A new method of monitoring osteomyelitis.

Chronic infections of bone such as osteomyelitis are frequent events, especially in immunocompromised or diabetic patients, and costly on a national level. Incorrect treatment or delayed diagnosis may lead to loss of the affected extremity or mandible. The aim of this study was to assess the possible value of urinary lysylpyridinoline (LP) and hydroxylysylpyridinoline (HP) concentrations in the monitoring of mandibular osteomyelitis. Patients were assigned to the following groups: group 1 (n=85), control; group 2a (n=38), patients with active disease; group 2b (n=25), patients of group 2a 6 months after successful treatment; group 2c (n=7), patients of group 2a with ongoing osteomyelitis 6 months after treatment. The range and upper limit of normal values (HP(max) and LP(max)) were determined in group 1. Levels of LP and HP were measured by high-performance liquid chromatography and fluorescence detection. There was a significant decrease (mean 45.43% for HP and 32.12% for LP) in samples of group 2b compared to 2a (P<0.001 for HP and LP). There was a significant increase in HP values in samples from group 2c compared to 2a (P=0.018). The urinary concentrations of HP and LP appear to act as a marker of disease activity, with a decrease reflecting treatment success and an increase or stable values indicating persistent disease. An inexpensive tool (US$5 per analysis) for the monitoring of osteomyelitis is described.

Serious complications after radiosynoviorthesis. Survey on frequency and treatment modalities.

AIM: Radiosynoviorthesis using intraarticular injection of beta-emitting radiocolloids is increasingly performed throughout Europe in patients with inflammatory joint disease. It is a cost-effective and safe treatment, local complications are very rare with only eight cases mentioned in the literature so far. No recommendations for therapy of tissue necrosis, infection or thromboembolism after radiosynoviorthesis are available. METHODS: Using a standardized questionary, 260 nuclear medicine physicians and 20 medical liability insurances were asked for the kind and frequency of complications after radiosynoviorthesis between 1998 and 2003. The survey was terminated after nine months with a response of only 25.7%. RESULTS: A total of 53 severe complications were documented (28 necroses, 12 thromboses, 13 joint infections). Eight other complications were seen but difficult to correlate directly with radiosynoviorthesis. Tissue necroses from yttrium-90 were successfully treated by surgical excision and closure of the defect. Rhenium-186-induced ulcers healed by hyperbaric oxygen therapy in two cases. Lesions from erbium-169 showed restoration by conservative treatment. Thromboembolic events happened after radiosynoviorthesis in joints of the lower limb only, mostly treated by conventional anticoagulation. Intraarticular infections showed restoration after intraarticular antibiotics in the majority of cases. CONCLUSION: Severe complications after radiosynoviorthesis seem to be rare. However, because of the low return rate, a reliable frequency cannot be calculated. Nevertheless, important advices regarding treatment concepts can be taken from our data.

High-dose treatment with (186)Re-HEDP or (153)Sm-EDTMP combined with amifostine in a rabbit model.

UNLABELLED: The aim of this experimental study was to investigate the myeloprotective potential of amifostine in rabbits receiving high-dose treatment with either (153)Sm-ethylenediaminetetramethylene phosphonate (EDTMP) or (186)Re-hydroxyethylidene diphosphonate (HEDP) and to check for drug interactions impairing the skeletal uptake of these radiopharmaceuticals by amifostine. METHODS: To a total of 24 rabbits, we administered 1,000 MBq of either (153)Sm-EDTMP (n = 12) or (186)Re-HEDP (n = 12). Six animals of each group received 500 mg amifostine intravenously 10-15 min before injection of the radiopharmaceutical, whereas the other 6 animals served as controls. Up to 8 wk after treatment, blood samples were collected every 3-5 d to measure platelet and leukocyte counts. Furthermore, whole-body images were acquired at 3 min, 3 h, and 24 h after injection of the radiopharmaceutical to quantify the skeletal uptake. RESULTS: For (186)Re-HEDP, the mean decrease in platelets was significantly less in the amifostine group (35.5% +/- 2.4%) than in the control group (61.3% +/- 5.4%, P < 0.001). Similar results were found for (153)Sm-EDTMP (36.5% +/- 8.3% vs. 52.3% +/- 14.0%, P < 0.05). No significant differences in leukocyte counts were found for (186)Re-HEDP (75.3% +/- 12.3% in the amifostine group and 72.5% +/- 4.1% in the control group, P > 0.05), whereas rabbits treated with (153)Sm-EDTMP plus amifostine showed a significantly greater decrease in leukocytes (69.2% +/- 10.8%) than did the control group (56.6% +/- 4.0%, P < 0.05). Bone uptake in percentage of initial total whole-body activity was significantly decreased in animals treated with amifostine compared with the control groups for both (186)Re-HEDP (15.8% +/- 3.1% vs. 30.9% +/- 1.9%, P < 0.001) and (153)Sm-EDTMP (31.7% +/- 8.9% vs. 44.0% +/- 6.5%, P < 0.05). CONCLUSION: For amifostine, we found a highly significant cytoprotective effect on platelets but no leukoprotective effect. The latter probably relies on the intrinsic myelotoxicity of high-dose amifostine, which seemed to potentiate the leukodepression of the radiopharmaceuticals. The lower bone uptake in amifostine-treated animals may be caused by the chemical structure of amifostine, which is a potentially complex-forming compound that may be able to displace bisphosphonates from the rhenium- and samarium-bisphosphonate complexes, resulting in altered biodistribution patterns.

Increased plasma homocysteine in liver cirrhosis.

Background: Homocysteine (Hcy), is an atherogenic and thrombogenic risk factor which has also been proposed to be involved in hepatic fibrinogenesis. Hcy metabolism, depends on the cofactors folate, vit. B12, and the vit. B6 vitamer pyridoxalphosphate (PLP). Metabolism of these vitamins is frequently disturbed in cirrhotics, but little is known about plasma Hcy levels in these patients. Methods: Plasma levels of Hcy, methionine, serine, cysteine, PLP, vit. B12 and folate, and standard clinical/biochemical parameters of liver disease were measured in 43 postabsorptive patients with biopsy proven cirrhosis of different origin. Results: 74% of the patients had elevated plasma Hcy levels defined as >13.4 µmol/l (mean+2SD of healthy age matched controls). Increased plasma Hcy concentrations were seen in alcoholic as well as in non-alcoholic cirrhosis. Excluding patients with impaired renal function (n=7), Hcy concentrations remained elevated in 69% of the patients. We found a high prevalence of pathological plasma vitamin concentrations of 33% for increased vit. B12 levels and 5% and 80% for decreased folate and vit. B6 levels, respectively. Mean plasma vitamin B12 concentrations increased, folate remained unchanged and PLP concentrations decreased with deteriorating liver function. Hcy concentrations were correlated with levels of creatinine (r=0.44, P<0.01), serine (r=-0.46, P<0.01), and cysteine (r=0.38, P<0.05), but showed no association with parameters of liver function and with plasma levels of folate, vit. B12 und vit. B6. This was contrary to data obtained in healthy individuals. In a stepwise multiple regression serine and cysteine best explained the variance in Hcy levels. Conclusions: Elevated basal Hcy-plasma levels are frequently seen cirrhotic patients. Variations of Hcy concentration in liver cirrhosis are not explained by plasma levels of cofactors of Hcy metabolism.

[Lymph scintigraphy and pre- and intraoperative gamma probe measurements for localization of sentinel lymph nodes (SLN) in breast cancer]. / Lymphszintigraphie sowie prä- und intraoperative Sondenmessung zur Darstellung des Sentinel Lymph Node (SLN) beim Mammakarzinom.

UNLABELLED: Aim of this study was to prove the clinical value of nuclear medicine procedures to detect the sentinel lymph node (SLN) for SLN biopsy. METHODS: In 132 patients with breast cancer we performed lymph scintigraphy of the breast as well as both pre- and intraoperative gamma probe measurements correlating the results with the findings of histopathology. RESULTS: SLN were detectable in 62 of 110 patients according to a sensitivity of 56% when scanning was performed only at 1-2 h p.i. while the sensitivity increased to 86% (19 of 22 pts.) if sequential images were acquired up to 2 h p.i. One or more SLN were identified by a hand-held gamma probe transcutaneously prior to surgery in 96% (113 of 118 pts.) of the patients who showed up with no clinically suspected lymph node metastases. Intraoperatively, in additionally 2 patients the SLN could be found resulting in a sensitivity of 97% (115 of 118 pts.). In only 3 patients with clinically no tumor spread to axillary lymph nodes no SLN could be identified by the probe. Skip lesions, i.e. lymph node metastases in patients with tumor-free SLN, occurred in 2 cases: due to SLN biopsy in these patients lymph node staging was false negative compared to conventional staging by means of axillary lymph node dissection. CONCLUSION: The results demonstrate a high preoperative detection rate of SLN in patients with breast cancer using lymph scintigraphy and gamma probe measurements. Thus, nuclear medicine is capable of providing the basic requirements for SLN biopsy in the daily routine.

Radiation exposure to the personnel in the operating room and in the pathology due to SLN detection with Tc-99m-nanocolloid in breast cancer patients.

UNLABELLED: AIM of this study was to assess the radiation exposure for the personnel in the operating room and in the pathology laboratories caused by radioguided SLN localization in breast cancer. METHODS: In 15 patients dose rates were measured at various distances from the breast and tumor specimens during operation and pathological work-up at 3-5 h after peritumoral injection of 30 MBq Tc-99m-nanocolloid. RESULTS: The dose rates were 84.1 +/- 46.4 microGy/h at 2.5 cm, 3.57 +/- 2.14 microGy/h at 30 cm, 0.87 +/- 0.51 microGy/h at 100 cm, and 0.40 +/- 0.20 microGy/h at 150 cm in the operating room and 44.4 +/- 27.8 microGy/h at 2.5 cm, and 1.66 +/- 1.34 microGy/h at 30 cm in the pathology laboratories. From these data the radiation exposure was calculated for 250 operations per year assuming a mean exposure time of 30 min for the surgical team members and of 10 min for the pathology staff. Under these conditions the finger dose is 10.5 mGy for the surgeon, and 5.55 mGy for the pathologist. The whole-body doses are 0.45 mSv, 0.11 mSv, 0.05 mSv, and 0.21 mSv for the surgeon, the operating room nurse, the anesthetist, and the pathologist, respectively. CONCLUSION: Since the radiation risk to staff members is low, a classification of the personnel in the operating room and in the pathology laboratories as occupational radiation exposed workers is not necessary.

Network therapy using videotape disclosures for adult sexual abuse survivors.

Treatment of childhood sexual abuse survivors may be enhanced by a technique designed to generate a therapeutic constituency for the survivor around the disclosure of childhood abuse experiences. The need for validating relationships is hypothesized as a condition for successful treatment. The videotaped disclosure process proceeds in five stages: (1) Deciding to make a tape, (2) making a videotape following a semistructured interview format, (3) the patient viewing the tape, (4) showing the tape to potential therapeutic team members, and (5) possibly using the tape for a confrontation with the abuser. The technique has been used on 27 cases. Case histories are given to illustrate the procedure. Discussion includes potential mechanisms of action and issues in treatment that arise with the use of the method described.

Plasma folate but not vitamin B(12) or homocysteine concentrations are reduced after short-term vitamin B(6) supplementation.

Adverse effects of high vitamin B(6) intake include peripheral neuropathy. Recent studies focussing on the reduction of plasma homocysteine as a risk factor for vascular disease showed that vitamin B(6) reduces plasma folate levels. The significance of this finding is unclear. We therefore analyzed plasma folate and basal homocysteine levels as well as the response to an oral methionine loading test in 8 healthy individuals before and after a controlled supplementation with oral doses of 25 mg pyridoxine for 10 days. Plasma pyridoxal phosphate increased from 40.6 +/- 13.6 to 426.8 +/- 200.3 nmol/l (p < 0.001), whereas plasma folate decreased from 6.3 +/- 1.6 to 4.6 +/-1.5 ng/ml (p < 0.01), respectively. Plasma vitamin B(12) and basal homocysteine levels remained unchanged (234.0 +/- 27.8 vs. 217.1 +/- 50.4 pg/ml and 10.9 +/- 4.8 vs. 10.1 +/- 3.6 micromol/l). There was no significant effect of vitamin B(6) supplementation on the area under methionine and homocysteine concentration versus time curve. Significant correlations were found between pre- and post-supplement levels of folate as well as PLP levels (r = 0.73, p < 0.05; r = 0.75, p < 0.05). These data suggest that a dose of 25 mg vitamin B(6) supplemented for 10 days reduces plasma folate but did not affect basal and postprandial homocysteine levels suggesting (1) a normal cellular availability of folate or (2) a compensation of impaired homocysteine remethylation by increased transsulfuration.

Assessment of the viability of microvascularized bone grafts after mandibular reconstruction by means of bone SPET and semiquantitative analysis.

The purpose of this study was to investigate the value of bone scintigraphy including single-photon emission tomography (SPET) and semiquantitative analysis for the assessment of graft viability following microvascularized bone transplantation. We evaluated 60 scintigraphic studies of 36 patients with 39 bone grafts. Thirty-four investigations were performed 6-11 days (early bone scans) and 26 up to 11 months (late bone scans) after mandibular reconstruction. After administration of 550 MBq technetium-99m methylene diphosphonate, planar scintigrams and a SPET study were performed. The data were reconstructed iteratively. Scans were evaluated visually and semiquantitatively by a region of interest technique using the ratio between transplant and cranium (T/C). Patients with uncomplicated healing showed a T/C ratio >1.0 in early and late bone scans. In cases with necrosis, the T/C ratio was below 1.0 when performing early bone scans. However, in late bone scans, some patients with necrosis showed a slightly increased uptake and a T/C ratio >1.0. The data demonstrate that as early as 6-11 days after mandibular reconstruction, increased tracer uptake proves that the surgery has been successful and indicates a normal healing process. Especially in the early bone scans no false-positive or false-negative results were observed and the T/C ratio clearly differentiated between vital and non-vital bone grafts. At later times false-positive findings could be observed; these were, however, rare because of the significantly higher tracer uptake of the healthy grafts when compared with completely or partially necrotic transplants.

Localization of a pheochromocytoma using I-123 MIBG adrenal scintigraphy.

In a patient with the clinical diagnosis of pheochromocytoma, the localization of the tumor is essential for planning treatment. Recently, we have performed I-123 metaiodobenzylguanidine (MIBG) adrenal scintigraphy in a patient presenting with a history of paroxysmal hypertension. Scintigraphy accurately located an ectopic unilateral pheochromocytoma. The scintigraphic diagnosis was confirmed by surgery and a diagnosis of ectopic unilateral pheochromocytoma was made by histopathological examination. This case report illustrates the specific diagnosis of pheochromocytoma by I-123 MIBG scintigraphy which is especially useful when other diagnostic procedures are equivocal.

Correlation between 18-fluorodeoxyglucose accumulation in large vessels and serological markers of inflammation in polymyalgia rheumatica: a quantitative PET study.

OBJECTIVE: To quantify 18-fluorodeoxyglucose (FDG) accumulation in large vessels in patients with polymyalgia rheumatica by positron emission tomography (PET), and to compare these data with serological markers of inflammation. METHODS: 13 untreated patients with active polymyalgia rheumatica underwent FDG positron emission tomography; eight were analysed in a second PET when in clinical remission. Six patients with other highly inflammatory conditions served as controls. For quantitative analysis, FDG uptake over nine defined vascular regions, divided by an individual background value, was expressed as a region of interest (ROI) index. These data were compared with the clinical status of the patient and with erythrocyte sedimentation rate (ESR), C reactive protein, haemoglobin, and platelet and leucocyte counts. RESULTS: By visual evaluation, 12 of the 13 patients showed an increased tracer uptake of the aorta or its major branches. By quantitative analysis, FDG uptake was significantly increased in polymyalgia rheumatica. In patients with active disease, the mean ROI index for all vascular regions exceeded that of controls by 70% (mean (SD): 1.58 (0.37) v 0.93 (0.12); p<0.001). In the eight patients who underwent follow up PET, the index declined substantially. In active polymyalgia rheumatica, FDG uptake was significantly correlated with C reactive protein (r = 0.8), ESR (r = 0.79), and platelet counts (r = 0.68). CONCLUSIONS: The observed FDG accumulation in the aorta and its branches and a strong correlation between tracer uptake and markers of inflammation is suggestive of large vessel arteritis. Quantitative ROI analysis appears to be a sensitive tool for detecting such inflammation.

SPECT with HMPAO compared to PET with FDG in Huntington disease.

OBJECTIVE: It is the aim of this study to compare the performance of 99mTc-d,l-hexamethylpropyleneamine oxime (HMPAO) SPECT with that of [18F]fluorodeoxyglucose (FDG) PET in detecting striatal dysfunction as it occurs in Huntington disease (HD). MATERIALS AND METHODS: For the determination of regional cerebral glucose consumption, the PET camera PC-4096 was used; the cerebral uptake of HMPAO was measured using the three-head SPECT camera TRIAD. Eight patients with manifest HD, seven subjects at risk for HD, and nine normal individuals were included in the study. In both modalities data evaluation was performed using caudate-to-whole-slice (C/S) ratios. The patients' data were compared to 95% confidence intervals determined in the nine controls. RESULTS: The PET and SPECT C/S values correlated significantly (n = 24; r = 0.87; p < 0.0001). The C/S values were significantly reduced in PET in all eight and in SPECT in seven of the eight HD patients studied. Five of the seven at-risk subjects had normal C/S values in PET and SPECT, one showed reduced C/S values in both diagnostic methods, and the remaining at-risk individual showed a reduced C/S value in PET only. Thus, concordant results between PET and SPECT were obtained in seven of eight patients and six of seven at-risk subjects studied, corresponding to an 87% accuracy of SPECT in the detection of striatal dysfunction as compared to the "gold standard" PET. CONCLUSION: With use of a multidetector camera, HMPAO-SPECT comes near the performance of FDG-PET in the diagnosis of striatal dysfunction as it occurs in HD.

Collagen crosslink excretion and staging of oral cancer.

Lysylpyridinoline (LP) and hydroxylysylpyridinoline (HP) are collagen crosslink residues of which the urinary concentration reflects the level of connective-tissue turnover. HP is ubiquitous in tissue, whereas LP is specific for bone. The purpose of this investigation was to assess the sensitivity and specificity of an increased urinary concentration of both HP and LP in indicating infiltration of mandibular bone by an oral squamous cell carcinoma (OSCC) or recurrence of the disease after successful therapy. We investigated the history and urine levels in 116 adult patients, who were divided into the following groups. Group 1: patients with OSCC with bone infiltration (n=17); group 2: patients with confirmed OSCC (n=12) without evidence of bone infiltration; group 3: patients with recurrence of an OSCC (n=13); group 4: patients without clinical evidence of disease (n=74). The range and upper limit of normal values (HP(max) and LP(max)) were measured from the normal controls in group 4. Levels of LP and HP were measured by HPLC and fluorescence detection. There was a significant difference in the average urinary levels of LP and HP between groups 1-4 (P<0.001). The presence of mandibular bone infiltration could be detected with a sensitivity and specificity of 100% when comparing groups 1 and 2. Presence of tumour tissue could be detected with a sensitivity of 90%. In conclusion, a normal LP concentration in patients with an OSCC strongly suggests that bone invasion by the disease has not taken place. If both urinary HP and LP are elevated, disease recurrence is highly likely.

Sentinel lymph-node biopsy in head and neck cancer.

The aim of the study was to assess the diagnostic value of the sentinel node method in patients suffering from squamous cell carcinoma of the upper aerodigestive tract. In 50 patients with oral, pharyngeal or laryngeal carcinomas staged N0 up to 50 MBq technetium-99m colloid were injected peritumorally. Sentinel nodes were localised using a gamma-probe in the setting of an elective neck dissection. Pathological findings of sentinel nodes and corresponding neck specimens were compared. In 46 patients sentinel nodes were detected. Of these 34 patients were free of metastatic disease in the sentinel nodes and in the neck specimens. In 12 patients clinically occult metastases were found in the sentinel nodes. Three metastases were detected only after additional sectioning of the sentinel nodes. In four patients, a sentinel lymph node could not be localised. Our results support the sentinel node concept in head and neck cancer and a definition of the sentinel nodes as the three nodes with the highest activity. Careful clinical staging of the neck and thorough pathological evaluation of the sentinel nodes are necessary to avoid false-negative results.