Detection of residual disease by cytology in patients with cervical intraepithelial neoplasia III post-large loop excision of the transformation zone

OBJECTIVE: To evaluate the diagnostic accuracy of cytology in detecting residual disease in patients with cervical intraepithelial neoplasia (CIN) III post-large loop excision of the transformation zone (LLETZ). METHODS: This prospective study was performed between February 1994 and August 1999 at the Department of Obstetrics and Gynecology, Ramathibodi Hospital, and involved 90 patients who underwent LLETZ and had histologic confirmation of CIN III. Simple hysterectomy was performed in all patients 2-3 months after LLETZ. Two Papanicolaou smears were taken using Ayre spatula on each patient 6 weeks after LLETZ and 1 day before hysterectomy. Histologic findings of hysterectomy specimens were used as the 'gold standard'. RESULTS: Forty-six cases (51.1%) were found to have residual diseases: seven cases with CIN I, 11 cases with CIN II, 27 cases with CIN III and one case with invasive squamous cell carcinoma. Using the most severe diagnosis of two Papanicolaou smears performed on each patient as the cytologic diagnosis, the sensitivity, specificity, positive predictive value and negative predictive value were 28.3, 93.2, 81.3 and 55.4%, respectively. The accuracy rate was 60.0%. Residual diseases were found in 62.5 and 39.0% of cases with the presence and absence of CIN at the margin of the LLETZ specimen, respectively. CONCLUSION: Cytology using the Ayre spatula has low accuracy in detecting residual disease in the cervix post-LLETZ.     

Comparison of the in-vitro activity of amodiaquine and its main metabolite, monodesethyl-amodiaquine, in Plasmodium falciparum

After its rehabilitation for therapeutic use in uncomplicated falciparum malaria, there is renewed interest in amodiaquine. After oral administration, the drug undergoes rapid metabolism to monodesethyl-amodiaquine, and in patients with normal hepatic function the parent drug usually becomes undetectable within a few hours. The main antimalarial activity is therefore mainly due to the metabolite. In a comparative study in northwestern Thailand, 21 fresh isolates of Plasmodium falciparum were tested, in parallel, for their in-vitro sensitivity to both compounds, using the WHO micro-test Mark II, measuring the inhibition of schizont maturation. The geometric mean cut-off concentrations of schizont maturation were 1826 nM (related to blood) for amodiaquine, and 1654 nM for monodesethyl-amodiaquine. The log-probit regressions for both compounds showed good fits to the data points. The EC50 values were 331 nM and 291 nM, and the EC90 values 1337 nM and 993 nM for amodiaquine and monodesethyl-amodiaquine, respectively. Differences between regression slopes and effective concentrations were well below statistical significance. Both compounds showed highly significant activity correlation. These findings suggest that the sensitivity of Plasmodium falciparum to amodiaquine closely reflects its sensitivity to monodesethyl-amodiaquine.     

Nerve transfer to deltoid muscle using the nerve to the long head of the triceps,part I: an anatomic feasibility study

PURPOSE: To experimentally evaluate the feasibility of restoring the motor function of the deltoid muscle in patients with complete C5-C6 root injury (upper brachial plexus injury) by transferring the nerve to the long head of the triceps to the anterior branch of the axillary nerve through a posterior approach. METHODS: The study was performed on shoulder girdles of 36 formalin-embalmed cadavers. The number, diameter, and length of the branches of the axillary nerve at the level of the quadrilateral space were noted. The length and diameter of the nerves to the long head and to the lateral head of triceps at the level of triangular space were recorded. The distances from the acromion angle to the bifurcation of the anterior branch of the axillary nerve, to the origins of the nerve to the long head, and to the origin of the lateral head of the triceps were recorded as well. Nerve biopsy specimens of the axillary nerve and the nerve to the long head of the triceps were obtained from 6 fresh cadavers for histomorphometric evaluation. RESULTS: The average length of the anterior branch of the axillary nerve in this study, measured from the quadrilateral space to the innervating site, was 44.5 mm (range, 26-62 mm), and the average length of the nerve to the long head of triceps, measured from its origin to the innervating site, was 68.5 mm (range, 30-69 mm). The average diameter of the anterior branches of the axillary nerve and the nerve to the long head of the triceps were 2.1 and 1.1 mm, respectively. The average number of axon fibers in the anterior branch of the axillary nerve was 2,704 and in the nerve to the long head of the triceps was 1,233. CONCLUSIONS: Using the acromial angle as the landmark, the combined length of the two 2 nerves was longer than the distance between them. The diameter, the number of axons, and the anatomic proximity of the nerve to the long head of the triceps make it a potential source for reinnervation of the anterior branch of the axillary nerve by direct nerve transfer without nerve grafting through posterior approach for the management of upper brachial plexus injuries.     

Karyotypic evolution in squamate reptiles: comparative gene mapping revealed highly conserved linkage homology between the butterfly lizard (Leiolepis reevesii rubritaeniata, Agamidae, Lacertilia) and the Japanese four-striped rat snake (Elaphe quadrivirgata, Colubridae, Serpentes)

The butterfly lizard (Leiolepis reevesii rubritaeniata) has the diploid chromosome number of 2n = 36, comprising two distinctive components, macrochromosomes and microchromosomes. To clarify the conserved linkage homology between lizard and snake chromosomes and to delineate the process of karyotypic evolution in Squamata, we constructed a cytogenetic map of L. reevesii rubritaeniata with 54 functional genes and compared it with that of the Japanese four-striped rat snake (E. quadrivirgata, 2n = 36). Six pairs of the lizard macrochromosomes were homologous to eight pairs of the snake macrochromosomes. The lizard chromosomes 1, 2, 4, and 6 corresponded to the snake chromosomes 1, 2, 3, and Z, respectively. LRE3p and LRE3q showed the homology with EQU5 and EQU4, respectively, and LRE5p and LRE5q corresponded to EQU7 and EQU6, respectively. These results suggest that the genetic linkages have been highly conserved between the two species and that their karyotypic difference might be caused by the telomere-to-telomere fusion events followed by inactivation of one of two centromeres on the derived dicentric chromosomes in the lineage of L. reevesii rubritaeniata or the centric fission events of the bi-armed macrochromosomes and subsequent centromere repositioning in the lineage of E. quadrivirgata. The homology with L. reevesii rubritaeniata microchromosomes were also identified in the distal regions of EQU1p and 1q, indicating the occurrence of telomere-to-telomere fusions of microchromosomes to the p and q arms of EQU1.     

Receptor-based 3D-QSAR studies of checkpoint Wee1 kinase inhibitors

One hundred and seventy-four pyrrolo[3,4-c]carbazole-1,3(2H,6H)-dione derivatives reported as inhibitors of the kinase Wee1 were used for a molecular docking and three-dimensional quantitative structure-activity relationship (3D-QSAR) study. Due to the availability of the three-dimensional structure of the Wee1 kinase a receptor-based alignment strategy was applied. Six available Wee1-inhibitor crystal structures were analyzed using the docking program GOLD resulting in a good reproduction of the experimentally derived position and interaction of the cocrystallized inhibitors. Since only a low correlation between docking scores and inhibitory activities was obtained for the series of 174 inhibitors a receptor-based 3D-QSAR study was performed, dividing the data set into 144 training set molecules and an external test set of 30 compounds. Besides the ligand alignment derived from the docking study we tested several other alignment procedures as basis for the 3D-QSAR analysis. The most predictive model was obtained using the alignment from the GOLD docking study. The CoMFA model was found to be robust (q(LOO)(2)=0.764 and r(2)=0.870). The predictive ability of the model was further examined by carrying out leave-20%-out and leave-50%-out cross-validation (q(2)=0.747 for leave-20%-out and 0.737 for leave-50%-out) and predicting the activities of 30 inhibitors used as external test set (r(pred)(2)=0.790). The graphical analysis of the CoMFA contour plot together with the key residues of the binding pocket provided important insight into the relevant interactions of the inhibitors. The results not only provide information about the essential features of potent Wee1 inhibitors but also show the advantage of using receptor-based alignment for 3D-QSAR analysis.     

Cytotoxic mycoepoxydiene derivatives from an endophytic fungus Phomopsis sp. isolated from Hydnocarpus anthelminthicus

Mycoepoxydiene ( 1) and derivatives, deacetylmycoepoxydiene ( 2) and 2,3-dihydromycoepoxydiene ( 3), were isolated from a broth extract of the endophytic fungus, phomopsis sp., which was isolated from a Thai medicinal plant, Hydnocarpus anthelminthicus. Compounds 1 and 2 exhibited potent cytotoxic activity, while a dihydro derivative 3 was inactive. The present work suggests that the alpha,beta-unsaturated lactone moiety in mycoepoxydienes might be responsible for the cytotoxicity.     

Evaluating the potential impact of the new Global Plan to Stop TB: Thailand, 2004-2005

OBJECTIVE: WHO's new Global Plan to Stop TB 2006-2015 advises countries with a high burden of tuberculosis (TB) to expand case-finding in the private sector as well as services for patients with HIV and multidrug-resistant TB (MDR-TB). The objective of this study was to evaluate these strategies in Thailand using data from the Thailand TB Active Surveillance Network, a demonstration project begun in 2004. METHODS: In October 2004, we began contacting public and private health-care facilities monthly to record data about people diagnosed with TB, assist with patient care, provide HIV counselling and testing, and obtain sputum samples for culture and susceptibility testing. The catchment area included 3.6 million people in four provinces. We compared results from October 2004-September 2005 (referred to as 2005) to baseline data from October 2002-September 2003 (referred to as 2003). FINDINGS: In 2005, we ascertained 5841 TB cases (164/100 000), including 2320 new smear-positive cases (65/100 000). Compared with routine passive surveillance in 2003, active surveillance increased reporting of all TB cases by 19% and of new smear-positive cases by 13%. Private facilities diagnosed 634 (11%) of all TB cases. In 2005, 1392 (24%) cases were known to be HIV positive. The proportion of cases with an unknown HIV status decreased from 66% (3226/4904) in 2003 to 23% (1329/5841) in 2005 (P< 0.01). Of 4656 pulmonary cases, mycobacterial culture was performed in 3024 (65%) and MDR-TB diagnosed in 60 (1%). CONCLUSION: In Thailand, piloting the new WHO strategy increased case-finding and collaboration with the private sector, and improved HIV services for TB patients and the diagnosis of MDR-TB. Further analysis of treatment outcomes and costs is needed to assess this programme's impact and cost effectiveness.     

Ultrastructural changes in cirrhotic and noncirrhotic patients due to hepatectomy

Background/Purpose

Alterations at the ultrastructural level can be identified prior to histological change in the early phase of irreversible cell damage. The aim of this investigation was to compare the ultrastructural changes in cirrhotic and noncirrhotic liver in response to ischemic and reperfusion injury due to hepatectomy.

Methods

Hepatic resections using the same technique were performed in cirrhotic and noncirrhotic patients. Three biopsy specimens (Tru cut) from each patient, in the unresected part of the liver, were studied by transmission electron microscopy: immediately after laparotomy, before releasing of the porta hepatis clamp (ischemic phase), and 30–45?min after reperfusion.

Results

All patients did well after surgery, except for 1 cirrhotic patient who died of liver failure. There were no significant differences in operative time, blood loss, and inflow occlusion times in any of the 15 patients. We found that morphological changes were the same in the 10 non-cirrhotic and 4 cirrhotic patients. Changes during the ischemic phase included nuclear membrane deformity, focal chromatin condensation at the nuclear margin, and swelling of both mitochondria and endoplasmic reticulum. In the reperfusion phase, there were early irreversible changes in the nuclei of some hepatocytes and intramitochondrial particles and increased vacuolization in cytoplasm. Endothelial cells, Kupffer cells, bile canaliculi, and Ito cells were not affected in either the ischemic or the reperfusion phase. However, in the 1 cirrhotic patient who died of liver failure, there were marked swelling and dilated cristae in mitochondria during the ischemic phase and deformity of Ito cells during the reperfusion phase.

Conclusions

In this, the first report of ultrastructural changes due to hepatectomy in cirrhotic patients, we found that the changes were the same as those in non-cirrhotic patients, except for the one cirrhotic patient who had postoperative liver failure.