Dosimetric analysis of a compartmental model for radioligand uptake in tumor lesions.

Radioligand therapy is a targeted cancer therapy that delivers radiation to tumor cells based on the expression of specific markers on the cell surface. It has become an important treatment option in metastasized neuroendocrine tumors and advanced prostate cancer. The analysis of absorbed doses in radioligand therapies has gained much attention and remains a challenging task due to individual pharmacokinetics. As an alternative to the often used sum of exponential functions in intra-therapeutic dosimetry, a basic compartmental model for the pharmacokinetics of radioligands is described and analyzed in this paper. In its simplest version, the model behavior is determined by the uptake capacity and the association constant and can be solved analytically. The model is extended with rates for excretion from the source compartment and externalization from the lesion compartment. Numerical calculations offer an insight into the quantitative effects of the model parameters on the absorbed dose in the tumor lesion. This analysis helps understanding the importance of clinically relevant factors, e.g. the effect on absorbed doses of modified radioligands that bind to albumin. Using clinical data, the potential application in intra-therapeutic dosimetry is illustrated and compared to the bi-exponential function which lacks a mechanistical basis. While the compartmental model is found to constitute a feasible alternative in these examples, this has to be confirmed by further clinical studies.

A prospective study with ten years follow-up of two-hundred patients with proximal femoral fracture.

BACKGROUND: The proximal femoral fracture is one of the most common injuries in the elderly. Nevertheless, no results beyond the second year post surgery have been reported in the literature. Therefore, the purpose of this study was to evaluate any revision and mortality within 10 years follow-up as well as the walking ability of still alive patients. METHODS: A total of 200 consecutive patients were included. A prospective database was first used to collect the demographic data. Exactly ten years after the surgery, a final evaluation was conducted by telephone for every patient. Any revision, any contralateral as well as other fractures and the date of death were recorded. For all patients who were still alive, the mobility score according to Parker was also surveyed. RESULTS: The average age was 79.0 years (SD: 12.5); women were affected at higher numbers (73.5%). The total surgical revision rate was 17.5% (35/200), due in particular to hematoma (9×) or infection (7×). A surgical revision later than two years was only needed in three patients (1.5%). The risk of another fracture caused by a fall was 19% (38/200), most often a contralateral femoral fracture (22/200; 11%) that happened on average 51.9 months (1-97) after the initial surgery. The risk of a contralateral femoral fracture was 15.4% (22/143) in patients who survived the first year post surgery. The postoperative mortality was 1, 2, 5 and 10 years or 23.5%, 32.5%, 55% as well as 81.5%, respectively. An average Parker's mobility score of 6.3 points (0-9) was determined for the 37 patients (18.5%) who were still alive at the time of the follow-up. CONCLUSION: The long-term study showed that revision surgery was only required in 3/200 patients (1.5%) beyond the second year of that surgery. On the other hand, more than half of all patients had already passed away five years after the initial surgery. The exact incidence of a contralateral femoral fracture was 11.9%, climbing to 15.4% if the patient survived at least one year. Nearly every fifth patient experienced another fall resulting in a severe fracture requiring treatment during the long-term course.

Peri-implant femoral fractures: The risk is more than three times higher within PFN compared with DHS.

INTRODUCTION: Information is lacking regarding incidence rates, treatment regimens, and outcomes concerning peri-implant femoral fractures (PIF). Therefore, we performed a retrospective study to provide scientific data concerning incidence and outcome of PIF following osteosynthesis of proximal femoral fractures (PFF). MATERIAL AND METHODS: We retrospectively included all patients who received osteosynthesis for PFF between 2006 and 2015 and in whom PIF was confirmed postoperatively. All available patients with PIF were contacted minimum one year post-surgery. RESULTS: A total of 1314 osteosynthesis procedures were performed, of which 705 were proximal femoral nails (PFNs), 597 were dynamic hip screws (DHSs), and 12 were screws appliances only. During the same period, 18 PIFs (1.4%) were reported. However, PIF was 3.7 times higher within PFN when compared to DHS (15/705:2.1% versus 3/597:0.5%; odds ratio: 3.7). The following analysis also included 8 patients with PIF who were referred from other hospitals, resulting in a total of 26 patients. Mean patient age was 84.8 years (range, 57-95), with a predominance in female (23×) and in the left femur (19×). PIF occurred after an average of 23.6 months (range, 1-81) post-surgery. The fractures, most of which were spiral-shaped, were most commonly treated with locking plate osteosynthesis. The surgical revision rate was 7.7%, and the one-year mortality was 23.1%. At an average of 43.0 months (range, 12-100) post-surgery, it was possible to contact 18/26 patients (69.2%), and their mean Parker Mobility Score was 5.2 points (range 2-9). CONCLUSIONS: Peri-implant femoral fracture is a rare incident within the old age traumatology of PFF. However, based on our small number of cases, it occurred within PFN much more frequently compared with DHS. Locking plate osteosynthesis has been shown to be effective and reliable. Surgical revision and mortality rates do not appear to be increased when compared to those with the initial treatment of proximal femoral fractures.

Occlusal caries extension in relation to visual and radiographic diagnostic criteria: results from a microcomputed tomography study.

OBJECTIVE: This in vitro study aimed to evaluate occlusal caries extension in relation to visual and radiographic diagnostic criteria and their clinical value to indicate operative or preventive dental care. METHODS: A total of 196 third molars with clinically sound occlusal fissures or noncavitated lesions were collected. Before microcomputed tomography (µCT) investigation, each tooth was examined visually and radiographically. Kühnisch's µCT-based caries-extension index (CE index) was used to determine the caries depth on a numeric scale (0 = sound; 0.01-0.99 = enamel caries; 1.0-1.99 = dentin caries). Sensitivities (SEs), specificities (SPs), and area under the receiver operating characteristic curve (Az value) were also calculated. RESULTS: Based on µCT data, the following mean CE index values and standard deviations (SDs) were documented according to the visual criteria: sound = 0.6 (0.4); first visible signs = 0.9 (0.4); established lesions = 1.3 (0.3); microcavities = 1.4 (0.2); dentin exposure = 1.5 (0.2); and large cavities = 1.5 (0.3). The radiographic categories according to Marthaler (enamel caries [D0-2], caries in the outer half of dentin [D3], and caries in the inner half of dentin [D4]) were related to CE index values of 0.9 (0.4), 1.4 (0.2) and 1.6 (0.4), respectively. Caries detected visually or radiographically showed an SE of 84% and an SP of 85% (Az = 0.85). When both methods were used to predict dentin involvement simultaneously, SE = 27%, SP = 100%, and Az = 0.63; this combined visual and radiographic approach was associated with a perfect specificity and no false-negative decisions. The proportion of false-positive diagnoses was moderately high, and lesion extension in these cases was mainly limited to the outer 20% of the dentin. CONCLUSIONS: Our results might be useful for differentiating between preventive and operative dental care for pits and fissures.

Irregularities below the enamel-dentin junction may predispose for fissure caries.

This study investigated the structure of the fissure fundus on occlusal surfaces with respect to the detection of possible irregularities below the enamel-dentin junction (EDJ). Occlusal surfaces were examined by micro-computed tomography (µCT). In total, 203 third molars with clinically sound occlusal fissures or non-cavitated lesions were selected. All specimens were scanned with µCT. Subsequently, each tooth was sectioned, and each slice was investigated by stereomicroscopy. In 7 of 203 molars (3.4%), demarcated radiolucencies below the EDJ were detected by µCT. These defects were obviously of non-carious origin, because the µCT images revealed no gradient of demineralization in the dentin. In all cases, a direct pathway between the oral cavity and the dentin was evident. The comparison of the µCT sites with conventional histological images also revealed defects in the dentin. These results demonstrate that demarcated radiolucencies below the EDJ may not necessarily be caries lesions according to µCT images and may be classified as possible developmental irregularities. To avoid misinterpreting µCT data, dental researchers should carefully consider this condition when analyzing µCT images. The clinical significance of this finding is that these defects may predispose molar teeth to early-onset caries in occlusal pits and fissures.

Measurements and predictions of light scattering by clear coatings.

Comparisons are made between calculated and measured angle-resolved light-scattering distributions from clear dielectric isotropic epoxy coatings over a range of rms roughness conditions, resulting in strongly specular scattering to diffuse scattering characteristics. Calculated distributions are derived from topography measurements performed with interferometric microscopes. Two methods of calculation are used. One determines the intensity of scattered light waves with a phase integral in the Kirchhoff approximation. The other is based on the reflection of light rays by locally flat surfaces. The angle-resolved scattering distributions for the coatings are measured with the spectral trifunction automated reference reflectometer (STARR) developed by the National Institute of Standards and Technology. Comparisons between measured and calculated results are shown for three surfaces with rms roughness values of approximately 3, 150, and 800 nm for an angle of incidence of 20 degrees .

Dialysis adequacy versus metabolic factors in the clinical assessment of CAPD.

We performed a cross sectional study of our continuous ambulatory peritoneal dialysis (CAPD) patients (n = 98) to examine the relation between parameters of adequacy of dialysis [KT/V, weekly creatinine clearance (Ccr)], urea kinetics (PCR), biochemical parameters (serum albumin), and clinical status of these patients. We also investigated the predictive value of these parameters in the determination of clinical outcomes. The clinical status of each patient was assessed by patient self-assessment and objectively by physicians and nurses. On this basis a total clinical assessment score was assigned. Individuals with a score of 3 or less were judged to be clinically stable (group 1, n = 61), while a score of 4 or more was considered "not doing well" (group 2, n = 37). A good correlation (r = 0.7) between subjective and objective assessments was observed. No correlation between total clinical assessment score and KT/V, PCRN (normalized protein catabolic rate), or Ccr was obtained, while serum albumin levels correlated inversely (r = -0.30; p < 0.003), suggesting that parameters of dialysis adequacy (weekly KT/V, Ccr) and urea kinetics (PCRN) are not predictive of clinical outcome in CAPD patients, in contrast with hemodialysis (HD) patients. Serum albumin levels were observed to be correlated with clinical outcome in CAPD patients. Hypoalbuminemia was observed in group 2 patients, despite statistically insignificant different values of KT/V, Ccr, and PCRN in the two groups. Therefore, clinical assessment and parameters such as serum albumin must be considered when determining the total well-being of CAPD patients.

Impact of epoetin beta on dialyzer clearance and heparin requirements.

The present studies were undertaken to determine whether treatment with recombinant human erythropoietin (epoetin beta [Marogen Sterile Powder, Chugai-Upjohn, Rosemont, IL] ) necessitates an alteration in dialysis prescription or in heparin requirements. All patients had end-stage renal disease (ESRD), were on chronic hemodialysis (either high-flux or conventional) for more than 3 months, and had participated in large-scale, multicenter epoetin beta clinical trials. Nine patients were entered into the clearance study. Blood chemistry values, dialyzer clearances, and hematocrit values were determined before beginning epoetin beta administration and after approximately 40 weeks of treatment. The mean hematocrit value at the beginning of the study was 0.229 (22.9%); by week 40, it averaged 0.313 (31.3%). The mean percent change in urea clearance was -1.9%, and a mean percent change of +12.7% in blood urea nitrogen (BUN) was noted. The mean percent change in creatinine clearance was -15.3, while the mean percent change in serum creatinine was +0.2%. The mean percent change in phosphate clearance was -10.1%, and the mean percent change in serum phosphate was +44.1%. Heparin profiling was performed for nine patients (four participated in the clearance study). Seven patients showed increased requirements for heparin, with a mean percent change of +24.3%. These results underscore the necessity for careful attention to the changing status of the dialysis patient on epoetin beta. While epoetin beta treatment does not, in general, adversely affect either clearance or blood chemistry values, these values may fluctuate in individual patients in response to the increasing hematocrit values and to dietary changes that result from an increased sense of well-being.(ABSTRACT TRUNCATED AT 250 WORDS)

Subclavian vein stenosis as a complication of subclavian catheterization for hemodialysis.

Thirteen patients had placement of a subclavian vein catheter for temporary vascular access for hemodialysis. Peripheral venography was performed within two to six weeks of catheter placement. Forty-six percent (six of 13 patients) developed subclavian vein narrowing, which resolved in two patients. The duration of catheter placement had no impact on the incidence of this complication. Subclavian vein catheterization can frequently lead to subclavian vein stenosis, which often will resolve spontaneously. Consideration should be given to placement of subclavian lines on the contralateral side of a planned permanent vascular access.

Long-term follow-up after mitral valve reconstruction: incidence of postoperative left ventricular outflow obstruction.

Reconstructive surgery of the mitral valve has been an alternative to mitral valve replacement in patients with mitral regurgitation. Previously, we reported on postoperative left ventricular outflow tract obstruction associated with systolic anterior motion of the anterior mitral leaflet. The current study was designed to evaluate the incidence of this complication and the long-term results of mitral valve reconstructive surgery. Sixty-five patients, aged 19 to 78 years, had mitral valve reconstructive surgery. Two patients died perioperatively, and three died late after surgery. The 60 surviving patients were studied by M mode, two-dimensional, and Doppler echocardiography 1 to 55 months postoperatively (mean 21). Fifty patients had no evidence of postoperative mitral regurgitation, two patients had moderate mitral regurgitation, three patients had mild mitral regurgitation, and five patients had trace mitral regurgitation. No significant mitral stenosis was detected in any patient postoperatively. After surgery, the diameter of the left ventricular outflow tract was significantly smaller than that before surgery. The echocardiograms of six patients showed abnormal systolic anterior motion of the anterior mitral leaflet that was not observed preoperatively. Doppler echocardiography demonstrated pressure gradients across the left ventricular outflow tract between 10 and 64 mm Hg. Inhalation of amyl nitrite increased these gradients. An additional patient who had systolic anterior motion but no gradient developed a 36 mm Hg gradient after inhalation of amyl nitrite. The remaining patients had no gradient induced by amyl nitrite. Abnormal systolic anterior motion of the anterior mitral leaflet may be surgically induced by changes in left ventricular geometry and the size of the left ventricular outflow tract during systole.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of eosinophilia in patients undergoing peritoneal dialysis and hemodialysis.

Eosinophilia (E) has been noted in hemodialysis (HD) patients, but its etiology is not clear. In an effort to clarify this phenomenon, we prospectively studied patients initiating dialysis in our outpatient HD and peritoneal dialysis programs. Rate of E was greatest for a small group of four continuous cycling peritoneal dialysis patients (75%), less for 63 HD patients (41%), and least for 66 continuous ambulatory peritoneal dialysis (CAPD) patients (21%, P less than .05, HD v CAPD). Increasing E rates among the groups paralleled increased frequency of tubing changes. There were no differences in etiology of renal disease, medications, types of dialyzers, types of access, or transfusion frequency that could account for the E. IgE levels did not correlate with E. The data suggest that the dialysis procedure or the tubing changes may be causing the E, but the possibility that uremia, itself, is important in the pathogenesis of dialysis E is also discussed.

A comparative study of continuous ambulatory peritoneal dialysis and center hemodialysis. Efficacy, complications, and outcome in the treatment of end-stage renal disease.

We retrospectively compared 92 patients treated with center hemodialysis (CHD) and 72 patients receiving continuous ambulatory peritoneal dialysis (CAPD) over a 26-month period. The groups were comparable with respect to underlying disease and demographic characteristics. Biochemical control was also similar, with higher bicarbonate levels and hematocrits in patients receiving CAPD, despite fewer transfusions and minimal administration of anabolic steroid and iron therapy. Hospitalization rates were also similar (1.58 +/- 2.89 vs 1.43 +/- 3.35 days per patient month for patients receiving center hemodialysis vs CAPD, respectively). Access complications were the most frequent cause of hospitalization in both groups, but cardiovascular causes were more frequent among patients receiving CHD. Diabetic patients had significantly higher hospitalization rates, which were similar in both groups. Twenty-nine percent of the peritonitis episodes necessitated hospitalization. Mortality and dropout rates were virtually identical in the two groups, with a 70% retention rate during the 26-month study. Continuous ambulatory peritoneal dialysis is comparable with CHD with regard to biochemical results, complications, hospitalization rates, and outcome. It is widely applicable, as 44% of our new patients with end-stage renal disease are being sent home receiving this treatment.

Effect of converting enzyme inhibitors on prostaglandin synthesis by isolated glomeruli and aortic strips from rats.

In addition to their effect on angiotensin and bradykinin metabolism, converting enzyme inhibitors (CEI) may also alter prostaglandin (PG) synthesis. We therefore examined two CEI, SQ 14,225 (captopril) and SQ 20,881, for their in vitro effect on PG synthesis by glomeruli and aortic strips from rats. Glomeruli incubated in test tubes produced predominantly PGE2 and PGF2 alpha. Both CEI selectively stimulated PGE2 synthesis with maximal effects at 25 microM. During superfusion of glomeruli with captopril (25 microM) synthesis of PGE2 increased 5- to 10-fold and that of 6-keto-PGF1 alpha doubled. No significant change in PGF2 alpha or thromboxane B2 occurred. This effect of CEI was independent of angiotensin or bradykinin. In contrast captopril had no effect on PG synthesis by aortic strips, which produced predominantly prostacyclin assayed as 6-keto-PGR1 alpha and little PGE2 and PGF2 alpha. These results demonstrate that CEI can directly stimulate PG synthesis in glomeruli. This additional mechanism of action of CEI may require reinterpretation of the role of angiotensin based on results obtained with CEI.

Reversible acute renal insufficiency and hyperkalemia following indomethacin therapy.

We noted five cases of reversible acute deterioration of renal function in patients with very mild to moderate renal insufficiency who received indomethacin for an acute gouty attack. This decrease in renal function was consistent with a primary decrease in renal blood flow. In addition, hyperkalemia developed in the patients, which we attribute to a decrease in renin and aldosterone secretion, a decrease in distal tubular delivery of sodium, and, more importantly, to a decrease in urine flow. This report is intended to alert physicians to the possible complications of indomethacin therapy in patients with mild renal insufficiency.

Serum lipid changes during contraceptive administration in obese women: relation to serum insulin levels.

Previous reports agree that estrogen and estrogen-containing contraceptives increase serum triglyceride levels of normal women, but disagree on their effect on serum cholesterol levels. Since obesity is often accompanied by hyperinsulinemia and since hyperinsulinemia may participate in production of hypertriglyceridemia, we investigated the effect of oral contraceptives on the serum lipids of obese women. Serum triglycerides and cholesterol were measured before and after 3 months administration of the contraceptives. The mean triglyceride level increased 23% in the obese and 21% in the normal women. The mean cholesterol level increased 6% (P less than 0.05) in the obese and did not change in the normal women. The increase in cholesterol occurred mostly in those with initial levels less than 225 mg/100 ml; in those with initial levels above 250 mg/100 ml the level usually decreased with treatment. The serum lipid changes were not related to the serum insulin levels.

Monoribosomal attachment to messenger ribonucleic acid in sodium fluoride-treated rabbit reticulocytes.

Mild proteolysis with Pronase selectively dissociates ribosomes not attached to mRNA into subunits; ribosomes attached to mRNA remain intact. A portion of monoribosomes from reticulocytes incubated with NaF resisted proteolytic dissociation. Recovery of mRNA from monoribosomes of NaF-treated reticulocytes therefore may be explained by persistent attachment of some monoribosomes to mRNA.