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Biomedical subjects

E Hungerhuber

Publications and source records attributed to E Hungerhuber.

18 recordsLinked to original sources
PubMed2006

Lymphoscintigraphy in penile cancer: limited value of sentinel node biopsy in patients with clinically suspicious lymph nodes.

The staging lymph node dissection in patients with penile carcinoma is accompanied with a high morbidity. As many patients are free of nodal metastases the lymphoscintigraphic sentinel node biopsy is supposed to minimize perioperative morbidity in these patients. In the current study the accuracy of the lymphoscintigraphic sentinel node biopsy was verified against the gold standard of radical inguinal dissection. In particular, patients with enlarged lymph nodes have also been included since one half of these patients is known to have histologically negative lymph nodes. Between 2000 and 2004 fifteen patients with penile carcinoma were elected to undergo bilateral groin dissection, thus 30 inguinal areas have been dissected. Nine patients have had clinically palpable nodes. All patients underwent lymphoscintigraphy after injection of Tc99-nanocolloid subcutaneously into the peritumoral area. Intraoperatively the sentinel nodes were identified with the aid of a gamma ray detection probe and excised. Afterwards a standard groin dissection was performed and the different lymph nodes were histopathologically assessed separately. In all patients lymph nodes with high radioactivity uptake were detected bilaterally. In 10 out of 30 inguinal areas histopathologically positive lymph nodes were present. In four of them the sentinel node was positive for tumor but in six dissection areas lymph node metastases were found despite a negative sentinel node. These patients had clinically palpable lymph nodes in their histologically positive inguinal regions. If no palpable nodes were present dynamic sentinel biopsy detected the positive nodes. The current study showed that dynamic sentinel node biopsy in patients with clinically suspicious lymph nodes is of low value for detection of lymphatic spread in penile cancer. Therefore the gold standard in these patients remains the radical groin dissection. However, dynamic sentinel node biospy is still a promising strategy to identify lymphatic spreading in clinically N0 patients and therefore to prevent unnecessary groin dissection.

Adult↗
PubMed2006

[Condylomata acuminata: an indication for prophylactic HPV vaccination?].

HPV infection is one of the most common sexually transmitted infections worldwide. Although most infections are transient, persistent ones can lead to condylomata acuminata, genital intraepithelial neoplasia and genital cancer. The recent approval of vaccines against HPV has raised great hopes. Since 1990, 5,392 urological investigations for HPV were carried out in 1,792 men in special HPV centres. We report on the epidemiology and natural course of condylomata, techniques for HPV detection, treatment surveillance and long-term sequelae. Condylomata acuminata proved to be pathognomonic; partner infections were diagnosed in 50% and more. Systematic HPV DNA analyses in partner investigations or as screening investigations cannot be recommended. Ultimately, within the spectrum of therapeutic options for condylomata, no method is really superior to others; recurrences occurred in 30-70% of cases. We definitely need the HPV vaccination programme to get rid of one of the oldest and up to now unsolved problems of mankind.

Condylomata Acuminata↗
PubMed2003

Fluorescence diagnosis: a novel method to guide radical inguinal lymph node dissection in penile cancer.

In penile cancer there is still a diagnostic dilemma between over treatment of lymph node-negative patients and the missing of occult metastases by watchful waiting. In the current study the value of fluorescence diagnosis during radical inguinal lymph node dissection was evaluated. Five patients with penile cancer were elected to undergo groin dissection. All patients received 5-aminolevulinic acid (5-ALA) orally before the operation for fluorescence diagnosis. Intraoperatively, fluorescence detection of the lymph nodes was performed by visual detection and spectroscopy. Two of the five patients had positive inguinal lymph nodes. Fluorescence in tumor-bearing tissue was detectable in the exposed lymph nodes. Protoporphyrin IX (PPIX) is accumulated in tumor-positive lymph nodes, making fluorescence diagnosis in penile cancer possible. More studies with higher patient numbers are necessary to evaluate optimal dosage and excitation conditions to detect tumor-bearing nodes in vivo.

Fluorescence↗
PubMed2003

[Papules, fungi, protozoa--or cancer? Many skin conditions of the penis can be confirmed with biopsy].

The male genitals can be affected by infections, neoplastic and inflammatory dermatoses. This means that numerous diseases have to be included in differential diagnostic considerations to discriminate premalignant from malignant penile tumors. Basically, penile carcinoma cannot be excluded by clinical examination alone. Apparently clinically benign penile lesions may be the cause of a misdiagnosis persisting of lengthy periods. Therefore, the correct diagnosis should be confirmed by timely biopsy whenever there is a doubt. The identification of known risk factors and the early detection and treatment of all precancerous lesions are indispensable for preventing cancer of the penis.

Biopsy↗
PubMed2003

[Carcinomas of the upper urinary tract. With early diagnosis 80-100% of patients survive 5 years].

About 5% of all urothelial cancers develop in the upper urinary tract, i.e. in the ureter or renal pelvis. 40-70% of the tumors appear to be associated with cigarette smoking. The most common symptom seen in ureteral cancer is painless hematuria. The diagnosis is established by radiography and endoscopy. The most important diagnostic aids are urinary status, ultrasonography, excretory urography, ureteropyelography and endoscopy. Owing to the fact that this tumor entity is often multifocal, cystoscopy to exclude involvement of the bladder is mandatory. Superficial "low-grade" tumor stages can be treated endoscopically, in particular in the case of patients with only a single kidney or bilateral involvement. For more advanced stages, nephroureterectomy, together with the removal of a "cuff" of the bladder and ipsilateral lymphadenectomy, is indicated.

Adenocarcinoma↗
PubMed2003

[Urological emergencies].

Urological emergencies that require specialist treatment include testicular torsion, gross hematuria, urogenital injuries and acute flank pain. After initial symptoms-adapted therapy, patients should be transferred immediately to an urological department for imaging (e.g. ultrasound, IVP, CT) and further specific examinations (e.g.blood tests, urine analysis, microbiology). Acute lower abdominal and scrotal pain in young men may be symptomatic of testicular torsion, which requires immediate urological surgery. Gross hematuria is usually not a life-threatening emergency. Nevertheless, urogenital tumor has to be ruled out by an urologist. Patients with urogenital injuries are triaged into surgical and non-surgical treatments. Differential diagnosis of acute flank pain falls into several medical fields. After initial symptom-related therapy, further diagnostic procedures have to be performed. Septic presentation may be symptomatic of infectious hydronephrosis which requires immediate urological intervention.

Diagnosis, Differential↗
PubMed2003

Neuroprotective efficacy of intra-arterial and intravenous magnesium sulfate in a rat model of transient focal cerebral ischemia.

BACKGROUND: Many neurovascular procedures necessitate temporary occlusion of cerebral arteries. In this situation neuroprotective drugs may increase the safety of the procedures. Magnesium may inhibit ischemic damage by anti-excitotoxic, calcium channel blocking and vasodilatory action. Some evidence suggests that intra-arterial administration might provide a much higher degree of protection than intravenous treatment. In this study the neuroprotective efficacy of intra-arterial and intravenous magnesium administration was examined in a rat model of transient focal ischemia. METHODS: 34 male Sprague-Dawley rats were subjected to 90 minutes of middle cerebral artery occlusion (MCAO) by an intraluminal thread. Before ischemia, animals received an infusion of either (1) vehicle (0.9% NaCl) (2) MgSO4 intra-arterially or (3) MgSO4 intravenously. Local cortical blood flow (LCBF) was continuously measured by laser-Doppler flowmetry. Functional deficits were quantified daily, infarct volumes were assessed histologically after 7 days. FINDINGS: There was no difference between the treatment groups concerning LCBF. Magnesium serum levels increased from approximately 1 mmol/l to approximately 1.8 mmol/l by either route of administration. Both intra-arterial and intravenous treatment improved neurological recovery and equally reduced total infarct volume by approximately 25%. INTERPRETATION: The results indicate that there is no advantage of intra-arterial over intravenous magnesium administration. A comparison with previous studies suggests that even within the normal range of serum magnesium concentrations, low-normal levels may be hazardous and high-normal levels may be protective in transient focal ischemia.

Animals↗
PubMed2002

Penile carcinoma. Is Nd:YAG laser therapy radical enough?

PURPOSE: Penile carcinoma is a difficult disease to treat due to its aggressive nature and the psychological effects of amputation, which is often the recommended therapy. Outcome data from the last 13 years on patients with penile carcinoma treated with Nd:YAG laser coagulation were evaluated and compared with outcome data on conventional organ sparing techniques. MATERIALS AND METHODS: For the last 13 years 29 patients were treated with Nd:YAG laser coagulation, including 17 with carcinoma in situ, and 10 with stage T1 and 2 with T2 cancer. Mean patient age was 55.1 years and mean followup was 46.7 months. RESULTS: All patients are alive. Disease recurred in 1 patient with T1 tumor and 1 with carcinoma in situ. All patients were satisfied with the cosmetic and functional result. CONCLUSIONS: Recurrence rates after Nd:YAG laser treatment for T1 tumors are comparable to those after partial amputation. Excellent cosmetic and functional results can be achieved without compromising oncological principles. For patients with metastasis prognosis is limited by the distant disease and, therefore, amputation is only necessary to achieve local control.

Adult↗
PubMed2000

Neurological impairment in rats after transient middle cerebral artery occlusion: a comparative study under various treatment paradigms.

The assessment of the functional outcome - in addition to the conventional endpoints as histomorphometry of the ischemic brain damage - for the evaluation of cerebroprotective therapies is increasingly recommended, although there is little consensus on appropriate procedures. We evaluated a battery of sensorimotor tasks in rats after transient middle cerebral artery occlusion (MCAO) to select those with the highest potential to discriminate between various degrees of neuronal damage. A total of 40 Sprague-Dawley rats were subjected to 90 min of MCAO and assigned to one of four treatment arms: (1) sham-operated controls, (2) vehicle-treated controls, (3) moderately effective neuroprotection by 2x100 mg/kg alpha-phenyl-N-tert-butyl nitrone (PBN), (4) highly effective neuroprotection by mild hypothermia (33 degrees C). Functional deficits were daily quantified using the beam balance task (1.5 cm, 2.5 cm diameter rectangular and 2.5 cm diameter cylindrical beam), the prehensile traction task, the rotarod, and a six-point neuro-score. Infarction of cerebral cortex and basal ganglia was assessed one week after ischemia. Treatment with PBN significantly reduced cortical infarction (-31%), while treatment with hypothermia resulted in a significantly smaller infarct volume of cortex (-94%) and basal ganglia (-27%). Beam balance, prehensile traction and rotarod failed to demonstrate any difference in motor performance. The six-point neuro-score showed a significant correlation with cortical infarction from day 2 and with total infarct volume from day 3. The smaller the reduction of infarct volume, the later the corresponding difference in neuro-score became apparent. Functional outcome after MCAO in rats can be assessed by a relatively simple measurement of neurological deficit. The slope of functional recovery is closely related with the degree of the morphological, particularly cortical damage. If expected treatment effects are small, an observation period of at least 3 days should be planned for the study design. The functional impairment from focal brain ischemia and its subsequent recovery could provide valuable information for future studies evaluating the neuroprotective potential of novel agents and procedures.

Animals↗
PubMed2000

Neuroprotective effects of the novel brain-penetrating antioxidant U-101033E and the spin-trapping agent alpha-phenyl-N-tert-butyl nitrone (PBN).

Literature on the therapeutic efficacy of free radical scavengers suggests that drugs that are able to cross the blood-brain barrier are more effective in protecting the brain from ischemic damage. However, the exact mechanisms by which brain-penetrating antioxidants act have yet not been delineated. We compared the neuroprotective potential of the newly discovered pyrrolopyrimidine U-101033E with that of alpha-phenyl-N-tert-butyl nitrone (PBN) and investigated their influence on cerebral blood flow. Thirty male Sprague-Dawley rats were subjected to 90 min of middle cerebral artery (MCA) occlusion by an intraluminal filament. Local cerebral blood flow (LCBF) was bilaterally recorded by laser Doppler flowmetry. Neurological deficits were quantified daily. Infarct volume was assessed after 7 days. MCA occlusion reduced ipsilateral LCBF to 20-30% of baseline. After reperfusion, postischemic hyperemia was followed by a decrease in LCBF to about 70% of baseline. There was no difference in LCBF among groups. U-101033E improved neurological function and reduced infarct volume by 52% (P < 0.05). Improvement of neurological function and reduction of infarct volume (-25%) in animals treated with PBN was not significant. We conclude that U-101033E has superior neuroprotective properties compared with PBN. Neither drug improves blood flow during ischemia and 1 h of reperfusion. The mechanisms by which these brain-penetrating antioxidants act remain to be clarified.

Animals↗
PubMed1999

Neuroprotective efficacy of combination therapy with two different antioxidants in rats subjected to transient focal ischemia.

The vascular endothelium and parenchyma of the brain have both potential pathways to generate free radicals under pathological conditions. We evaluated the neuroprotective efficacy of two different antioxidants, a microvascularly acting 21-aminosteroid (U-74389G) and a brain-penetrating pyrrolopyrimidine (U-101033E) alone and in combination. Forty Sprague-Dawley rats were randomly assigned to one of four treatment groups: (1) vehicle-treated controls, (2) U-74389G, (3) U-101033E, (4) U-74389G+U-101033E. Drugs were administered in a dosage of 3x3 mg/kg i.v. before, during, and after ischemia. All animals were subjected to 90 min of middle cerebral artery occlusion. Local cortical blood flow (LCBF) was continuously recorded by bilateral laser Doppler flowmetry. Functional deficits were quantified by daily neurological examinations. Infarct volume was assessed after 7 days. There were no significant differences in LCBF among groups. U-101033E improved neurological function from postoperative day 4 to 7, while U-74389G did not improve neurological recovery. Animals treated with both drugs showed significantly less deficits from postoperative day 1 to 7. U-101033E and combination therapy reduced total infarct volume by 53% and 54% (P<0.05). U-74389G non-significantly reduced total infarct volume by 25%. Cortical infarct volume was significantly reduced in all treatment groups but only U-101033E and combination therapy protected the basal ganglia from infarction. In conclusion, brain-penetrating antioxidants have superior neuroprotective properties compared to microvascularly acting agents. Combination therapy, affording antioxidation plus radical scavenging in blood vessels and brain parenchyma, might yield the highest degree of neuronal protection from peroxidative damage. The neuroprotective efficacy seems to be independent of CBF.

Analysis of Variance↗
PubMed1999

EEG burst suppression is not necessary for maximum barbiturate protection in transient focal cerebral ischemia in the rat.

Barbiturates have been demonstrated to reduce the cerebral metabolic rate (CMR) in a dose-dependent manner but investigations of a dose-response relationship for their neuroprotective efficacy are scant. It has been suggested that barbiturates possess other mechanism of action that may be critical to their protective effect. If so, it is conceivable that the peak effect of such mechanisms does not parallel the reduction in CMR. Thus, maximal neuroprotection may be achieved with a substantially lower dose of the drug. Thirty Sprague-Dawley rats were subjected to 2 h of middle cerebral artery occlusion while either anesthetized with (1) halothane (control) or (2) intravenous thiopental titrated to cause mild EEG suppression or (3) thiopental titrated to maintain EEG burst suppression. Cortical blood flow was recorded by continuous bilateral laser Doppler flowmetry (LDF). Infarct volume was assessed after 3 h of reperfusion. Low-dose thiopental decreased blood flow to 80% of baseline and high-dose thiopental to 70% of baseline. LDF did not indicate improvement of blood flow by thiopental in the ischemic area. Compared to controls, low-dose thiopental significantly decreased infarct volume by 28% and high-dose thiopental by 29%. The results of this study and a review of literature indicate that barbiturates provide cerebral protection but that the magnitude of this effect has been overestimated. Other mechanisms than CMR reduction seem to contribute to their beneficial effects, and high doses administered to the point of burst suppression may not be required to obtain maximal protection.

Animals↗
PubMed1999

Neuroprotective effects of combination therapy with tirilazad and magnesium in rats subjected to reversible focal cerebral ischemia.

OBJECTIVE: Cell death after cerebral ischemia is mediated by release of excitatory amino acids, calcium influx into cells, and generation of free radicals. We examined the hypothesis that concurrent administration of tirilazad, a well-known antioxidant, and magnesium, an antagonist of calcium and excitatory amino acids, would result in a synergistic neuroprotective effect. METHODS: Sprague-Dawley rats were subjected to transient middle cerebral artery occlusion and assigned to one of four treatment arms (n = 10 in each): 1) vehicle, 2) tirilazad, 3) MgCl2, or 4) tirilazad and MgCl2. Cortical blood flow was recorded using laser Doppler flowmetry. Functional deficits were quantified by performing daily neurological examinations. Infarct volume was assessed after 7 days. RESULTS: There was no difference in cortical blood flow among groups. Animals that received tirilazad or MgCl2 monotherapy had significantly better neurological function compared with control animals only on postoperative Days 3 and 4, whereas animals treated with both drugs had significantly better neurological function than did control animals from postoperative Days 2 through 7. Magnesium reduced total infarct volume by 25% (nonsignificant), tirilazad by 48% (P<0.05), and combination therapy by 59% (P<0.05) compared with control data. CONCLUSION: Combined therapy with antagonists of excitatory amino acids and free radicals provides better neuroprotection from the effects of transient focal ischemia than does therapy with either antagonist alone. In contrast to many experimental agents, tirilazad and magnesium offer the advantage of being licensed for clinical use. This drug combination could be of great benefit when administered before temporary artery occlusion in patients undergoing cerebrovascular surgery.

Animals↗
PubMed1999

Combination drug therapy and mild hypothermia: a promising treatment strategy for reversible, focal cerebral ischemia.

BACKGROUND AND PURPOSE: Hypothermia has been suggested to be the most potent therapeutic approach to reduce experimental ischemic brain injury identified to date, and mild hypothermia is increasingly used for neuroprotection during neurovascular surgery. We have recently demonstrated that combined administration of tirilazad mesylate and magnesium provides for an overall enhanced neuroprotective effect. The present study was designed to determine whether the efficacy of mild hypothermia (33 degrees C) can be increased by combination pharmacotherapy with tirilazad and magnesium (MgCl(2)). METHODS: Forty Sprague-Dawley rats were subjected to transient, middle cerebral artery occlusion and were randomly assigned to 1 of 4 treatment arms (n=10 each): (1) normothermia+vehicle, (2) normothermia+tirilazad+MgCl(2), (3) hypothermia+vehicle, or (4) hypothermia+tirilazad+MgCl(2). Cortical blood flow was monitored by a bilateral laser-Doppler flowmeter, and the electroencephalogram was continuously recorded. Functional deficits were quantified by daily neurological examinations. Infarct volume was assessed after 7 days. RESULTS: Tirilazad+MgCl(2), hypothermia, and hypothermia+tirilazad+MgCl(2) reduced total infarct volume by 56%, 63%, and 77%, respectively, relative to controls. In animals treated with both hypothermia and combination pharmacotherapy, cortical infarction was almost completely abolished (-99%), and infarct volume in the basal ganglia was significantly reduced by 55%. In addition, this treatment provided for the best electrophysiological recovery and functional outcome. CONCLUSIONS: The neuroprotective efficacy of hypothermia can be increased by pharmacological antagonism of excitatory amino acids and free radicals by using clinically available drugs. This treatment strategy could be of great benefit when applied during temporary artery occlusion in cerebrovascular surgery.

Animals↗
PubMed1998

Monotherapy with dextromethorphan or tirilazad--but not a combination of both--improves outcome after transient focal cerebral ischemia in rats.

Cell death after cerebral ischemia is mediated by a massive release of excitatory amino acids, generation of free radicals, and - a crucial step - calcium influx into cells. We examined the hypothesis that concurrent administration of drugs ameliorating brain damage via different mechanisms would result in a synergistic neuroprotective effect. The neuroprotective efficacy of two clinically available drugs - the N-methyl-D-aspartate and calcium-channel antagonist dextromethorphan (DM) and the antioxidant tirilazad - were studied in monotherapy and in combination in a rat model of transient focal ischemia. Male Sprague-Dawley rats were subjected to 90 min of middle-cerebral-artery occlusion by an intraluminal filament technique. The animals were randomly assigned to one of four treatments (n=10 each): (1) vehicle-treated controls, (2) DM, (3) tirilazad, (4) DM+tirilazad. Drugs or vehicles were administered 15 min before ischemia and at reperfusion. Local cerebral blood flow (LCBF) was bilaterally recorded by continuous laser Doppler flowmetry. Functional deficits were quantified by daily neurological examinations. Infarct volume was assessed planimetrically after 7 days. DM prevented post-ischemic hypoperfusion. Tirilazad did not influence LCBF. Monotherapy with DM or tirilazad improved neurological function and reduced infarct volume by 45% and 48%, respectively. Combination therapy failed to influence neurological recovery and infarct volume. Although, from pharmacological point of view, a synergistic neuroprotective effect is expected, combination of dextromethorphan and tirilazad may lead to mutual inhibition or potentiate adverse effects.

Animals↗
PubMed1998

A critical reevaluation of the intraluminal thread model of focal cerebral ischemia: evidence of inadvertent premature reperfusion and subarachnoid hemorrhage in rats by laser-Doppler flowmetry.

BACKGROUND AND PURPOSE: The intraluminal thread model for middle cerebral artery occlusion (MCAO) has gained increasing acceptance. Numerous modifications have been reported in the literature, indicating that the technique has not been standardized. The present study was performed to evaluate and optimize the reliability of this model. METHODS: One hundred Sprague-Dawley rats were subjected to MCAO by 2 different intraluminal filaments. Cortical blood flow was continuously monitored over both hemispheres by laser-Doppler flowmetry (LDF). In part I (3-0 filament), we evaluated the incidence of adequate MCAO, subarachnoid hemorrhage (SAH), intraluminal thrombus formation, and the effects of heparinization. In part II (silicone-coated 4-0 filament), we also determined the influence of insufficient MCAO on morphological and functional outcome and the incidence of postischemic hyperthermia. RESULTS: In part I, SAH occurred in 30% and premature reperfusion in 24%. All animals with a decrease in contralateral flow had suffered SAH. Thrombus formation was not observed in any group. In part II, SAH occurred in 8% and premature reperfusion in 26%. There was no difference in outcome between rats with primary MCAO and rats with filament correction. Animals with uncorrected premature reperfusion had significantly smaller infarct volumes and fewer neurological deficits. CONCLUSIONS: SAH and insufficient MCAO may be more common in the intraluminal thread model than previously reported. Inadvertent premature reperfusion contributes to the interanimal variability associated with this model. The incidence of valid experiments increases with the use of a silicone-coated 4-0 filament. Continuous bilateral LDF is indispensable to monitor adequate MCAO and is highly sensitive to recognize SAH.

Animals↗
PubMed1997

Superior neuroprotective efficacy of a novel antioxidant (U-101033E) with improved blood-brain barrier permeability in focal cerebral ischemia.

BACKGROUND AND PURPOSE: The vascular endothelium and parenchyma of the brain have the potential to generate free radicals under pathological conditions, but it is unclear which of these two sites prevails in the production of free radicals and should be the primary target of therapeutic intervention. To clarify this issue, we compared the neuroprotective properties of a 21-aminosteroid (U-74389G) that acts on the microvasculature and a pyrrolopyrimidine (U-101033E), a novel antioxidant compound that has significantly improved potential to enter the brain parenchyma. METHODS: In Sprague-Dawley rats the middle cerebral artery was occluded for 90 minutes by an intraluminal filament. Local cortical blood flow was recorded by bilateral laser Doppler flowmetry throughout ischemia and 1 hour of reperfusion. Three groups of rats were studied: controls that received vehicle only and animals that received either U-74389G or U-101033E. Neurological examinations were performed daily, and infarct size was assessed histologically 7 days after ischemia. RESULTS: U-101033E reduced infarct volume significantly by 51%, whereas U-74389G led to a nonsignificant decrease in infarct volume. U-101033E improved neurological function immediately after ischemia, whereas U-74389G led to improvement only at the end of the observation period. Laser Doppler measurements showed no significant difference in local cortical blood flow among the treatment groups. CONCLUSIONS: We conclude that for treatment of transient focal ischemia, an antioxidant that crosses the blood-brain barrier might be superior to agents that predominantly act on the endothelium of the cerebral microvasculature.

Animals↗