SPG15 is the second most common cause of hereditary spastic paraplegia with thin corpus callosum.

OBJECTIVE: Hereditary spastic paraplegias (HSPs) are very heterogeneous inherited neurodegenerative disorders. Our group recently identified ZFYVE26 as the gene responsible for one of the clinical and genetic entities, SPG15. Our aim was to describe its clinical and mutational spectra. METHODS: We analyzed all exons of SPG15/ZFYVE26 gene by direct sequencing in a series of 60 non-SPG11 HSP subjects with associated mental or MRI abnormalities, including 30 isolated cases. The clinical data were collected through the SPATAX network. RESULTS: We identified 13 novel truncating mutations in ZFYVE26, 12 of which segregated at the homozygous or compound heterozygous states in 8 new SPG15 families while 1 was found at the heterozygous state in a single family. Two of 3 splice site mutations were validated on mRNA of 2 patients. The SPG15 phenotype in 11 affected individuals was characterized by early onset HSP, severe progression of the disease, and mental impairment dominated by cognitive decline. Thin corpus callosum and white matter hyperintensities were MRI hallmarks of the disease in this series. CONCLUSIONS: The mutations are truncating, private, and distributed along the entire coding sequence of ZFYVE26, which complicates the analysis of this gene in clinical practice. In our series of patients with hereditary spastic paraplegia-thin corpus callosum, the largest analyzed so far, SPG15 was the second most frequent form (11.5%) after SPG11. Both forms share similar clinical and imaging presentations with very few distinctions, which are, however, insufficient to infer the molecular diagnosis when faced with a single patient.

Autosomal dominant spastic paraplegia with peripheral neuropathy maps to chr12q23-24.

OBJECTIVE: Hereditary spastic paraplegias (HSP) are genetically exceedingly heterogeneous. To date, 37 genetic loci for HSP have been described (SPG1-41), among them 16 loci for autosomal dominant disease. Notwithstanding, further genetic heterogeneity is to be expected in HSP, as various HSP families do not link to any of the known HSP loci. In this study, we aimed to map the disease locus in a German family segregating autosomal dominant complicated HSP. METHODS: A genome-wide linkage analysis was performed using the GeneChip Mapping 10Kv2.0 Xba Array containing 10,204 SNP markers. Suggestive loci were further analyzed by mapping of microsatellite markers. RESULTS: One locus on chromosome 12q23-24, termed SPG36, was confirmed by high density microsatellite fine mapping with a significant LOD score of 3.2. SPG36 is flanked by markers D12S318 and D12S79. Linkage to SPG36 was excluded in >20 additional autosomal dominant HSP families. Candidate genes were selected and sequenced. No disease-causing mutations were identified in the coding regions of ATXN2, HSPB8, IFT81, Myo1H, UBE3B, and VPS29. SPG36 is complicated by a sensory and motor neuropathy; it is therefore the eighth autosomal dominant subtype of complicated HSP. CONCLUSION: We report mapping of a new locus for autosomal dominant hereditary spastic paraplegia (HSP) (SPG36) on chromosome 12q23-24 in a German family with autosomal dominant HSP complicated by peripheral neuropathy.

SPG3A is the most frequent cause of hereditary spastic paraplegia with onset before age 10 years.

Seven families with six different SPG3A mutations were identified among 106 with autosomal dominant hereditary spastic paraplegia (HSP). Two mutations were novel (T162P, C375R). SPG3A was twice as frequent as SPG4 in patients with onset before age 10 years (31.8%). Later onset was not observed. The phenotype was pure HSP, but disease duration was longer than in non-SPG3A/SPG4 patients, leading ultimately to greater handicap.

Preoperative shift from glibenclamide to insulin is cardioprotective in diabetic patients undergoing coronary artery bypass surgery.

AIM: The cardioprotective effects afforded by volatile anesthetics, i.e. isoflurane, during heart surgery may be due to preconditioning of the myocardium through the activation of KATP channels. The aims of this study were to establish whether glibenclamide prevents the isoflurane-induced cardioprotection in diabetic patients undergoing coronary surgery (CABG) and whether this cardioprotective effect can be restored by preoperative shift from glibenclamide to insulin therapy. METHODS: We enrolled 60 patients undergoing CABG. Twenty consecutive non-diabetic patients were randomized to receive conventional anesthesia (CA) or conventional anesthesia plus isoflurane (ISO) (added to the inspired oxygen before starting cardiopulmonary bypass); 40 consecutive diabetic patients in chronic treatment with oral glibenclamide were randomized to conventional anesthesia (G-CA), conventional anesthesia plus isoflurane (G-ISO), conventional anesthesia after shifting to insulin (I-CA) or conventional anesthesia plus isoflurane after shifting to insulin (I-ISO). Serum levels of cardiac troponin I (CTnI) and CK-MB, as markers of ischemic injury, were obtained 1, 24, 48 and 96 hours, postoperatively. RESULTS: Postoperative peak levels of CTnI and CK-MB were lower in ISO than in CA (0.5+/-0.3 vs 2.8+/-2.2 ng/ml, p<0.05 and 61+/-27 vs 79+/-28 U/L, p<0.05, respectively), as well as in I-CA and I-ISO than G-CA and G-ISO groups (0.5+/-0.7 and 0.7+/-0.9 vs 3.5+/-3 and 2.7+/-2.5 ng/ml, p<0.05; 47+/-7 and 41+/-5 vs 85+/-28 and 50+/-23 U/L, p<0.05, respectively). No significant differences were detected in postoperative hemodynamic variables or in-hospital outcome. CONCLUSION: This prospective randomized study shows a cardioprotective effect of preoperative administration of isoflurane during CABG. Such an effect is prevented by glibenclamide, but can be restored in diabetic patients by preoperative shift from glibenclamide to insulin.

Early diagnosis of acute mesenteric ischemia after cardiopulmonary bypass.

BACKGROUND: The aim of this study is to identify significant risk factors and eventual clinical markers associated with acute mesenteric ischemia (AMI) after cardiopulmonary bypass. METHODS: The study was retrospectively performed on a group of 19 patients (group A) undergoing cardiac surgery between January 1991 and December 1999, who developed AMI within 30 days of their hospitalization. A control group of 48 patients (group B) was compared in order to define preoperative and operative risk factors for AMI. RESULTS: At the abdominal operation, a non-occlusive mesenteric ischemia was found in every case. In-hospital mortality was 84.2% (16/19). Compared to the control, there was a significant difference in aortic cross-clamp time (p<0.001) and use of inotropic drugs (p<0.01). Postoperatively, the studied group (group A) had a significantly higher mean value of the enzymatic serum levels at any time. CONCLUSIONS: A high index of suspicion for mesenteric ischemia after cardiopulmonary bypass should be considered in patients with conditions of hypoperfusion. The early laboratory signs of AMI might be searched during the first postoperative hours.

Troponin I release after CABG surgery using two different strategies of myocardial protection and systemic perfusion.

BACKGROUND: Controversies still exist over the optimal temperature for blood cardioplegia and systemic perfusion. This study investigates the effect of temperature of blood cardioplegia and systemic perfusion on the release of troponin I and other biochemical markers. METHODS: One hundred and fifty-four consecutive patients were randomly assigned to one of two cardioplegic and systemic perfusion strategies of cold blood cardioplegia with moderate systemic hypothermia (27 degrees C) or tepid blood cardioplegia with mild systemic hypothermia (33 degrees C). Cardiac troponin I and other biochemical markers were measured at baseline, at the end of surgery, at 12 hours and daily thereafter. A two-way ANCOVA for repeated measure was performed to test the effect of cardioplegia on enzyme release independently of variables that were different between the two groups. RESULTS: The time course of dismission of troponin I, creatine kinase MB, and lactate dehydrogenase were significantly lower with tepid blood cardioplegia and mild systemic perfusion independently of the number of distal anastomoses, CPB time, cross clamp time or total volume of cardioplegia. There were no differences between the two groups in the release of total creatine kinase, aspartate transaminase and alanine transferase. CONCLUSIONS: Both strategies of myocardial protection and systemic perfusion guarantee subclinical minor myocardial damage. The strategy of tepid whole blood cardioplegia and mild systemic hypothermia seems to preserve myocardium better than whole blood cold cardioplegia.

[Aortocoronary bypass in severe left ventricular dysfunction: 9 years of clinical experience and mid-term results]. / Il bypass aortocoronarico nella disfunzione ventricolare sinistra severea: nove anni di esperienza clinica e risultati a medio termine.

BACKGROUND: Compared with medical therapy alone, coronary artery bypass surgery improves survival in patients with coronary disease and left ventricular dysfunction. Many of these patients have a hibernating myocardium secondary to chronic ischemia with the potential for improvement in left ventricular function and heart failure symptoms following revascularization therapy. Cardiac transplantation remains the treatment of choice for patients with severe congestive heart failure. METHODS: From January 1992 to June 2000, 351 consecutive patients (318 men, 33 women, mean age 62.8 +/- 8.9 years) with a left ventricular ejection fraction (EF) < or = 35% and with multivessel coronary artery disease underwent isolated coronary artery bypass grafting. Preoperatively 226 patients were in CCS class III-IV and 113 in NYHA class III-IV. The mean number of grafts was 3.4 +/- 0.8/patient and complete revascularization was achieved in 98.6% of cases. The internal mammary artery was used in 341 patients (97.2%) and in 328 (96%) as a graft for the left anterior descending artery. Follow-up was obtained in 97% of the patients and on average lasted 42 +/- 28 months. RESULTS: The hospital mortality was 5.9%. At multivariate analysis urgent operation (p < 0.01) and a lower EF (25.9% in deaths vs 29.1%, p < 0.05) were predictors of an increased operative mortality. EF (assessed postoperatively at transthoracic echocardiography in survivors) improved from 28.9 +/- 5.7 to 34.4 +/- 7.7% (p < 0.0001). At 1, 3, 5, 7, and 9 years respectively, the all-cause survival was 93 +/- 1.5, 85 +/- 2.2, 77 +/- 3.1, 69 +/- 4.9, and 60 +/- 7.3% and the freedom from cardiac death was 94 +/- 1.4, 89 +/- 1.9, 88 +/- 2, 80 +/- 4.7, and 76 +/- 5.7% with an improvement in the anginal and congestive heart failure status (p < 0.0001). CONCLUSIONS: In patients with coronary artery disease and severe left ventricular dysfunction, after evaluation of the clinical presentation, of the usefulness of vessels as grafts and of the presence of myocardial viability, 1) coronary artery bypass grafting can be performed with a low mortality and a good mid-term survival, 2) improvement in left ventricular function can be documented after coronary bypass surgery, 3) the internal mammary artery can be safely used as a graft, 4) the quality of life is improved as demonstrated by the improvement in the anginal and congestive heart failure status.

[Isolated aortic valve replacement with CarboMedics mechanical prosthesis: 9-year clinical experience and mid-term results]. / Sostituzione valvolare aortica isolata con protesi meccanica carbomedics: nove anni di esperienza clinica e risultati a medio termine.

BACKGROUND: Appraisal of the medium-term results of isolated aortic valve replacement with a CarboMedics mechanical prosthesis. METHODS: We assessed the clinical data of 195 consecutive patients (mean age 59.7+/-10.9 years) operated on between January 1992 and June 2000. Valve disease consisted of aortic stenosis regurgitation in 94 patients (48.2%), isolated aortic failure in 57 (29.2%) and isolated stenosis in 44 (22.6%). One hundred and four patients were in NYHA functional class III and 25 in NYHA functional class IV Follow-up was by telephone interview to 100% of the patients (average follow-up 39+/-20 months). RESULTS: The operative mortality was 3.6% (5% in the period January 1992-December 1995, 1.3% in the period January 1996-June 2000). Sixteen deaths occurred in the long term. Thus, the actuarial survivals at 36 and 72 months were 92+/-7% and 82+/-16% respectively. In the group of survivors, 139 patients (81%) were in NYHA class 1,26 (15%) in NYHA class II, and 7 (4%) in NYHA class III. The freedom from embolic events was 96+/-3.7% and that from hemorrhagic events was 90+/-9.4%. All the events occurred during the first 36 months; none of the patients developed infections or periprosthetic leaks. CONCLUSIONS: At the medium term, the CarboMedics mechanical valve prosthesis appears to be reliable, with an actuarial survival, quality of life and incidence of morbidity comparable to those reported for other types of second-generation mechanical prostheses.

[Atrial septal aneurysm with cerebral ischemia: potential pathogenetic role of associated cerebral vascular malformation]. / Aneurisma del setto interatriale ed eventi ischemici cerebrali: il possibile ruolo patogenetico di una malformazione vascolare cerebrale associata.

Atrial septal aneurysm can be associated with other cardiovascular diseases such as atrial septal defect, patent ductus arteriosus, pulmonary hypertension and cerebrovascular events (transient ischemic attack or stroke). The introduction of transthoracic and more recently transesophageal echocardiography allowed for a more frequent observation of this pathology and also suggested that atrial septal aneurysm is a risk factor for cerebral ischemia. However, the pathophysiological pathway is still unclear. In January 1997 a 33-year-old man was admitted to our hospital because of atrial septal aneurysm and a previous cerebrovascular event. Magnetic resonance imaging revealed a cerebrovascular malformation and transesophageal echocardiography confirmed the presence of atrial septal aneurysm. We hypothesize that a common etiopathogenetic pathway may cause both the cardiac and cerebrovascular anomaly and that the latter may be responsible alone for cerebral ischemic events; thus in the presence of an atrial septal aneurysm associated with a cerebrovascular malformation, a conservative medical approach may be the treatment of choice.

[Bentall-DeBono intervention: 8 years of clinical experience]. / Intervento di Bentall-DeBono: otto anni di esperienza clinica.

BACKGROUND: Annulo-aortic ectasia is a dilation of the aortic root with the involvement of the Valsalva sinuses. In 1968 Bentall and DeBono proposed to replace the aortic valve, the Valsalva sinuses and the ascending aorta with a composite tube graft containing aortic valve prosthesis. Consequently coronary ostia had to be reimplanted on the prosthetic tube. Recently the use of new materials has resulted in a more acceptable operative risk, and postoperative bleeding and late mortality have been reduced. METHODS: From January 1991 to December 1998, 44 out of 241 patients were operated on with the Bentall-DeBono procedure, affected by dissecting or expansive aneurysm of the ascending aorta. Of the 44 patients (35 males, 9 females, mean age 53.7 years), 3 presented with acute aortic dissection, 5 were asymptomatic, 10 were in NYHA functional class II, 14 in class III, 9 in class IV, and 2 in CCS class 4; 1 patient had dysphonia; 37 patients presented with isolated aortic regurgitation, and 7 associated aortic valvular stenosis. The diagnosis of acute dissection was made by transesophageal echocardiography and that of expansive aneurysm by thorax helical computed tomographic scanning and/or magnetic resonance imaging and cardiac catheterization. Follow-up was obtained in 100% of the patients for an average of 23 +/- 20.9 months (range 4-79 months). RESULTS: Four patients (9%) died; in 4 patients (9%) postoperative bleeding needed reoperation, in 5 (11.4%) a permanent pacemaker for atrioventricular block was implanted, and 1 patient (2.3%) had transient hemiparesis. At univariate analysis predictive factors for operative risk were NYHA functional class IV (p < 0.005) and atherosclerotic etiology (p < 0.05). At follow-up 7 late deaths occurred for an actuarial survival at 24 months of 75 +/- 9%. Causes were sudden death in 3 patients, cardiac failure in 3 and stroke in 1 patient; 31 surviving patients (94%) were in NYHA functional class I and 2 patients in class II (6%). CONCLUSIONS: The Bentall-DeBono procedure involves moderate risk with good results; clinical presentation and associated valvular pathology influence early and mid-term results.

Beneficial impact of isoflurane during coronary bypass surgery on troponin I release.

BACKGROUND: Experimental studies indicate that isoflurane, a commonly used volatile anesthetic, mimics the cardioprotective effects of ischemic preconditioning, probably through ATP-sensitive K+ (KATP) channel activation. The aim of this study was to evaluate the impact of isoflurane during coronary bypass surgery (CABG) on troponin I release. MATERIAL AND METHODS: Forty consecutive patients with chronic stable angina and multivessel disease undergoing isolated CABG were randomized to a control (16 men and 4 women, aged 51 to 73 years, mean 62) or isoflurane (15 men and 5 women, aged 51 to 77 years, mean 65) group before aortic cross-clamping and cardioplegia. Serum levels of troponin I and creatine kinase (CK)-MB, as markers of ischemic injury, were obtained at 24 hours after CABG. Regional wall motion score and left ventricular ejection fraction (LVEF) at transthoracic echocardiography were assessed 5 days postoperatively. Comparisons between groups were performed in the entire population and, subsequently, in those patients with preoperative LVEF < 50%. RESULTS: There were no significant differences between isoflurane-treated patients and controls in cross-clamp time (49 +/- 14 vs 51 +/- 13 min, p = ns), peak values of troponin I (0.9 +/- 0.7 vs 1.4 +/- 1.3 ng/ml, p = ns) and CK-MB (62 +/- 27 vs 64 +/- 27 U/l, p = ns), or postoperative echocardiographic score (26 +/- 7 vs 22 +/- 5, p = ns) and LVEF (53 +/- 10 vs 55 +/- 7%, p = ns). When the comparisons were restricted to those patients with preoperative LVEF < 50%, at 24 hours the isoflurane-treated patients exhibited a smaller release of troponin I and of CK-MB than controls (1.1 +/- 0.7 vs 2.3 +/- 1.3 ng/ml, p = 0.03, and 39 +/- 10 vs 57 +/- 22 U/l, p = 0.04, respectively). CONCLUSIONS: Isoflurane reduces myocardial injury in patients with impaired left ventricular function undergoing CABG; thus, it can be safely used as an additional cardioprotective tool during routine CABG in high-risk patients with poor left ventricular function.

Mid-term results of conventional bypass surgery for complex proximal left anterior descending coronary artery stenoses.

BACKGROUND: The significant involvement of proximal left anterior descending (LAD) coronary artery affects patient prognosis and must be treated. Recently, as alternative methods to conventional coronary bypass (CABG), minimally invasive direct coronary artery bypass grafting (MIDCAB) and percutaneous transluminal coronary angioplasty with stent implantation (PTCA/S) have been proposed to reduce costs and patient discomfort. The aim of this study was to obtain early and medium-term results of CABG in patients with complex LAD disease in whom the expected results with PTCA/S or MIDCAB would have been suboptimal. METHODS: We retrospectively examined one hundred consecutive patients subjected to isolated CABG who received either a single graft to LAD or several grafts to LAD and diagonal branches. The choice of CABG was due to poor expectable results with PTCA/S or MIDCAB because of anatomical characteristics of the lesion, inclusion in ongoing randomized study comparing surgical versus non-surgical revascularization, or preference on the part of the cardiologist or patient. RESULTS: Left internal mammary artery (LIMA) was grafted to LAD in 99 (99%) patients; 65 (65%) patients received at least one saphenous graft to the diagonal branches. No death was observed within 30 days from the operation. One (1%) patient had a perioperative non-Q myocardial infarction (MI). At a mean follow-up time of 38 +/- 16 months (range 2-60), there were no cardiac deaths and no new MI. Six patients complained of recurrent angina: in all cases but one (vein graft failure to a diagonal branch), there were no clinical or diagnostic signs suggesting other graft failures. The probability of freedom from early and late events, including cardiac death, MI and recurrence of angina regardless of site, was 99% at 1 year and 86% at 5 years. CONCLUSIONS: At present, conventional CABG seems to be the "gold standard palliation" of LAD disease in most cases. It can be performed safely with excellent early and medium-term results in terms of freedom from cardiac events. Its comparison with percutaneous transluminal techniques and MIDCAB needs to be addressed in further prospective studies.

[LagoZ and LagZ, 2 genes depleted of CpG dinucleotides, derived from the LacZ gene for the study of epigenetic control]. / LagoZ et LagZ, deux gènes appauvris en dinucléotides CpG dérivés du gène LacZ pour l'étude des contrôles épigénétiques.

The methylation of 5'CpG 3' dinucleotides within genes creates potential targets for protein complexes that bind to methylated DNA sequences and to histone deacetylases (MBD-HDAC). This can lead to transcriptional repression by modification of chromatic. To test the importance of this repression in vivo and to determine when during development these epigenetic controls are placed on genes, two novel genes have been engineered by directed mutagenesis of the CpG-rich LacZ gene that are depleted of (LagZ) or completely lacking (LagoZ) CpG sequences. We report that the expression (transcriptional and translational) of the three genes is indistinguishable in transient assays in cleaving mouse embryos. Therefore, the complete absence of CpG sequences within three kilobases of coding sequence is compatible with its maintenance in the nucleus and with its expression. These molecules can now be used to study the ontogenesis of the CpG-dependent repressive system in intact organisms.

Initiation, establishment and maintenance of Hox gene expression patterns in the mouse.

Spatially and temporally restricted expression of the Hox genes along the main and appendicular axes is essential for correct patterning of vertebrate embryos. In this overview we discuss the latest data that shed light on the mechanisms underlying the generation of the expression domains of the Hox genes. The molecular genetic interactions governing initial transcription of the Hox genes in the posterior part of the primitive streak during mouse and chick gastrulation remain enigmatic. But the recent discovery by Kondo and Duboule (Cell, 97, 1999, 407-417) of a "cluster repressive regulation", will undoubtedly lead to a better understanding of the molecular genetic mechanism underlying colinear and sequential initiation of Hox gene transcription. Recently progress has been booked in characterizing the basal processes driving progression of the Hox expression domains during their establishment. Hox expression is still labile while being established. The transcriptional state of Hox genes in anterior tissues can be reprogrammed under the influence of more posterior locations. Posteriorizing activity may involve RA and FGF signaling. It is only when these interactions and, in some cases at least, regulatory interactions with Hox and cdx gene products occur appropriately, that the Hox expression domains would be correctly established. After the Hox expression domains have been established, regulatory processes involving the products of Polycomb and trithorax- Group genes start operating, perpetuating the transcriptional state of the Hox genes within and outside the expression domains. Whether control at the level of chromatin structure, believed to operate during the late maintenance phase of Hox gene expression, is also involved in regulating concerted initial expression of these genes, is a possibility that has been suggested.

Relief of a repressed gene expression state in the mouse 1-cell embryo requires DNA replication.

In the mouse, transcriptional permissiveness is established in the fertilized egg prior to the activation of zygotic genes at the 2-cell stage. Therefore, gene inactivity initiated at the end of gametogenesis results from a complex process, involving more than an inhibition of the basal transcriptional apparatus. We have examined the ability of the first intron (I1) of the human hypoxanthine phosphoribosyl transferase gene, which functions as an enhancer in embryonic stem cells, to activate a reporter gene when placed proximally to or at a distance from the HSV-tk promoter, or when integrated into the mouse genome as part of a stable transgene. In microinjected embryos, I1 functions as an enhancer sequence; however, its competence for long-range activation appears only after the late 1-cell stage and depends on the first DNA replication. Moreover, activation of microinjected transgenes from proximal enhancers occurs in the late 2-cell embryo and in the male pronucleus of 1-cell embryos blocked for DNA replication; whereas, for integrated transgenes, proximal enhancer activity is subject to position effects in the 2-cell embryo and first occurs at the 2- or 4-cell stage, but only after completion of DNA replication. Therefore, the absence of long-range activation and a non-permissive genomic state (the relief of which both depend on DNA replication), together with an inactive transcriptional apparatus, appear to converge to prevent any gene activity in the 1-cell embryo. We propose that the embryo exploits the process of DNA replication to relieve the transcriptionally repressive state that was initially established to fulfil two purposes: (1) to arrest maternal gene expression in the maturing oocyte and (2) to protect the unicellular egg and 1-cell embryo from premature differentiation. Reactivation of gene expression by DNA replication would therefore serve to coordinate cell proliferation and differentiation in the preimplantation embryo.

[Bullous pneumopathy and spontaneous pneumothorax. Atypical radiologic patterns of Pneumocystis carinii pneumonia]. / Pneumopatia bollosa e pneumotorace spontaneo. Quadri radiologici atipici della polmonite da Pneumocystis carinii.

Pneumocystis carinii pneumonia (PCP) is certainly the most frequent opportunistic pulmonary infection in AIDS patients. Besides the conventional radiographic features demonstrating bilateral infiltrates and airspace consolidation, atypical radiologic patterns are reported in the literature, which are characterized by spontaneous pneumothorax and by the presence of bullae, cysts and areas of pulmonary cavitation. Forty consecutive PCP patients were investigated, ten of them presenting with atypical radiographic findings: 1 case of spontaneous pneumothorax with no evidence of bullae and 9 cases of bullous lung disease--5 of them complicated by spontaneous pneumothorax. Several pathogenetic hypotheses were considered; lesions evolution and the differential radiologic diagnosis were discussed. As for diagnosis, the value of chest CT scans is emphasized, together with that of HRCT which is extremely valuable to localize, characterize and evaluate bullous lesions and associated parenchymal signs.

[Computerized tomography in the study of tuberculosis]. / La tomografia computerizzata nello studio della tubercolosi.

Twenty-five HIV-negative patients with proven tuberculosis were studied; 10 of them had had bacteriologic confirmation, 1 tuberculin conversion, 2 biopsy confirmation and in 12 cases ex juvantibus criteria had been followed. All patients underwent X-ray and CT exams of the chest which were useful for diagnosis, prognosis and treatment in 22/25 patients. CT yielded better results than conventional radiography in the following cases: miliary cases (1 CT-positive case vs no positives at conventional X-rays), cavities (12 CT-positive cases vs 6 at conventional X-rays), bronchogenic spread (10 CT-positive cases vs 7 at conventional X-ray), nodules (4 CT-positive cases vs 2 at conventional X-rays), consolidations (5 CT-positive cases vs 1 at conventional X-rays), adenopathies (10 CT-positive cases vs 7 at conventional X-ray), extrapulmonary lesions (3 CT-positive cases vs no case at conventional X-ray). In 13 patients with negative sputum CT helped the diagnosis to be made. Chest radiography is currently the major exam for the first approach to tuberculosis. Nonetheless, CT yields valuable information when clinical signs or bacteriologic information are poor.

A regulatory function for K10 in the establishment of dorsoventral polarity in the Drosophila egg and embryo.

Several lines of evidence suggest that the origin of pattern formation of Drosophila embryos must be traced back to oogenesis, to the polarity of the egg chamber. A few early-acting genes, K10, top, grk and cni, have been identified which are assumed to function in a signal transduction process between the germline oocyte and the somatic follicle cells, during which the egg chamber acquires a dorsoventral polarity. K10 has been cloned and was shown to encode a putative transcription factor specifically acting in the oocyte nucleus. In order to characterize further the function of K10, we have analyzed its genetic interactions with grk, top and cni. We show that grk behaves as a dominant partial suppressor of K10. Analysis of the rescuing process of the K10 phenotype by grk shows that: (1) K10 is not indispensable for the establishment of dorsoventral polarity of the egg chamber, since its lack of function can be compensated for by reducing the grk wild-type copy number; (2) grk function is highly dose-sensitive; (3) the rescue process shows an anteroposterior effect suggesting that K10 may also interact with genes involved in anteroposterior pattern formation. These results are compatible with a model in which grk is a dorsalizing signal emanating from the oocyte nucleus, whose level of expression is regulated negatively by the K10 product.