Antisolvent membrane crystallization of pharmaceutical compounds

This article describes a modification of the conventional membrane crystallization technique in which a membrane is used to dose the solvent/antisolvent composition to generate supersaturation and induce crystallization in a drug solution. Two operative configurations are proposed: (a) solvent/antisolvent demixing crystallization, where the solvent is removed in at higher flow rate than the antisolvent so that phase inversion promotes supersaturation and (b) antisolvent addition, in which the antisolvent is dosed into the crystallizing drug solution. In both cases, solvent/antisolvent migration occurs in vapor phase and it is controlled by the porous membrane structure, acting on the operative process parameters. This mechanism is different than that observed when forcing the liquid phases through the pores and the more finely controllable supersaturated environment would generate crystals with the desired characteristics. Two organic molecules of relevant industrial implication, like paracetamol and glycine, were used to test the new systems. Experiments demonstrated that, by using antisolvent membrane crystallization in both configurations, accurate control of solution composition at the crystallization point has been achieved with effects on crystals morphology. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:4902–4913, 2009     

Vascular lesions secondary to osteotomy by corticotomy

Management of vascular traumas is frequently delayed. Vascular injuries after elective operation for bone lengthening or correction of a deformity are very'rare situations. We describe 3 cases. Case 1: male, aged 22, undergoing corticotomy for bone lengthening; immediately presented acute limb ischaemia due to a partial lesion of the popliteal artery, documented by U.S. After 7 h, direct reconstruction of the artery and fasciotomies were performed. Case 2: male, aged 27, undergoing directional osteotomy for genu varus correction. For 30 days, constant increase in leg volume and decrease in function. US showed an important haematoma at the popliteal level; arteriography documented a partial lesion of the infra-genicular popliteal artery and a voluminous false aneurysm. Direct correction of the artery and fasciotomies were performed. Case 3: male, aged 22, undergoing corticotomy for leg lengthening; immediately presented leg pain with decreased distal pulses. After 4h, there was an increase in leg volume, and arteriography showed a total lesion of the infra-genicular popliteal artery and an arteriovenous fistula. Popliteo-tibial bypass with the contralateral greater saphenous vein and fasciotomies were performed. After 1 month endovascular closure of the fistula was obtained. All patients had recovered after two months with only minor leg insufficiency. Patency of the bypass and absence of infections or delayed false aneurysms were achieved. Vascular injuries after elective orthopaedic procedures are very rare situations. Such lesions are caused by an osteotomy via corticotomy performed percutaneously. The variety of clinical presentations accounts for the difficulty in diagnosing such lesions and for the delays in implementing treatment. It is very important to obtain an early diagnosis complete with an arteriography.     

Analbuminemia in a Swedish male is caused by the Kayseri mutation (c228_229delAT)

BACKGROUND: Analbuminemia is a rare autosomal recessive disorder manifested by the absence, or severe reduction, of circulating serum albumin. Here we report the first case of hereditary analbuminemia in the ethnic Swedish population, and we define the molecular defect that causes the analbuminemic trait. METHODS: Total DNA, extracted from peripheral blood samples from the analbuminemic proband and his parents, was PCR-amplified using oligonucleotide primers designed to amplify the 14 exons, the exon-intron splice junctions, and the 5' and 3' untranslated regions of the albumin gene. The products were screened for mutations by single-strand conformation polymorphism and heteroduplex analyses. The latter allowed the identification of the abnormal fragment, which was then sequenced. RESULTS: The analbuminemic trait of the proband was caused by a homozygous AT deletion at nucleotides c. 228-229, the 91st and 92nd bases of exon 3. This defect, previously identified as Kayseri mutation [M. Galliano, M. Campagnoli, A. Rossi, et al. Molecular diagnosis of analbuminemia: a novel mutation identified in two Amerindian and two Turkish families. Clin Chem 2002;48: 844-849.], produces a frameshift leading to a premature stop, two codons downstream. CONCLUSIONS: The Kayseri mutation appears to be the most common cause of analbuminemia in humans, and is found in individuals belonging to geographically distant, and apparently unrelated ethnic groups.     

Surgical treatment of tumors involving the inferior vena cava. Personal experience

AIM: Leiomyosarcoma of the inferior vena cava (IVC) is a rare tumor that frequently produces non-specific symptoms. Surgical treatment is complex. In this review of our experience, we highlight replacement modalities of the vena cava or other vessels after complete tumor resection. METHODS: During the last 20 years, we treated 12 patients (6 women and 6 men; age range, 38-72 years) with IVC leiomyosarcoma, all apparently free of distant metastases. Tumor location, graft patency, long-term survival and tumor recurrence were recorded. The tumor arose from the IVC in 8 patients; in 2 cases the intracaval mass reached the right atrium; in 4 patients the tumor arose from the femoroiliac axis. Surgical approach was by sternolaparotomy in 5 cases and by median xyphopubic access in 7. Extracorporeal circulation (ECC) was needed in 2 cases. All tumors were removed by en bloc resection. The IVC was directly sutured in 2 patients and patched in 4; no reconstruction was necessary in 2 patients; the IVC was replaced in the remaining cases. Four patients had an additional arteriovenous fistula. One patient underwent bifurcated Dacron graft replacement of the aortic carrefour involved by tumor. RESULTS: Two patients died postoperatively. One patient developed late stenosis of the polytetrafluoroethylene (PTFE) graft, which was treated by stenting. The mean follow-up period was 35 months. The 4-year survival rate was 51% and survival free of recurrence was 63%. CONCLUSION: Leiomyosarcoma of the IVC is an uncommon tumor that produces non-specific symptoms. In the absence of distant malignancy, an aggressive approach can obtain late survival free of recurrence.     

Use of cardiac troponin t rapid assay in the diagnosis of a myocardial injury secondary to electrical cardioversion

Background and hypothesis: This study was carried out to determine whether cardiac troponin T test in rapid assay gives positive results in patients previously submitted to cardioversion or electrical defibrillation. Methods: Forty patients with supraventricular tachyarrhythmias lasting no more than 2 days were treated with electrical cardioversion. The total creatine phosphokinase (CPK)-MB isoenzyme and troponin T in rapid assay were measured at baseline and at 6, 12, and 24 h thereafter. Results: Total CPK baseline levels were normal in all cases; within 4 h, the serum CPK levels increased by 98%, at 6 h by 111.5%, at 12h by 168%, and at 24 h by 225% (p<0.01). The CPK-MB isoenzyme showed no percentage increase of total CPK higher than 5%, measured at 6, 12, and 24h after the shock, independent of the number of attempts of cardioversion. The troponin T test was also negative in all cases at baseline and at 6, 12, and 24 h after cardioversion. Conclusion: We conclude that the absence of elevations in CPK-MB levels and cardiac troponin T levels matched clinical and electrocardiographic results showing absence of myocardial damage after electrical cardioversion.