT), histamine release and specific IgE compared with the outcome of oral challenge. METHODS: In total, 936 unselected adults (female : male 479 : 457, median age 33.7 years) were examined for pollen sensitization and clinical cross-reactivity with pollen-related fruits and vegetables by questionnaire, SPT, histamine release, specific IgE and oral challenge. RESULTS: The prevalence of pollen sensitization was 23.8% (n = 223). The probability of a clinical reaction to pollen-related foods in the respective pollen-sensitized groups was: 24% (birch), 4% (grass), 10% (mugwort), 35% (birch + grass), 8% (grass + mugwort) and 52% (birch + grass + mugwort). The odds ratio of a clinical reaction to pollen-related fruits and vegetables in symptomatic pollen-sensitized adults was as high as four times (birch + grass) the odds ratio of a clinical reaction in asymptomatic pollen-sensitized adults. CONCLUSION: This study not only demonstrates a high prevalence of clinical reactions to fruits and vegetables in pollen-sensitized adults, but also a discrepancy between the prevalence of sensitization to fruits and vegetables and the clinical relevance in different pollen-sensitized groups with symptoms in the pollen season as a significant factor.

Adult↗

PubMed1998

The morphologic and molecular genetic categories of posttransplantation lymphoproliferative disorders are clinically relevant.

BACKGROUND: Posttransplantation lymphoproliferative disorders (PT-LPDs) are a well-known complication of immunosuppression associated with solid organ transplantation. The clinical course of PT-LPDs is unpredictable; some patients experience regression of all lesions with a reduction in immunosuppression, whereas other patients, despite chemotherapy, radiation therapy, or surgery, rapidly die of their disease. In this study, the authors attempted to establish whether the previously described morphologic and molecular genetic categories of PT-LPD--plasmacytic hyperplasia (PH), polymorphic PT-LPD (polymorphic), and malignant lymphoma/multiple myeloma (ML/MM)--are clinically relevant and helpful in predicting the clinical outcome of patients who develop these lesions. METHODS: To determine the clinical significance of the morphologic and molecular genetic categories of PT-LPDs, the clinical characteristics of 32 solid organ transplant recipients (26 heart, 5 kidney, and 1 lung), including age, time from transplantation to development of PT-LPD, stage of disease, and clinical outcome, were compared with the morphologic and molecular genetic features of the 41 PT-LPDs that they developed (15 PH in 12 patients, 19 polymorphic in 16 patients, and 7 ML/MM in 6 patients). Clinical outcome was defined by the following categories: 1) regression (after a reduction in immunosuppression) and surgical resolution (by surgical excision, with or without a reduction in immunosuppression); 2) medical resolution (by chemotherapy and/or radiation therapy); and 3) no response. RESULTS: Although there was no difference in the time from transplantation to PT-LPD development among patients belonging to the three morphologic and molecular genetic categories, there was a significant difference in patient age at the time of PT-LPD development (P < 0.0098). Younger patients developed PH (mean age of 19 years), whereas older patients developed polymorphic PT-LPD (mean age of 35 years) and ML/MM (mean age of 56 years). Patients with PH presented with lower stages of disease (Stages I-II) than patients with ML/MM (P < 0.0004). Furthermore, there was a statistically significant trend between morphologic and molecular genetic category and clinical outcome, with decreased likelihood that lesions categorized as PH, polymorphic, or ML/MM would regress with a reduction in immunosuppression or be resolved by surgery, whereas those classified as ML/MM were more likely to exhibit no response to aggressive clinical intervention (P < 0.00006). Furthermore, no patients with PH died, whereas 20% with polymorphic PT-LPD and 67% with ML/MM died as a direct result of their PT-LPDs. CONCLUSIONS: This study strongly suggests that classification of PT-LPDs into the morphologic and molecular genetic categories PH, polymorphic, PT-LPD and ML/MM is clinically relevant.

Adult↗

PubMed2004

Clinical relevance of calcaneal bone cysts: a study of 50 cysts in 47 patients.

The clinical relevance and nature of calcaneal cysts is controversial. The risk of pathologic fracture is undefined and diagnostic criteria to differentiate between cysts in patients who can be treated nonoperatively and patients who require surgical intervention are not available. To address these questions, 50 calcaneal bone cysts in 47 patients were evaluated. The majority of cysts (40 of 50) were asymptomatic and were treated nonoperatively. Cysts reaching a critical size, defined as 100% intracalcaneal cross section in the coronary plane and at least 30% in the sagittal plane, are at risk for becoming symptomatic and at risk for fracture. Fracture is a significant complication and occurred in four of 47 patients, three of whom were treated by open reduction internal fixation and bone grafting. In addition, six patients with symptomatic critical size cysts without apparent fracture were treated by curettage and subsequent autogenous bone grafting or calcium-phosphate cement filling, and there were no recurrences. We report one of the largest series of cysts in the calcaneus. The results suggest that calcaneal cysts are clinically relevant because of the potential risk of fracture and that size is a significant factor in terms of the treatment of the cyst.

Adolescent↗

PubMed2006

Clinical relevance of biological variation: the lesson of brain natriuretic peptide (BNP) and NT-proBNP assay.

The clinical relevance of brain natriuretic peptide (BNP) and N-terminal (NT)-proBNP assays as a diagnostic tool and prognostic marker in patients with cardiovascular diseases has recently been confirmed. However, several studies demonstrated variation of intra-individual BNP concentrations of >30% (ranging from 30% to 50%) with reference change values at the 95% confidence interval (i.e., the estimated critical difference) ranging from 99% to 130% in healthy subjects and heart failure patients. According to this estimated confidence interval, only a great variation in plasma BNP levels should be considered significant in an individual patient (for example, a decrease of >50% or an increase of more than two-fold). Many recent clinical studies have demonstrated that BNP variations below this estimated critical difference could also have clinical relevance. Like the concentration of other neuro-hormones, levels of plasma BNP fluctuate widely and rapidly along with heart rhythm and blood pressure variations in response to physiological stimuli. However, biological variation of BNP should not be interpreted strictly as random fluctuation around a homeostatic set point, as assumed by the common model used in all studies on biological variation of BNP reported in the literature. These results cannot be directly transferred to clinical practice. While awaiting more accurate studies, we suggest that variations of plasma BNP three-fold greater than the analytical imprecision should be considered as potentially relevant from a physiological and clinical point of view.

Heart Failure↗

PubMed2001

In vivo-in vitro model for the assessment of clinically relevant antimalarial cross-resistance.

Cross-resistance may be considered one of the most important factors leading to decreased drug susceptibility of Plasmodium falciparum. The study aimed to determine whether clinically relevant cross-sensitivity of P. falciparum existed between artemisinin and mefloquine. Seventy-six patients with falciparum malaria were admitted and treated with artemisinin derivatives. Treatment response parameters were assessed and in vitro drug sensitivity tests were performed with artemisinin, mefloquine, quinine, and chloroquine. Distinct in vitro cross-sensitivity between artemisinin and mefloquine was observed (p = 0.604; P < 0.001). To assess the relevance of this finding for clinical cross-resistance, we used an analytical model based on the relation of in vivo treatment response parameters (fever, parasite and symptom clearance) to a single reference drug with in vitro drug sensitivity data of several other drugs. Artemisinin (R = 0.554; P = 0.009) and mefloquine (R = 0.615; P = 0.002) in vitro drug sensitivities were equally well reflected in the in vivo treatment response to artemisinin, thereby suggesting the clinical relevance of in vitro cross-sensitivity.

Adult↗

PubMed1982

Clinical relevance of postextrasystolic potentiation.

The significance and clinical relevance of postextrasystolic potentiation resides in the fact that any change in duration of the cardiac cycle results in a change in the contractile behavior of the heart. Since neither a normal nor a diseased heart ever beats strictly regularly, postextrasystolic potentiation is continuously operative, and all hemodynamic or circulatory data obtained in the intact organism are affected by it. This means that postextrasystolic potentiation should be taken into account when cardiovascular clinical data are analyzed and subsequently used for diagnosis or treatment. Postextrasystolic potentiation used as an intervention for the evaluation of residual viable myocardium in scar tissue areas in patients with coronary heart disease may contribute to out insights in the prognosis of and therapeutic judgments in those patients. Postextrasystolic potentiation is a fundamental physiologic property of all myocardium under all circumstances and as such does not allow for integrating or averaging data obtained during more than one cardiac cycle, if cardiac rhythm has not been strictly regular. This fact is insufficiently appreciated in nuclear cardiology and two-dimensional echocardiography.

Animals↗