Ophthalmic findings associated with Australian tick paralysis (holocyclotoxicity) in hospitalized domestic dogs and cats.

OBJECTIVE: To describe ophthalmic findings in hospitalized canine and feline patients with tick paralysis (TP) and investigate possible predisposing factors. ANIMALS STUDIED: Forty-seven dogs and 28 cats hospitalized with TP assessed with an ophthalmic examination performed by an ABVO resident. METHODS: Dogs and cats were hospitalized with TP from October 2021 to January 2022 and had an ophthalmic examination performed by an ABVO resident. Patient signalment data, information regarding tick number and location, hospitalization duration, medications used, and patient paralysis grades were recorded. Statistical analysis was performed to correlate findings. RESULTS: Corneal ulcers developed in up to 34.8% of dogs and up to 42.9% of cats hospitalized with TP. An absent palpebral reflex ipsilaterally increased the odds of a concurrent corneal ulcer being present by 14.7× in dogs and 20.1× in cats (p < .0001). Palpebral reflexes were absent in 38.3% of dogs and 35.7% of cats hospitalized with TP and were correlated with more severe gait paralysis (p = .01) and respiratory paralysis (p = .005) in dogs, and respiratory paralysis in cats (p = .041). STT-1 findings <10 mm/min were present in 27.7% of dogs and 57.1% of cats examined and were associated with increasing gait paralysis (p = .017) and respiratory paralysis (p = .007) in dogs, and increasing gait paralysis in cats (p = .017). CONCLUSIONS: Simple corneal ulcers, loss of a complete palpebral reflex, and reduced STT-1 scores frequently occurred in dogs and cats hospitalized for TP. The frequency of these findings increased as the degree of patient paralysis increased.

Performance of cone-beam computed tomography and multidetector computed tomography in diagnostic imaging of the midface: A comparative study on Phantom and cadaver head scans.

PURPOSE: To compare multidetector computed tomography (MDCT) and cone-beam computed tomography (CBCT) regarding radiation, resolution, image noise, and image quality. METHODS: CBCT and 256-MDCT were compared based on three scan protocols: Standard-dose (≈24 mGy), reduced-dose (≈9 mGy), and low-dose (≈4 mGy). MDCT images were acquired in standard- and high-resolution mode (HR-MDCT) and reconstructed using filtered back projection (FBP) and iterative reconstruction (IR). Spatial resolution in linepairs (lp) and objective image noise (OIN) were assessed using dedicated phantoms. Image quality was assessed in scans of 25 cadaver heads using a Likert scale. RESULTS: OIN was markedly higher in FBP-MDCT when compared to CBCT. IR lowered the OIN to comparable values in standard-mode MDCT only. CBCT provided a resolution of 13 lp/cm at standard-dose and 11 lp/cm at reduced-dose vs. 11 lp/cm and 10 lp/cm in HR-MDCT. Resolution of 10 lp/cm was observed for both devices using low-dose settings. Quality scores of MDCT and CBCT did not differ at standard-dose (CBCT, 3.4; MDCT, 3.3-3.5; p > 0.05). Using reduced- and low-dose protocols, CBCT was superior (reduced-dose, 3.2 vs. 2.8; low dose, 3.0 vs. 2.3; p < 0.001). CONCLUSION: Using the low-dose protocol, the assessed CBCT provided better objective and subjective image quality and equality in resolution. Similar image quality, but better resolution using CBCT was observed at higher exposure settings. KEY POINTS: • The assessed CBCT device provided better image quality at lower doses. • Objective and subjective image quality were comparable using higher exposure settings. • CBCT showed superior spatial resolution in standard-dose and reduced-dose settings. • Modern noise-reducing tools are used in CBCT devices currently. • MDCT should be preferred for assessment of soft-tissue injuries and oncologic imaging.

An exploratory study investigating the metabolic activity and local cytokine profile in patients with melanoma treated with pazopanib and paclitaxel.

BACKGROUND: There is a medical need for new drugs in patients with BRAF wild-type metastatic melanoma. Pazopanib is a multitarget tyrosine kinase inhibitor with antitumour and antiangiogenic activity. OBJECTIVES: The primary aim was to investigate the metabolic response to pazopanib monotherapy and pazopanib plus paclitaxel in patients with BRAF wild-type melanoma. Secondary end points were the early cytokine and chemokine profiles and histological findings. METHODS: Pazopanib (400 mg twice daily) was administered orally from days 1 to 10 and from days 14 to 70. An intravenous infusion with paclitaxel (150 mg m-2 body surface) was administered on days 14, 35 and 56. Metabolic response evaluation was performed before treatment, after treatment with pazopanib (day 10) and after treatment with pazopanib and paclitaxel (day 70). Skin biopsy of metastatic tissue for chemokine and cytokine expression analysis and histology and immunohistochemistry (CD68, CD163) evaluation, and blood samples were taken at the same time points. RESULTS: Two patients failed screening and 17 were dosed. Of 67 adverse events, nine (13%) were grade 3 or 4. Five of 14 evaluable patients had a partial metabolic response at day 10 under pazopanib monotherapy. The response rate at day 70 under combined pazopanib-paclitaxel treatment was 0%. Immunohistochemistry revealed an increase of M2-like macrophages in nonresponders compared with responders. We observed a significant upregulation of five cytokines (CXCL1, CXCL2, CXCL13, CCL22 and SPP1) in responding vs. nonresponding lesions. Overall, the median progression-free survival was 70 days (range 5-331), which did not differ significantly between responders (148 days) and nonresponders (70 days, P = 0·17). CONCLUSIONS: In this patient population pazopanib efficacy was limited. Response is associated with low M2-like macrophage density and increased expression of several chemokines.

Alterations in classical and nonclassical HLA expression in recurrent and progressive HPV-induced usual vulvar intraepithelial neoplasia and implications for immunotherapy.

Immunotherapy of usual vulvar intraepithelial neoplasia (uVIN) is promising; however, many patients still fail to show clinical responses, which could be explained by an immune escape through alterations in human leukocyte antigen (HLA) expression. Therefore, we analyzed a cohort of patients with a primary (n = 43) and subsequent recurrent uVIN lesion (n = 20), vaccine-treated uVIN patients (n = 12), patients with human papillomavirus (HPV)-induced vulvar carcinoma (n = 21) and healthy controls (n = 26) for the expression of classical HLA-class I/II and nonclassical HLA-E/-G and MHC class I chain-related molecule A (MICA). HLA-class I was downregulated in 70% of uVIN patients, including patients with a clinical response to immunotherapy. Downregulation of HLA-class I is probably reversible, as only 15% of the uVIN cases displayed loss of heterozygosity (LOH) and HLA-class I could be upregulated in uVIN keratinocyte cultures by interferon γ. HLA-class I downregulation is more frequently associated with LOH in vulvar carcinomas (25-55.5%). HLA-class II was found to be focally expressed in 65% of uVIN patients. Of the nonclassical molecules, MICA was downregulated in 80% of uVIN whereas HLA-E and -G were expressed in a minority of cases. Their expression was more prominent in vulvar carcinoma. No differences were found between the alterations observed in paired primary and recurrent uVIN. Importantly, downregulation of HLA-B/C in primary uVIN lesions was associated with the development of recurrences and progression to cancer. We conclude that downregulation of HLA is frequently observed in premalignant HPV-induced lesions, including clinical responders to immunotherapy, and is associated with worse clinical outcome. However, in the majority of cases downregulation may still be reversible.

Retrospective assessment of ophthalmic disease development in domestic dogs and cats when hospitalised with tick paralysis caused by Ixodes holocyclus.

OBJECTIVE: To investigate the incidence and predisposing factors leading to the development of corneal ulcers and the loss of a palpebral reflex in hospitalised canine and feline patients with tick paralysis (TP). ANIMALS STUDIED: A total of 102 dogs and 100 cats retrospectively were assessed from previously hospitalised patients. METHODS: A retrospective cohort study was performed on 102 different canine and 100 different feline patients who were hospitalised for TP from October 2020-January 2022. Patient data were collected, and logistic regression was conducted to determine factors affecting the palpebral reflex and the development of corneal ulcers. RESULTS: Corneal ulcers occurred in 23/102 (22.5%) dogs during hospitalisation and were strongly associated with an incomplete palpebral reflex ipsilaterally during hospitalisation (P < 0.001), hospitalisation ≥3 days (P = 0.004), mechanical ventilation ≥3 days (P = 0.015) or a tick location cranial to C1 (P = 0.003). An incomplete palpebral reflex during hospitalisation was observed in 29/102 (28.4%) dogs and was significantly associated with decreasing patient weight (P = 0.018), increasing days hospitalised (P = 0.001), having a tick found cranial to C1 (P = 0.004), highest recorded GP grade (P = 0.01), highest recorded RP grade (P = 0.005), use of amoxycillin-clavulanic acid during hospitalisation (P = 0.002) and use of piperacillin/tazobactam during hospitalisation (P = 0.003). There was a significant association between the loss of a complete palpebral reflex and mortality during hospitalisation in dogs (OR = 4.5, P = 0.029). Corneal ulcers occurred in 10/100 (10.0%) cats during hospitalisation, and was significantly more likely to occur to an eye if an incomplete palpebral reflex was observed ipsilaterally during hospitalisation (OR = 20.1, P < 0.0001) and with increasing patient age (P = 0.019). The absence of a complete palpebral reflex during hospitalisation was observed in 18/10 (18.0%) cats and was significantly associated with increasing days hospitalised (P = 0.034). There was no significant association between the loss of a complete palpebral reflex and mortality during hospitalisation in cats. CONCLUSIONS: The frequency of corneal ulcers and loss of palpebral reflexes were significant in dogs and cats hospitalised by TP, with many factors contributing to the risk of these developing.

Multi-modality imaging of aggressive submural neoplasia of the hoof in two horses.

This case series presents a 20-year-old Quarter horse gelding and a 10-year-old Thoroughbred gelding with a histologic diagnosis of aggressive submural neoplasia, including an anaplastic sarcoma and a squamous cell carcinoma respectively. The current case series describes these neoplasias with radiography, computed tomography, magnetic resonance imaging and histopathology with immunohistochemistry. The purpose of this case series is to identify the clinical pattern of chronic reoccurring lameness in these cases and highlight the appearance of expansile osteolytic pathology of the distal phalanx with adjacent hoof wall abnormalities. Advanced imaging has the potential to assist with a differential diagnosis list and surgical planning in patients such as these however obtaining a cellular sample for histopathological examination remains necessary for definitive diagnosis.

Causes of Death in Endovascularly Treated Patients with Acute Stroke.

BACKGROUND AND PURPOSE: Because stroke therapy has changed with the introduction of endovascular stroke treatment as a standard approach, studies on intrahospital causes of death from stroke are no longer up-to-date. The purpose of this observational study was to present the causes of death during hospitalization of patients with ischemic stroke who received endovascular stroke treatment, with the focus on a differentiation of curative and secondary palliative treatment. MATERIALS AND METHODS: We studied a total cohort of 1342 patients who received endovascular stroke treatment in a tertiary stroke center (Aachen, Germany) between 2010 and 2020 and analyzed the causes of death in all 326 consecutive deceased patients. We distinguished between curative treatment and a secondary palliative approach and analyzed causes of death and treatment numbers across the years. RESULTS: In the entire cohort of 326 deceased patients, the most common cause of death was of a cerebrovascular nature (51.5%), followed by pneumonia and sepsis (25.8%) and cardiovascular causes (8.3%). Neurovascular causes constituted 75.8% of reasons for palliation. In the group with a secondary palliative approach, causes of death were neurovascular in 54.0% of patients and pneumonia and sepsis in 26.0% of patients. CONCLUSIONS: Cerebrovascular causes in patients with stroke play a major role in the intrahospital causes of death and reasons for palliation. Considering the large proportion of secondarily palliative-treated patients, reasons for palliation should be considered instead of causes of death to avoid concealment by, for example, life-terminating measures.

Quantification of radiation dose savings in cardiac computed tomography using prospectively triggered mode and ECG pulsing: a phantom study.

OBJECTIVE: To quantify radiation dose reduction in cardiac computed tomography (CT) using a prospectively triggered mode compared with a retrospective ECG-gated helical mode. METHODS: Absorbed organ doses in cardiac 64-row multidetector CT were quantified using an anthropomorphic male Alderson phantom with 74 thermoluminescence dosimeters. Three different imaging protocols were applied: retrospective ECG-gating, retrospective ECG-gating with additional ECG-pulsing, and a prospectively triggered mode. The measured organ doses were compared with dose estimation by a mathematical phantom. RESULTS: Compared with the retrospective ECG-gating mode, the mean relative organ doses were reduced by 44% using ECG pulsing and by 76% using the prospectively triggered mode. The range of dose savings varied from 34% to 49% using ECG pulsing and from 65% to 87% using the prospectively triggered mode. The effective dose was 16.5 mSv using retrospective gating, 9.2 mSv using retrospective gating with ECG pulsing and 4.0 mSv using the prospectively triggered mode. CONCLUSIONS: Our measurements confirm the high dose-saving potential of the prospectively triggered technique in cardiac CT. The reduction in the organ doses measured corresponds to estimates determined by the mathematical phantom. The effective dose calculated by the mathematical phantom was, in some cases, significantly lower than that calculated using the anthropomorphic phantom.

Simulated low-dose computed tomography in oncological patients: a feasibility study.

OBJECTIVE: Image quality of chest and abdominal computed tomographic (CT) scans was evaluated at different doses to assess the lowest value of x-ray dose at which the image quality was not being affected. MATERIALS AND METHODS: Using multislice CT (MSCT), 29 patients who submitted to follow-up examinations were examined using a combined MSCT protocol of the chest and the abdomen on 4-raw MSCT (Siemens, Erlangen, Germany). For each examination, approximately 120 mL of contrast agent (Bracco-Altana, Konstanz, Germany) was applied intravenously. The raw data were transferred to an external personal computer equipped with an image reconstruction software (CardioRecon 6; Siemens, Forchheim, Germany) to simulate 5 different dose levels. To simulate them correctly, a milliampere second-dependent noise was added to every image, so that the changes in a current-time product could be imitated. The images were compared in consensus by 2 radiologists who were not informed about the technical scanning parameters, that is, dose parameters, and were graded in 4 different subcategories on a 1-to-5-point scale. For statistical analysis, the Friedman test was used. Additional evaluations for lesions smaller than 1.0 cm were performed and analyzed separately. RESULTS: For image noise, there was a significant change between 40 and 60 mA s. For lesion detection, there was no significant change. The contour of the small objects did not differ between 90, 60, and 40 mA s. However, a dose reduction to 30 mA s had a significant effect. The contrast did not differ between 90, 60, 40, and even down to 30 mA s. Only a maximal dose reduction to 20 mA s had a significant effect on the contrast. The level of noise was most sensitive to the current. Whereas a dose reduction to 60 mA s did not yet have a significant effect, there was a significant increase of noise at 40 mA s. CONCLUSIONS: The MSCT can be applied with a lower dose than that usually selected in examinations at present to follow-up and stage the oncological patients adequately.

Protein profiling of non-malignant and malignant ascites by SELDI-TOF MS: proof of principle.

Ascites is a common clinical symptom in liver cirrhosis, inflammatory disorders of the abdomen and a major late manifestation of metastatic malignancies. Standard cytopathological techniques and immunocytochemistry have specificities and sensitivities of approximately 95 and 60%, respectively for the presence of tumor cells. Development of faster and more accurate screening methods would be of great clinical utility. In this work we examined differential analysis of the unbound proteins in the supernatant of ascites fluid by Protein-Chip SELDI mass spectrometry. There were 21 tumor cell-positive and 34 tumor cell-negative samples. We used principal component analysis coupled with linear regression applied to the mass spectra of the samples to distinguish between the sample groups. Two sample sets for statistical analysis were created after randomization, a training set with 37 samples and a validation set with 18 samples resulting in a specificity of 93% and a sensitivity of 83% on the training set. The validation set yielded a specificity and sensitivity of 75%. This study suggests that SELDI-TOF mass spectrometry appears to have great potential as a surrogate diagnostic tool to evaluate effusion specimens.

Sacroplasty in a cadaveric trial: comparison of CT and fluoroscopic guidance with and without balloon assistance.

Sacral insufficiency fractures can cause severe, debilitating pain to patients concerned. The incidence of this fracture type correlates with the appearance of osteoporosis in the elderly population. A polymethylmethacrylate (PMMA) cement injection procedure called sacroplasty has been recently described as an optional method for the treatment of this fracture type. However, the correct cement placement in the complex anatomical structure of the sacrum is a surgical challenge. The aim of the study is to compare the precision, safety, and radiation exposure of standard multiplanar fluoroscopy and computed tomography (CT) guidance for PMMA application to the sacrum using both balloon-assisted sacroplasty and conventional sacroplasty. A controlled experimental investigation in a human cadaver trial has been performed. Two imaging and two application modalities to monitor percutaneous PMMA injection to the sacrum were examined. The application forms were randomized from side to side of the pelvis. We found less cement extravasation in the CT-guided groups, but also a significant higher radiation exposure (P < 0.05) by using CT guidance. The conventional fluoroscopy-guided sacroplasty revealed the shortest procedure time (incision to closure time) of all treatment groups (P < 0.01). These findings show no difference regarding cement extravasation between ballon-assisted and conventional sacroplasty. Further, in comparison to fluoroscopy-assisted technique, the CT-guided cement injection seems to decrease the risk of cement extravasation, irrespective of the use of an additional balloon assistance. However, we have to consider a greater radiation exposure using CT guidance. Further investigations will proof the suitability in the normal course of clinical life.

Effects of neuron-specific ADAM10 modulation in an in vivo model of acute excitotoxic stress.

A disintegrin and metalloprotease (ADAM) 10 is the main candidate enzyme for the alpha-secretase processing of the amyloid precursor protein (APP). Neuron-specific ADAM10 overexpression proved beneficial in the APP[V717I] mutant Alzheimer mouse model [Postina R, Schroeder A, Dewachter I, Bohl J, Schmitt U, Kojro E, Prinzen C, Endres K, Hiemke C, Blessing M, Flamez P, Dequenne A, Godaux E, van Leuven F, Fahrenholz F (2004) A disintegrin-metalloproteinase prevents amyloid plaque formation and hippocampal defects in an Alzheimer disease mouse model. J Clin Invest 113:1456-1464]. Since Alzheimer patients have a high prevalence for epileptic seizures, we investigated the effects of ADAM10 modulation under conditions of experimentally induced epileptic seizures. In this context we also examined whether ADAM10 effects were influenced by APP levels. Therefore we compared severity of kainate-induced seizures, neurodegeneration and inflammation in double transgenic mice overexpressing functional ADAM10 or a dominant negative ADAM10 mutant in the APP[V717I] background with single transgenic ADAM10 modulated mice. Double transgenic dominant negative ADAM10dn/APP[V717I] mice suffered from stronger epileptic seizures, had a longer recovery period and showed more neurodegeneration and glial activation in the hippocampal region than double transgenic mice moderately overexpressing functional ADAM10 (ADAM10mo/APP[V717I]) and APP[V717I] mice with endogenous ADAM10 levels. This suggests that ADAM10 activity is necessary to provide neuroprotection against excitotoxicity in the APP[V717I] mouse model. Interestingly, increased expression of functional ADAM10 above the endogenous level did not correlate with a better protection against seizures and neurodegeneration. Furthermore, ADAM10 dominant negative mice without transgenic APP overexpression (ADAM10dn) were seizing for a shorter time and showed less neuronal cell death and neuroinflammation after kainate injection than wild-type mice, which shows beneficial effects of ADAM10 inhibition in context with neurodegeneration. In contrast, mice with a high ADAM10 overexpression showed more seizures and stronger neuronal damage and inflammation than wild-type mice and mice with moderate ADAM10 overexpression. Hence, additional cleavage products of ADAM10 may counterbalance the neuroprotective effect of alpha-secretase-cleaved APP in the defense against excitotoxicity. Our findings highlight the need of a careful modulation of ADAM10 activity for neuroprotection depending on substrate availability and on neurotoxic stress conditions.

[Integration of cardiac computed tomography into pulmonary vein isolation in patients with paroxysmal atrial fibrillation]. / Integration einer präinterventionellen Computertomografie des Herzens in die therapeutische Pulmonalvenenisolation bei Patienten mit paroxysmalem Vorhofflimmern.

PURPOSE: Detailed anatomic information of the left atrium is necessary for securely performing radiofrequency ablation of atrial fibrillation-triggering ectopies in the pulmonary vein ostia. In this study the impact of a preinterventionally acquired cardiac computed tomography (CT) on pulmonary vein isolation (PVI) was assessed. MATERIALS AND METHODS: Examinations of 54 patients with paroxysmal atrial fibrillation undergoing PVI were analyzed. In 27 patients a supplementary cardiac CT was obtained prior to PVI (CT group, 12 women, 15 men, 59.7+/-9.9 years of age): 16 x 1.5 mm collimation, 0.2 pitch, 120 kV tube voltage, 400 effective mAs. The fluoroscopy time, effective dose and quantity of radiofrequency (RF) pulses of the following catheter ablation were compared to 27 patients undergoing stand-alone PVI (11 women, 16 men, 62.0+/-9.9 years of age). Mann-Whitney tests served for statistical comparison. RESULTS: CT datasets were successfully integrated into the ablation procedure of each patient in the CT group. The mean quantity of RF pulses was significantly lower in the CT group (22.1+/-8.0 vs. 29.1+/-11.9, p=0.030), and a significant reduction of fluoroscopy time was found (41.8+/-12.0 min vs. 51.2+/-16.0 min, p=0.005). Effective doses of the catheter ablation differed in an equivalent dimension but altogether not significantly (14.9+/-10.0 mSv vs. 20.0+/-16.0 mSv, p=0.203). The mean additive effective dose of the cardiac CT was 8.5+/-0.3 mSv. CONCLUSION: CT-guided ablation of atrial fibrillation requires less fluoroscopy time than stand-alone PVI. Due to the multi-faceted dependency of individual fluoroscopy doses, a consistent reduction of the effective dose was not observed. Since supplementary CT constitutes an additive dose, optimized CT atriography needs to be designed in order to provide sufficient image quality while reducing X-ray exposure. The reduction in RF pulses implies an increase in the effectiveness and safety of catheter ablation.

[Image quality of thickened slabs in multislice CT chest examinations: postprocessing vs. direct reconstruction]. / Bildqualität aufaddierter Schichten bei MSCT-Untersuchungen des Thorax: Bildnachverarbeitung versus Direktrekonstruktion.

PURPOSE: Postprocessing offers the possibility of real-time creation of thickened slabs from a set of thin slices. This allows the interactive change from thick to thin slices for better evaluation of unclear lesions. As a result the clinical workflow of MSCT evaluation can be improved. However, to be able to apply this postprocessing software in the clinical routine, degradations in the image quality (compared to standard original reconstructed images) have to be avoided. The purpose of this study was to compare the image quality of thickened slabs from MSCT chest examinations that have either been directly reconstructed from the raw data or have been retrospectively generated via postprocessing. MATERIALS AND METHODS: Chest MSCT examinations of 20 patients (mean age: 56 years) were performed on a 16-slice MSCT scanner (Mx8000IDT16, Philips, Best, Netherlands) using the following scan parameters: 120 kV, 94 effective mAs, 16 x 1.5 mm collimation, 512 x 512 matrix, field of view 371 x 371 mm, CTDIvol = 6.3 mGy, DLP = 210 mGyxcm). Slices with a thickness of 3 and 5 mm were generated for each examination both directly from the raw data and via postprocessing. Corresponding images from postprocessing and direct reconstruction (lung/soft tissue window) were evaluated by two radiologists with respect to 5 criteria on the basis of a five-point scale: organ structure, contour of small objects, contrast, image noise and artifacts. Differences between both data sets regarding image quality were assessed for each of the 5 criteria using a Wilcoxon test with Bonferroni correction. In addition, image noise was analyzed quantitatively in a region of interest in the aorta. RESULTS: For the lung and soft tissue window, both reviewers and all criteria, no differences in image quality were detected between the thickened slices obtained via direct reconstruction and the postprocessing method. In 96 % and 95 % of the cases images of the two reconstruction methods were graded identically for 3 mm and 5 mm slices. In the remaining 4 % and 5 %, the evaluations differed only by one point on the five-point scale. The median grade of the first reviewer was 1 and that of the second reviewer was 2. There were no differences in the quantitative analysis of image noise between both methods. CONCLUSION: The interactive creation of thickened slices is an effective tool for the evaluation of MSCT examinations. For the defined scan parameters in this study there were no differences in image quality between postprocessing methods (e. g. slab viewer) and direct image reconstruction.

[Three patients with differing manifestations of uterine sarcoma]. / Drie patiënten met verschillende manifestaties van uterussarcoom.

A 70-year-old woman with postmenopausal blood loss proved to have a stage-IV high-grade endometrial stromal sarcoma; 9 months after resection the patient was well. In a 53-year-old woman with symptoms of neurological deficit and weight loss accompanying an increase in abdominal girth and postmenopausal vaginal blood loss a high-grade leiomyosarcoma at stage IV was diagnosed. Despite treatment the neurological symptoms worsened and the patient died within 2 months of diagnosis. Another woman, aged 53, with abdominal pain but no blood loss proved to have a high-grade leiomyosarcoma at stage 1. Nine months after resection and radiotherapy the patient was well. The incidence of carcinomas of the uterus in The Netherlands is on average 113 women per year. They manifest themselves in different ways which can sometimes be misleading. The most common symptom is vaginal bleeding, in combination with abdominal pain or a pelvic mass. The only curative therapy is surgical excision. The 5-year survival rate is 50% in tumours confined to the uterus as opposed to 20% in those that spread further.

The in situ polymerase chain reaction for detection of chlamydia trachomatis.

The in situ polymerase chain reaction (PCR) is a technique that has important applications in the diagnosis of viral and bacterial diseases. This study investigated an in situ PCR assay established to detect the presence of Chlamydia trachomatis in endocervical swabs. In addition, histological sections of endocervical squamous cell carcinoma were analyzed because previous studies had revealed a significant association with C. trachomatis. A total of 20 cervical neoplasms (squamous cell carcinoma in situ; n = 10; invasive squamous cell carcinoma; n = 10) and endocervical smears taken from five patients with and without inflammatory changes were analyzed by conventional PCR. Chlamydial DNA was found in 10 histological samples (six carcinomas in situ, four invasive carcinomas) and in one endocervical swab from a patient with known C. trachomatis infection. Positive specimens were used for establishing an in situ PCR assay (IS-PCR). After IS-PCR, these samples showed dense cytoplasmic staining of endocervical cells (smears) and non-neoplastic epithelial cells (cervical neoplasms). The other tumor samples and smears did not demonstrate positive PCR reaction. The results indicate that in situ PCR is an effective technique for localizing C. trachomatis in target cells because IS-PCR detection of chlamydial DNA correlated with histological and cytological features.

Sterylsulfatase expression in normal and transformed human placental cells.

Isolated cytotrophoblast cells and choriocarcinoma cell lines are commonly applied in-vitro systems for the study of human placental endocrine function. We tested these normal and transformed placental cells for expression of the enzyme sterylsulfatase which is necessary for the production of free steroids from sulfoconjugated precursors in the placenta as well as in other human tissues, and compared the results with respective data obtained from term placental tissue. Specific sterylsulfatase activity was highest in placental homogenates but was lower by about a factor of 5 to 10 in homogenates of freshly isolated cytotrophoblast or JEG-3 cells and by about a factor of 100 in BeWo cell homogenates; the enzyme activity could not be detected in Jar cells. Sterylsulfatase mRNA levels as analyzed by Northern blotting roughly paralleled the levels of enzyme activity measured in cytotrophoblast, JEG-3, and BeWo cells; in Jar cells, RNA species complementary to the specific probe were clearly detectable but differed by size from the mRNA species found in the other cells. Our results indicate that sterylsulfatase activity is differently expressed in normal and transformed placental cells due to different rates or products of gene transcription in these cells.

Gene expression analysis of the catalytic subunit of human telomerase (hEST2) in the differential diagnosis of serous effusions.

Diagnostic accuracy in effusion cytology based on morphologic examination is not always satisfactory. Therefore, various diagnostic adjuncts such as immunocytochemistry or deoxyribonucleic acid cytometry are employed in this diagnostic field. Recently, demonstration of telomerase activity has been proposed as a possible marker for malignancy. In this study a seminested reverse transcription-polymerase chain reaction (RT-PCR) strategy for expression analysis of the catalytic subunit of human telomerase (hEST2) was used in 58 serous effusions. RT-PCR results correlated with cytologic diagnoses in 14 of 17 malignant effusions. In eight effusions cytologically suspicious for malignancy, PCR results were in accordance with the clinical follow-up. However, hEST2 RT-PCR was also positive in six of 15 cytologically benign effusions that consisted predominantly of inflammatory and mesothelial cells. Using the telomeric repeat amplification protocol, it could be demonstrated that cultured, proliferating benign mesothelial cells may present a weak telomerase activity, as is known in other benign cells including activated lymphocytes. In conclusion, the simple and rapid method of hEST2 RT-PCR serves to support the cytologic diagnosis of malignancy, but false-positive PCR results resulting from activated lymphocytes and proliferating mesothelial cells must be considered.

Long-term photoepilation using a broad-spectrum intense pulsed light source.

BACKGROUND: The goal of laser or flashlamp photoepilation is to produce long-term, cosmetically significant hair removal. We document the long-term efficacy achieved with an intense pulsed light source for photoepilation. DESIGN: Prospective study comparing long-term results of single vs multiple treatments, and effects of anatomic site and skin type on efficacy of photoepilation with a device emitting broad-spectrum, noncoherent (nonlaser) radiation from 550- to 1200-nm wavelengths, in macropulses divided into 2 to 5 minipulses. SETTING: Private dermatology practice. PATIENTS: Thirty-four patients (8 men, 26 women) with hirsutism. INTERVENTIONS: Parameters for the study were wavelength of 615 to 695 nm, pulse duration of 2.6 to 3.3 milliseconds, fluence of 34 to 42 J/cm(2), 10 x 45-mm exposure field, and application of 1 degrees C cooling gel. MAIN OUTCOME MEASURES: Hair removal efficiency, calculated as percentage ratio of the number of hairs present compared with baseline counts, and patient satisfaction questionnaire completed at last follow-up. RESULTS: The mean hair removal efficiency achieved was 76% after a mean of 3.7 treatments. More than 94% of the sites reached mean hair removal efficiency values greater than 50%. Hair removal efficiency was not significantly related to skin type, hair color, anatomic site, or number of treatments. Side effects were mild and reversible and occurred in a minority of patients (hyperpigmentation in 3 and superficial crusting in 2). CONCLUSIONS: Our data document the long-term clinical efficacy of intense pulsed light source-induced hair removal in light and dark skin phenotypes. Maximal photoepilation was achieved from the initial 1 to 3 treatments; only a small added benefit was seen after more treatments.

Screening of dysfibrinogenaemia using the fibrinogen function versus antigen concentration ratio.

The diagnosis of inherited and acquired dysfibrinogenaemia is usually suspected in patients with otherwise unexplained prolonged thrombin time or other tests with thrombin-like enzymes (1). Confirmation of the diagnosis requires discordant results from the investigation of functional fibrinogen and its antigen concentration. However, the issue of the difference between the two results required to confirm dysfibrinogenaemia has rarely been addressed. A difference of at least 0.5 g/l between functional fibrinogen using the method of Clauss and heat precipitation method according to Schulz has been suggested as a prerequisite (1). In the case of acquired dysfibrinogenaemia with an underlying liver disease the discordance should reach at least 1.0 g/l (2). Rodgers and Garr (3) suggested to establish a ratio between fibrinogen function and antigen concentration. In that study plasma from healthy blood donors was investigated using the Clauss method and radial immunodiffusion. We applied this approach to randomly selected patients at the time of admission to a University Hospital Department. Since fibrinogen is one of the major acute phase proteins, the determination of the C-reactive protein (CRP) was included for comparison.