Short-term changes in drug agglomeration within interactive mixtures following blending.

The objective was to investigate the nature and extent of short-term dynamic changes to dissolution within specific interactive mixtures following blending. Two micronized drugs, nitrazepam and flunitrazepam, were formulated into lactose-based interactive mixtures containing a micronized surfactant. The dissolution rate of the drugs decreased significantly over a period of days after preparation. The dissolution was modelled using a multi-exponential equation, allowing estimation of agglomeration and dissolution rate. From this model, decreasing dissolution rates were consistent with increasing agglomeration. Particle-sizing studies provided evidence of an increase in drug agglomerates over the same timescale. This is the first study to report short-term dissolution changes immediately following secondary processing. Several hypotheses are proposed for increases in agglomeration, which potentially relate to changes in surface charge, particle rearrangements, recrystallisation at surfaces and the role of moisture, although the role of mechanical processing on agglomerate behaviour remains poorly understood. The observations from this study may have wider implications, for dissolution and for other powder-based drug delivery systems which include interactive mixtures with fine powders. This study emphasizes the need for improved understanding if we are to implement a "Quality by Design" ethos to improve control and risk management over the performance and stability of these systems.

Percutaneous CT-guided fine-needle aspiration of pulmonary lesions: Results and complications in 409 patients.

The purpose of this study was to report our centre's experience in the results and complications of percutaneous CT-guided lung biopsy. A retrospective review of 409 patients who underwent percutaneous CT-guided fine-needle aspiration of suspicious lung lesions for more than 5 years was carried out. Nodule sizes ranged from 0.6 to 10 cm. The calibre of the needle used was 21-23 G. Specimen adequacy and patient outcome were evaluated. Each case was reviewed for complications. Sufficient diagnostic material was obtained in 369 (90%) of the 409 fine-needle aspirations. Diagnosis was malignancy in 290 (70%) samples, four (1%) samples were suspicious for malignancy, 65 (16%) samples were negative for malignancy and definite benign findings were identified in 10 (3%) specimens. There were 25 false-negative cases and one false-positive case. Sensitivity was 92% and specificity 98%. Pneumothorax was the most common complication and occurred in 17 (4%) patients. Only one of them required thoracic drainage. Blood effusion around the lesion or along the needle track was detected on the post-biopsy CT in 8 (2%) patients. However, only one of them suffered from a mild haemoptysis. Percutaneous CT-guided biopsy is an effective and fast procedure for diagnosis of suspected pulmonary malignancy, with a low complication rate.

Radiofrequency ablation of intra-articular osteoid osteoma of the hip.

Diagnosis and treatment of intra-articular osteoid osteoma is challenging. We present 16 patients with intra-articular osteoid osteomas of the hip treated with percutaneous radiofrequency ablation. Eight osteoid osteomas were located in the femoral head, six in the femoral neck, and two in the acetabulum. Three of the 16 patients had had an incorrect previous diagnosis. Percutaneous radiofrequency ablation was a clinical and technical success in all 16 patients. Within the first 24 h after the procedure, pain improved in all patients. Five patients had pain relief within the first 3 days after the procedure, nine patients within the first week and two patients within 2 weeks. Residual or recurrent symptoms were not reported by the last follow-up. At the 12-month follow-up, computed tomography and magnetic resonance imaging showed complete ossification and bone regeneration at the site of the lesion in three patients, partial ossification in six patients and no changes in seven patients. Computed tomography-guided percutaneous radiofrequency ablation is a simple, minimally invasive, safe and effective method for the treatment of most intra-articular osteoid osteomas.

Biexponential T2 relaxation time analysis of the brain: correlation with magnetization transfer ratio.

RATIONALE AND OBJECTIVES: To measure T2 relaxation times of normal white and gray matter using a novel CPMG sequence and investigate if any correlation exists between magnetization transfer ratio (MTR) and T2 relaxation-related parameters. MATERIALS AND METHODS: Seventeen normal volunteers participated on this study. A single-slice 32-echo sequence was used to calculate the T2 relaxation time of frontal and occipital white matter and cortical gray matter. T2 relaxation analysis included monoexponential and biexponential fitting whereas an F test was used to determine if biexponential fitting was statistically more accurate than monoexponential fitting. Short and long T2 constants were calculated as well as the signal fractions of each pool. MTR calculations were based on a three-dimensional gradient echo (3D FFE) proton density weighted sequence with and without an on-resonance composite prepulse. MTR and T2 relaxation times were calculated and linear regression analysis was applied. RESULTS: Biexponential fitting was more accurate comparing with monoexponential fitting in all WM and GM regions (F > 2.47, P < 0.01). Mean values of short T2 constant for frontal white matter (fWM), occipital white matter (oWM) and gray matter (GM) were 8.10, 9.36, and 22.23 milliseconds, respectively, whereas the mean values of long T2 constant were 85.1, 93.02, and 118.72 milliseconds, respectively. Mean restricted water percentages (RWP)-corresponding to the signal fraction of the protons with short T2-for the fWM, oWM, and GM were 22.01%, 23.36%, and 18.7%. Mean free water percentages (FWP)-corresponding to the signal fraction of the protons with long T2-for the fWM, oWM and GM were 77.99%, 76.64%, and 81.3%. Mean MTR values for fWM, oWM and GM were 68.4%, 68.2%, and 61.3%, respectively. No significant correlation was found in fWM and oWM between MTR and RWP, short and long T2 components while a moderate correlation existed in GM between MTR and RWP (r = 0.57; P = 0.02), MTR and short T2 component (r = -0.69; P = 0.004) and MTR and long T2 component (r = -0.62; P = 0.012). CONCLUSIONS: Two proton pools with different T2 decay characteristics can be separated in normal gray and white matter when using a multiecho sequence with short echo spacing. MTR and T2 relaxation times were significantly correlated in gray matter and the combination of both types of measurements may be helpful in studying myelin related disorders.

Perforation of the alimentary tract: evaluation with computed tomography.

BACKGROUND: To assess the value of computed tomography (CT) in the diagnosis of perforation of the alimentary tract (AT). METHODS: During a 4-year period 76 patients with proven AT perforation underwent CT within 1 week before surgery or endoscopy. We retrospectively reviewed these CT scans to determine the signs of AT perforation. There were 41 men and 35 women (28-90 years old). Our goal was to establish the diagnosis of AT perforation and, if this was possible, to identify the site and cause of the AT wall rupture. The CT diagnosis of perforation was based on (a) direct findings of extraluminar air or gastrografin and (b) indirect findings of an abscess or an inflammatory mass surrounding an enterolith in the region of appendix or a bowel wall-related phlegmon or abscess with fluid in the mesentery or surrounding radiopaque foreign body. RESULTS: There were 65 true-positive and 11 false-negative cases. Levels of perforation were the esophagus (two), stomach (five), duodenum (12), small bowel (15), appendix (six), and colon (36). Causes were peptic ulcer (11), foreign body (five), trauma (seven), iatrogenic (nine), appendicitis (six), diverticulitis (21), Crohn disease (five), AT carcinoma (eight), and ischemia (four). Level and cause were correctly predicted in 55 and 51 instances, respectively. The sensitivity was estimated to 85.5%. CONCLUSION: CT is a valuable method in the diagnosis of AT perforation. The diagnosis can be established rapidly, without patient preparation and with a high sensitivity.

Peritoneal metastases from transitional cell carcinoma of the urinary tract: CT and MR imaging.

We present three patients with peritoneal metastases from transitional cell carcinoma of the urinary tract. CT scan in one patient showed massive ascites with subtle peritoneal thickening and infiltration of omental fat. We had the opportunity to study the other patients with both CT and MR. Both examinations showed numerous large and small peritoneal implants in the abdomen and pelvis, mostly in the greater omentum.

Infarction of the corpus callosum: computed tomography and magnetic resonance imaging.

OBJECTIVE: To describe the computed tomography (CT) and magnetic resonance (MR) features of corpus callosum (CC) infarctions. METHODS: We reviewed retrospectively 352 consecutive cranial CT and MR scans showing cerebral infarcts. Involvement of the CC was identified in 28 patients. RESULTS: Infarctions of the CC were diffuse (n = 3) or focal (n = 25). The former were seen in the setting of diffuse cerebral ischemia secondary to cardiopulmonary arrest or status epilepticus. The latter were divided into those affecting predominantly the genu, body or splenium. The most common location of the insult was the splenium (n = 13), followed by the body (n = 6) and genu (n = 3). In the remaining three patients combined genu/body infarctions were seen. CONCLUSION: Infarction of the CC may be more common than previously thought and is most often the result of cerebral embolism. MR is better suited than CT for the detection of vascular lesions of the CC.

MR cholangiopancreatography at 0.5 T with a 3D inversion recovery turbo-spin-echo sequence.

The objective of this study was to assess the diagnostic value of magnetic resonance cholangiopancreatography (MRCP) at 0.5 T. The MRCP technique was performed in 28 patients with symptomatology referrable to the biliary system. A three-dimensional (3D) inversion recovery turbo-spin-echo (TSE) sequence was used to create 3D reconstructions of the bile ducts. Dilation of the biliary tree or pancreatic duct in 23 patients due to tumor, calculi, or strictures was depicted with excellent contrast resolution. The approximate level of obstruction and all calculi were accurately predicted by MRCP. In another 3 patients no cause was found for the biliary dilatation. In the last 2 cases no abnormalities were found by either MRCP or endoscopic retrograde cholangiopancreatography (ERCP). The MRCP technique at 0.5 T is an accurate method for the assessment of pathology of the biliary tree.

Acute subarachnoid haemorrhage: detection with magnetic resonance imaging.

The purpose of this study was the evaluation of fluid attenuated turbo inversion recovery (FLAT TIRE) MR pulse sequence for detecting acute subarachnoid hemorrhage (SAH). Seven patients with SAH were studied within 6 days of ictus. Six of them underwent both CT and MRI and one MRI only. Pulse sequences included T1 spin echo (SE), PD and T2 turbo spin echo (TSE) and FLAT TIRE (TR/TI/TE = 6500/1800/140-180). All studies were performed on a 0.5 T system (Gyroscan T5, Philips Medical Systems). Simulated acute SAH was also studied with MRI. The FLAT TIRE sequence was better than the SE and TSE in all seven cases and better than CT in two cases. In two cases MRI was equivalent to CT, and in another two MRI underestimated the extent of SAH. The simulated acute SAH could be detected easily with the FLAT TIRE sequence, with difficulty on the T1 weighted images and not at all on the PD/T2 weighted images. The specific FLAT TIRE sequence used seems promising for the detection of acute SAH.

Bone marrow lesions: evaluation with fat-suppression turbo spin echo MR imaging at 0.5 T.

The purpose of this study was the assessment of the diagnostic value of fat-suppression T2-weighted images for a variety of bone marrow lesions. We performed 40 studies of the axial or appendicular skeleton in 33 patients (age range 4-80 years) with neoplastic, inflammatory or traumatic lesions with a 0.5 T system (Gyroscan T5, Philips Medical Systems, Best, The Netherlands). Fat-suppression T2-weighted images [turbo spin echo (TSE) with spectral presaturation with inversion recovery (SPIR)] were obtained in addition to the routine T1-weighted SE and T2-weighted TSE sequences. Fat-suppression TSE T2-weighted images were better than standard TSE T2-weighted images in 25 studies. In 11 of them demonstration and characterization of the lesions (known from T1-weighted images) was possible only after fat suppression. In the other 14 patients demonstration of the full extent of the lesion especially to the nearby soft tissues was possible only after fat suppression. In 13 studies no advantage was conferred by SPIR, whereas in two instances T2-weighted images were better. Fat-suppression T2-weighted images are diagnostically useful in a variety of lesions of the musculoskeletal system, but their limitations should be known.

Relaxed specificity of endoproteinase Asp-N: this enzyme cleaves at peptide bonds N-terminal to glutamate as well as aspartate and cysteic acid residues.

Asp-N, an endoproteinase specific for cleavage of protein or polypeptide bonds N-terminal to aspartate or cysteic acid residues, has been shown to possess a similar affinity for certain glutamate residues. Of 18 glutamate residues present in 2 cyanogen bromide fragments of apolipoprotein A-I, 5 residues were cleaved at rates comparable to that of cleavage at the 12 internal aspartate residues present in these polypeptides (all of which were cleaved). Cleavage of these 5 glutamate residues was obtained under standard enzyme digestion conditions, and the identities of all peptides obtained by Asp-N digestion were determined by amino acid sequencing of peaks obtained from reversed-phase high performance liquid chromatography.

[Role of three dimensional computed tomography in the decision of the therapeutic plan in craniomaxillofacial surgery]. / E chrese axonikes tomographias trion diastaseon gia ton kathorismotou therapeutikou schematos sten kraniognathoprosopike cheirourgike.

The three-dimensional computerized tomography (3D-CT) gives the possibility of recomposing the 3D features, using the data pictures of successive slices of ordinary computerized tomography. In this paper we present the 3D-CT technique, as well as representative cases of patients with fractures and residual deformities in the craniomaxillofacial area. We also discuss the way the 3D-CT helped in the therapeutic evaluation. Moreover the pictures taken with this technique are compared with other diagnostic methods used in this area. In conclusion the present paper shows the significance of the 3D-CT both in the accurate diagnosis and in the pre-operative evaluation of severe maxillofacial problems.

The marrow heterotopia in thalassemia.

The subject of marrow heterotopia has been reviewed on the basis of 15 cases suffering from thalassemia. Other cases reported in the literature were also reviewed. Using conventional radiography, scintigraphy, computerized tomography and myelography, 17% of the cases admitted into the hospital with the diagnosis of Thalassemia, were found to have macroscopic masses of marrow heterotopia. The most common site of development of these masses was the costovertebral gutter, followed by the anterior end of the ribs and the extradural space of the spinal canal. In one case, masses were located in the maxillary antra. The clinical implications, the pathogenesis of the masses and the differential diagnosis from other tumour-like entities are discussed. Three patients presented with symptoms and signs of spinal cord compression. All three patients were treated satisfactorily with small doses of radiotherapy.

Therapy of acromegaly with SMS 201-995: long-term studies.

Fourteen acromegalic patients, half of whom had been unsuccessfully treated with surgery, radiotherapy, or bromocriptine, were given the somatostatin analogue SMS 201-995 parenterally as the sole therapeutic regimen after a single administration had demonstrated suppression of serum growth hormone (GH). An impressive and sustained clinical improvement was documented in all patients, including those in whom bromocriptine had failed; most marked was the decrease in soft tissue swelling and headache and an improved performance status. GH levels decreased each time SMS 201-995 was injected but returned to basal levels within 8 h in most of the patients. With chronic therapy, 24-h mean levels were significantly suppressed, and the GH stimulability of thyrotrophin-releasing hormone and growth-hormone-releasing hormone (pl-44) was markedly reduced. Discontinuation of SMS 201-995 therapy was associated with a return of symptoms and abnormal GH dynamics. The efficacy and safety of chronically administered SMS 201-995 in active acromegaly opens new horizons for its treatment.

Detection of pericardial heart disease by computed tomography.

The findings on computed tomography (CT) in 10 cases of pericardial disease, nine of which were surgically confirmed, are presented. The 10th patient (Case 10), whose CT diagnosis was 'pericarditis', was found to have a myxosarcoma at surgery. In some of these cases, echocardiographic and conventional radiographic investigation gave inconclusive information regarding the underlying pathology. Our results support the conclusion that CT complements echocardiography: in the quantitative and qualitative assessment of pericardial effusions, in the localisation of space-occupying lesions involving the pericardium and in diagnosis of constrictive pericarditis. As echocardiography is so very much operator-dependent, CT may well be a more reliable method of obtaining a result which indicates both the diagnosis and the extent of the disease.

The use of computed tomography in the assessment of cardiac masses.

Computed tomography has been found to be a useful tool in the evaluation of cardiac masses. It can be most effacious in the detection of a lesion and in the delineation of its size and location, as well as the demonstration of its relationships to intra- and extracardiac structures. It can be especially useful in areas of the heart where echocardiography can be difficult. This is particularly true for the left atrium, where lesions such as small thrombi can be missed.

CT prognostic criteria of survival after malignant glioma surgery.

The serial pre- and postoperative computed tomographic (CT) scans of 115 patients entered in the Cooperative Brain Tumor Study between 1975 and 1982 were analyzed in order to define CT prognostic criteria and to test the hypothesis that radical glioma surgery prolongs patient survival. The CT parameters of mass size, associated edema, and intensity of enhancement were quantitated on all scans. Clinical parameters evaluated included gender, age, length of survival, and useful (Karnofsky greater than 30) survival. Data analyses indicated postoperative residual tumor burden was inversely related to length of survival (p less than 0.01). Postoperative associated edema and intensity of image enhancement were also of prognostic value and showed an inverse relation to survival. Younger patients proved more likely than older patients to attain long-term survival. Residual tumor burden of less than 45 mm diameter on postoperative CT scans was associated with 70% chance of long-term survival. These findings support the radical surgical management of glioma.