A surgical activity model of laparoscopic cholecystectomy for co-operation with collaborative robots.

BACKGROUND: Laparoscopic cholecystectomy is a very frequent surgical procedure. However, in an ageing society, less surgical staff will need to perform surgery on patients. Collaborative surgical robots (cobots) could address surgical staff shortages and workload. To achieve context-awareness for surgeon-robot collaboration, the intraoperative action workflow recognition is a key challenge. METHODS: A surgical process model was developed for intraoperative surgical activities including actor, instrument, action and target in laparoscopic cholecystectomy (excluding camera guidance). These activities, as well as instrument presence and surgical phases were annotated in videos of laparoscopic cholecystectomy performed on human patients (n = 10) and on explanted porcine livers (n = 10). The machine learning algorithm Distilled-Swin was trained on our own annotated dataset and the CholecT45 dataset. The validation of the model was conducted using a fivefold cross-validation approach. RESULTS: In total, 22,351 activities were annotated with a cumulative duration of 24.9 h of video segments. The machine learning algorithm trained and validated on our own dataset scored a mean average precision (mAP) of 25.7% and a top K = 5 accuracy of 85.3%. With training and validation on our dataset and CholecT45, the algorithm scored a mAP of 37.9%. CONCLUSIONS: An activity model was developed and applied for the fine-granular annotation of laparoscopic cholecystectomies in two surgical settings. A machine recognition algorithm trained on our own annotated dataset and CholecT45 achieved a higher performance than training only on CholecT45 and can recognize frequently occurring activities well, but not infrequent activities. The analysis of an annotated dataset allowed for the quantification of the potential of collaborative surgical robots to address the workload of surgical staff. If collaborative surgical robots could grasp and hold tissue, up to 83.5% of the assistant's tissue interacting tasks (i.e. excluding camera guidance) could be performed by robots.

A learning robot for cognitive camera control in minimally invasive surgery.

BACKGROUND: We demonstrate the first self-learning, context-sensitive, autonomous camera-guiding robot applicable to minimally invasive surgery. The majority of surgical robots nowadays are telemanipulators without autonomous capabilities. Autonomous systems have been developed for laparoscopic camera guidance, however following simple rules and not adapting their behavior to specific tasks, procedures, or surgeons. METHODS: The herein presented methodology allows different robot kinematics to perceive their environment, interpret it according to a knowledge base and perform context-aware actions. For training, twenty operations were conducted with human camera guidance by a single surgeon. Subsequently, we experimentally evaluated the cognitive robotic camera control. A VIKY EP system and a KUKA LWR 4 robot were trained on data from manual camera guidance after completion of the surgeon's learning curve. Second, only data from VIKY EP were used to train the LWR and finally data from training with the LWR were used to re-train the LWR. RESULTS: The duration of each operation decreased with the robot's increasing experience from 1704 s ± 244 s to 1406 s ± 112 s, and 1197 s. Camera guidance quality (good/neutral/poor) improved from 38.6/53.4/7.9 to 49.4/46.3/4.1% and 56.2/41.0/2.8%. CONCLUSIONS: The cognitive camera robot improved its performance with experience, laying the foundation for a new generation of cognitive surgical robots that adapt to a surgeon's needs.

[Robots in the operating room-(co)operation during surgery]. / Robotik im Operationssaal ­ (Ko­)Operieren mit Kollege Roboter.

Background: Medical robotics has the potential to improve surgical and endoluminal procedures by enabling high-precision movements and superhuman perception. Objectives: To present historical, existing and future robotic assistants for surgery and to highlight their characteristics and advantages for keyhole surgery and endoscopy. Methods: In particular, historical medical robots and conventional telemanipulators are presented and compared with minimally invasive continuum robots and novel robotic concepts from practice and research. In addition, a perspective for future generations of surgical and endoluminal robots is offered. Conclusion: Robot-assisted medicine offers great added value for quality of intervention as well as safety for surgeons and patients. In the future, more surgical steps will be performed (semi-)autonomously and in cooperation with the experts.

Predictors of bone mineral density testing among older women on Medicare.

Although dual-energy X-ray absorptiometry (DXA) is recommended for all women ≥65 and is covered by Medicare, 40 % of women on Medicare report never having had a DXA. In a longitudinal cohort of 3492 women followed for two decades, we identified several risk factors that should be targeted to improve DXA testing rates. INTRODUCTION: DXA is used to measure bone mineral density, screen for osteoporosis, and assess fracture risk. DXA is recommended for all women ≥65 years old. Although Medicare covers DXA every 24 months for women, about 40 % report never having had a DXA test, and little is known from prospective cohort studies about which subgroups of women have low use rates and should be targeted for interventions. Our objective was to identify predictors of DXA use in a nationally representative cohort of women on Medicare. METHODS: We used baseline and biennial follow-up survey data (1993-2012) for 3492 women ≥70 years old from the nationally representative closed cohort known as the Survey on Assets and Health Dynamics among the Oldest Old (AHEAD). The survey data for these women were then linked to their Medicare claims (1991-2012), yielding 17,345 person years of observation. DXA tests were identified from the Medicare claims, and Cox proportional hazard regression models were used with both fixed and time-dependent predictors from the survey interviews including demographic characteristics, socioeconomic factors, health status, health habits, and the living environment. RESULTS: DXA use was positively associated with being Hispanic American, better cognition, higher income, having arthritis, using other preventative services, and living in Florida or other southern states. DXA use was negatively associated with age, being African-American, being overweight or obese, having mobility limitations, and smoking. CONCLUSIONS: Interventions to increase DXA use should target the characteristics that were observed here to be negatively associated with such screening.

Performance of calorimetric methods for the investigation of microbial systems in combination with additional sensors.

Calorimetric methods are used in combination with online oxygen measurement (using an amperometric sensor) and determination of the optical density (using a fibre optic sensor) to investigate microbial growth behaviour. The calorimetric curves of different batch experiments show a characteristic and reproducible course. Changes in the slope of the DeltaT-time curves indicate the effects of limiting factors on the microbial activity during the cultivation. A first limitation could be correlated with the depletion of oxygen in the medium; a second correlates with the depletion of the carbon source. Measurements of optical density in some cases provide reliable information about the growth of a microorganism culture. Our measurements show a good correlation of the universal calorimetric signal (heat-time curve) to the signal of the miniaturised photometric (OD) sensor.

Diffuse large B-cell lymphoma: a clinicopathologic analysis of 444 cases classified according to the updated Kiel classification.

The purpose of this study was: to compare the survival of diffuse large B-cell lymphomas (DLBCL) stratified according to the up-dated Kiel classification. A retrospective study of a cohort of 1378 cases was organized in 1996 by the Non-Hodgkin's Lymphoma Classification Project, and the DLBCL were classified according to the updated Kiel classification. The distribution of the different types and subtypes was as follows: centroblastic (CB, 85.4%), composed of the polymorphic (CB-PM, 58.6%), monomorphic (CB-MM, 17.1%) and multilobated (CB-ML, 9.7%) subtypes; immunoblastic (IB, 11.2%), with (8.3%) or without (2.9%) plasmacytoid differentiation; and anaplastic large cell lymphoma (ALCL) of B-cell type (3.4%). The rate of diagnostic agreement between pathologists was 78% for CB and 65% for IB lymphoma. The 5-year overall survival (OAS) for the entire group was 47% and the 5-year failure-free survival (FFS) was 42%. No significant differences in survival were found between the three major groups (CB, IB, ALCL). However, the 5-year OAS and FFS of patients with DLBCL not containing immunoblasts (CB-MM+CB-ML) was 51 and 52%, respectively, and was significantly better than the survival of those containing immunoblasts (CB-PM+IB+ALCL), which was 44 and 38% (p = 0.06 and p = 0.037), respectively. These results did not appear to be due to differences in the clinical features of the two groups, and was most significant for patients with low stage or low risk disease. However, histologic subtyping was not an independent risk factor for the entire group by multivariate analysis. In conclusion, patients with CB-MM and CB-ML (without immunoblasts) had a significantly better OAS and FFS than those with CB-PM, IB and ALCL (with immunoblasts). Therefore, we conclude that additional studies are still needed to further evaluate the importance of immunoblastic differentiation in DLBCL.

Peripheral T-cell lymphoma (excluding anaplastic large-cell lymphoma): results from the Non-Hodgkin's Lymphoma Classification Project.

BACKGROUND: Peripheral T-cell lymphoma (PTCL) is rare in most parts of the world. Therefore, we have evaluated the 96 cases of PTCL diagnosed within the Non-Hodgkin's Lymphoma Classification Project (NHLCP) (1378 cases) for their geographical distribution, pathologic features and diagnostic reliability, as well as clinical presentation and outcome. MATERIALS AND METHODS: Diagnoses of all cases were rendered independently by five experienced hematopathologists based on morphology only, and after introduction of the immunophenotype and clinical data. Divergent diagnoses were jointly discussed and a final consensus diagnosis was established in each case. Reliability of the diagnoses was evaluated statistically, and the clinical features and outcome were analyzed according to the consensus diagnoses. RESULTS: Seven per cent of all non-Hodgkin's lymphoma (NHL) cases reviewed were classified as PTCL and the frequency varied from 1.5% to 18.3% in different countries. The interobserver agreement with the consensus diagnosis of PTCL was 86% in the Revised European-American Lymphoma (REAL) classification, but the designation of subtypes was less reliable. Diagnostic reliability improved from 41% to 86% after immunophenotyping, but did not improve further with the addition of detailed clinical data. Clinically, angiocentric nasal lymphoma presented in young females (median age 49 years) at extranodal sites, but with few adverse risk factors, whereas angioimmunoblastic lymphoma presented most often in older males (median age 65 years) at nodal and extranodal sites with numerous risk factors. The 5-year overall and failure-free survivals for patients with PTCL treated with doxorubicin (Adriamycin)-containing regimens were only 26% and 20%, respectively. Both failure-free and overall survival were strongly correlated with the performance status and International Prognostic Index scores at presentation, but differences in survival were not observed between the major histological types. However, within the PTCL 'not otherwise specified' category, but not angioimmunoblastic lymphoma, the number of transformed blasts was prognostically relevant. CONCLUSIONS: PTCLs can be diagnosed reliably by experienced hematopathologists, but immunophenotyping is absolutely necessary. Currently, all types of PTCL should be considered high-grade lymphomas. An increased ability to distinguish T-lymphocyte subsets is needed in order to better subclassify the PTCLs for therapeutic and prognostic purposes.

Systemic anaplastic large-cell lymphoma: results from the non-Hodgkin's lymphoma classification project.

Anaplastic large-cell lymphoma (ALCL) is a heterogeneous process that may have a T-cell, B-cell, or indeterminant (null) phenotype and which may or may not express the anaplastic lymphoma kinase (ALK) oncoprotein. Because the clinical significance of these variants of ALCL is unclear, we evaluated the cases of ALCL-T/null and ALCL-B identified in the Non-Hodgkin's Lymphoma Classification Project. We evaluated 1,378 cases of non-Hodgkin's lymphoma (NHL), and a consensus diagnosis of ALCL-T/null was made in 33 patients (2.4%) with a diagnostic accuracy of 85%. Compared to 96 patients with other forms of peripheral T-cell lymphoma (PTCL), those with ALCL-T/null were significantly younger, less likely to have advanced-stage disease or bone marrow involvement, more likely to have a low International Prognostic Index score, and had a significantly better survival. Among those with ALCL-T/null, there were no significant differences in the clinical features or survival on the basis of ALK expression. A consensus diagnosis of ALCL-B was made in 15 patients (1.1%), and the diagnostic accuracy was 67%. However, compared to 366 patients with other forms of diffuse large B-cell lymphoma (DLBCL), those with ALCL-B were no different with regard to clinical features or survival. We conclude that patients with ALCL-T/null have favorable prognostic features and excellent survival and should be separated from those with other forms of PTCL for prognostic and therapeutic purposes. In contrast, patients with ALCL-B appear to be similar to those with other forms of DLBCL.

Marginal zone B-cell lymphoma: A clinical comparison of nodal and mucosa-associated lymphoid tissue types. Non-Hodgkin's Lymphoma Classification Project.

PURPOSE: In the International Lymphoma Study Group classification of lymphoma, extranodal marginal zone B-cell lymphoma (MZL) of mucosa-associated lymphoid tissue (MALT) type is listed as a distinctive entity. However, nodal MZL is listed as a provisional entity because of questions as to whether it is truly a disease or just an advanced stage of MALT-type MZL. To resolve the issue of whether primary nodal MZL without involvement of mucosal sites exists and whether it is clinically different from extranodal MALT-type lymphoma, we compared the clinical features of these two lymphomas. PATIENTS AND METHODS: Five expert hematopathologists reached a consensus diagnosis of MZL in 93 patients. Seventy-three were classified as having MALT-type MZL because of involvement of a mucosal site at the time of diagnosis, and 20 were classified as having nodal MZL because of involvement of lymph nodes without involvement of a mucosal site. RESULTS: A comparison of the clinical features of nodal MZL and MALT-type MZL showed that more patients with nodal MZL presented with advanced-stage disease (71% v 34%; P =. 02), peripheral lymphadenopathy (100% v 8%; P <.001), and para-aortic lymphadenopathy (56% v 14%; P <.001) than those with MALT-type MZL. However, fewer patients with nodal MZL had a large mass (> or = 5 cm) than those with MALT-type MZL (31% v 68%; P =.03). The 5-year overall survival of patients with nodal MZL was lower than that for patients with MALT-type MZL (56% v 81%; P =.09), with a similar result for failure-free survival (28% v 65%; P =.01). Comparisons of patients with International Prognostic Index scores of 0 to 3 showed that those with nodal MZL had lower 5-year overall survival (52% v 88%; P =.025) and failure-free survival (30% v 75%; P =.007) rates than those with MALT-type MZL. CONCLUSION: Nodal MZL seems to be a distinctive disease entity rather than an advanced stage of MALT-type MZL because the clinical presentations and survival outcomes are different in these two types of MZL. Clinically, nodal MZL is similar to other low-grade, node-based B-cell lymphomas, such as follicular and small lymphocytic lymphomas.

Clinical significance of follicular lymphoma with monocytoid B cells. Non-Hodgkin's Lymphoma Classification Project.

Although follicular lymphoma (FL) is very common in the Western world, very little information is available regarding the frequency and significance of monocytoid B cells (MBC) in FL. We recently completed a clinicopathologic study of 1,378 cases of non-Hodgkin's lymphoma. In this study, a research data sheet was designed to conduct research on several types of lymphomas, one part of which was evaluating the presence of intrafollicular clear cells and extrafollicular MBC in 326 cases diagnosed as FL by one of the pathologists (B.N.N.). For each case diagnosed as FL, the presence of intrafollicular clear cells or extrafollicular MBC was scored as pure FL (no intrafollicular clear cells or extrafollicular MBC), FL with intrafollicular clear cells, FL with less than 5% MBC, and FL with greater than 5% MBC. Of 326 cases classified as FL, 252 (77%) had no intrafollicular clear cells or extrafollicular MBC and therefore were called pure FL. In 36 cases (11%), intrafollicular clear cells were seen, but no extrafollicular MBC. There were no clinical differences between such cases and the 252 cases of pure FL. In eight cases of FL (2%), MBC clusters were rare (<5%). In contrast, 30 cases of FL (9%) had a prominent (>5%) proliferation of extrafollicular MBC; these 30 cases had a significantly shorter failure-free survival (P = .001) and overall survival (P = .04) than the 252 cases of pure FL. The shorter survival of these 30 cases appeared to be independent of the international prognostic index (IPI), stage, and treatment. The FFS of this group remained shorter than that of cases with pure FL when the analysis was restricted to patients treated with Adriamycin-containing regimens and either a favorable (0 to 3) IPI score (P = .001) or advanced stage (III/IV) disease (P = .015). In conclusion, FL with a prominent (>5%) MBC component constitutes a substantial proportion (9%) of FL and has distinctive morphology, and these patients have a significantly shorter survival than those with pure FL.

The smoking cessation efficacy of varying doses of nicotine patch delivery systems 4 to 5 years post-quit day.

BACKGROUND: This study was undertaken to evaluate the long-term smoking cessation efficacy of varying doses of transdermal nicotine delivery systems 4 to 5 years post-quit day. METHODS: A follow-up study was conducted 48 to 62 months after quit day among patients who were enrolled in the Transdermal Nicotine Study Group investigation. The latter study included group smoking cessation counseling and randomized assignment to 21, 14, or 7 mg nicotine patches or placebo patches. Seven of nine smoking cessation research centers participated in the long term follow-up investigation. RESULTS: The self-reported continuous quit rate among patients originally assigned 21 mg (20.2%) was significantly higher than rates for patients assigned 14 mg (10.4%), 7 mg (11.8%), or placebo patches (7.4%). Log rank survival analysis found no difference in relapse rates after 1 year postcessation. Smokers under age 30 years were significantly less likely to be abstinent at long term follow-up compared to smokers > or = 30 years of age (3 vs 13%, respectively). Mean weight gain in confirmed continuous quitters was 10.1 kg in men and 8.0 kg in women. Of the 63 continuous abstainers surveyed, 30 respondents (48%) reported that they no longer craved cigarettes, and no individual reported daily craving for cigarettes. CONCLUSIONS: Nicotine patch therapy with 21 mg/day patches resulted in a significantly higher long-term continuous abstinence rate compared to lower dose patches and placebo. Relapse rates among the various treatment conditions were similar after 1 year postcessation.

Estrogen profiles in postmenopausal African-American women in a wheat bran fiber intervention study.

High dietary fiber intake has been hypothesized to lower blood estrogen concentrations, an effect thought to be beneficial for decreasing breast cancer risk. This study investigated the association between dietary supplementation of wheat bran and circulating estrogen levels in postmenopausal African-American women participating in a community intervention trial. Seventeen postmenopausal women (aged 63 +/- 1.6 yr) participated in the study. Nutritional status was assessed and blood and 24-hour urine samples were collected before and after five to six weeks of daily supplementation of the diet with 35 g of wheat bran cereal (11.6 g insoluble dietary fiber) marked with 28 mg of riboflavin. Riboflavin confirmed that all postmenopausal participants adhered to the intervention protocol. Nine of the 17 postmenopausal women were taking some form of estrogen replacement therapy (PM-ERT). Baseline hormone levels in the PM-ERT group did not significantly change after the dietary intervention. Estradiol (96.8 +/- 20.3 vs. 113.8 +/- 23.3 pg/ml), androstenedione (0.47 +/- 0.06 vs. 0.45 +/- 0.06 ng/ml), and sex hormone-binding globulin (SHBG, 107 +/- 13.5 vs. 106.6 +/- 13.3 nmol/l) levels remained constant. In the eight postmenopausal women who were not receiving exogenous hormones (PM), wheat bran consumption was not associated with predicted decreased levels of estradiol (25.7 +/- 2.7 vs. 31.0 +/- 1.9 pg/ml), estrone (38.3 +/- 10.1 vs. 39.3 +/- 10.6 pg/ml), and androstenedione (0.78 +/- 0.08 vs. 0.68 +/- 0.11 ng/ml) or with increased concentrations of SHBG (35.2 +/- 6.4 vs. 34.8 +/- 6.5 nmol/l). Participants receiving ERT had baseline and postintervention levels of estradiol and SHBG significantly higher and androstenedione significantly lower than those not receiving ERT. No association between wheat bran supplementation and hormone levels was found in PM or PM-ERT African-American participants. These results in postmenopausal women are in contrast to findings of earlier studies in premenopausal women indicating that wheat bran fiber decreases serum sex hormones. Estrogen levels in postmenopausal women are only 5-10% of those in premenopausal women; therefore, a high wheat bran fiber diet alone may not be sufficient to depress these low levels even further.

Potassium and magnesium retaining triamterene derivatives.

This work represents a summary of studies carried out with potassium and magnesium retaining triamterene derivatives. The synthesis, analytics and physico-chemical characteristics of those substances are described. Furthermore, the relationships between the chemical structure and electrolyte excretion, pharmacokinetics, metabolism and toxicity are demonstrated. An expanded model regarding the mode of action of triamterene and its derivatives is also presented.

Lengthening spells of uninsurance and their consequences.

The lengths of time adults are without health insurance have increased since 1988, as shown by data from 1,235 household interviews completed during 1992 in Nebraska. Rural residents without insurance have experienced longer such spells than their urban counterparts. Thus, while rates of uninsurance are nearly the same between urban and rural residents, important differences exist. The relationship between insurance status and physician utilization is consistent during the five years (1989 to 1993) covered in this study. Continuously insured persons have the most physician visits, followed by those intermittently insured, followed by those continuously uninsured. The number of physician visits was expected to increase when respondents moved from uninsured to insured status. However, among urban respondents, the number of visits declined; among residents in rural frontier counties (fewer than six person per square mile) and for respondents in rural nonfrontier counties, there was no significant difference. This study points out some differences between rural and urban populations regarding insurance status, even when the overall rates of uninsurance are equal.

Potassium and magnesium retaining potency and efficacy of triamterene and analogues in conscious saline-loaded rats.

The effect of triamterene and analogues on the acute renal excretion of K+ and Mg2+ was investigated in conscious saline-loaded rats. The maximum retention (Emax) value of the potassium and magnesium retaining efficacy is almost independent of the structure of the compound and depends only on the initial basal value of ion excretion (E0). Triamterene and analogues display a comparable magnesium retaining efficacy. This can be explained by activity against the same renal Mg2+ transportation system. There was a relation between the ED50 values for the potassium and magnesium retaining properties of triamterene derivatives. Both the potassium and the magnesium retaining potency are dependent on the basicity as well as on the lipophilicity of the side chain of the triamterene derivatives. The part of the molecule responsible for the antimagnesiuretic properties of the derivatives seems to be sensitive to steric influences.

Investigations on the acute toxicity of acidic and basic triamterene derivatives.

Acidic and basic triamterene derivatives were evaluated with respect to their acute toxicity. After single intravenous application in mice, derivatives with a basic side-chain were much more toxic than compounds with an acidic side-chain. There is a significant correlation between the potassium retaining properties (measured as ED50) and the acute toxicity (measured as LD50) of the substances. The low acute toxicity after oral application of the compounds can be explained by their low oral bioavailability.

Facial morphometry of Ecuadorian patients with growth hormone receptor deficiency/Laron syndrome.

Facial morphometry using computerised image analysis was performed on patients with growth hormone receptor deficiency (Laron syndrome) from an inbred population of southern Ecuador. Morphometrics were compared for 49 patients, 70 unaffected relatives, and 14 unrelated persons. Patients with growth hormone receptor deficiency showed significant decreases in measures of vertical facial growth as compared to unaffected relatives and unrelated persons with short stature from other causes. This report validates and quantifies the clinical impression of foreshortened facies in growth hormone receptor deficiency.

Serine 90 is required for enzymic activity by tRNA-guanine transglycosylase from Escherichia coli.

An Escherichia coli mutant described by Noguchi et al. [Noguchi, S., et al. (1982) J. Biol. Chem. 275, 6544-6550] contains tRNA lacking the hypermodified wobble nucleoside queuosine (Q) due to an inactive tRNA-guanine transglycosylase (TGT). TGT catalyzes the posttranscriptional base exchange of the Q precursor preQ1 with the genetically encoded guanine in tRNA(Asp,Asn,His,Tyr). The mutant tgt gene was cloned and sequenced; it contained a single point mutation resulting in the change of serine 90 to phenylalanine. Overexpression of the mutant gene yielded TGT(S90F) that showed a reduced solubility and did not purify in the same fashion as the wild-type enzyme. TGT(S90F) has no detectable enzymic activity. To determine whether serine 90 performs a catalytic role in the TGT reaction or whether the loss of activity was caused solely by a conformational change of the enzyme, we used site-specific mutagenesis to construct serine-to-alanine (S90A) and serine-to-cysteine (S90C) mutants. Both S90A and S90C mutants were purified in a manner identical to that used for the wild-type enzyme. SDS-PAGE of dimethyl suberimidate-cross-linked mutants showed a pattern identical to that of the wild-type TGT, indicative of a trimeric quaternary structure. Native PAGE of wild-type and mutant TGTs in the absence and presence of substrate tRNA exhibited band shifts indicating that both mutants retain the ability to bind tRNA.(ABSTRACT TRUNCATED AT 250 WORDS)

Preparation and diuretic properties of novel amiloride analogues.

Fifteen novel amiloride analogues were synthesized and their diuretic properties compared to amiloride and triamterene in white wistar rats. Whereas none of the 6-substituted derivatives exhibited significant natriuretic and antikaliuretic effects, five of the compounds modified in the 2-position were found equal or better than standards. The results are discussed with respect to chemical structure and physiochemical properties.

Synthesis, natriuretic, antikaliuretic and antimagnesiuretic properties of an acidic triamterene derivative.

2,4,7-Triamino-6-(4-methanesulfonamidophenyl) pteridine (RPH 3048) is a new acidic triamterene derivative. Relevant physico-chemical constants were determined (solubility at pH 7.4 = 3.7 mg/l; logP at pH 7.4 = 0.2) and pharmacokinetic as well as pharmacodynamic properties were investigated, using male Wistar rats. After intravenous application of the test substances urine was collected, its volume and electrolyte composition determined, and the urine recovery of the drugs was analysed. The comparison of RPH 3048 with triamterene (CAS 396-01-0) revealed almost equipotent natriuretic and potassium-retaining effects for both drugs and an additional relative magnesium-sparing activity of RPH 3048. The urine recovery of RPH 3048 after 6 h was higher (20.6%) than that of triamterene (12.9%). No metabolite of RPH 3048 could be detected in the urine whereas a triamterene metabolite was found. Due to its good solubility in alkaline medium RPH 3048 could be dissolved (at pH 11-12) and then administered intravenously together with a loop diuretic (furosemide). Urinary electrolyte excretion following administration of two different combinations of RPH 3048 and furosemide (combination A: 12.5 mumol/kg RPH 3048 and 25 mumol/kg furosemide; combination B: 25 mumol/kg RPH 3048 and 25 mumol/kg furosemide) was compared to urinary electrolyte excretion of a control group and a group only treated with furosemide (25 mumol/kg). The additional application of RPH 3048 reduced in both groups potassium and magnesium excretion to control level but did not compromise furosemide induced natriuresis. In contrast to earlier investigations these results suggest that it is possible to develop acidic triamterene derivatives with potent antikaliuretic effects.