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Biomedical subjects

Horst Koch

Publications and source records attributed to Horst Koch.

At least 19 recordsLinked to original sources

Tenascin-C protein is induced by transforming growth factor-beta1 but does not correlate with time to tumor progression in high-grade gliomas.

BACKGROUND: Tenascin-C is an extracellular matrix protein known to correlate with prognosis in patients with glioblastoma, probably by stimulation of invasion and neoangiogenesis. Transforming Growth Factor-beta1 (TGF-beta1) plays an important role in the biology of high-grade gliomas, partly by regulating invasion of these tumors into parenchyma. This study was designed to evaluate if TGF-beta1 induces the expression and deposition of Tenascin-C in the extracellular matrix of high-grade gliomas which may be pivotal for the invasion of these tumors into healthy parenchyma. METHODS: A series of 20 high-grade gliomas was stained immunohistochemically with Tenascin-C- and TGF-beta1- specific antibodies. Expression levels of both proteins were evaluated and correlated with each other, time to progression and molecular and morphological markers of invasion. A quantitative PCR assay was performed evaluating the induction of Tenascin-C mRNA by treatment with TGF-beta1 in vitro. RESULTS: Tenascin-C was expressed in 18 of 19 (95%) evaluable tumors, whereas 14 of 20 tumors (70%) expressed TGF-beta1 in a significant percentage of cells. Treatment with TGF-beta1 did induce the expression of Tenascin-C at the mRNA and protein level in vitro. The expression of Tenascin-C and TGF-beta1 did neighter statistically correlate with each other nor with time to progression. CONCLUSION: In our series, Tenascin-C and TGF-beta1 were expressed in the vast majority of high-grade gliomas. We could not detect a correlation of one of the proteins with time to progression. Nevertheless, we describe induction of Tenascin-C by TGF-beta1, possibly providing a mechanism for the invasion of high-grade gliomas into healthy parenchyma.

Adult↗

Cerebrospinal fluid tau and beta-amyloid in Alzheimer patients, disease controls and an age-matched random sample.

We prospectively evaluated the diagnostic accuracy of cerebrospinal fluid (CSF)-beta-amyloid1-42 (Abeta42), -total-tau (tau) and -phosphorylated-tau181 (p-tau181) as measured by sandwich ELISAs in the clinical routine of a community state hospital to discriminate between patients with Alzheimer's disease (AD), healthy controls (HC), non-AD-dementias, a group composed of various psychiatric disorders (non-AD-dementias, mental diseases) and an age-matched random sample (RS) (total N=219). By comparing patients with AD to HC as reference, tau revealed sensitivity (sens)/specificity (spec) of 88%/80%, p-tau(181) 88%/80%, tau/Abeta42-ratio 81%/85% and phospho-tau(181)/Abeta42-ratio 81%/78%. Discriminative power between HC and all dementias under investigation was estimated lower for tau (78%/77%) and p-tau(181) (73%/79%). Relative to patients with AD, ROC analysis for the RS revealed highest sens/spec for p-tau181 (79%/77%) and p-tau181/Abeta42 ratio (78%/75%). Differentiation between AD versus a group made of patients with various psychiatric disorders was optimised by using CSF-p-tau181 (80%/77%). Under clinical routine conditions current CSF-biomarkers show a substantial capacity to discriminate between AD and HC as reference and to mark off AD patients from RS and heterogeneous diagnostic groups composed of non-AD dementias and other psychiatric conditions. Despite a residual substantial overlap between the groups, we conclude that current CSF markers are well suited to support AD-related diagnostic procedures in every-day clinics.

Aged↗

Evidence of a polyclonal nature of myositis ossificans.

Myositis ossificans is a localized, self-limiting, reparative lesion that is composed of reactive hypercellular fibrous tissue and bone. Although it is clearly a benign lesion, its clinical, radiological, and histological appearance may sometimes mimic a malignant tumor. Whether myositis ossificans represents a monoclonal or polyclonal hyperplastic proliferation is not yet known. To address this question, we therefore extracted DNA from the respective paraffin-embedded tumor tissues of nine women with a median age of 50 years at diagnosis (range: 20-84 years) and studied the X inactivation pattern by means of methylation-sensitive polymerase chain reaction and primers that target the polymorphic CGG trinucleotide repeat of the FMR1 gene. The fact that we did not detect any skewing of the X inactivation pattern in the five successfully analyzed cases corroborates the notion that myositis ossificans results from a polyclonal proliferation and confirms that it is a reactive, reparative process. Analysis of the X inactivation pattern may, thus, supplement the differential diagnostic work-up of cases with an uncertain histology, at least in the informative proportion of female patients.

Adult↗

Detection of cardiac right-to-left shunts by contrast-enhanced harmonic carotid duplex sonography.

OBJECTIVE: Paradoxical embolization by cardiac right-to-left shunts (RLS) is increasingly recognized as an important factor for embolic stroke. Contrast-enhanced transcranial Doppler sonography (ce-TCDS) is an established diagnostic tool for RLS detection but is frequently limited because of an inadequate temporal acoustic bone window. The purpose of this study was to determine whether extracranial sonography (ECS) using harmonic frequencies improves detection of RLS. METHODS: Extracranial color duplex sonography using harmonic frequencies enables visualization of even single ultrasound contrast agent microbubbles because of oscillation. Patients with stroke and positive RLS findings on transesophageal echocardiography underwent a simultaneous extracranial and transcranial sonographic examination of the proximal common carotid artery (CCA) and middle cerebral artery (MCA) on the same side. A Valsalva strain was performed for 10 seconds after intravenous bolus injection of a galactose-based nontranspulmonary contrast agent. The B-mode frame sequences of the transverse plane of the CCA obtained by harmonic ECS and the ce-TCDS recordings of high-intensity transient signals from the MCA were analyzed offline. RESULTS: In all patients with RLS, the shunts could be identified by harmonic ECS. A close correlation could be seen between the count of visualized microbubbles in the CCA and the number of high-intensity transient signals detected on ce-TCDS in the ipsilateral MCA. CONCLUSIONS: The results of this study indicate that contrast-enhanced ultrasound harmonic imaging of the CCA using a Valsalva strain might be an optional screening tool for detection of cardiac RLS in patients with insufficient acoustic bone windows.

Carotid Artery, Internal↗

Minimal hepatic encephalopathy impairs fitness to drive.

It has been suggested that the ability to drive a car is impaired in patients with cirrhosis of the liver and minimal hepatic encephalopathy (MHE). However, the only study using an on-road driving test did not reveal such an impairment. In a prospective controlled study, we evaluated patients with cirrhosis of the liver for MHE and the ability to drive a car. MHE was diagnosed using three psychometric tests: Number Connection Test Part A, Digit Symbol Test, and a Complex Choice Reaction Test. In a standardized on-road driving test (22 miles, 90 minutes), designed for patients with brain impairment, a professional driving instructor blind to the subjects' diagnosis and test results assessed the driving performance. Four global driving categories (car handling, adaptation to traffic situation, cautiousness, maneuvering), 17 specific driving actions (e.g., changing lanes, overtaking, etc.), and a total score of driving performance were rated using a 6-point scale. Of 274 consecutive patients with liver cirrhosis, 48 fulfilled the medical and driving inclusion criteria, 14 of them with and 34 without MHE. Forty-nine subjects in a stable phase of chronic gastroenterological diseases and with normal liver findings served as controls. The total driving score of patients with MHE was significantly reduced in comparison to either cirrhotic patients without MHE or to controls (P <.05). Significant differences in ratings were found in the following driving categories: car handling, adaptation, and cautiousness. Significant differences were also found in specific driving actions. The instructor had to intervene in the driving of 5 of the 14 MHE patients to avoid an accident, significantly more than in cirrhotic patients without MHE and in controls. There was no significant difference in any driving category or specific driving action in cirrhotic patients without MHE compared to controls. In conclusion, fitness to drive a car can be impaired in patients with MHE. Therefore, patients with liver cirrhosis should be tested for MHE and informed in the case of abnormal test results. Therapy known to improve psychometric test results should be initiated.

Adult↗

Clinical application of the retrograde arterialized venous flap.

Retrograde arterialized venous flaps were applied to skin and soft-tissue defects in 13 patients with an average age of 34.4 years. Ten defects were located on the hand, and three on the lower leg. All flaps were harvested from the flexor aspect of the forearm; they ranged in size from 2 x 1 to 11 x 7 cm. There was venous congestion with superficial epidermolysis in six flaps, but not in the other seven. Partial skin necrosis in two of the lower-extremity flaps necessitated secondary skin grafts. Our results suggest that retrograde perfusion enhances blood flow in the periphery of arterialized venous flaps and gives good results in terms of flap survival, especially on the upper extremity.

Adult↗

The posterior interosseous artery in the distal part of the forearm. Is the term "recurrent branch of the anterior interosseous artery" justified?

In 1993 Angrigiani raised the question as to whether the distal part of the posterior interosseous artery (AIP) is a recurrent branch of the anterior interosseous artery (AIA) and forms a "choke"--anastomosis with the AIP in the middle of the forearm. A dissection study was conducted on 66 upper extremities to evaluate the diameters of the dorsal branch of the anterior interosseous artery, the anastomotic branch, the diameter of the posterior interosseous artery at the point of origin of the septocutaneous perforators in the middle of the forearm and the diameter of the posterior interosseous artery at the point of emergence in the dorsal compartment. We further tried to identify different forms and types of the "distal" anastomosis and the connections to the dorsal carpal arch and the ulnar artery. A distal anastomosis between the AIA and AIP was found in 65 of the 66 upper extremities. Three different types of anastomosis could be identified. The smallest diameter was found at the middle of the forearm (mean diameter AIA 1.28 mm; anastomotic branch 0.6 mm; AIP at the middle of the forearm 0.39 mm; AIP prox. 1.35 mm). A branch through the fifth extensor compartment was present in all of our specimens (mean diameter 0.54 mm). A branch through the forth extensor compartment could be found in 16 specimens. Based on our findings and the embryological development, we conclude that the AIP is only present in the proximal half of the forearm. In the distal part, the dorsal branch of the anterior interosseous artery forms a vascular arcade, which gives off branches to the dorsal carpal arch, the ulnar head and the ulnar artery. This arcade anastomoses with the posterior interosseous artery in the middle of the forearm by means of a choke anastomosis. We also conclude that the term "recurrent branch of the anterior interosseous artery" for the distal part of posterior interosseous artery is correct.

Adult↗

Necrotizing fasciitis after ambulatory phlebectomy performed with use of tumescent anesthesia.

The high cost of treatment of varicose veins has an important role in public health care. The search for a less expensive and office-based procedure led to introduction of tumescent local anesthesia for use in ambulatory phlebectomy. Although the overall infection rate is low, severe infection has been reported after liposuction with tumescent anesthesia. We report necrotizing fasciitis, an infection with a mortality rate of 30% to 50%, after ambulatory phlebectomy and stripping of the long saphenous vein with use of tumescent anesthesia.

Ambulatory Surgical Procedures↗

Maintenance therapy with 13-cis retinoid acid in high-grade glioma at complete response after first-line multimodal therapy--a phase-II study.

BACKGROUND: Approximately 5% of patients with malignant glioma achieve complete response (CR) after first-line combined modality treatment. Although these patients will invariably suffer from tumor recurrence, they usually do not receive any further treatment to maintain remission. According to in vitro and in vivo clinical studies, 13-cis retinoic acid (cRA) may be a promising agent for maintenance therapy in these patients. OBJECTIVE: We initiated a clinical study to evaluate the feasibility and toxicity of high-dose cRA as maintenance therapy in patients with high-grade glioma in complete remission after first-line multimodal treatment. METHODS: A prospective single-arm phase-II study in patients with CR after combined first-line therapy (neurosurgery, radio- and chemotherapy) was performed. Patients were treated with cRA at 60 mg/m2 BS from day 1 to 21 in four-weekly cycles with a dose escalation of up to 100 mg/m2 BS until tumor recurrence. Clinical controls were performed every 4 weeks, magnetic resonance imaging every 8 weeks. RESULTS: Twenty-three patients (10, grade IV; 13, grade III) were evaluable using an intention-to-treat analysis. Treatment was well tolerated for up to 149 weeks with moderate dermatological symptoms in all patients. No grade 4 toxicities were observed. Median time to progression was 41 weeks, median overall survival 74 weeks after inclusion in the protocol. DISCUSSION: There is an urgent need for strategies maintaining remission in patients with malignant glioma. Maintenance therapy with high-dose cRA is feasible and well tolerated over long periods of time. A controlled clinical trial to test the efficacy of cRA as a maintenance treatment in malignant glioma is warranted.

Adult↗

[The situation of caregiver counselling in patients with frontotemporal lobar dementia in old psychiatry].

Caregiver counselling is an indispensable feature of current concepts for dementia treatment. Self-support groups and psychoeducative programms for caregivers of patients with Alzheimer's disease may reduce the burden of nursing and psychological strain. Specific caregiver needs from patients with frontotemporal lobar dementia (FTLD [frontotemporal dementia, semantic dementia, progressive aphasia, corticobasal degeneration]) are only partially taken into account. We conducted a German wide epidemiologic study which revealed that specific counselling for supporting relatives and caregivers of patients with FTLD is only fragmentary in hospital services for old age psychiatry. In most cases, they are referred to the local Alzheimer's disease Associations (89 %). Besides that, the existence of large hospital care units has significant negative repercussions on psychosocial supply for caregivers of patients with FTLD. To establish decentralized support units by these hospitals would lead to a significant improvement of medical and social care in this field.

Aged↗

Verrucous carcinoma of the skin: long-term follow-up results following surgical therapy.

BACKGROUND: Owing to the benign appearance and slow growth of verrucous carcinoma of the skin, its diagnosis and therapeutic management still pose problems. OBJECTIVE: This study was undertaken to point out clinical and histopathologic features of verrucous carcinoma of the skin and to provide diagnostic and therapeutic guidelines on the basis of the long-term results from 20 patients. METHODS: A retrospective study of the long-term results of 20 patients treated surgically for verrucous carcinoma of the skin is presented. In 16 cases, a wide resection with histopathologic examination of the margins was possible. Two tumors were shaved; 1 case required below-knee amputation and 1 patient refused primary amputation. In April 1999, 9 of the 10 surviving patients underwent physical examination, ultrasonography of the regional lymph nodes and the abdomen, and chest X-ray. The protocols of autopsies or postmortem examinations of the deceased patients were consulted. RESULTS: The deceased patients achieved an average tumor-free survival period of 86.1 months; eight of the surviving patients had an average tumor-free follow-up of 127.4 months. Two patients suffered recurrences. CONCLUSION: Curative treatment can be achieved by timely and complete resection of verrucous carcinoma of the skin, even in advanced cases.

Aged↗

The treatment of painful neuroma on the lower extremity by resection and nerve stump transplantation into a vein.

Lower extremity neuroma resection with nerve stump transposition into a vein was employed in eight patients (five male, three female). The neuromas resulted from amputations (four patients), vein stripping procedures (two patients), tumor resection, and toe-harvest for thumb reconstruction. Follow-up averaged 17 months (range, 8-37). Four of the patients experienced complete and permanent relief of pain; in three patients mild pain recurred within 3 months. All of these patients were satisfied with the result and did not request further treatment. In one case, a painful neuroma recurred. Our results suggest the possibility of inhibiting the formation of painful neuromas by nerve transposition into a vein. Further use of this method is encouraged.

Adult↗

Expression levels of melanoma inhibitory activity correlate with time to progression in patients with high-grade glioma.

Melanoma inhibitory activity (MIA) is related to disease progression in patients with malignant melanoma and to invasion and metastasis of melanoma in vivo and in vitro. An alternative splice product termed MIA(splice) was described recently. In addition to melanoma, both proteins are expressed in a substantial subset of high-grade gliomas. We hypothesize that expression levels of both proteins correlate with early tumor progression and parameters of disseminated disease in patients with high-grade glioma. We examined the correlation of expression levels of MIA and MIA(splice) with time to progression and morphological and clinical markers of disseminated disease (defined as multifocal occurrence, gliomatosis, invasion or metastasis) in a series of 24 newly-diagnosed human high-grade gliomas. Homogenates of surgical specimens, cell cultures and blood samples were analyzed. Significant levels of MIA and MIA(splice) protein were detected in 71% of homogenates of high-grade glioma, but not in the related blood samples. Patients with early tumor progression had lower expression levels of MIA than patients with late progression, and the expression level of MIA was inversely related to time to progression. In addition, MIA expression correlated with a high fiber content of the extracellular matrix, suggesting a role in dissemination as known from malignant melanoma. Expression levels of MIA in homogenates of surgical specimen directly relate to a more benign clinical prognosis in patients with high-grade glioma. While a mechanistic relation has not yet been verified, factors such as a high fiber content of the extracellular matrix may explain this observation.

Adult↗

Salvage therapy in patients with glioblastoma: is there any benefit?

BACKGROUND: Survival after first-line therapy is poor for patients with glioblastoma. The role of second-line treatment for recurrent disease is controversial. The authors studied the outcome in a subset of patients with glioblastoma who were selected for an aggressive reintervention strategy at the time of progression. Their objectives were to improve patients' overall survival with sustained quality of life and to make comparisons with overall survival in unselected patients. METHODS: Overall, 168 patients were eligible for retrospective analysis. Ninety patients received specific therapy for disease recurrence (reintervention group) by specific criteria. RESULTS: In the reintervention group, promising median overall survival (mOS) results after diagnosis (61.5 weeks) and progression (33 weeks) were obtained. The progression-free survival (PFS) rate at 12 months and the overall survival rate were superior in the reintervention group (71% at 12 months and 32% at 24 months) compared with the total cohort (45% and 20%, respectively) and the standard group (15% and 5%, respectively). A matched-pair analysis (n = 46 in each group), with an mOS period of 65.5 versus 28.5 weeks, confirmed these data. Quality of life was stable or slightly improved during reinterventions in a subset of patients treated within clinical studies. CONCLUSIONS: The majority of patients in the current series were treated with a reintervention strategy, which had an impact on PFS and mOS. A second resection, focal radiotherapy (in selected cases), and additional chemotherapeutic regimens should be considered for patients with recurrent glioblastoma.

Adult↗

Retrograde arterialized venous flap: an experimental study.

An experimental model was established to study circulation in retrograde arterialized venous flaps (RAVF). Venous flaps measuring 7 x 4 cm with a matching venous system were harvested from both forearms of 10 fresh human cadavers. In each trial, both flaps were simultaneously perfused with heparinized human blood driven by a pulsatile circulation model. In each trial there was one flap with retrograde perfusion, and one flap with antegrade perfusion. Clinical assessment, measurement of outflow, and angiographic examination with digitally assisted assessment after 3 h of perfusion showed better results for retrograde perfusion in 8 of the 10 trials. This study indicates that blood circulation in the periphery of arterialized venous flaps can be enhanced by retrograde arterialization.

Angiography↗

Free osteocutaneous lateral arm flap: anatomy and clinical applications.

For many surgeons, the potential to reconstruct skin, fascia, tendon, or bone in a single-stage procedure has made the lateral arm flap the technique of choice for reconstruction of complex defects. The aim of this study was to examine more closely how the humeral bone is supplied by the posterior collateral radial artery. To this end, we dissected 30 cadaver arms to determine the vascular relationship of the lateral arm flap to the humerus. The number of directly supplying vessels, and height to the lateral epicondyle of the humerus, were examined. The reconstructive potential of the osteocutaneous flap in different indications is analyzed in a series of five clinical cases. In all dissected extremities, we found one or two branches of the posterior collateral artery directly and constantly supplying the bone between 2-7 cm proximal to the lateral epicondyle. In five cases, combined defects, including bone, were successfully reconstructed with lateral arm flaps, including vascularized bone.

Adolescent↗

Management of neuromas.

After nerve injury and regeneration, significant pain may be associated with the scar and altered sensation observed within the distribution of the injured nerve. A bulbous swelling may form at the severed nerve end, constituting a traumatic neuroma. The development of a painful neuroma may be more disabling to the patient than an area of anesthesia or even loss of motor function. Effective treatment of the painful neuroma remains a difficult problem. Diminished productivity, alterations in patient lifestyle, and possible progression to chronic pain syndromes must be considered within the scope of neuroma management, and treatment must focus on alleviating the pain and restoring the functional loss caused by the nerve injury. Careful patient selection is the cornerstone of successful outcomes. Once the patient has been selected, the surgical management of the painful neuroma throughout the body is based on basic principles that vary only slightly from region to region. Using these tenets, a neuroma management algorithm has been developed based on the pathophysio-logy of the neuroma, the results of experimental studies, review of patient outcomes, and understanding the psychology of pain in the surgical patient.

Extremities↗