Francis Zech

Reproducibility of osseous landmarks used for computed tomography based three-dimensional cephalometric analyses

PURPOSE The aim of this paper was to measure the reproducibility of osseous landmark identification from two recently described three-dimensional (3D) cephalometric analyses: 3D-ACRO and 3D-Swennen analyses. The study population consisted of 13 patients examined with spiral 3D computed tomography (CT). We used a previously validated low-dose CT protocol. For each analysis, 22 cephalometric reference landmarks were identified on 3D CT surface renderings. Forty-four reference landmarks were identified per patient. Two series of identifications were performed by two independent observers. In total, 3432 imaging measurements were completed. The intra-observer reconstructed mean log was 1.210+/-1.042mm for the 3D-ACRO analysis, and 1.311+/-1.042mm for 3D-Swennen analysis (comparison: p=0.17 NS). The inter-observer reconstructed mean log was 1.799+/-1.037mm for the 3D-ACRO analysis, and 2.465+/-1.036mm for 3D-Swennen analysis (comparison: p=0.000000002). The difference between the intra- and inter-observer reconstructed mean logs were 1.486+/-1.057mm for 3D-ACRO and 1.880+/-1.056mm for 3D-Swennen analysis. In conclusions: 3D-ACRO analysis was significantly more reproducible than 3D-Swennen analysis (p=0.0027) due to the use of a majority of highly reproducible cephalometric landmarks. Finally, we propose a classification scheme and exclusion criteria for reference landmarks used in 3D cephalometrics, based on inter-observer reproducibility and anatomical reality.

Elevation of serum thyroxine-binding globulin (but not of cortisol-binding globulin and sex hormone-binding globulin) associated with the progression of human immunodeficiency virus infection.

PURPOSE In order to assess the relation of thyroid function tests to human immunodeficiency virus (HIV) infection, we determined the levels of serum thyroid hormones, serum binding proteins [thyroxine-binding globulin (TBG), cortisol-binding globulin (CBG), and sex hormone-binding globulin (SHBG)], and serum tumor necrosis factor (TNF) in HIV-seropositive subjects at different clinical stages. PATIENTS AND METHODS Thirty-seven HIV-seropositive patients were studied: 7 at stage II, 13 at stage III, and 17 at stage IV (eight ambulatory and nine hospitalized) according to the Centers for Disease Controls criteria. RESULTS As compared with stage II and stage III patients, stage IV patients had significantly higher mean TBG and total thyroxine (TT4) values, similar and normal total triiodothyronine (TT3) levels, and similar and abnormally low reverse triiodothyronine (rT3) concentrations. However, stage IV hospitalized patients had significantly lower TT3 values than stage IV ambulatory patients. In contrast to TBG, mean levels of CBG and SHBG were comparable in the three groups and within normal limits. For the whole population of HIV patients, there was a highly significant correlation between the CD4 lymphocyte count and TBG (r = -0.529, p less than 0.001) but not with CBG and SHBG levels. Finally, TNF values higher than 10 pg/mL were detected in six of the 17 stage IV patients and in only one of the 13 stage III patients (p = 0.059); elevated TNF levels correlated with a lower CD4 count (p less than 0.01) but not with serum TBG levels. CONCLUSION The progression of HIV infection is associated with an elevation of serum TNF and TBG, but not of CBG or SHBG. HIV-infected patients have an unexpectedly normal TT3-low rT3 state.

Performance of the Pulmonary Embolism Rule-out Criteria (the PERC rule) combined with low clinical probability in high prevalence population.

INTRODUCTION PERC rule was created to rule out pulmonary embolism (PE) without further exams, with residual PE risk<2%. Its safety is currently not confirmed in high PE prevalence populations even when combined with low clinical probability assessed by revised Geneva score (RGS). As PERC rule and RGS are 2 similar explicit rules with many redundant criteria, we hypothesized that the combination of PERC rule with gestalt clinical probability could resolve this limitation. METHODS We collected prospectively documented clinical gestalt assessments and retrospectively calculated PERC rules and RGS from a prospective study of PE suspected patients. We analyzed performance of combinations of negative PERC with low clinical probability assessed by both methods in high overall PE prevalence population. RESULTS Among the final study population (n = 959), the overall PE prevalence was 29.8%. Seventy-four patients (7.7%) were classified as PERC negative and among them, 4 patients (5.4%) had final diagnosis of PE. When negative PERC was combined with low pretest probability assessed by RGS or gestalt assessment, PE prevalence was respectively 6.2% and 0%. This last combination reaches threshold target of 2% and unnecessary exams could easily have been avoided in this subgroup (6%). However, it confidence interval was still wide (0%; CI 0-5). CONCLUSIONS PERC rule combined with low gestalt probability seems to identify a group of patients for whom PE could easily be ruled out without additional test. A larger study is needed to confirm this result and to ensure safety.

Prevalence and clinical relevance of pathological hepatic changes occurring after neoadjuvant chemotherapy for colorectal liver metastases.

BACKGROUND Hepatotoxicity from neoadjuvant chemotherapy before liver resection for colorectal metastases (CRLM) has been recently reported. The purpose of the present study was to evaluate the prevalence and the clinical relevance of this phenomenon. It was a retrospective study conducted at an academic secondary referral hospital. METHODS One hundred patients suffering from CRLM and having undergone the resection of at least 1 liver segment (114 hepatectomies; 100 first, 13 second, 1 third) were enrolled. The surgical specimens were reviewed using standardized criteria for diagnosis and grading of pathological liver changes. Their impact on perioperative bleeding, transfusion, morbidity, and mortality rates after liver resection was studied. RESULTS Sinusoidal congestion was the single hepatotoxic lesion significantly more frequently encountered in patients having received neoadjuvant chemotherapy (P = .0014), even in patients having received chemotherapy more than 6 months before liver resection, but was not related to the type of chemotherapy. Despite a significant increase in perioperative blood losses, the presence of sinusoidal lesions, even severe, had no clinically significant effect on postoperative mortality, morbidity, and transfusion rates. CONCLUSION Neoadjuvant chemotherapy before operation for CRLM is significantly associated to sinusoidal congestion, irrespective of the type of chemotherapy but without any significant impact on postoperative clinical outcome. Sinusoidal lesions may persist more than 6 months after the end of chemotherapy.

Hyperhomocysteinemia and venous thromboembolism: a risk factor more prevalent in the elderly and in idiopathic cases.

Fasting plasma homocysteine level and the related clinical findings were analysed in 240 consecutive patients with venous thromboembolism. Hyperhomocysteinemia, defined as a plasma level above 20 micromol/l (corresponding to the percentile 95th in the controls), was present in 11.2% of the patients. Plasma homocysteine level was similar in patients presenting with either deep venous thrombosis, pulmonary embolism or both conditions. It was significantly higher in patients with primary (unprovoked) VTE than in patients with secondary disease (associated with at least one risk factor): 12.3 vs. 9.55 micromol/l (p < 0.005). Mean homocysteine was higher in male than in female patients (14.51 vs. 12.9 micromol/l, p < 0.05) and increased significantly with age. Hyperhomocysteinemia was more frequent in patients with relapsing disease (14 of 76, 18.4%) than in those presenting with a single episode (13 of 164, 7.9%) (p = 0.034). Furthermore, hyperhomocysteinemia was correlated with reduced protein C level (p = 0.013). In a multivariate analysis, two factors were significantly associated with hyperhomocysteinemia: older age (p < 0.0001) and idiopathic occurrence (p < 0.02). Since the frequency of homozygous MTHFR thermolabile variant was rather similar in patients and controls, testing for C677T mutation was not helpful in screening VTE patients. However, the homozygous mutation was significantly more prevalent among hyperhomocysteinemia patients, confirming its role in the genesis of hyperhomocysteinemia. According to its prevalence, to the putative role in venous and arterial disease and the availability of an effective and low-cost corrective therapy, hyperhomocysteinemia deserves interest, especially in the elderly and in the patients with idiopathic VTE disease.

Intracardiac allogeneic mesenchymal stem cell transplantation elicits neo-angiogenesis in a fully immunocompetent ischaemic swine model

OBJECTIVES Autologous mesenchymal stem cell transplantation has been shown to improve myocardial function in ischaemic cardiomyopathy. We studied one hypothetical mechanism, neo-angiogenesis, using allogeneic mesenchymal stem cell transplantation in an ischaemic swine model. METHODS Allogeneic mesenchymal stem cells were injected in the peri-infarct area (1×10(6) cells kg(-1)) 2 weeks after myocardial infarction. Myocardial infarction alone (n=3) served as a control group. In the myocardial infarction-mesenchymal stem cells group (n=6), tacrolimus was given from day 0 to day 12. Capillary density and inflammatory/rejection processes (anti-factor VIII and anti-CD3/CD68 monoclonal antibodies, respectively) were compared between groups. RESULTS In scarred myocardium, capillary density was similar between both ischaemic groups: 15.4 (±15.3) and 14.7 (±15.2) vessel/field in myocardial infarction-mesenchymal stem cells and myocardial infarction-alone groups (non-significant). In viable myocardium adjacent to the infarction, capillary density was significantly increased in the myocardial infarction-mesenchymal stem cells group than in the myocardial infarction-alone group (p=0.002). The number of infiltrating CD3+ cells was equivalent in both myocardial infarction-alone and myocardial infarction-mesenchymal stem cells groups (CD3+: 8.6% vs 9.3%, non-significant). However, CD68+ cell infiltration was more prominent after mesenchymal stem cell transplantation (4.7% vs 2% in myocardial infarction alone, p<0.01). CONCLUSIONS Allogeneic mesenchymal stem cell transplantation enhances angiogenesis after myocardial infarction. This effect is limited to the viable myocardium. Using a concomitant 12-day course of tacrolimus, no mesenchymal stem cell-specific cellular immune response was demonstrated.

Sinusoidal obstruction syndrome (SOS) related to chemotherapy for colorectal liver metastases: factors predictive of severe SOS lesions and protective effect of bevacizumab

OBJECTIVES The most frequent presentation of chemotherapy-related toxicity in colorectal liver metastases (CRLM) is sinusoidal obstruction syndrome (SOS). The purpose of the present study was to identify preoperative factors predictive of SOS and to establish associations between type of chemotherapy and severity of SOS. METHODS A retrospective study was carried out in a tertiary academic referral hospital. Patients suffering from CRLM who had undergone resection of at least one liver segment were included. Grading of SOS on the non-tumoral liver parenchyma was accomplished according to the Rubbia-Brandt criteria. A total of 151 patients were enrolled and divided into four groups according to the severity of SOS (grades 0-3). RESULTS Multivariate analysis identified oxaliplatin and 5-fluorouracil as chemotherapeutic agents responsible for severe SOS lesions (P < 0.001 and P = 0.005, respectively). Bevacizumab was identified as having a protective effect against the occurrence of SOS lesions (P = 0.005). Univariate analysis identified the score on the aspartate aminotransferase : platelets ratio index (APRI) as the most significant biological factor predictive of severe SOS lesions. Splenomegaly is also significantly associated with the occurrence of severe SOS lesions. CONCLUSIONS The APRI score and splenomegaly are effective as factors predictive of SOS. Bevacizumab has a protective effect against SOS.

A retrospective study about the use of cotrimoxazole as diagnostic support and treatment of suspected cerebral toxoplasmosis in AIDS.

The aim of this retrospective study was to define a diagnostic strategy and to evaluate the efficacy of cotrimoxazole (CTMX) for presumed cerebral toxoplasmosis in patients with AIDS. Twelve patients with toxoplasma encephalitis were reviewed. The best diagnostical signs of reactivated acute cerebral toxoplasmosis were the association of neurological symptoms indicative of focal cerebral lesions, and a radiological picture showing ring contrast enhanced hypodense mass-lesions; serology was unreliable for the diagnosis. Five patients out of twelve were treated without delay and until death with CTMX. Only these improved their clinical and radiological status obviously. Moreover, their median survival time was clearly longer (160 days, versus 9 days) and their autopsy demonstrated the absence of active necrotizing lesions of toxoplasma encephalitis. So, CTMX seems to be an efficient therapy for suspected cerebral toxoplasmosis in AIDS. Nevertheless, further prospective randomized therapeutic trials are required to confirm this impression.

Prevalence of activated protein C resistance and analysis of clinical profile in thromboembolic patients. A Belgian prospective study

Objectives. To assess the prevalence of activated protein C resistance (APC‐R) among healthy subjects and thromboembolic patients and to determine the clinical characteristics associated with APC‐R.

Isolation of Brucella melitensis from human sperm.

1. Norris JR: Sporosarcina and Sporolactobacillus. In: Berkeley RCW, Goodfellow M (ed): The aerobic endospore-forming bacteria, Volume 4. Academic Press, London, 1981, p. 337-357. Z Claus D, Fahmy F: Genus Sporosarcina Khuyver and Van Niel. 1936. In: Sheath PHA, Mair NS, Sharpe ME, Holt JG (ed): Bergeys manual of systematic bacteriology. Volume 2. Williams and Wilkins, Baltimore, 1986, p. 1202-1206. 3. Claus D: The genus Sporosarcina. In_ Starr MP, Stolp H, Trtlper HG, Balows A, Schlegel HG (ed): The prokaryotes volume 2. Springer Verlag, Berlin, 1981, p. 1804-1807.