Interim evidence of the renoprotective effect of the angiotensin II receptor antagonist losartan versus the calcium channel blocker amlodipine in patients with chronic kidney disease and hypertension: a report of the Japanese Losartan Therapy Intended for Global Renal Protection in Hypertensive Patients (JLIGHT) Study

Background. Insufficiency of renal function and high blood pressure influence each other and eventually result in life-threatening endstage renal disease. It has been proposed that proteinuria per se is a determinant of the progression of chronic kidney disease (CKD). The therapeutic strategy for patients with proteinuric CKD and hypertension should therefore be targeted with a view not merely toward blood pressure reduction but also toward renoprotection. Methods. We examined the effect of the angiotensin (AT)₁ receptor antagonist losartan and the calcium channel blocker amlodipine, throughout a period of 12 months, on reduction of blood pressure and renoprotection. This was done by assessing amounts of urinary protein excretion, serum creatinine (SCr), and creatinine clearance (CCr) in patients with hypertension (systolic blood pressure [SBP] 140mmHg or diastolic blood pressure [DBP] 90mmHg) and CKD (male, body weight [BW] 60kg: 1.5 SCr < 3.0mg/dl; female or male BW < 60kg: 1.3 SCr < 3.0mg/dl), manifesting proteinuria of 0.5g or more/day. Losartan was administered once daily at doses of 25 to 100mg/day, and amlodipine was given once daily at 2.5 to 5mg/day. No antihypertensive combination therapy was allowed during the first 3-month period. Results. A 3-month interim analysis revealed that, despite there being no difference in blood pressure between the two groups, there was a significant reduction in 24-h urinary protein excretion in the losartan group (n = 43), but there was no change in the amlodipine group (n = 43). Analysis of stratified subgroups with proteinuria of 2g or more/day and less than 2g/day showed that losartan lowered proteinuria by approximately 24% in both subgroups, while amlodipine lowered proteinuria by 10%, but only in the subgroup of less than 2g/day (NS). SCr and CCr did not change throughout the period of 3 months in either group. No severe or fatal adverse event was experienced in either group during the study period. Conclusions. Losartan appeared to be efficacious for renoprotection in patients with proteinuric CKD and hypertension, with the mechanism being independent of its antihypertensive action.     

Role of endogenous interferon gamma in murine tumor growth and tumor necrosis factor alpha antitumor efficacy

Background: The anticancer role of tumor necrosis factor-alpha (TNF-) has been limited by toxicity. These experiments evaluate blocking endogenous interferon-gamma (IFN-) activity to abrogate TNF- toxicity. Methods: C57Bl/6 mice bearing MCA 105 tumor were treated with TNF- and anti-IFN- antibody (Ab) to evaluate the effect on the acute lethality of TNF- and their efficacy as evaluated by tumor growth rate, tumor histology, and survival. Results: Anti-IFN- Ab decreased TNF- lethality. Anti-IFN- Ab alone increased tumor growth significantly more than did nonimmune IgG (p₂<0.0001). Tumor-bearing mice that received nonimmune IgG and TNF- had slower tumor growth (p₂<0.02) and a trend toward improved survival (p=0.07) compared with saline-treated controls. Anti-IFN- Ab abrogated the antitumor effect of TNF-, prevented acute tumor necrosis histologically, and resulted in tumor growth rate and host survival similar to that of controls. The findings in mice that received anti-IFN- Ab and high-dose TNF- were comparable with those in mice that received a lower, equitoxic dose of TNF- alone. Conclusions: Blocking endogenous IFN- accelerates tumor growth in this model and partially abrogates the toxic and antitumor activity of exogenous TNF- equally. This suggests that blocking endogenous IFN- activity is not a useful strategy for limiting TNF- treatment toxicity.Presented in part at the 45th Annual Cancer Symposium of The Society of Surgical Oncology, New York, New York, March 15–18, 1992.     

Intracranial meningiomas: Analysis of recurrence after surgical treatment

Summary Recurrence of intracranial meningiomas after surgery has long been recognized, but there is still no consensus about factors responsible for recurrence. To better understand such factors, we analysed data on 276 patients with meningiomas who were treated at our institution from 1976 to 1990 (mean follow-up=5.1 years). Effects of sex, tumour histology, tumour site, and radiotherapy on recurrence were closely studied. Using World Health Organization criteria to define malignancy, 254 of the tumours were benign and 22 were atypical or malignant. For data analysis, distinction was made between recurrence (i.e., reappearance of tumour after total resection) and regrowth (i.e., tumour enlargement after subtotal removal). Recurrence was seen in 2 of 183 benign meningiomas and in 10 of 16 malignant meningiomas. Recurrence and regrowth rates for malignant meningiomas far exceeded those for benign meningiomas (p=0.001). Neither sex nor tumour site was associated with subsequent recurrences in patients whose tumours had been completely resected.The influence of radiotherapy was studied in terms of its effects on benign versus malignant meningiomas, whether given after complete or incomplete resection, and whether given after primary resection or on reoperation. We found that radiotherapy did not decrease recurrence or regrowth regardless of when administered, either at first resection or on recurrence. This was true for benign as well as malignant meningiomas. However, due to the small number in our series, we cannot conclude that radiotherapy has no beneficial role in the treatment of meningiomas.We do believe that the rate of recurrence for benign meningiomas is far lower than has been reported and that the majority of recurrences are in fact regrowths representing continuous tumour growth after incomplete removal. In fact, whenever recurrence is seen after complete surgical removal, chances are that tumour was atypical or malignant.     

Safety of Contrast Venography prior to Caval Interruption in Patients with Renal Insufficiency

We undertook this study to determine whether the use of contrast venography would adversely affect renal function in patients with renal insufficiency requiring caval interruption. We conducted a retrospective review of all inferior vena cava (IVC) filters inserted at our institution over a 2-year period (January 2002 to January 2004). The indication for caval interruption, insertion technique, type of filter used, pre- and postintervention creatinine level, and the presence of diabetes and hypertension were analyzed. A total of 282 IVC filters were inserted, with 38 of them placed in patients with renal insufficiency as defined by a serum creatinine level of > 1.5 mg/dL. Contrast venography with 15 to 30 mL of iohexol (Omnipaque 300) was used in all cases, and no special measures other than proper hydration were used for renal protection. All filters were successfully deployed. The mean±SD preintervention creatinine level was 2.38±0.79 mg/dL. The mean±SD postintervention creatinine levels at 2 and 30 days were 2.26±0.45 mg/dL and 2.12±0.94 mg/dL, respectively. No patients required hemodialysis following caval interruption, and no adverse effect on renal function was noted. Contrast venography accurately delineates venous anatomy and facilitates proper caval filter placement with no apparent adverse effect on renal function. We believe contrast venography is safe even in the presence of renal insufficiency.     

Guidelines for a short-term therapy of a torture depression

Psychotherapeutic work with torture traumas and their aftereffects are made difficult through a number of factors. Six guiding principles are presented in this publication through which make it possible to influence the actual symptomatology within the limits of the short therapy, even under difficult conditions. Creative images, described in detail as process fantasies, are the focus of this short therapy. Situative experiences in the treatment process are not interpreted with reference to the subject or the concrete trauma. This leads to the intra-psychic patterns being unlinked from traumatic torture experience patterns. With the aid of a model which discusses the torture as a superinfection with psychogenic violence-viruses, the penetration and resistance to therapy towards the torture trauma can be illuminated so that a differentiation of social and psychological factors of the torture experience is made possible.     

A new safe and aesthetic approach to suction abdominoplasty

Suction abdominoplasties are associated with a number of surgical complications, mainly in obese people and diabetic patients. The aesthetic result is often spoiled by poor balance caused by improper distance between the guide points of an harmonious abdomen (e.g., minimum of 10 cm between the pubic scar and the umbilicus). Almost all surgical complications are caused by extensive undermining and can be avoided by an en bloc resection without any undermining (the suction lipectomy of the upper flat creates a mesh undermining which is almost as efficient). A new neo-umbilicoplasty, described here, can be situated in the right position with good aesthetic results.     

Absorptiometry and “osteoporosis”: problems

connecting the dots between diverse clinical and other matters and an updated bone physiology reveals relationships that could modify some ideas about the roles and uses of absorptiometry in osteoporosis work. Herein, absorptiometry means that part of clinical densitometry that depends on X-ray absorption by bone and other tissues, thus excluding ultrasound methods and magnetic resonance imaging. The modifications concern, in part, some limitations of bone mineral density data, the kinds of physiological information that absorptiometry can and cannot provide, the relative importance of bone mass and whole-bone strength, how to define and study bone health and osteoporosis, and two kinds of osteoporotic fractures. As those modifications concern important national health care issues, they deserve answers based on hard evidence. Identifying those modifications might help others to evaluate them.     

Polymeric pyelotomy

A non-toxic, soluble polymeric preparation MAG with controlled period of gelation was synthetized for the extraction of stones from the pyelocalyceal system during surgery for urolithiasis.With respect to toughness the preparation proved superior to the fibrinogenthrombin mixture, used in the so-called fibrin pyelotomy according to Dees. Its biologic testing in animals (rabbits, dogs and pigs) yielded excellent results.By analogy with fibrin pyelotomy we took the liberty to propose the term polymeric pyelotomy.     

Urethro-vesical function during spinal shock

Summary Twenty spinal shock patients were investigated with simultaneous urethrovesical, anal and rectal pressure recordings and EMG of the external urethral and anal sphincters. Dynamic and static urethral pressure profiles (UPP) were carried out with empty and full bladder. Baldder filling was accompanied by an increased resistance in the internal sphincter zone, which in turn was paralleled in the majority of cases by an elevation of pressure in the membranous urethra without concomitant increase of its EMG activity. This is suggestive of an increased sympathetic activity in the bladder neck area and in the smooth muscle component of the external urethral sphincter. Dynamic pullthrough UPP's displayed higher resistances in the membranous urethra than static interrupted UPP's pointing to the role played by the urethral muscosal receptors in eliciting artefactual results. Higher pressures were recorded in the juxtabulbar portion of the membranous urethra than in its mid portion pointing to a gradient of pressure within the external urethral sphincter itself. The amount of EMG activity recorded in the anal and urethral sphincters at rest was somewhat decreased; high pressures and distinct reflex activity were recorded in both sphincters showing that they escape spinal shock characterized primarily by areflexia. After defining spinal shock a rational explanation based upon neuroanatomical and neurophysiological findings is offered as to why somatic activity of the sacral segments escapes it as evidenced by clincial, urodynamic, and electromyographic recordings.     

„Multi-targeting drugs“ und „multi-drug targeting“ beim metastasierten Nierenzellkarzinom

Ohne ZusammenfassungD. Rohde: Vorstandsmitglied der AUO.Association for Urogenital Oncology (AUO): Multi-targeting drug and multi-drug targeting in metastatic renal cell carcinoma. Co-inhibition of EGF-R     

82. Fragen der chirurgischen Weiterbildung: Gegenwärtiger Stand

Zusammenfassung Weiterbildung — die Einführung eines approbierten Arztes in ein anerkanntes Fachgebiet — ist im Begriff und System von Ausbildung (des Studenten) und lebenslanger Fortbildung (des fertigen Arztes) zu unterscheiden. Sie schafft das Fundament, auf dem sich Wissen und Können der Angehörigen einer Disziplin aufbauen, und setzt damit Wertmaßstäbe im eigenen Land und über die Grenzen hinaus. Weiterbildungsordnung (WO) und als Richtlinien bezeichnete Ausführungsbestimmungen regeln den Ablauf der Weiterbildung (W). Neu ist im wesentlichen die Verlängerung der Weiterbildungszeit von 5 auf 6 Jahre, die Einführung von Teilgebieten (in der Chirurgie Teilgebiet Kinder-Chirurgie und Teilgebiet Unfall-Chirurgie) mit dem Ziel, abgerundeten Subspezialitäten im Rahmen des Gesamt-Fachgebiets eine Autonomie zu geben, sowie ein umfangreicher Operations-Katalog. Die WO ist damit richtungweisend für die weitere Entwicklung des Fachgebietes und begründet erhebliche Anforderungen sowohl an den Facharzt-Aspiranten als auch an den Erfahrenen, der die W leitet. Die Einführung eines Befähigungsnachweises als einer in der ausschließlichen Kompetenz der ärztlichen Selbstverwaltung gelegenen Abschlußkontrolle wird befürwortet.

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Summary Postgraduate medical education in an approved specialty by definition and set-up differs from both undergraduate medical education and the life-long continuing medical education after completion of training. Postgraduate education in medicine is the basis for the knowledge and proficiency of a specialist and sets standards at home and abroad. Postgraduate education is laid down in principle in the Weiterbildungsordnung and regulated by the Richtlinien. Major innovations are a prolongation of training from 5 to 6 years, the introduction of subspecialties (pediatric surgery, traumatology), in order to give these established groups autonomy within the field of surgery and finally a sizable list of operations to be performed. The new Weiterbildungsordnung will guide the future development of surgery and imposes demands both on those in training and those responsible for it. An examination as "proof of competence"' is recommended, but should remain within the competence of the medical profession.

     

Serum hippuric acid concentration in renal allograft rejection,ureter obstruction,and tubular necrosis

Plasma from 35 renal allograft recipients (21 males and 14 females) was sampled daily and analyzed for hippuric acid (HA) by highperformance liquid chromatography (HPLC) and serum creatinine. Twelve of these patients experienced an acute renal allograft rejection or a ureter obstruction as proven by clinical signs and biopsy, as well as by radiography or ultrasound, respectively. Two patients suffered from tubular necrosis followed by rejection during the postoperative period. Mean serum HA increased by 39.9 mol/l from baseline (range 20.4–115.5 mol/l) in patients with acute rejection 3 days after an initial increase that was observed 24 h before the mean serum creatinine increased by 107.1 mol/l (range 21–193 mol/l). In cases of ureter obstruction, HA rose by 1.6 mol/l (range 1–8.2 mol/l), significantly less than elevations due to rejection. The increase in creatinine, however, amounted to 65.3 mol/l (range 22–140 mol/l) and was not different from the change in rejecting patients. Successful antirejection treatment coincided with a decrease in serum HA starting 24 h earlier than the decrease in the serum creatinine concentration. Of special interest was the observation of a parallel decrease in HA with creatinine concentration in patients with tubular necrosis after allotransplantation; HA increased in cases of an additional rejection. Our data suggest that HA, which is excreted by tubular secretion and glomerular filtration, could be a sensitive and early marker of acute allograft rejection. Furthermore, it seems to discriminate between acute renal allograft rejection and ureter obstruction. It might, therefore, be of value in the diagnosis of rejection complicating tubular necrosis after transplantation.     

Treatment of alar cartilages: Should the “domes” be interrupted?

The author emphasizes that conservative rhinoplasty techniques are frequently satisfactory, but in certain techniques there is a limit to which nasal tips can be reshaped. In certain circumstances, therefore, interruption of the domes of the alar cartilages is suggested to achieve the most satisfactory aesthetic results.     

33. Der „kalte” Schilddrüsenknoten

Zusammenfassung Der kalte Schilddrüsenknoten gilt als typischer Verdachtsbefund für ein Schilddrüsencarcinom. Seine tatsächliche Dignität ist mit klinischen Mitteln sowie Szintigraphie und Sonographie letztlich nicht zu klären. Das beste abgrenzende Selektionskriterium ist die Feinnadel-Punktionscytologie, wodurch mit Gültigkeit für das Kropfendemiegebiet etwa die Hälfte als suspekte Befunde von dem anderen Teil hochwahrscheinlich gutartiger Veränderungen getrennt und für die Operationsindikation reserviert werden kann.     

Triple approach for diagnosis and grading of meningiomas: Histology,morphometry of Ki-67/feulgen stainings,and cytogenetics

Summary With regard to meningioma grading and the recently introduced atypical meningioma, we evaluated 160 cases retrospectively by conventional histology and image analysis. For that, the cell nuclei were stained with a Ki-67 (MIB1)/Feulgen-method on paraffin sections, thus enabling the assessment of both the Ki-67 proliferation index and nuclear morphometric features, such as tumour cell arrangement, nuclear pleomorphism, and cellularity.It could be demonstrated that the Ki-67 proliferation index is the most important criterion for distinguishing anaplastic meningiomas (WHO grade III) (mean Ki-67 index: 11%) from those of common type (WHO grade I) (mean Ki-67 index: 0.7%). The parameter for the relative volume weighted mean nuclear volume is another valuable morphometric feature. The atypical meningioma (WHO grade II) which should represent an intermediate category between common type and anaplastic meningiomas is characterized by a mean Ki-67 proliferation index of 2.1%. Common type meningiomas which comprise almost 50% of the cases of this series have a relapse rate of 9%. Atypical and anaplastic meningiomas recurred in 29% and 50%, respectively. Since the term atypical meningioma is confusing in the context of tumour grading, the term intermediate type meningioma is proposed.Furthermore, the results of cytogenetic analyses of 142 cases of this series were evaluated and compared with the meningioma grades. Thereby, 25 cases disclosed, independent of the typical loss of one chromosome 22, cytogenetic features assumed to be progression-associated, e.g., the gain or loss of different chromosomes and the deletion of the short arm of one chromosome 1 (hyperdiploidy, increased hypodiploidy, Ip-), when correlated to the histological and morphometric findings or the high relapse rate.For meningioma diagnosis and grading, a practical guideline is proposed based upon histology, morphometry (Ki-67), and cytogenetics.     

381. Die operative Therapie beim Thoraxtrauma — eine retrospektive Studie

Zusammenfassung Nach multiplem Trauma sinken intracelluläre Aktivität und Konzentration der Elastase in polymorphkernigen Leukocyten (PMNL), die aus Blut ( = 67 U und 6154 g/10⁹ PMNL) und bronchoalveolärer Lavage (BAL)-Flüssigkeit ( = 44 U und 5957 g/10⁹ PMNL) isoliert wurden im Vergleich zu PMNL Gesunder ( = 106 U und 9962 g/10⁹ PMNL). Gleichzeitig wurde ein Anstieg der extracellulären Elastase-Konzentration in Plasma von = 84 g/1 auf = 399 g/1 und in BAL Flüssigkeit von = 8 g/1 auf = 561 g/1 beobachtet. Die durch Stimulation freigesetzte Elastase wird teilweise von einem spezifischen Receptor auf PMNL erneut gebunden. Die Ergebnisse unterstützen die PMNL-vermittelte ARDS-Pathogenese.     

The no-reflow phenomenon is a post-mortem artifact

Summary Post-ischemic reperfusion impairment, (no-reflow phenomenon), was studied in rats subjected to 8–30 minutes of global brain ischemia. During ischemia, rapid and complete loss of cerebral blood flow, EEG and³¹P-high energy phosphates (ATP/PCr) was observed.Brain intravascular perfusion defects were examined by injecting carbon blackintravenously in a group of rats with stable cardiopulmonary function and in another group subjected to rapid thoracotomy andintraarterial infusion of the carbon marker. Results indicate that global brain ischemic or non-ischemic control rats givenintraarterial carbon black after thoracotomy had varying degrees of vessel filling defects in brain resulting in pale tissue areas suggestive of impaired perfusion (no-reflow). All rats given carbon blackintravenously whether global brain ischemic or not, showed normal cerebrovascular filling of the carbon black and absence of pale tissue areas. In addition, post-ischemic cerebral reperfusion following 8–30 minutes global brain ischemia can reverse neuroelectric, energy metabolite and cerebral blood flow loss in rats whose cardiopulmonary function is not compromised.These findings indicate that the no-reflow phenomenon is an agonal or post-mortem artifact observed in the presence of cardiopulmonary failure.     

Prognostic evaluation before operative extirpation and radiotherapy of solitary brain metastasis

Summary This is a retrospective study of 134 patients operated on for solitary brain metastasis at the University Hospital in Uppsala, Sweden between 1963 and 1982. All the patients underwent postoperative radiation therapy. A statistical evaluation of different prognostic factors was made in order to create a prognostic model, a so-called risk profile, to be used for future patients. The most important factors for the making of risk profiles were found to be the histological diagnosis followed by the location in the brain, then the state on admission and the age at admission in that declining order. All these variables separately and together,i.e., as risk profiles, were matched against the outcome during survival as Karnofsky's scores and against the length of survival time. The results are shown in a diagram giving the surgeon grounds for his decision-making for or against operation and also for pre-operative information.     

“Kissing” bilateral large carotid-ophthalmic aneurysms

A case of unruptured bilateral large carotid-ophthalmic aneurysms, which appear to be adjoining and kissing each other when visualized by three-dimensional computed tomographic angiography (3-D CTA), is reported. Although bilateral carotid-ophthalmic aneurysms are not rare, bilateral large ones are quite rare, and direct imaging of kissing aneurysms of this portion has not been reported. Since 3-D CTA is becoming a useful tool for the diagnosis of cerebral aneurysms, we propose that these and similar bilateral large carotid-ophthalmic aneurysms are good candidates for the term kissing aneurysms.     

Estrogen Receptor Alpha in Human Breast Cancer: Occurrence and Significance

Estrogens have long been recognized as being important for stimulating the growth of a large proportion of breast cancers. Now it is recognized that estrogen action is mediated by two receptors, and the presence of estrogen receptor (ER)³ correlates with better prognosis and the likelihood of response to hormonal therapy. Over half of all breast cancers overexpress ER and around 70% of these respond to anti-estrogen (for example tamoxifen) therapy. In addition, the presence of elevated levels of ER in benign breast epithelium appears to indicate an increased risk of breast cancer, suggesting a role for ER in breast cancer initiation, as well as progression. However, a proportion of ER-positive tumors does not respond to endocrine therapy and the majority of those that do respond eventually become resistant. Most resistant tumors remain ER-positive and frequently respond to alternative endocrine treatment, indicative of a continued role for ER in breast cancer cell proliferation. The problem of resistance has resulted in the search for and the development of diverse hormonal therapies designed to inhibit ER action, while research on the mechanisms which underlie resistance has shed light on the cellular mechanisms, other than ligand binding, which control ER function.