An immunohistochemical study of the breast using antibodies to basal and luminal keratins,alpha-smooth muscle actin,vimentin, collagen IV and laminin

Summary The distribution of simple epithelial (K8/18/ 19) and basal (myoepithelial) (K5/14) keratins, -smooth-muscle actin, vimentin, collagen IV and laminin in normal mammary glands and in benign proliferative lesions was studied using monoclonal antibodies (mAbs). These antibodies (Abs) identified myoepithelial cells and luminal cells specifically. In lesions with adenosis and papillomas, the two-layered formation resembled that of normal glands with a purely myoepithelial-epithelial differentiation. In scleradenotic lesions, the main cell was of myoepithelial immunophenotype with intermixed trabecular-tubular proliferations of simple-type epithelium. The sclerosis seems to be the result of an irregular basal lamina synthesis by the myoepithelial cells. In contrast to these lesions, epitheliosis represents a purely intraluminal cell proliferation of clearly simple epithelial immunophenotype and of cells with a basal keratin phenotype, lacking myoepithelial differentiation antigen actin. The basal keratin type epithelium may represent post-stem or intermediate cells developing into luminal epithelium. Epitheliosis appears to be a purely epithelial hyperplasia with striking similarity to the regeneration of normal breast epithelium. The different proliferative patterns may give an explanation for differences in potential cancer risks of patients with these lesions.Dedicated to Prof. Dr. G. Seifert on the occasion of his 70th birthday     

Das Tumorrezidiv am Hals nach papillarem Schilddrüsenkarzinom Eine statistische Analyse zur Rezidivwahrscheinlichkeit nach Radikaloperation

Zusammenfassung 308 Patienten mit papillärem Schilddrüsenkarzinom (82,6% des Gesamtkrankengutes, Operation 19522–1987), die postoperativ als tumorfrei eingestuft worden waren, wurden retrospektiv analysiert. Die Beobachtungszeit reicht von 1 Monat bis zu 29,4 Jahren (mediane Beobachtungszeit 4,58 Jahre). Bei 32 Patienten (10,4%) wurde ein Tumorrezidiv am Hals diagnostiziert (lokal und/oder regionär). 8 davon sind am Ende der Beobachtungszeit nicht tumorfrei, 6 sind am Tumor verstorben (tumorbedingte Todesrate 18,8%, relative Mortalität 66,7%, im Gesamtmaterial 2,9% bzw. 29,0%). Die kumulative Rezidivwahrscheinlichkeit beträgt 9,98% nach 5 und 16,98% nach 10 Jahren. Die statistische Analyse der Rezidivwahrscheinlichkeit erfolgte nur an Patienten, die mindestens 5 Jahre beobachtet wurden oder innerhalb dieses Zeitraumes verstarben. Als Einflußgrößen wurden neben Alter and Geschlecht, tumorstadium und histologische Kriterien des Tumors berücksichtigt. Als bestimmend für das Auftreten eines Rezidivs nach 5 Jahren Beobachtungszeit erweisen sich der Status der regiondren Lymphknoten, der Differenzierungsgrad des Tumors und das Geschlecht der Patienten. Zur Verbesserung der Rezidivrate wird eine abgestufte therapeutische Radikalität in Abhängigkeit von den Einflußgrößen empfohlen.

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Cervical tumour recurrence after papillary thyroid carcinoma. A statistical analysis on the recurrence after potentially curative surgery

Summary 308 cases of papillary thyroid carcinoma (82.6% of our patients operated on between 1952 and 1987) who had undergone potentially curative surgery were analysed postoperatively. The follow-up ranges from 1 month to 29.4 years (median 4.58 years). In 32 cases (10.4%) a cervical tumour recurrence (local recurrence and/or cervical lymph nodes) was found. 8 of these are not free of tumour at the end of the follow-up, 6 had died of thyroid carcinoma (case fatality rate 18.8%, mortality rate 66.7%, in the entire material 2.9% and 29.0% respectively). The cumulative recurrence rate is 9.98% after 5 years and 16.98% after 10 years. A statistical analysis of the probability of recurrence was carried out only for patients who could be followed at least 5 years or those who died within 5 years. Age, sex, stage of tumour and histological criteria were taken into account as statistical variables. The state of cervical lymph nodes, the differentiation of the tumour and the patients' sex turned out to be determining factors for tumour recurrence after 5 years. In order to improve the recurrence rate a differentiated surgical radicality, depending on the above mentioned variables, is recommended.

     

Treatment of severe sepsis in bone marrow transplant recipients with teicoplanin in combination with β-lactams and aminoglycosides

Summary We evaluated teicoplanin for suspected gram-positive infections after inadequate response to initial empiric beta-lactam and aminoglycoside combination therapy. All 20 patients included in this study received either an allogeneic (8 patients) or an autologous (12 patients) bone marrow transplant for acute myeloid leucaemia (AML), non-Hodgkin's-lymphoma (NHL, high grade) or other malignant diseases. All patients developing primary septicaemia of unknown origin (18 patients) or catheter-related septicaemia (2 patients) were treated with 400 mg teicoplanin, administered i.v. once daily in combination with a cephalosporin and an aminoglycoside (ceftazidime 2 g i.v., t.i.d.; netilmicin 400 mg once daily). All patients responded to therapy, 19 patients were clinically cured and one patient improved under therapy. The therapeutic regimen was well tolerated; only one adverse drug reaction was observed. We did not observe any delayed take or prolonged neutropenia or thrombocytopenia with this therapeutic regimen when our patients were compared to other bone marrow transplant patients (who did not receive this antimicrobial therapy). Our results suggest that teicoplanin is a potentially effective and well tolerated antimicrobial agent in bone marrow transplant patients with infections not responding primarily to beta-lactams and aminoglycosides.

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Teicoplanin in Kombination mit -Laktamen und Aminoglykosiden bei Knochenmarktransplantatempfängern mit schwerer Sepsis

Zusammenfassung Wir untersuchten Teicoplanin bei vermuteten grampositiven Infektionen nach ungenügendem Ansprechen auf die anfängliche Kombinationstherapie von -Laktam-Antibiotika und Aminoglykosiden. Alle 20 in dieser Studie erfaßten Patienten wurden entweder allogen (8 Patienten) oder autolog (12 Patienten) transplantiert mit folgenden Grundkrankheiten: akute myeloische Leukämie (AML), Non-Hodgkin-Lymphom (NHL) oder andere maligne Erkrankungen. Alle Patienten, die eine primäre Septikämie unbekannten Ursprungs entwickelten (18 Patienten) oder unter einer Katheter-bedingten Septikämie (2 Patienten) litten, wurden mit 400 mg Teicoplanin behandelt. Die Verabreichung von Teicoplanin erfolgte einmal täglich intravenös in Kombination mit einem Cephalosporin und einem Aminoglykosid (Ceftazidim 2 g i.v., 3 ×/die, Netilmicin 400 mg, 1 ×/die). Alle behandelten Patienten sprachen auf diese Therapie an. 19 Patienten wurden klinische geheilt, ein Patient besserte sich unter dieser Therapie. Die Kombinationstherapie wurde gut vertragen, unerwünschte Arzneimittelwirkungen traten während der Studie nicht auf. Wir beobachteten kein verzögertes Angehen des Knochenmarks oder eine Verlängerung der Thrombozytopenie unter dieser Behandlung im Vergleich zu anderen knochenmarktransplantierten Patienten, die diese antimikrobielle Behandlung nicht erhielten. Unsere Ergebnisse zeigen, daß Teicoplanin ein wirksames und gut verträgliches Antibiotikum für knochenmarktransplantierte Patienten ist, die primär nicht auf die Kombinationstherapie mit -Laktam-Antibiotika und Aminoglykosiden ansprechen.

     

Repair and mutagenesis of plasmid DNA modified by ultraviolet irradiation or N-acetoxy-N-2-acetylaminofluorene.

Plasmid DNA was modified in vitro to various extents with N-acetoxy-N-2-acetylaminofluorene or UV irradiation. The modified plasmid DNAs were then used to transform Escherichia coli strains having different repair capabilities. Both survival and mutagenesis frequencies of the plasmid were measured as a function of the number of lesions per plasmid molecule. The majority of N-2-acetylaminofluorene (AAF) adducts, like thymine dimers, were repaired by the excision (uvrA+-dependent) pathway. In rec+ strains, dose-dependent mutagenesis occurred in either AAF- or UV-modified plasmid DNA. This is in contrast with results obtained in recA- strains, in which only AAF adducts gave rise to a lower, but dose-dependent, mutagenesis frequency. In these recA- strains there was no UV mutagenesis. Unlike what is observed with phages, induction of the "SOS" functions by UV irradiation of the bacteria prior to transformation did not increase the survival or the mutagenesis of the plasmid.     

Mikrochirurgie lumbaler Bandscheibenvorfälle Üerlegene Ergebnisse der Mikrochirurgie im Vergleich zu Standard- und perkutanen Verfahren (Literaturübersicht)

In a meta-analysis of 69 prospective and retrospective studies, we investigated the value of various surgical techniques in the treatment of lumbar disk herniations. This analysis includes standard diskectomy (5080 patients from nine series), microdiskectomy (5354/23), and comparison of both techniques (2494/10) and furthermore chemonucleolysis (2729/16), laser therapy (881/3), percutaneous nucleotomy (3506/18), comparisons of percutaneous techniques (942/5) with microdiskectomies (561/5) and standard diskectomies (1020/6). Outcomes were rated according to Macnab's criteria: I "excellent", II "good", III "improved", IV "same as before", V "worse", I/II "markedly improved", III "partially improved", IV/V "not improved", I-III "successful", and IV/V "unsuccessful". Results after microdiskectomy were "successful" more often (90% vs. 95%), "good/excellent" more often (82% vs. 73%), and patients left the hospital sooner than with standard diskectomy. Recurrence rates were comparable (4%). Results of both open techniques were clearly superior to those from any type of percutaneous treatment: chemonucleolysis und laser therapy were "successful" in 69% and 70% of cases respectively, with recurrence rates of 17% and 18%, endoscopic nucleotomy was "successful" in 84% of cases, and recurrence rate was 14%. Please ask the author for the reference database.     

Endourologische Operationstechniken bei interstitieller Zystitis

Endourological surgical procedures (transurethral resection and fulguration, Nd-YAG-laser application) for the treatment of interstitial cystitis (IC) have been evaluated only in a few studies. Theoretically, they could be the next step in a therapeutic concept after conservative measures have failed and before open surgery is performed as an ultima ratio. However, our review of the literature suggests that to date there is no scientific evidence to support endourological techniques in the treatment of IC.     

Sildenafil in the treatment of sexual dysfunction in spinal cord-injured male patients

OBJECTIVES: The aim of this study was to evaluate the efficacy and safety of sildenafil in the treatment of erectile dysfunction (ED) in spinal cord-injury (SCI) patients. Moreover, we looked for neurological conditions permitting therapeutic success and for the ideal dose needed to achieve sufficient erections. METHODS: 41 SCI patients were prospectively examined. Sexual dysfunction was assessed by means of anamnesis, the International Index of Erectile Function (IIEF) questionnaire, and neurological examination. Psychogenic erection capacity was tested by audiovisual stimulation and reflexive erection using a vibrator device. Neurophysiological recordings and cystomanometry were performed in parallel to clinical examinations. Neurophysiological recordings included sympathetic skin responses (SSR), pudendus somatosensory evoked potentials (pSSEP), and bulbocavernous reflex (BCR). Urodynamics aimed at classifying the neurogenic bladder dysfunction (upper motoneuron lesion versus lower motoneuron lesion). Intracavernous injection tests with PGE1 were performed in all patients to exclude major organic disease. 50 mg sildenafil was first given 3 times. Thereafter, the doses were adapted according to patients' reports. RESULTS: Clinically, 28 subjects preserved either reflexive erections (24) or psychogenic erections (4), 11 had both types and only 2 presented with a complete loss of erection. 38 patients (93%) had a positive response to sildenafil and reached a penile rigidity sufficient to permit sexual intercourse. 3 patients dropped out because of non-response despite having increased the dosis up to 100 mg. 22 patients (58%) showed functional erections 1 h after 50 mg sildenafil, whereas 14 (37%) required higher doses of 75-100 mg. By comparing the IIEF questionnaire scores before and after therapy, there was a significant improvement in erectile function and intercourse satisfaction from 9.2+/-4.4 SD) and 4.5 (+/-2.5 SD) to 25.5 (+/-4.2 SD) and 10.5 (+/-2.1 SD) points, respectively (p<0.05). Nearly 10% (4/41) suffered from side effects such as headache or dizziness. Two of them stopped therapy because of the side effects. At least 36 patients (88%) continue treatment with sildenafil. Absence of both psychogenic (nonsomesthetic supraspinally elicited) and reflexive (somesthetic spinally elicited) erections, confirmed by urodynamical and electrophysiological findings (SSR perineum, BCR and pSSEP), seems to exclude a successful treatment. In contrast, SCI male patients with preserved function of at least one component of the erection phenomenon (psychogenic/reflexive) responded well to sildenafil and the dose required to achieve erections sufficient for sexual intercourse did not differ between the two groups. CONCLUSIONS: Sildenafil proves to be a valuable and safe therapeutic management in ED of SCI patients. Therefore, patient acceptance and satisfaction are high. The most common dose required to achieve a satisfying erection is 50 mg. The efficacy of sildenafil depends on sparing of either sacral (S2-S4) or thoracolumbar (T10-L2) spinal segments which, in this study, have been shown to be of relevance in mediating psychogenic erections in male SCI patients. Complete disturbance of any neurogenic impulses excludes successful treatment.     

Vom Antigen zum Tumormarker Forschungsergebnisse zu PSA und ihre klinische Umsetzung

The determination of prostate-specific antigen is credited with dramatic advances in the early detection of men with prostatic carcinoma. This report summarizes the history of biochemical research and current status of prostate-specific antigen in tumor diagnostics.     

Five meters of H(2)O: the pressure at the urinary bladder neck during human ejaculation

BACKGROUND: There are no data in the literature on pressure changes in the prostatic urethra during ejaculation. In healthy men, it has always been postulated that there must be a pressure gradient in order to prevent retrograde ejaculation, but scientific proof for that is pending. METHODS: In five healthy male volunteers, the pressure profile in the prostatic urethra was registered during ejaculation, using a 10 French balloon catheter with 16 pressure channels. The channels were arranged in pairs at 5-mm intervals, beginning just below the balloon at the bladder neck and extending down to the external urethral sphincter. RESULTS: In the proximal part of the prostatic urethra, a pressure of up to 500 cm of H(2)O was measured in all subjects. Contrary to that, pressures did not exceed 400 cm of H(2)O distally to the verumontanum. CONCLUSIONS: A novel method to register the pressure profile in the lower urinary tract during ejaculation (ejaculomanometry) is presented. This study adds to the knowledge of the normal physiology of reproductive function and may be useful in the evaluation of male sexual and reproductive disorders.     

Effects of Nicotine on Bone and Calciotropic Hormones in Growing Female Rats

Limited research in young adults and immature animals suggests a detrimental effect of tobacco on bone during growth. This study investigated the effects of nicotine, the major alkaloid component of tobacco, on calciotropic hormone concentrations and bone status in growing female rats. One-month-old animals received either saline (n = 10), nicotine at 3.0 mg/kg/day (n = 10), or nicotine at 4.5 mg/kg/day (n = 10) administered subcutaneously via osmotic minipumps for either 2 or 3 months. Sera, femora, tibiae, and lumbar vertebrae (3–5) were collected at necropsy. The concentrations of serum calcium, phosphorus, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, parathyroid hormone, calcitonin, and insulin-like growth factor-I were determined. Bone variables evaluated included mineral content and density (vertebrae and femora), cancellous and cortical histomorphometry (tibiae), and bone strength (vertebrae and femora). Statistically significant differences in serum mineral and hormone concentrations were not associated with nicotine dose or exposure time. No significant nicotine treatment effects were detected for bone mineral content and density, bone histomorphometry, or bone strength. We conclude that nicotine treatment for 2 or 3 months at serum concentrations in the upper range of those found in smokers has no detrimental effect on bone mass, volume, or strength in the growing rat. Received: 20 May 1999 / Accepted: 21 January 2000