Assessment of radiological vertebral fractures in HIV-infected patients: clinical implications and predictive factors.

OBJECTIVES: The aim of this study was to evaluate the clinical impact of including lateral spine X-ray in the screening of bone diseases in HIV-positive patients. METHODS: A total of 194 HIV-positive patients underwent dual-energy X-ray absorptiometry (DEXA), lateral spine X-ray and bone biochemical analysis. Vertebral fractures were identified using a morphometric analysis of X-rays and classified using the semiquantitative scoring system of Genant et al. For each patient, a spine deformity index (SDI) score was calculated by summing the grades of vertebral deformities. Reductions in vertebral body height of > 25% were considered vertebral fractures, and those < 25% were considered vertebral deformities. Risk factors associated with vertebral fractures were evaluated by univariate and multivariate analysis. RESULTS: Vertebral fractures were detected in 24 patients (12.4%) and vertebral deformities in 17 patients (8.7%); 153 patients (78.9%) did not show any vertebral deformity. Among patients with fractures, only two with SDI > 10 reported lumbar pain; the remaining were asymptomatic. Patients over 50 years old showed a higher prevalence of vertebral fracture [24.4% versus 11.8% in patients 41-50 years old (P = 0.05) and 1.9% in patients ≤ 40 years old (P = 0.04)]. No significant increase in the prevalence according to bone mineral density (BMD) reduction was observed, and 70% of fractures were diagnosed in nonosteoporotic patients. Older age [adjusted odds ratio 1.09; 95% confidence interval (CI) 1.03-1.13; P = 0.001] and steroid use (adjusted odds ratio 3.64; 95% CI 1.29-10.3; P = 0.01) were independently associated with vertebral fracture; no association was found with HIV- or highly active antiretroviral therapy (HAART)-related variables. CONCLUSIONS: A prevalence of vertebral fractures of 12.4% was observed in our HIV-positive cohort. Given that two-thirds of fractures occurred in nonosteoporotic patients, spine X-ray may be considered in patients at increased risk, irrespective of BMD; that is, in elderly patients and/or patients using steroids.

Polytherapy in bone regeneration: clinical applications and preliminary considerations.

Polytherapy, namely the simultaneous application of three fundamental elements necessary for bone regeneration (growth factors, osteogenic cells and osteoconductive scaffolds) seems to lead to a very high success rate in the treatment of complex non-union (NU) cases and critical bone defects. NU are reported in 5-10% of long bone fractures. The use of autologous bone grafts has been long-considered the gold standard for the treatment of these cases. However the harvesting procedure from the iliac crest increases surgery time and presents some donor site complications which may be elevated. In recent years, surgeons have some alternatives to autologous grafting such as: application of organic or synthetic bone substitute, application of mesenchymal stromal cells (MSC) or growth factors (GF). In the literature there are many studies available about their application in monotherapy, but unfortunately the healing rate doesn't exceed 90%. Polytherapy seems to be a logical option to improve the healing rate, nevertheless, there are not still extensive studies that validate this strategy and moreover, some questions are not resolved.

Protein S mRNA in patients with protein S deficiency.

A protein S gene polymorphism, detectable by restriction analysis (BstXI) of amplified exonic sequences (exon 15), was studied in seven Italian families with protein S deficiency. In the 17 individuals heterozygous for the polymorphism the study was extended to platelet mRNA through reverse transcription, amplification and densitometric analysis. mRNA produced by the putative defective protein S genes was absent in three families and reduced to a different extent (as expressed by altered allelic ratios) in four families. The allelic ratios helped to distinguish total protein S deficiency (type I) for free protein S deficiency (type IIa) in families with equivocal phenotypes. This study indicates that the study of platelet mRNA, in association with phenotypic analysis based upon protein S assays in plasma, helps to classify patients with protein S deficiency.

The G20210A mutation of the prothrombin gene in patients with previous first episodes of deep-vein thrombosis: prevalence and association with factor V G1691A, methylenetetrahydrofolate reductase C677T and plasma prothrombin levels.

A common G to A transition at nucleotide 20210 of the prothrombin gene is associated with an increased risk for deep-vein thrombosis (DVT) and high plasma levels of prothrombin. We calculated the prevalences of prothrombin G20210A, factor V G1691A (also associated with high risk for DVT) and homozygous methylenetetrahydrofolate reductase (MTHFR) C677T (associated with increased susceptibility to develop hyperhomocysteinemia) in 118 patients with a first episode of DVT and in 416 healthy controls. 15.9% of the patients and 2.3% of the controls had prothrombin G20210A (odds ratio [OR]: 8.7, 95% C.I.: 3.8-21.4); 21.1% of the patients and 3.2% of the controls had factor V G1691A (OR 7.8, 3.9-17.1); 20.5% of the patients and 21% of the controls had homozygous MTHFR C677T (OR: 1.0, 0.7-1.2). Exclusion of patients with other hereditary risk factors for DVT did not substantially modify the results. Mutant factor V and prothrombin coexisted in three patients but in no control. The concomitant presence of the MTHFR mutation did not increase the thrombotic risk associated with prothrombin G20210A. 63.2% of individuals with prothrombin G20210A had plasma levels of prothrombin in the upper quartile of distribution. After adjustment for age and sex, subjects with prothrombin levels in the upper quartile carried a slightly higher risk for thrombosis than those with lower prothrombin concentrations (OR: 1.9, 1.1-3.2). In conclusion, we found that prothrombin G20210A is relatively common in Italy and is associated with high prothrombin levels and an 8.7-fold increase in the risk for DVT. Such risk is independent of the coexistence of other known inherited risk factors for thrombosis and increases in patients with associated mutant factor V. Whether it is due to the associated increase in plasma prothrombin levels remains to be established.

Plasma factor VII levels are influenced by a polymorphism in the promoter region of the FVII gene.

Genetic factors play a role in determining the variability of plasma factor VII (FVII) levels in healthy individuals. There is also evidence that high serum lipids are associated with high FVII levels in plasma. In the promoter region of the human FVII a DNA polymorphism has been described, originating from a decanucleotide insert present in the less frequent allele. This biallelic system, reflecting the absence (AA) or presence (Aa) of the decanucleotide, can be detected by a DNA enzyme immunoassay of PCR products. We evaluated the association between the polymorphic alleles and the levels of FVII:Ag and FVII:C in 100 healthy individuals and in 19 hypertriglyceridemic individuals. Among healthy individuals, mean FVII:Ag and FVII:C levels of those with the homozygous genotype (A/A; mean FVII:Ag 112%, mean FVII:C 109%) were significantly higher (P < 0.001) than the mean levels of those with the heterozygous genotype (A/a, mean FVII:Ag 80%, mean FVII:C 90%; P < 0.001). Similar genotype-associated differences for FVII:Ag and FVII:C were found in individuals with triglycerides above 250 mg/dl (P < 0.05). FVII:C and FVII:Ag levels were positively related to triglycerides only in individuals without the insert (P < 0.01); there was no significant relationship in those carrying the allele with the insert (A/a; P = 0.43 and 0.08). Our findings of genotype-associated differences in FVII levels and interactions with triglycerides are similar to those obtained with the amino acid dimorphism at position 353 of the factor VII protein.

Cardiac and pulmonary calcification in a hemodialysis patient: partial regression 4 years after parathyroidectomy.

AIMS: The reversibility of extraskeletal calcifications in dialysis patients is an important and unresolved issue. Although periarticular calcifications have been shown to be reversible, little data are available on vascular or parenchymal calcifications. CASE HISTORY: A patient on maintenance hemodialysis with severe hyperparathyroidism, hypercalcemia and hyperphosphatemia was admitted to undergo parathyroidectomy. A preoperative total body bone scintigraphy was performed to better evaluate a lytic lesion in the pelvis, the histology of which proved to be a "brown tumor". The scan showed the typical findings of renal osteodystrophy, but also a diffuse extra-skeletal uptake of bone tracer in the lungs, kidneys, femoral arteries and myocardium. After surgery, good control of serum calcium, phosphate (Ca x P product < 50 mg2/dl2) and PTH levels was maintained during 4 years of follow-up. Bone scans were repeated after 2 and 4 years, showing marked improvement of periarticular uptake at the ends of long bones. Extraosseous calcium deposition was still markedly evident, but progressively decreased (at 4 years: heart -36%, lungs -18%). CONCLUSION: In this dialysis patient, extraskeletal calcification of visceral organs (particularly in the heart and the lungs) due to prolonged hypercalcemia and hyperphosphatemia was partially reversible by parathyroidectomy followed by good long-term control of serum phosphate and calcium.

Interventional radiology with venous port (chemotherapy and infusional support).

A completely portable permanent central venous access, consisting of a steel capsule sealed with a silicone membrane and connected to a silicone catheter (Port-a-Cath), was implanted in the subcutaneous tissue of 36 patients, most of whom no longer had accessible peripheral veins and needed to continue chemotherapy or undergo total parenteral nutrition. The access vessel was mostly the subclavian vein and the capsule was sutured to the pectoral fascia. Total subcutaneous implantation seems to afford optimum safety from infection and freedom for personal hygiene, produced no noteworthy complications and proved relatively simple to maintain.

A rare case of polyostotic fibrous dysplasia assessed by bone scintigraphy with Tc-99m methylene diphosphonate (MDP).

A 66-year-old man affected by polyostotic form of fibrous dysplasia in consequence of worsening of lower extremity bone pain aggravated by walking and concomitant increase of serum alkaline phosphatase and osteocalcin, was subjected first to a radionuclide study. Bone scan demonstrated a pathological uptake of the radiotracer in the craniofacial bones, right scapula, left and right posterior ribs, right hemipelvis and lower extremities confirming the diagnosis but establishing especially the extent of bone involvement, greater than expected on the basis of symptoms and X-ray findings, underlying the importance of nuclear medicine imaging in the assessment and follow-up of this rare disease.

Post-stress end-systolic left ventricular dilation: a marker of endocardial post-ischemic stunning.

Several studies have shown the accuracy of gated single photon emission computed tomography (SPECT) using thallium-201 and technetium tracers in the assessment of myocardial perfusion and function. Gated SPECT has been successfully utilized to detect post-stress left ventricular ejection fraction (LVEF) reduction resulting from post-ischemic stunning in patients with coronary obstruction. The aim of this study was to evaluate whether the post-stress LVEF impairment could be related to the post-stress end-systolic ventricular dilation resulting from post-ischemic endocardial stunning. Two hundred and eighty-two consecutive patients were studied by conventional diagnostic 2 day stress/rest gated SPECT following injection of 925 MBq of 99mTc-tetrofosmin using a dual-headed SPECT camera. One hundred and forty-seven of these patients (52%) showed reversible perfusion defects, 69 (24%) permanent defects and the remaining 66 (24%) had normal perfusion. One hundred and thirty-eight of these patients had a history of myocardial infarction (MI) and 19% underwent coronary angiography without an intervening cardiac event. Perfusion was analysed on ungated images using 20 segments scored on a five-point scale (0, normal; 4, no uptake), while wall thickening (WT) was assessed visually on stress/rest end-systolic images using a four-point score (0, normal; 3, absence of WT). LVEF and volumes were calculated using an automatic algorithm. The post-stress and rest ratios were determined for both end-diastolic (EDV) and end-systolic (ESV) volume. Normal values for all these parameters were obtained using data from 149 patients with a low likelihood (<5%) of coronary artery disease (CAD). In 50 of the 147 (34%) of patients with reversible perfusion defects, post-stress LVEF was >5% lower than rest values (stunned group), while the remaining 97 patients did not show a significant LVEF change (group 2A). The percentage of patients who developed exercise-induced angina, the percentage of patients who underwent coronary angiography and the segmental summed perfusion and WT scores were significantly higher in the stunned group compared with group 2A. Only ESV increased significantly post-stress, and this increase occurred only in stunned patients. Both EDV and ESV ratios were significantly higher in the stunned group compared with normal controls (P=0.008 and P<0.000001, respectively) and with the subgroup 2A (P=0.011 and P<10(-12), respectively). The ESV stress/rest ratio correlated significantly with the summed WT difference score by univariate analysis in stunned patients. It can be concluded that the post-stress ESV dilation, obtained by stress/rest gated SPECT, seems to be due to endocardial post-ischemic stunning. The stunned patients showed more severe clinical, angiographic, perfusion and function parameters.

Effects of infusion of glucose-insulin-potassium on myocardial function after a recent myocardial infarction.

UNLABELLED: We studied the effects of glucose, insulin, and KCl infusion (GIK), on regional myocardial perfusion and function by 99m-Tc-tetrofosmin-gated SPECT. METHODS: We studied 21 male patients with their first uncomplicated acute myocardial infarction (AMI). All patients underwent a rest and submaximal stress before and after 24-hour infusion of GIK-solution (group A) or saline solution (group B). RESULTS: Group A showed better stress tolerance and ischaemic threshold improvement after GIK infusion whilst no statistical differences were found between basal and post-infusion test in group B. At first the stress test in group A, of the 192 segments analysed, 52 (27%) showed reversible perfusion defect. In group B, of 144 segments analysed, 31 (21%) showed reversible perfusion defect. A post-infusion analysis in group A showed a post-GIK end-diastolic significant count improvement in 21 segments, and a post-GIK end-systolic count improvement in 22 segments. In group B, perfusion increase was observed only in 4 segments, whilst systolic thickening increase was observed only in 1 segment. CONCLUSION: These data demonstrate the efficacy of GIK infusion to improve regional myocardial perfusion and function mainly in segments adjacent to the recently infarcted area.

Labelled leukocytes for diagnosis of infectious diseases. Our experience in labelling and clinical usefulness.

BACKGROUND: To review our experience in infectious diseases diagnosis, using a simple labelling technique. METHODS: We made 101 scans in 91 patients with suspected infectious diseases confirmed by clinical, histologic or cultural specimens; a clinical or instrumental follow-up was available for every patient. Patients were divided into four subgroups: A: Inflammatory Bowel Diseases; B: Septic Syndromes; C: Bone diseases; D: Others. We used 99mTc-HMPAO in 80 scans and 111In in 21. In 20/80 frozen and stored HMPAO was used. RESULTS: 99mTc-HMPAO frozen and stored labelling yield was: 60%(SD15%), 99mTcHMPAO: 62(12)(p n.s.), 111In 75%(10%), (p < 0.05). Frozen-stored HMPAO was sterile and apyrogen. 27 had positive scan without leukocytosis or neutrophilia. No correlation between leukocytosis or neutrophilia and yield was observed. Transit lung times ranged between 14-16 min without differences among three radiopharmaceuticals. In each Group and in the sample as a whole True Positive, False Positive, True Negative, False Negative, Sensitivity, Specificity and Accuracy, were calculated. In Group B and in the sample as a whole Predictive Positive Value and Negative Predictive Value were also evaluated. CONCLUSIONS: Labelling yields and "viability" were good using the three radiopharmaceuticals; labelling procedure was simple and safe. Accuracy PPV, NPV, cost-effectiveness were good; 111In is the choice for diagnosis of bone and joint infections. Frozen-stored HMPAO should be introduced as a cost-saving labelling procedure in practice.

Apparently dominant transmission of a recessive disease: deficiency of factor VII in Iranian Jews.

In inherited disorders transmitted as autosomal recessive traits the children of affected individuals are usually asymptomatic and phenotypically normal because they are heterozygous for the defect. In an Iranian Jewish family with moderately severe deficiency of coagulation factor VII (an autosomal recessive bleeding disorder) the son of an affected woman was also affected. DNA analysis of the factor VII gene showed that this unusual situation was due to the fact that he inherited an abnormal allele with the Ala244Val missense mutation from both the homozygous mother and the heterozygous father. The parents, although not overtly consanguineous, belong to the same ethnic group of Iranian Jews, among whom this factor VII gene mutation reaches high frequencies (between 2 and 3%) in the heterozygous state.

[Detection and assessment of myocardial stunning with perfusion tomographic scintigraphy using gated SPECT]. / Rivelazione e valutazione di stordimento miocardico mediante tomoscintigrafia di perfusione con metodica gated-SPECT.

BACKGROUND: Gated-SPECT using 99mTc-labeled flow tracers provides the simultaneous assessment of global and regional myocardial perfusion and function. The aim of this study was to identify patients with stress-induced postischemic stunning, among those with reversible stress perfusion defects, and patients with artifactual defects among those with fixed defects, in order to assess the value of the functional data provided by gated acquisition of perfusion imaging in the characterization of ischemia. METHODS: We studied 221 consecutive patients who underwent conventional diagnostic dual day stress/rest gated-SPECT following injection of 925 MBq of 99mTc-tetrofosmin using a dual head SPECT camera, 115 of whom (52%) showed reversible perfusion defects, and 66 (30%) fixed defects. Perfusion was analyzed on ungated images using 20 segments scored on a 5-point scale (0 = normal, 4 = no uptake), while wall thickening was assessed visually on stress/rest end-systolic images using a 4-point score (0 = normal, 3 = absence of wall thickening). Left ventricular ejection fraction and volumes were calculated using an automatic algorithm (quantitative gated-SPECT). Fifty-two out of 221 (23.5%) patients underwent coronary angiography. RESULTS: In 40/115 (35%) patients with reversible perfusion defects, post-stress left ventricular ejection fraction was > 5% lower than that at rest (Group A: stunned), whereas in the remaining 75 patients, post-stress left ventricular ejection fraction was either +/- 5% or greater than that at rest (Group B: non-stunned). Peak exercise angina and ischemic electrocardiographic response to exercise were present in 79 and 58% respectively of Group A patients and in 33 and 39% of Group B patients. The number of patients with multivessel disease was significantly higher in Group A compared to Group B (58 vs 41%, p < 0.05). The total stress and rest perfusion scores were significantly higher in Group A than in Group B (p < 0.01); even the total stress wall thickening score was significantly higher in Group A (p < 0.001). As for global parameters, post-stress end-systolic volume was significantly higher in the stunned group (p < 0.05). In 40 out of 66 (60.5%) patients without reversible ischemia fixed defects were judged to be ischemic (Group C), while in 26/66 (39.5%) they were attributed to attenuation artifacts (Group D). Eighty percent of Group C patients had a previous myocardial infarction against none of Group D. Stress/rest perfusion and wall thickening scores were significantly higher in Group C than in Group D. CONCLUSIONS: Gated-SPECT myocardial perfusion evaluation allowed us to identify a subgroup of post-stress stunned coronary artery diseased patients. The post-stress left ventricular ejection fraction reduction in this population seems to be due to the increase in end-systolic volume. The stunned patients showed more severe perfusion defects and wall thickening abnormalities.

Treatment of long bone non-unions with polytherapy: indications and clinical results.

The incidence of long bone non-unions has been estimated to range between 5 and 10%. Autologous bone graft usually harvested from the iliac crest continues to be the gold standard for biological enhancement of atrophic non-unions. However, its use has been hampered by minor and major donor site complications. Moreover despite possessing the properties of osteogenecity, osteoconductivity and some osteoinductivity the overall results of treatment have not been consistent with disappointing success rates at times. The concept of polytherapy for the treatment of non-unions, namely the simultaneous application of the three fundamental elements of the diamond concept, osteoprogenitor cells, growth factor and osteoconductive scaffold, appears to be an attractive alternative but more studies are desirable to validate this strategy.

Tibial pilon fractures: which method of treatment?

A comprehensive review of the existing literature, related to treatment options and management principles of pilon fractures was performed, and its results are presented. The identified series advocate in favour of a number of different treatment strategies and fixation methods. Decision making was mostly dependent on the severity of the local injury, the fracture pattern, the condition of the soft tissues, patient's profile and surgical expertise. External fixation and conservative treatment did not provide sufficient articular congruence in many cases. Internal fixation allowed excellent restoration of joint congruity in Rüedi type I and II fractures. A staged approach, consisting of fibular plating and temporary bridging external fixation, later substituted by an internal minimal invasive osteosynthesis or by a definitive external fixation, was favourable for Rüedi type III fractures. Closed pilon fractures with bad soft tissue conditions (Tscherne ≥ 3) or open pilon fractures are regarded as contraindication of open reduction plate fixation. Anatomic reduction of the fracture, restoration of joint's congruence, reconstruction of the posterior column, with minimal soft tissue insult, were all highlighted as of paramount importance.