Biomedical subjects

R Kunkel

Publications and source records attributed to R Kunkel.

At least 19 recordsLinked to original sources

PubMed2005

A procedure to define natural groundwater conditions of groundwater bodies in Germany.

Commissioned by Germany's Working Group of the Federal States on Water Problems (LAWA) the authors developed a procedure to define natural groundwater conditions from groundwater monitoring data. The distribution pattern of a specific groundwater parameter observed by a number of groundwater monitoring stations within a petrographically comparable groundwater typology is reproduced by two statistical distribution functions, representing the "natural" and "influenced" components. The range of natural groundwater concentrations is characterized by confidence intervals of the distribution function of the natural component. The applicability of the approach was established for four hydrochemically different groundwater typologies occurring throughout Germany. Based on groundwater monitoring data from 7920 groundwater monitoring stations, 15 different hydrochemical parameters were evaluated for each groundwater typology. For all investigated parameters the range of natural groundwater concentrations has been identified. According to the requirements of the EC Water Framework Directive (article 17) (WFD) this study is a basis for the German position to propose criteria for assessing a reference state for a "good groundwater chemical status".

Environmental Monitoring↗

PubMed2005

Management of regional German river catchments (REGFLUD) impact of nitrogen reduction measures on the nitrogen load in the River Ems and the River Rhine.

The REGFLUD-project, commissioned by Germany's Federal Research Ministry (BMBF), addresses the problem of reducing diffuse pollution from agricultural production. The objective of the project is the development and application of multi-criteria scientific methods, which are able to predict diffuse pollution in river basins subject to economic feasibility and social acceptability. The selected river basins (Ems and Rhine basins) cover a variety of landscape units with different hydrological, hydrogeological and socio-economic characteristics. This paper focuses on the analysis of the effects of certain policy measures to reduce diffuse pollution by nitrogen. For this purpose a model system consisting of an agricultural sector model, a water balance model and a residence time/denitrification model was developed and applied. First results indicate a wide range of annual nitrogen surpluses for the rural areas between less than 10 kg N/ha up to 200 kg N/ha or more depending on the type and intensity of farming. Compared to the level of nitrogen surpluses the level of nitrogen inputs into the surface waters is relatively moderate because of degradation processes during transport in soil and groundwater. Policy impact analysis for a nitrogen tax and a limitation of the livestock density stress the importance of regionally tailored measures.

Agriculture↗

PubMed2004

Groundwater-borne nitrate intakes into surface waters in Germany.

The nitrogen loads entering the surface waters in Germany via the groundwater path were quantified. For this purpose, the results of a nitrogen balance model (Bach et al., 2000), which considers the most important N-inputs to the soil (manure, inorganic fertiliser, atmospheric deposition) and N-removals from the soil through crop harvest, were combined with the groundwater residence time/denitrification model WEKU (Kunkel and Wendland, 1997; Wendland et al., 2001). The modelled groundwater-borne nitrogen inputs into surface waters were validated using results from the MONERIS model (Behrendt et al., 2000) concerning riverine nitrogen retention, nitrogen inputs from point sources as well as nitrogen inputs through direct run-off (drainage etc.). In the vicinity of surface waters and in solid rock areas, the groundwater borne nitrogen inputs into surface waters are considerably high compared to the inputs into the aquifer due to predominantly unfavourable de-nitrification conditions and short residence times of groundwater. In the North German lowlands, however, the groundwater-borne nitrate inputs into surface waters are considerably low compared to the inputs into the aquifer. There, the residence time of groundwater in the aquifer is high and the groundwater is predominantly oxygen free and contains pyrite and/or organic carbon compounds, allowing a halving of the nitrate loads in the groundwater within a period of 1 to 4 years (see Wendland and Kunkel, 1999).

Carbon↗

PubMed2002

The SOIL-N/WEKU model system--a GIS-supported tool for the assessment and management of diffuse nitrogen leaching at the scale of river basins.

The SOIL-N/WEKU model system was developed to estimate groundwater-borne nitrogen inputs into river systems. The core of this model system is composed of a soil nitrogen leaching model (SOIL-N) and a groundwater residence time/denitrification model (WEKU). The application of the model system was carried out in the framework of the EU-project RANR (Regional analysis of subsurface nitrogen retention and its impact on the nitrogen export from land to sea) for a macroscale study river basin in Germany (the Uecker basin, ca. 2,400 km2) and a mesoscale study catchment area in Denmark (the Gjern basin, ca. 200 km2). For both catchment areas, the modelled average nitrogen loads leached into the groundwater were about 40 kg N/ha a, while the remaining groundwater-borne nitrogen intake to rivers was quantified to an average of about 2 kg/ha a. The comparison with observed groundwater-borne riverine nitrogen loads showed a very good agreement, proving the key role nitrogen retention in groundwater plays in the two catchment areas.

Diffusion↗

PubMed2001

Local administration of dendritic cells inhibits established breast tumor growth: implications for apoptosis-inducing agents.

Dendritic cells (DCs) can efficiently acquire foreign antigen(s) from apoptotic cells and induce MHC class I-restricted, antigen-specific CTLs. An accumulation of DCs within solid tumor masses in situ has been associated indirectly with a more favorable prognosis. Therefore, DCs may offer an efficient means for triggering immune responses within tumors, particularly in those masses containing significant apoptosis. We examined whether delivery of DCs could, alone, impact on the progressive growth of a tumor with a relatively high apoptotic index. We detected significant early apoptosis within the mass of a s.c. growing murine MT-901 breast carcinoma. DCs could efficiently engulf MT-901 tumor apoptotic cells in vitro. Intratumoral injections of syngeneic but not allogeneic DCs resulted in significant inhibition of MT-901 tumor growth. Histological examination of the tumor revealed intense mononuclear cell infiltration during and after DC injections. Tumor growth inhibition was relatively radiosensitive and dependent on host-derived CD8+ T cells. The baseline level of tumor apoptosis could be increased substantially by tumor necrosis factor alpha administration, leading to a greater DC-mediated antitumor effect. The antitumor effect could also be enhanced by first pulsing DCs with the foreign helper protein, keyhole limpet hemocyanin, prior to intratumoral delivery and combining it with the systemic administration of interleukin 2. Splenocytes from treated animals showed heightened levels of specific CTL activity and production of cytokines. The level of in situ tumor apoptosis appears to play a critical role in DC-mediated antitumor effects. The potential implication of these findings in DC-based tumor therapy strategies is discussed.

Animals↗

PubMed2001

Effect of C1-esterase-inhibitor on capillary leak and inflammatory response syndrome during arterial switch operations in neonates.

OBJECTIVE: To determine if prophylactic administration of C1-esterase-inhibitor would have a beneficial effect on postoperative weight gain and the inflammatory response in neonates undergoing cardiac surgery with cardiopulmonary bypass (CPB). DESIGN: Randomized, double-blinded study. SETTING: University-affiliated heart center. PARTICIPANTS: Twenty-four neonates with transposition of the great arteries. INTERVENTIONS: In group inhibitor (INH) patients (n = 12), 100 IU/kg of C1-esterase-inhibitor (Berinert) was given 30 minutes before CPB. In group placebo (P) patients (n = 12), placebo was administered instead. Interleukin (IL)-6, C3a anaphylatoxin, C1 activity, prekallikrein, Hageman factor, D-dimers, and clinical parameters were measured 6 times perioperatively. MEASUREMENTS AND MAIN RESULTS: All 24 patients had an uneventful clinical course. Mean arterial pressure and pulmonary oxygenation after CPB were superior in group INH patients. The weight gain on postoperative days 1 to 4 was significantly less in group INH patients compared with group P (55 +/- 59 g vs. 340 +/- 121 g, day 1). The concentration of IL-6 (76 +/- 17 pg/mL vs. 262 +/- 95 pg/mL during CPB) was significantly lower in group INH patients compared with group P patients. In contrast, no influence on C3a anaphylatoxin and coagulation factors was found. CONCLUSION: Prophylactic application of C1-esterase-inhibitor in neonates undergoing arterial switch operations produces less inflammatory response compared with placebo. This difference may have contributed to improved clinical parameters, including less weight gain postoperatively.

Capillary Leak Syndrome↗

PubMed2001

Model system for the management of nitrogen leaching at the scale of river basins and regions.

In the framework of the EU-project RANR (Regional analysis of subsurface nitrogen retention and its impact on the nitrogen export from land to sea) a model system was developed to estimate groundwaterborne nitrogen inputs into river systems. The core of this model system is composed of a soil nitrogen leaching model (SOIL-N) and a groundwater residence time/denitrification model (WEKU). The application of the model system was carried out for the study catchment areas of the Uecker basin (ca. 2400 km2, Germany) and the Gjern basin (ca. 200 km2, Denmark). For both catchment areas, the modelled average nitrogen loads leached into the groundwater were about 40 kg N/ha a, while the remaining groundwaterborne nitrogen intake to rivers was quantified to an average of about 2 kg/ha a. The comparision with observed groundwaterborne riverine nitrogen loads showed a very good agreement, proofing the key role nitrogen retention in groundwater plays in the two catchment areas. With regard to the generalisation and transfer of the SOIL-N/WEKU model concept we assume that the model can be applicated in catchment areas in the European Pleistocene Lowland, which ranges from the Netherlands in the west to the Baltic States and the Ukraine in the east.

Agriculture↗

PubMed1999

Vascular endothelial-cadherin is an important determinant of microvascular integrity in vivo.

In the present paper, we characterize an antibody, mAb BV13, directed to mouse vascular endothelial (VE)-cadherin, a major adhesive protein of interendothelial adherens junctions. When added to cultured endothelial cells, BV13 induces a redistribution of VE-cadherin from intercellular junctions. VE-cadherin redistribution did not change the localization of platelet endothelial cell adhesion molecule or tight junction markers such as zonula occludens 1, cingulin, and junctional adhesion molecule. Intravenous administration of mAb BV13 induced a concentration- and time-dependent increase in vascular permeability in heart and lungs. By electron microscopy, interstitial edema and accumulation of mixed types of inflammatory cells in heart and lungs were observed. Injection of (rhodamine-labeled) Ricinus communis I lectin showed focal spots of exposed basement membrane in the alveolar capillaries and in some larger pulmonary vessels. These data indicate that VE-cadherin is required for vascular integrity and normal organ functions.

Animals↗

PubMed1998

Recruitment of non-patient volunteers with schizophrenia spectrum personality symptoms.

Authors aimed to evaluate the yield and effectiveness of recruiting community schizophrenia spectrum personality (SSP) subjects via targeted newspaper advertisements listing SSP traits. Eight newspaper advertisements listing SSP traits were placed in regional newspapers over a 3-year period. Respondents (n = 209) were screened thoroughly via telephone, and eligible subjects were invited for face-to-face clinical interviews. One hundred and one subjects (48% of the respondents) were screened out over the phone and another 30% were no-shows or refused. Of the 46 subjects who were interviewed, a majority (24 subjects; 52%) met this study's criteria for SSP. These subjects experienced significant psychotic-like symptoms, as ascertained by a self-rating scale, and showed a downward drift in their socio-economic status. One can successfully recruit SSP subjects, with high yield, using targeted telephone advertisements combined with thorough telephone screening.

Adult↗

PubMed1998

Spontaneous dyskinesia in subjects with schizophrenia spectrum personality.

OBJECTIVE: The study of spontaneous dyskinesia in schizophrenia is confounded by the widespread use of neuroleptics. The authors hypothesized that spontaneous dyskinesia would be present in subjects with schizophrenia spectrum personality (schizoid, paranoid, or schizotypal). They also tested the hypothesis that dyskinetic-like movements would increase after repeated dextroamphetamine challenge to the dopaminergic system. METHOD: Dyskinetic-like movements were assessed in 34 spectrum subjects and 22 normal subjects; nine subjects from each group were administered both placebo and repeated dextroamphetamine challenges. RESULTS: Spectrum subjects had more dyskinetic-like movements than normal subjects. Spontaneous dyskinesia was present in 12% of the spectrum subjects but was not seen in the normal subjects. Subjects with schizotypal personality had more dyskinetic-like movements than subjects with schizoid personality or normal subjects. Dyskinesia was present in 24% of the schizotypal subjects but not in the other groups. Dyskinetic movement scores correlated with positive symptom scores. With repeated amphetamine challenge, normal subjects showed a pattern of behavioral sensitization (an increase in dyskinetic-like movements), but spectrum subjects showed an abnormal response (fewer dyskinetic-like movements). CONCLUSIONS: Dyskinesia and dyskinetic-like movements are more common in subjects with schizophrenia spectrum personality (primarily schizotypal) than in normal subjects and are related to positive symptoms. A failure of normal behavioral sensitization mechanisms after dextroamphetamine challenge is seen in subjects with schizophrenia spectrum personality.

Comorbidity↗

PubMed1996

Long-term low-dose cyclosporine therapy for severe psoriasis: effects on renal function and structure.

BACKGROUND: The effectiveness of cyclosporine in the treatment of severe psoriasis is well known. OBJECTIVE: We evaluated the efficacy and toxicity of systemic cyclosporine in patients with severe psoriasis, observing short-term (12 weeks) and long-term (3 to 5 years) effects. METHODS: To further elucidate efficacy and safety, 42 patients with severe psoriasis were treated initially with cyclosporine 5 to 6 mg/kg per day for 12 weeks. A subset of 14 patients continued maintenance treatment for 3.5 years to study the long-term effects of cyclosporine on renal function and structure. Renal biopsies were performed after 2.5 years and 3.5 years of treatment. Renal histologic findings were correlated with renal function. RESULTS: By weeks 8 and 12, 64% (n = 27) and 86% (n = 36) of patients, respectively, were rated clear or almost clear of the psoriasis. However, a subpopulation of 15 patients did not respond to 5 mg/kg daily but improved when the dose was increased to 6 mg/kg daily. Clearance or near clearance was achieved in 67% of this subpopulation after 4 weeks. For the 29 patients whose glomerular filtration rate (GFR) was measured, mean GFR fell by 7% from baseline to week 4 (p < 0.05). This change was reversible when dosage was reduced by 1 mg/kg per day in each of these patients. Patients older than 45 years of age experienced significant elevation of mean diastolic blood pressure and had reduced GFR and increased serum creatinine. After 2.5 years, of the 14 patients who continued maintenance treatment, two had biopsy specimens that showed moderate interstitial fibrosis and tubular atrophy. The remainder showed only minimal to mild structural damage. After 3.5 years of cyclosporine treatment, repeat renal biopsy specimens revealed slight increases in structural changes in nine subjects. These changes correlated with increasing age and drug-induced hypertension. CONCLUSION: We conclude that 5 mg/kg of cyclosporine daily is usually an effective initial dose for psoriasis. Patients who do not respond will often benefit from elevation of the dose to 6 mg/kg daily. Older patients experience cyclosporine-induced hypertension and changes in renal function and structure more frequently than do younger patients.

Adult↗

PubMed1994

Bi-ventricular function assessed intraoperatively before and after anatomical correction of transposition of the great arteries.

After anatomical correction of transposition of the great arteries (TGA), the left ventricle (LV) is forced to develop systemic pressures without having had time for adaptation. Thus, one might expect dilatation of the LV at least in the very early intraoperative period following the operation. In nine patients with TGA aged 8-24 days (median 9.5 days) which were selected for arterial switch operation (ASO), Dacron-patch mounted thin piezoceramic transducers were attached intraoperatively by fibrin glue to opposite epicardial surfaces of the right (RV) and/or LV for continuous assessment of external minor diameters (RVD, LVD; sonomicrometry) before and after correction. Right and left ventricular pressures (RVP, LVP) were measured simultaneously and pressure-diameter loops were generated. Right and left ventricular power indices (RVPi, LVPi: = HRxVPxVsD) was calculated from heart rate, ventricular pressures, and systolic shortening of the respective ventricular diameter (RVsD, LVsD). Data obtained during circulatory steady-state immediately before extra-corporeal circulation (ECC) and up to 45 min after ECC were compared. By avoiding volume overload (CVP < or = 10 mmHg) at weaning off ECC and by lowering the systemic vascular resistance and, thus, LV afterload (approximately 8 micrograms.kg-1 min-1 dobutamine), the LV developed systemic pressure (70 +/- 7 vs. 41 +/- 4 mmHg) at unchanged diastolic LV end-diastolic pressure (LVedP) (10 +/- 3 mmHg). Left ventricular power index increased by 45 +/- 25%, although the extent of systolic shortening of LVD was reduced by 20 +/- 10%. Simultaneously, the RV was effectively unloaded (RVedP: 8 +/- 3 vs 11 +/- 6 mmHg; RVP: 39 +/- 7 vs 53 +/- 9 mmHg; RVPi: -42 +/- 27%).(ABSTRACT TRUNCATED AT 250 WORDS)

Extracorporeal Circulation↗

PubMed1994

Hypocholesterolemia and affective disorders.

The authors' specific aim was to assess hypocholesterolemia in 203 patients hospitalized because of affective disorders (depression, bipolar disorder, and schizoaffective disorder) compared with 1,595 self-referred subjects in an urban supermarket screening and with 11,864 subjects in the National Health and Nutrition Examination Survey II, a national probability sample. Low plasma cholesterol concentrations (< 160 mg/dL) were much more common in patients with affective disorders (20%) than in urban supermarket screenees (4%, P < or = 0.001) or in the National Health and Nutrition Examination Survey II subjects (10%, P < or = 0.001). When paired with supermarket screenees by age and sex, patients with affective disorders had much lower plasma total cholesterol (P < or = 0.0002), low-density lipoprotein cholesterol (P < or = 0.001), and high-density lipoprotein cholesterol (P < or = 0.0001), and higher triglyceride concentrations (P < or = 0.03). Neither the severity of the affective disorders nor severity-age interactions were associated with plasma cholesterol concentrations (P > 0.1); age and plasma cholesterol were positively associated (P = 0.01). None of the psychoactive drugs had a significant independent association with the patients' low-density lipoprotein cholesterol. Plasma cholesterol in patients hospitalized with affective disorders is shifted markedly downward toward hypocholesterolemic concentrations (< 160 mg/dL). There is no evidence that low plasma cholesterol could cause or worsen affective disorders.

Bipolar Disorder↗

PubMed1994

Replicative Legionella pneumophila lung infection in intratracheally inoculated A/J mice. A murine model of human Legionnaires' disease.

The role of host immune responses in the pathogenesis of Legionnaires' disease is incompletely understood, due in part to the current lack of an animal model that is both susceptible to replicative Legionella pneumophila-induced lung infection and for which species-specific immunological reagents are available. We have developed a model of replicative L. pneumophila lung infection in intratracheally inoculated A/J mice. L. pneumophila was obtained in the exponential growth phase and inoculated into the trachea of 6- to 8-week-old female A/J mice. Microbiological and histopathological evidence of infection was demonstrated in mice inoculated with 10(6) colony-forming units. Development of an acute pneumonia that resembled human Legionnaires' disease coincided with exponential growth of the bacteria in the lung 24 to 48 hours after intratracheal inoculation of L. pneumophila. This was associated with increased plasma levels of interferon-gamma at 24 hours after inoculation. After 48 hours, the bacteria were gradually eliminated from the lung over the next 5 days, corresponding with resolution of the inflammatory response in the lung, thereby mimicking the outcome frequently seen in the immunocompetent human host. Treatment of animals with anti-interferon-gamma antibody enhanced bacterial replication and disease progression, indicating an important role of host immune response in resolution of the infection. Because of the availability of murine-specific reagents, this model of replicative L. pneumophila lung infection in A/J mice after intrapulmonary inoculation of L. pneumophila potentially provides an important tool for future studies investigating the role of host immune responses in the pathogenesis of Legionnaires' disease in the immunocompetent host.

Animals↗

PubMed1993

Improvement in symptoms of depression and in an index of life stressors accompany treatment of severe hypertriglyceridemia.

In 14 men and nine women referred because of severe primary hypertriglyceridemia, our specific aim in a 54-week single-blind treatment (Rx) period was to determine whether triglyceride (TG) lowering with a Type V diet and Lopid would lead to improvement in symptoms of depression, improvement in an index of life stressors, change in locus of control index, and improved cognition, as serially tested by Beck (BDI), Hassles (HAS) and HAS intensity indices, Locus of Control index, and the Folstein Mini-Mental status exam. On Rx, median TG fell 47%, total cholesterol (TC) fell 15%, and HDLC rose 19% (all p < or = 0.001). BDI fell at all nine Rx visits (p < or = 0.001), a major reduction in a test of depressive symptoms. The HAS score also fell at all nine visits (p < or = 0.05 - < or = 0.001). Comparing pre-Rx baseline BDI vs BDI at 30 and 54 weeks on Rx, there was a major shift towards absence or amelioration of depressive symptoms (chi 2= 5.9, p = 0.016). On Rx, the greater the percent reduction in TG, the greater the percent fall in BDI (r = 0.47, p < or = 0.05); the greater the percent reduction in TC, the greater the percent fall in HAS (r = 0.41, p < or = 0.05). Improvement in the BDI and HAS accompanied treatment of severe hypertriglyceridemia, possibly by virtue of improved cerebral perfusion and oxygenation. There may be a reversible causal relationship between high TG and symptoms of depression.

Adult↗

PubMed1993

A role for glycosphingolipid accumulation in the renal hypertrophy of streptozotocin-induced diabetes mellitus.

Glucosylceramide (GlcCer) and related glycosphingolipids have been implicated as causal elements in both the growth of cells and in the regulation of hormonal signaling. We therefore studied whether the renal hypertrophy induced by diabetes was associated with enhanced synthesis of glycosphingolipids. 16 d after the induction of diabetes, increases in renal size and concentration of glucocerebroside and ganglioside GM3 were observed paralleling an increase in UDP-Glc concentration. GlcCer synthase and beta-glucosidase-specific activities were no different between control and diabetic kidneys. The apparent Km of the GlcCer synthase with respect to UDP-Glc was 250 microM and was unchanged in the diabetic kidneys. The observed concentrations of UDP-Glc were 149 and 237 microM in control and diabetic kidneys, respectively. The UDP-Glc level is thus rate limiting with regard to GlcCer synthesis. To determine whether the changes in glycolipid content were functionally significant, diabetic and control groups were treated with the GlcCer synthase inhibitor, D-threo-1-phenyl-2-decanoyl-amino-3-morpholino-1- propanol, 2 wk after the induction of diabetes. Kidney weights in the diabetic rats treated with D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol were no different than the control groups. Morphometric analysis of glomerular volumes paralleled changes in renal growth. Glycosphingolipid formation may therefore represent a significant pathway for glucose utilization in early diabetic nephropathy.

Animals↗

PubMed1992

Central venous catheterization in infants and children with congenital heart diseases: experiences with 500 consecutive catheter placements.

In a prospective study results of central venous catheter (CVC) placements in a consecutive group of 500 patients with less than 20 kg body weight undergoing cardiac surgery were evaluated. The incidence of previous cardiac surgery was 21% and the incidence of factors preventing the primary puncture of the right jugular or innominate vein was 13.4%. The anesthesiologists were free to select the catheterization technique, site of puncture, and catheter type. All CVC insertions were performed prior to surgery under continuous circulatory monitoring and optimal positioning of the anesthetized patient. Ninety-six percent of all catheterizations were successful, 81% of them on the first attempt. In the 4% of cases where catheterization failed, a CVC had to be placed by the surgeon. Of all catheters, 66% were positioned via the right internal jugular (IJV) or innominate vein (IV), 8% via the left, 16% via an external jugular vein (EJV), and 5% via other veins. Seventy-six percent of CVC insertions were performed with the Seldinger technique. Of the four catheter types used in this study, double lumen catheters were most frequently selected (38%). Placement of 22-ga single lumen catheters was preferred in infants with less than 5 kg body weight, in spite of their tendency to kink. Observed complications (10% arterial puncture, 4% hematoma, and 1% intrathoracic bleeding) never required immediate surgical intervention. Careful selection of appropriate catheters, as well as extensive experience and knowledge of the anatomical structures involved in special heart defects, helped to keep the risk of complications low.

Body Weight↗

PubMed1991

Experience with anatomical correction of transposition of the great arteries (TGA).

During the past seven years, 102 patients with TGA have been operated on using the switch operation. Overall early mortality was 5.9%, late mortality 2.%. Sixty-three newborns had an intact septum and were corrected between the 3th and 35th day after birth, 39 had a ventricular septal defect and/or associated anomalies. All operations were carried out under ECC and deep hypothermia. Myocardial function was recorded intraoperatively by using sonomicrometry. The data demonstrate that adaptation of the left ventricle to the new load conditions should be supported by drugs providing inotropic stimulation and afterload reduction. Mean follow-up time is 32.5 months, no rhythm problems have been recorded during that period, a few children revealed trivial pulmonary or aortic valve stenosis and/or incompetence. The switch operation permits good early results for newborns with TGA and intact septum and TGA with VSD. A decade has to pass in order to judge the long-term results.

Follow-Up Studies↗