Technical note: The use of a sonomicrometry system for monitoring uterine involution in postpartum dairy cows.

Sonomicrometry allows the measurement of the distance between 2 piezoelectric crystals and has been widely used to investigate the contractility of the heart and gastrointestinal tract. The objective of this study was to determine whether this method can be used to quantify the reduction in uterine size in cows postpartum. Seven healthy pluriparous Holstein Friesian cows (3.7±0.7 yr old, parity 2.4±0.5, mean±SD) were used. Three weeks before calving, 4 piezoelectric crystals were implanted via laparotomy in the myometrium of the greater curvature of the pregnant uterine horn in a longitudinal direction. Sonometric measurements were conducted daily from 2 d before parturition until 14 d after calving, followed by measurements every other day until d 28. Changes in the distance between neighboring crystals were presented as relative changes (%) from baseline values before parturition. The diameter of the previously pregnant uterine horn was measured using transrectal B-mode sonography from d 10 to 28 after calving. The cows were slaughtered 39±6 d postpartum and the uterus was evaluated for fixation of the crystals. The distances between neighboring crystals underwent changes with a reduction of greater than 50% until d 1 postpartum, but no further changes were recorded from d 1 to 7. In the second week, changes in all distances were affected by day postpartum. One distance was affected by day postpartum in wk 3 and 4. There was a positive correlation between the diameter of the previously pregnant horn and the distances between the crystals. Examination of the uterus after slaughter of the cows revealed that 8 crystals (29%) were no longer fixed in the myometrium. Seven of these (25%) could be evaluated completely or partially and 1 (4%) could not be analyzed. Sonomicrometry seems to be suitable for the objective measurement of reduction in uterine length in cows.

Prophylaxis of recurrent urinary tract infection after renal transplantation by cranberry juice and L-methionine.

BACKGROUND: Recurrent urinary tract infections (UTIs) increase mortality and reduce graft survival after renal transplantation. Strategies to prevent recurrent UTIs include L-methionine, cranberry juice, and antibiotics. Data on the efficacy of cranberry and L-methionine, however, are controversial in the general population; there are few data in renal transplant recipients. METHODS: We performed a retrospective analysis of 82 transplant recipients with recurrent UTIs, who underwent prophylaxis with cranberry juice (2 × 50 mL/d, n = 39, 47.6%), or L-methionine (3 × 500 mg/d, n = 25, 30.5%), or both modalities (n = 18, 21.9%). Thirty patients without prophylaxis served as controls. We analyzed symptoms, pyuria/nitrituria, and incidence of UTI events during 1 year before versus after initiation of prophylaxis. RESULTS: Prophylaxis highly significantly decreased the annual UTI incidence by 58.3% (P < .001) in the study population with no change in the control group (P = .85); in addition, 53.7% of symptomatic patients reported relief of symptoms and pyuria/nitrituria disappeared in 42.4% of the dipstick-positive patients (P < .001 each). Cranberry reduced the annual number of UTI episodes by 63.9% from 3.6 ± 1.4 to 1.3 ± 1.3/year (P < .001) and L-methionine by 48.7% from 3.9 ± 1.8 to 2.0 ± 1.3/year (P < .001). CONCLUSION: Cranberry juice and L-methionine successfully reduced the incidence of UTI after renal transplantation.

Factor XI deficiency in animal models.

The blood coagulation system forms fibrin to limit blood loss from sites of injury, but also contributes to occlusive diseases such as deep vein thrombosis, myocardial infarction, and stroke. In the current model of a coagulation balance, normal hemostasis and thrombosis represent two sides of the same coin; however, data from coagulation factor XI-deficient animal models have challenged this dogma. Gene targeting of factor XI, a serine protease of the intrinsic pathway of coagulation, severely impairs arterial thrombus formation but is not associated with excessive bleeding. Mechanistically, factor XI may be activated by factor XII following contact activation or by thrombin in a feedback activation loop. This review focuses on the role of factor XI, and its deficiency states as novel target for prevention of thrombosis with low bleeding risk in animal models.

[Therapy monitoring with 2-(18F)-FDG positron emission tomography after neoadjuvant radiation treatment of mouth carcinoma]. / Therapiemonitoring mittels 2-[18F]-FDG-Positronenemissionstomographie nach neoadjuvanter Strahlenbehandlung des Mundhöhlenkarzinoms.

BACKGROUND: Combined protocols of radiation therapy and surgical resection, as applied in advanced oral cancer, rely on objective and early assessment of treatment response to radiation therapy. Non-responders require immediate radical salvage surgery even in spite of substantial operative risks, while complete or subtotal response may give reasons for continuing the conservative approach. Therefore, we investigated radiation response by FDG-PET for early monitoring of oral cancer. PATIENTS AND METHODS: In 30 patients with advanced stages of oral cancer (Table 1), FDG-PET (Siemens, ECAT EXACT 922) was performed within 4 weeks after completion of preoperative radiation therapy (36 Gy). SUV of tumor regions were compared to the histologic degree of tumor regression in complete resection specimens. Statistic evaluation included correlation analysis of SUV vs tumor regression and ROC analysis for SUV cut-off values. RESULTS: While low FDG accumulation was found in tumors with histological complete remission (2.3 +/- 0.4) as well as in cases of residual tumor (3.4 +/- 1.8), high FDG uptake was a rather specific indicator of vital tumor tissue (Figure 2). Significant correlation (p = 0.045) between postradiotherapeutic FDG-uptake and histological tumor regression was recognized. A SUV > 2.75 as a clinically practicable threshold value for the identification of residual vital tumor resulted in a specificity of 88%, sensitivity of 68%, a positive predictive value of 94% and a negative predictive value of 50% (Figure 3). Based on our actual follow-up data we could not confirm a significant correlation between postradiotherapeutic SUV and patients' survival. CONCLUSION: Within a standardized protocol, FDG-PET recognize treatment response to radiation therapy in oral squamous cell carcinoma with a reasonable specificity and thus provides a basis for further therapeutic decisions. An increased SUV (> 2.75) may be the rational to justify an aggressive surgical approach even when patients face substantial surgical or anesthesiological risk. However, the posttherapeutic pattern of glucose uptake varies with the applied treatment modalities and has to be explored for the protocol applied.

Value of CD23 determination by flow cytometry in differentiating mantle cell lymphoma from chronic lymphocytic leukemia/small lymphocytic lymphoma.

Mantle cell lymphoma (MCL) and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) share many morphologic and immunophenotypic features. In addition to histomorphologic examination, it is customary to use the absence of CD23 to differentiate MCL from CLL/SLL, based primarily on reported comparisons of immunohistochemical staining of tissue sections. These findings are widely extrapolated to flow cytometric analysis, although available data are contradictory and not sufficiently detailed. We compared expression of CD23 by flow cytometry in 22 cases of MCL and 25 cases of CLL/SLL. Lymphoma cells in 12 of 22 MCLs were negative for CD23, and 10 showed dim expression. In contrast, none of 25 CLL/SLLs were negative for CD23, 4 were dimly positive, and 21 were moderately or brightly positive. Thus, a significant proportion of MCL exhibited overlap of CD23 expression in the low-intensity range with CLL/SLL. Clinically, there was no correlation between the intensity of CD23 expression and clinical stage at diagnosis or survival. These findings emphasize that by flow cytometry, MCL can be differentiated reliably from CLL/SLL using CD23 if negative expression is observed. However, with dimly positive expression, interpretation should be cautious.

[(18F)-2-fluorodeoxyglucose PET. Prospects for secondary prevention of mouth cavity carcinoma]. / [18F]-2-Fluordeoxyglukose-PET. Perspektiven der Sekundärprophylaxe des Mundhöhlenkarzinoms.

AIMS: The predominant cause of death due to oral cancer is the failure to control local tumor due to regional tumor recurrence. The sequelae of surgical resection and high-dose irradiation cause substantial changes in head and neck anatomy, leading to considerable problems in the early morphological detection of recurrent disease. Therefore, this study evaluates the verification of cancer recurrence by means of its pathologic glucose metabolism. MATERIALS AND METHODS: We reviewed a total of 50 [18F]-2-fluordeoxyglucose positron emission tomography (18FDG-PET) investigations performed in 44 patients who had undergone surgical resection of oral cancer. In 23 cases, re-staging (group A) was indicated due to suspicion of recurrent or secondary tumor manifestation. In 27 cases, PET served as a screening procedure (group B). Statistic evaluation included sensitivity, specificity, positive/negative predictive value and accuracy of 18FDG-PET for the detection of tumor manifestation. RESULTS: 18FDG-PET correctly identified 23 of 26 tumor sites (88%) in the re-staging group and 9 of 10 tumor sites (90%) in the screening group. We encountered a total number of 16 false-positive foci with an increased 18FDG-uptake. In six patients, 18FDG-PET detected tumor recurrence several months before a morphological correlative could be identified. In 5 of these 6 patients, the PET findings for the latter tumor sites determined the patient's fate. Specificity was 63% for local recurrence, 97% for secondary lymph node involvement and 90% for distant metastasis. CONCLUSION: According to these data, 18FDG-PET is the most effective diagnostic tool in the follow-up of oral cancer patients to date. Due to the high prevalence of recurrent disease in the follow-up of oral cancer, either the detection of early recurrence or the identification of additional, incurable tumors may add substantially to a rational therapeutic management. We therefore recommend 18FDG-PET for screening and re-staging of recurrent oral cancer.

Vulnerability of the nigrostriatal system as detected by transcranial ultrasound.

OBJECTIVE: To assess the incidence of a hyperechogenic substantia nigra (SN) by transcranial sonography (TCS) in healthy people and to evaluate whether an enlarged hyperechogenic SN area is associated with functional impairment of the nigrostriatal system. BACKGROUND AND METHODS: Until now, preclinical impairment of the nigrostriatal system could be identified only by functional neuroimaging techniques such as PET in selected groups of patients. TCS is a new, noninvasive ultrasound technique that has demonstrated an increased echogenicity of the SN in patients with PD, whereas in most healthy individuals, the SN is either barely detectable or undetectable by TCS. RESULTS: Of 330 healthy volunteers, 8.6% exhibited an increased echogenicity of the SN. From these, 10 clinically healthy individuals with distinct unilateral or bilateral hyperechogenic signals in the SN region (SN area above 0.25 cm2) underwent comprehensive motor testing, neuropsychological assessment, MRI, and [18F]-dopa PET examination. With regard to motor functions, these individuals did not differ from 10 age- and sex-matched controls with a low echogenic SN and an area of echogenic signals below 0.2 cm2. Enlargement of hyperechogenic areas in the 10 healthy individuals was associated with a marked decrease in the accumulation of [15F]-dopa in the caudate nucleus and putamen. CONCLUSIONS: Substantia nigra hyperechogenicity appears to indicate a functional impairment of the nigrostriatal system. Transcranial sonography may be a suitable method of identifying persons at risk of nigrostriatal alterations, making possible the introduction of early neuroprotective therapy.

Rehabilitation with dental implants of oral cancer patients.

The aim of this study was to evaluate the risks and complications of rehabilitation with dental implants after tumour surgery and radiotherapy. After a disease-free survival of 18 months, 29 patients who had undergone oral cancer treatment were rehabilitated with dental implants. The complication rate of implants in irradiated, non-irradiated and grafted bone was analyzed at least 3 years after implant placement. In the healing period, 28.6% of the implants in irradiated bone and 8.4% in non-irradiated bone showed soft tissue complications. Of the implants, 26.7% in the irradiated and 14.7% in the non-irradiated mandibular bone were lost in the first 36 months after placement. Thirty-one point two percent of implants inserted in non-irradiated bone grafts were affected and did not osseointegrate. Of 109 inserted implants, 70 were suitable for prosthetic rehabilitation. There are high complication rates after implant placement in oral cancer patients. Irradiation adversely affects soft tissue healing. Osseointegration is frequently disturbed, especially when implants were placed in non-vascularized bone grafts.

[Value of (F18)-2-fluorodeoxyglucose PET scanning in staging mouth cavity carcinoma. Comparative evaluation of PET findings before and after preoperative radiochemotherapy with histological and computerized tomography findings]. / Stellenwert der [F18]-2-Fluor-desoxyglukose-PET im Staging des Mundhöhlenkarzinoms. Vergleichende Auswertung von PET-Befunden vor und nach präoperativer Radiochemotherapie mit histologischen und computertomographischen Befunden.

OBJECTIVE: The lack of sensitivity and specificity of conventional imaging techniques based on morphological critera is responsible for considerable limitations in the staging and surveillance of oral cancer. Therefore, this study investigates the contribution of [F18]-2-fluordesoxyglucose (FDG) positron emission tomography (PET) to tumor management with special regard to lymphnode involvement and therapeutic monitoring after radiotherapy. DESIGN: Prospective observational study. PATIENTS: Twenty-one patients with advanced oral cancer, predominantly T3/T4. INTERVENTION: FDG-PET scans before and after preoperative radio(chemo)therapy. Standardized uptake values (SUV) were determined for the tumor site and lymphnode areas. PET scans were correlated to histological findings after ablative tumor surgery. RESULTS: FDG-PET yielded superior sensitivity and specificity for tumor and lymphnode assessment. The effect of radiotherapy was reflected by the metabolic activity of the tumor, which shows a close correlation between the decrease of FDG uptake and histologic tumor regression. PET detected distant metastases and simultaneous tumors. CONCLUSION: FDG-PET is a challenging imaging technique with the potential to improve staging procedures for oral cancer. In the monitoring of metabolic activity of the tumor in the course of radio(chemo)therapy, FDG-PET allows objective measurement of the treatment response.

ICAM-1-, -2- and LFA-1-independent homotypic T cell aggregation induced by a novel activating monoclonal antibody targeting the murine Thy-1 molecule.

We have previously reported that the murine T cell line EL-4 has an aggregating phenotype, displaying homotypic aggregation (HTA) when exposed to monoclonal antibodies targeting specific cell surface molecules such as leukocyte function-associated antigen-I (LFA-1). We have used this property of EL-4 cells to isolate additional HTA-inducing MAb by screening a panel of hybridomas that were generated from rats immunized with EL-4 cells. We have isolated a novel anti-Thy-1 MAb (termed FF-10) that is a powerful inducer of HTA in EL-4 cells. In addition to induction of HTA, FF-10 also induces splenocyte proliferation but inhibits anti-CD3-driven T cell proliferation. Thy-1-induced HTA cannot be blocked with MAb targeting intercellular adhesion molecule-I and -2 (ICAM-1, ICAM-2) or LFA-1. Thus, the FF-10 MAb represents a novel and unique tool to investigate the diverse roles of the murine Thy-I molecule in T cell activation, proliferation and apoptosis.

Enhanced tubular epithelial CD44 expression in MRL-lpr lupus nephritis.

The cell surface glycoprotein CD44 is expressed by cells of hematopoietic origin and constitutes a receptor for hyaluronic acid and matrix proteins. Because CD44 could play a role in recruiting inflammatory cells to sites of immune injury, we examined the renal CD44 expression in normal and in autoimmune MRL-lpr mice by immunohistochemistry and at a molecular level. In normal kidneys, immunoperoxidase staining for CD44 is restricted to interstitial cells and certain urothelial cells. In nephritic MRL-lpr, CD44 expression is prominent in perivascular inflammatory infiltrates and in glomerular crescents. Interestingly, CD44 is also focally expressed by cortical tubular epithelial cells (TEC) in nephritic MRL-lpr kidneys but not in normal kidneys. Reverse transcription-polymerase chain reaction (RT-PCR) as well as Northern blotting demonstrate that CD44 kidney mRNA levels are increased in nephritic MRL-lpr mice compared with normal mice. To further characterize the tubular CD44 expression, we examined cultured TEC (primary cultures and SV40-transformed TEC lines C1 and MCT). TEC constitutively express abundant cell surface CD44 that is modestly up-regulated in response to 18 hours stimulation with TNF-alpha (100 ng/ml), IFN-gamma (100 U/ml) and IL-1 (100 ng/ml). Northern analysis of TEC mRNA reveals a constitutive CD44 mRNA transcript at 3 kb. Stimulation with IFN-gamma or TNF-alpha for six hours markedly up-regulates CD44 mRNA expression in these cells. We conclude that mononuclear infiltration with CD44 positive cells and cytokine-induced up-regulation of CD44 by renal TEC is a prominent feature of MRL-lpr lupus nephritis. The contribution of CD44 induction on TEC to the pathogenesis of the autoimmune nephritic process in MRL-lpr remains to be determined.

[Demonstration of a fornix rupture in a newborn using 99mtc-mag3 kidney function scintigraphy]. / Nachweis einer Fornixruptur bei einem Neugeborenen mit Hilfe der 99mTc-MAG3-Nierenfunktionsszintigraphie.

In male newborns posterior urethral valves are the most frequent cause of subpelvine obstructions. A male newborn had to be delivered by caesarian section in the 36th week of pregnancy due to a progressive intrauterine hydronephrosis and excessive bladder filling. The condition could temporarily be normalized by catheterisation. However, following removal of the catheter on day 5 after birth an acute deterioration in the patient's general condition occurred due to an urine ascites. Scintigraphy using 99mTc-MAG3 led to the assumption that the cause was a fornix rupture in VURD syndrome (syndrome of posterior urethral Valve, Unilateral vesicorenal Reflux and renal Dysplasia), subsequently confirmed radiologically.

[Nuclear medicine diagnosis of focal liver lesions]. / Nuklearmedizinische Diagnostik fokaler Leberläsionen.

Confirmation and exclusion of benign focal liver lesions are the main object of liver studies in nuclear medicine. Hepatobiliary sequence scintigraphy (focal nodular hyperplasia, adenoma), blood pool scintigraphy (hemangioma) and, in some cases, colloid scintigraphy are the methods most frequently employed. Receptor scintigraphy with octreopeptides, immunoscintigraphy with monoclonal antibodies, PET and gamma camera scintigraphy with 18FDG, are used to solve special diagnostic problems, particularly in oncology. A stepwise diagnostic approach needs to be used for a successful classification of focal liver lesions and an extensive knowledge of indications for additional supplementary diagnostic procedures is required.

[A clinical evaluation of MAb BW 835/6 in breast and ovarian cancer]. / Klinische Prüfung mit MAk BW 835/6 bei Mamma- und Ovarialkarzinomen.

Studies with the 99mTc-labeled murine monoclonal antibody BW 835/6 in patients suspected of breast (n = 7) or ovarian cancer (n = 8) showed insufficient depiction of primary tumors and metastases of breast cancer, but promising results in the detection of primary tumors in ovarian cancer without metastases. The small number of patients does not allow statistical analysis.

[The demonstration and staging of bladder carcinoma. A comparative study between magnetic resonance tomography, computed tomography and radioimmunoscintigraphy]. / Nachweis und Stadieneinteilung des Harnblasenkarzinoms. Eine vergleichende Untersuchung zwischen Magnetresonanztomographie, Computertomographie und Radioimmunszintigraphie.

The purpose of the present study was to compare the effectiveness of MRI, CT and radioimmunoscintigraphy in the staging and detection of bladder cancers in 28 patients. We distinguish two groups: Group I included the tumour stages CIS-T3A and the second group the deep infiltrative tumours T3B-T4. MRI was slightly superior to CT in respect of tumour staging (75% correct results as compared to 63%). No understaging occurred with MRI, whereas in 22% of the cases the stage of the tumour was underestimated using CT diagnostics. Overstaging occurred in 25% of the MRI and 15% of the CT-diagnostics, respectively. RIS cannot distinguish the tumour groups, and hence this method is useful only for the detection of the primary tumour and metastases. In 77% of cases the tumour was detected and in 15% the tumour could be safely excluded.

[Tuberous sclerosis: broadening of the diagnosis using MR tomography and computed tomography]. / Tuberöse Sklerose: Erweiterung der Diagnostik durch MR-Tomographie und Computertomographie.

Ten children and a 22-y old women with tuberous sclerosis were studied. All children were epileptic but only 8 had skin lesions (white spots, sebaceous adenoma), 4 had rhabdomyoma of the heart and 4 children had astrocytoma of the retina; only in 4 children was the entire triad of tuberous sclerosis seen. The young woman with a hemorrhage of an angiolipoma of the kidney had no other symptoms of tuberous sclerosis. All patients had pathologic CT and MRT findings; 4 different types of lesion were seen in MRT. In order to elucidate human genetic aspects and to demonstrate the underlying disease all children with epileptic disorders and also all patients without the full triad of symptoms should be examined by MRT.

[The diagnosis of bone marrow lesions in the MR tomogram in children with diseases of the hematopoietic system with special reference to post-therapy changes]. / Zur Diagnostik von Knochenmarkläsionen im MR-Tomogramm bei Kindern mit Erkrankungen des hämatopoetischen Systems unter besonderer Berücksichtigung der posttherapeutischen Veränderungen.

119 MR-examinations of both tibiae, knees and the lower part of both femur were performed in 41 children suffering from bone marrow disease (27 ALL, 4 AML, 3 NHL, 1 agranulocytosis, 6 anaemia). T1- and T2-spin-echo sequences and a T2-gradient-echo sequence were used. Bone marrow changes in leukaemia were diffuse before therapy and patchy after therapy. Due to their different signal in T2-weighted images, differentiation of the post-therapeutic patchy findings into infiltrations, fibrosis, necrosis and siderosis seems to be possible. In future, MRI will be the method of choice for screening and controlling bone marrow disease if the examination time is shortened by using only a T1-spin-echo sequence and a T2-gradient-echo sequence.