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P Rudolph

Publications and source records attributed to P Rudolph.

At least 19 recordsLinked to original sources
PubMed2006

Systemic iodine absorption after preoperative antisepsis using povidone-iodine in cataract surgery-- an open controlled study.

After preoperative conjunctival and periorbital antisepsis with povidone-iodine (PVP-I), the systemic absorption of iodine after cataract surgery was measured to evaluate the risk of thyroid side effects. Five different combinations of PVP-I alone or in combination with PVP-I-free antiseptics were applied to the conjunctiva and periorbital skin. An iodine-free product served as control. Iodide and creatinine in urine were analyzed before intervention and 24 and 48 h postoperatively. Depending on the concentration and application site, 0.3-4.5% of the total applied iodine or 3.6-45.4% of the free iodine were absorbed. The range of urine iodine excretion was between 11.7 and 71.0 mug iodine/g creatinine, depending on the PVP-I concentration and the site of application. The increase in iodine excretion was significant at 24 h postoperatively in trials receiving PVP-I both periorbitally and conjunctivally, depending of the concentration used. Because the iodine absorption is only slight and of doubtful clinical relevance, presurgical conjunctival antisepsis can be achieved with 1.25% PVP-I; so far clinically manifest anamnestic thyroid disorders are excluded. Presently, periorbital skin antisepsis with PVP-I cannot be recommended until data on thyroid metabolism in the population have been collected and evaluated, especially in a region currently or previously deficient in iodine.

Absorption↗
PubMed2004

[Proliferation and hTERT expression in neuroblastoma].

BACKGROUND: Transcription of the catalytic subunit of telomerase, human Telomerase Reverse Transcriptase (hTERT), and increased tumor cell proliferation are powerful prognostic factors in neuroblastoma. We therefore investigated their relationship in a large group of neuroblastomas. METHODS: RT-PCR analysis was used to discriminate between the various hTERT transcripts. Tumor cell proliferation was assessed immunohistochemically using two different cell-cycle specific antibodies and the results were compared by statistical analysis. RESULTS AND CONCLUSIONS: 54 out of 115 neuroblastomas showed hTERT transcripts, 25 of which also possessed full-length transcripts. Full-length hTERT transcripts were correlated with MYCN-amplification, with a Ki67-proliferation index > or = 25% and a repp86-proliferation index > or = 10% (p<0,0001), but only a Ki67-proliferation index > or = 25% was associated with general hTERT transcription (p=0,001). Our data confirm the close relationship between hTERT transcription and tumor cell proliferation and further strengthen the exceptional prognostic power of the repp86-proliferation index.

Cell Division↗
PubMed2003

DNA topoisomerase IIalpha expression and the response toprimary chemotherapy in breast cancer.

The alpha isoform of Topoisomerase IIalpha (Topo IIalpha) is a proliferation marker as well as a target for several chemotherapeutic agents such as anthracyclines. In vitro studies have demonstrated the relationship between the Topo IIalpha expression level and chemosensitivity of target cancer cells. To verify this effect in vivo, we selected 125 patients presenting with T(2)>3 cm and T(3) N(0-1) M(0) breast tumours who were treated by six cycles of primary chemotherapy, including epirubicin before any surgery. Therapy response was assessed by clinical and X-ray mammogram measurements of tumour shrinkage. The pretherapeutic core biopsies were immunostained with a monoclonal antibody (Ki-S7) against Topo IIalpha. Ki-S7 positivity ranged from 0 to 50% (median, 15%). A high percentage of Ki-S7-positive cells (>15%) was associated with tumour regression under chemotherapy (OR=2.88, CI: 1.3-6.4, P=0.004). Ki-S7 further emerged as an independent predictor of tumour regression (OR=3.34, CI: 1.41-7.93, P=0.006), together with tumour size of less than 40 mm (OR=3.82, CI: 1.58-9.25, P=0.002) and negative oestrogen receptor (ER) status (OR=3.35, CI: 1.43-7.86, P=0.005), in a multivariate analysis including tumour size, SBR grade, ER and PR status, Ki-67, p53 and Her-2/neu. Our clinical results confirm in vitro data on the relationship between Topo IIalpha expression and tumour chemosensitivity and thus may have important practical implications.

Adult↗
PubMed2003

Resistance mechanisms of gastrointestinal cancers: why does conventional chemotherapy fail?

BACKGROUND: Gastrointestinal cancers belong to the most important causes of cancer death in the Western world. Because cure can be achieved only by complete surgical removal of the tumor, and most patients have metastasis at the time point of diagnosis, the majority of patients receive chemotherapy. DISCUSSION: Indications for chemotherapy are either the prevention of recurrence after tumor resection (neoadjuvant or adjuvant) or palliative treatment if the tumor is already widespread at diagnosis. Although gastrointestinal cancers often respond to primary treatment, the long-term results are disappointing. This is attributable to a variety of cellular resistance mechanisms, namely: (a) kinetic resistance due to slow growth rates that preclude the use of topoisomerase IIalpha inhibitors and related drugs; (b) genetic resistance due to mutations, for example, in the p53 gene, which impede the sensing of DNA damage and obstruct apoptotic pathways; (d) pharmacokinetic resistance, due to an excess of target proteins, inadequate drug metabolism, administration period, time or drug interactions; and (d) biological resistance due to tumor-induced environmental changes. These factors interfere specifically with the molecular mode of action of standard drugs used in the therapy of gastrointestinal cancers. CONCLUSION: Awareness of the various causes of drug resistance may help to devise individual tumor-adapted treatment designs. Notably, nonsteroidal antiphogistics may delay carcinogenesis, anticoagulants may increase the vulnerability of circulating tumor cells and reduce the nesting abilities of single tumor cells, inhibitors of angiogenesis may quell the growth of micrometastases, and kinase inhibitors may be administered as sensitizers to cytotoxic treatment.

Antigens, Neoplasm↗
PubMed2003

[The protective effect of dexpanthenol in nasal sprays. First results of cytotoxic and ciliary-toxic studies in vitro].

BACKGROUND: In Germany more than 60 million units of nasal decongestants are prescribed or sold over the counter. The cytotoxic and ciliary-toxic potential of alpha-sympathomimetic decongestants is well established. Furthermore, in many of the marketed products preservatives are added, predominantly benzalchonium-chloride, which can lead to a further alteration of cell- and ciliary function. Recently a protective effect of dexpanthenol was found for the human nasal mucosa. The objective of the present studies was to prove the hypothesis that dexpanthenol is able to neutralise the toxic effects of both alpha-sympathomimetic decongestants, in particular those of xylometazoline, and those of benzalconium-chloride. Therefore, systematic cytotoxic and ex vivo in vitro ciliary-toxic studies were performed. METHOD: After exposition to xylometazoline in concentrations of 0.1 % and 0.05 %, the influence of dexpanthenol (5 %) and benzalconium-chloride (0,01 %) was assessed by determination of a) cell growth of FL-cells of human amnion origin, and b) ciliary beat frequency of human nasal mucosa. All tests were performed placebo-controlled. RESULTS: Both hypotheses were confirmed. Dexpanthenol (5 %) reduces statistically significantly the concentration-dependent toxic effects of xylometazoline, and benzalchonium-cloride regarding cell growth and ciliary beat frequency (p < 0.001). The combination of xylometazoline with dexpanthenol, while benzalconium-chloride is eliminated, resulted in a further significant increase of cell growth and ciliary beat frequency (p < 0.001), similar to control. CONCLUSIONS: The additive application of dexpanthenol (5 %) with nasal decongestants and/or with preserved nasal sprays seems to be able to reduce the cell- and ciliary-toxic effects of these substances.

Administration, Intranasal↗
PubMed2003

[The tolerability of nasal drugs with special regard to preservatives and physico-chemical parameters].

BACKGROUND: Recent technical developments allow preservative-free nasal drug application in multi-dose systems. New pharmaceutical formulations for better tolerable nasal sprays are now possible and consequently reformulations introduced to the market. Therefore, a representative and systematic overview on comparable products is mandatory. METHODS: Marketed nasal products in the indication groups: decongestants, antiallergics, care and wound-healing, hormones and saline solutions were tested for their cytotoxic properties according to DIN EN 30 993 - 5, pH, and osmolality. RESULTS: In all indication groups reformulation to preservative-free application resulted in significant increase of cell growth and reduction of cytotoxicity. Physico-chemical galenic properties are of considerable importance too. With decongestants tolerability is dependant on the concentration of the active compound. CONCLUSIONS: Our data lead to the conclusion that preserved nasal sprays are obsolete, when preservative-free alternatives are available. Attention should be paid to galenic properties and dosage of the active.

Administration, Intranasal↗
PubMed2003

[Clinical implications of DNA-topoisomerases examination in renal biopsies from patients with nephritis].

AIM: To study expression of topoisomerases (TI) I and II alpha (DNA-bound enzymes involved in transcription and replication) in renal tissue as markers of activity and prognosis of glomerulonephritis (GN) decisive for choice of immunodepressive therapy. MATERIAL AND METHODS: TI expression was studied immunohistochemically in renal biopsies from 177 patients with different morphological variants of GN and in the samples of unaffected kidney tissue removed in 12 patients for local tumors. RESULTS: There are definite differences between proliferative and non-proliferative GN variants--elevation of TI levels and monocytic infiltration in proliferative GN. Focal-segmental glomerulosclerosis is characterized by a high TI II alpha level in mesangial cells and monocytic infiltration of the glomeruli which are typical for inflammation. A statistical relationship between TI levels in mesangial cells and glomerular epithelium suggests a pathogenetic relation between these links of the pathological process. Molecular markers of activation and proliferation of cells and direct inductors of the inflammatory process (cells of monocytic infiltrate) closely correlated with the activity index--an integral indicator of inflammatory activity, as well as with the integral indicator of sclerotic processes in renal tissue--sclerosis index. Monocytic infiltration in the interstitium correlated both with morphological manifestations of activity, progression of nephritis and their clinical equivalents. In high TI expression GN resistance to immunodepressive therapy rose. To overcome the resistance, immunodepressive therapy must be more active--large doses and duration of treatment. In patients with lupus nephritis and mesangiocapillary GN renal prognosis was worse in the presence of high TI expression in mesangial cells and epithelium of the renal canaliculi. CONCLUSION: The authors are the first to demonstrate TI expression in renal tissue of GN patients, correlation of its level with activity of renal process as well as its role in prediction of response to treatment and the rate of renal failure progression. It is suggested that high TI expression entails a progressive course of GN.

Biomarkers↗
PubMed2002

[Benign adnexal skin tumors].

Epithelial tumors of the cutaneous adnexae are considered to originate from three different structures, i.e., hair follicles, eccrine/apocrine sweat glands, and sebaceous glands. Although this derivation provides a practical basis for classification, some tumors may exhibit a mixed differentiation and thus should be categorized according to the prevailing phenotype. The overwhelming majority of hair follicle tumors are benign but the main diagnostic differential for malignant tumors is basal cell carcinoma. Despite a broad histological spectrum, benign tumors of sweat glands are readily recognized on the grounds of a well characterized morphology. However, it may be difficult to rule out malignancy as each benign entity has a malignant counterpart. True sebaceous neoplasms are rare when hyperplasia and hamartoma are disregarded and in extraocular locations most of them are benign.

Apocrine Glands↗
PubMed2002

[Melanocyte tumors. Classical and new diagnostic possibilities].

Melanocytic tumors are one of the major problems in diagnostic dermatopathology as they comprise benign nevi, malignant melanomas and borderline cases. Apart from a proportion of congenital lesions, most benign nevi are acquired tumors that arise during early adulthood and eventually may undergo regressive change. Histologically, they present as so-called common nevi, so-called dysplastic nevi, Spitz's nevi, blue nevi and their variants, and combined nevi. In typical cases, the distinction from a malignant melanoma is not difficult. However, benign simulators of malignancy exist as much as deceptively bland appearing melanomas and in some cases the diagnosis remains dubious despite careful weighting of criteria. Indeed, morphological features may not always suffice to disclose the nature of a melanocytic tumor. Ancillary techniques including immunohistochemistry and measurement of telomerase activity may be of assistance in this respect. One should nevertheless be aware that the biological behavior of certain borderline cases cannot be predicted with certainty.

Diagnosis, Differential↗
PubMed2002

[The dysplastic nevus. An Ariadne's thread through a conceptual labyrinth].

The concept of the dysplastic nevus is flawed by inconsistencies regarding the clinical presentation, histological features and biological considerations. With regard to basic mechanisms of malignancy, dysplastic nevi exhibit neither increased proliferation indices nor elevated telomerase activity. These traits denote a benign lesion that is highly prevalent among Caucasians. In rare cases, the distinction from malignant melanoma may pose problems.

Cell Division↗
PubMed2002

New aspects of the tolerance of the antiseptic povidone-iodine in different ex vivo models.

Investigating new possibilities for the application of 1% (v/v) iodophors, povidone-iodine (PVP-I) was better tolerated in the HET-CAM or explant test than 1% (w/v) silver nitrate or tetracycline. After application to the eye, at least 2.6% of used iodine were adsorbed. Therefore PVP-I is more effective than silver nitrate or erythromycin, meaning a possible alternative for the prevention of ophthalmia neonatorum. PVP-I is more active against methicillin-resistant Staphylococcus aureus (MRSA) in a human ex vivo skin model, which results in a complete eradication of S. aureus in the nasal cavity of volunteers after 2 daily applications and will be better tolerated by human nasal cilial epithelium than chlorhexidine. Having the same clinical tolerance as mupirocin, PVP-I is a useful alternative for the antiseptic therapy of germ carriers of MRSA. The synthesis of proteoglycans in articular cartilage of bovine sesamoid bones was increased after application of 5% (v/v) PVP-I without any increase in catabolism revealing possibilities for the use as irrigation solution in the joint.

Allantois↗
PubMed2002

Antimicrobial effectiveness of povidone-iodine and consequences for new application areas.

The microbicidal action spectrum of povidone-iodine (PVP-I) is broad - even after short onset times. Unlike local antibiotics and other antiseptic substances, no resistance develops. The high degree of bactericidal efficiency in respect of highly resistant gram-positive pathogenic micro-organisms, such as methicillin-resistant Staphylococcus aureus (MRSA) and enterococcus strains, is particularly significant for hospital hygiene. An in vitro study with 10 genotypically different MRSA isolates showed an optimum bactericidal effect (logarithmic reduction factor value >5) without protein load after just 30 s exposure and even in a dilution of Betaisodona solution (Mundipharma GmbH) of 1%. With protein load (0.2% albumin), the optimum in microbicidal effectiveness shifts to concentrations > or = 10% Betaisodona solution referring to an exposure time of 30 s. Since recent results are now also available on the toxicological safety of PVP-I preparations for the ciliated epithelium of the nasal mucosa and the good tolerability on skin and other mucous membranes is a known factor, a controlled clinical study is currently being carried out to eliminate colonizations of MRSA. Evidence has also recently been produced of the antiviral activity of PVP-I against herpes simplex, adeno- and enteroviruses, as well as its high degree of efficiency against Chlamydia. Hence alongside the classical fields of application, such as the disinfection of the skin and hands, mucosa antisepsis and wound treatment, there are also useful indications for the substance, i.e. rinsing of body cavities and joints and application to the eye.

Adenoviridae Infections↗
PubMed2001

Decline in the expression of the serine proteinase inhibitor maspin is associated with tumour progression in ductal carcinomas of the breast.

Maspin is an inhibitor of serine proteinases with tumour suppressor activity. Its expression appears to be reduced in advanced stages of breast cancer. A large series of archival breast tissue specimens has been examined, including normal glands (n=7), fibrocystic change (n=22), ductal carcinoma in situ (DCIS, n=12), infiltrating carcinomas (n=128) and their lymph node metastases (n=65), using a specific monoclonal antibody. Myoepithelium invariably showed strong maspin expression. In epithelial cells, the strongest expression was found in normal breast and fibrocystic change. A significant stepwise decrease in maspin expression (p<0.0001) occurred in the sequence DCIS - invasive cancer - lymph node metastasis. However, a subset of infiltrating carcinomas showed strong maspin expression, significantly associated with a lower rate of lymph node metastasis at the time of diagnosis (p<0.01). This was independent of tumour size and grade. The in vivo observations presented here are in keeping with data obtained in prior in vitro experiments. Maspin emerges as an indicator of tumour progression and metastatic potential, and might be exploited to predict breast cancer prognosis. According to in vitro data, its tumour suppressor activity is likely to involve both the modulation of cell motility/invasiveness and the inhibition of angiogenesis.

Biomarkers, Tumor↗
PubMed2001

A distinctive melanocytic lesion associated with melanoma-prone dysplastic naevus syndrome: the hybrid naevus.

Clinically and histologically, the concept of dysplastic nevi remains controversial. To elaborate more precise criteria for the nevi of patients with dysplastic naevus syndrome (DNS), we examined 58 nevi from seven DNS patients who developed one or several malignant melanomas. Clinical presentation and histomorphology were evaluated, and immunohistochemistry was performed using proliferation marker Ki-S5 and antibody DO-7 to the p53 protein. Sixty nevi from individuals without history of melanoma served as controls. Of the DNS nevi, 21 (36.2%) exhibited no morphological particularities. The remaining 37 nevi presented distinctive histological features consisting of a slight epidermal acanthosis, spitzoid vertically oriented nests of dyscohesive nevus cells, and single-standing atypical melanocytes in the basal cell layer of the epidermis. Immunohistochemical analysis revealed an average proliferation index of 2.5%, which significantly surpassed the mean growth fraction of conventional dysplastic nevi (<1%). No increase in p53 expression was observed. Characteristically, active proliferation was found in junctional single-standing melanocytes with or without nuclear atypia rather than in nest-shaped compounds. In conclusion, certain moles of patients with DNS possess distinctive features. The newly characterized criteria may provide a basis for the diagnosis of DNS and might help to identify patients at increased risk for malignant melanoma by examination of a single biopsy.

Adolescent↗