Primary tumour characteristics predict the invasiveness of lymph node metastases in papillary thyroid carcinoma patients.

OBJECTIVE: This study evaluated whether primary tumour characteristics are associated with specific features of metastatic lymph nodes in papillary thyroid carcinoma patients. METHOD: A retrospective review of 411 patients with pathologically diagnosed cervical lymph node metastasis was conducted. RESULTS: A metastatic lymph node focus size of at least 2 mm was independently associated with a primary tumour size of at least 1 cm (hazard ratio 1.962) and with male sex (hazard ratio 1.947). A number of at least five lymph node metastases was independently associated with a primary tumour size of at least 1 cm (hazard ratio 2.863), extrathyroidal extension (hazard ratio 1.737) and male sex (hazard ratio 1.689). Extranodal extension was independently associated with a primary tumour size of at least 1 cm (hazard ratio 2.288), extrathyroidal extension (2.201) and male sex (hazard ratio 1.733). CONCLUSION: Primary papillary thyroid carcinoma characteristics are related to the pathological features of lymph node metastases.

Stereocontrolled syntheses of carbocyclic C-nucleosides and related compounds.

Carbocyclic 9-deazapurine nucleosides (1-4), a spiranic pyrimidone carbocyclic compound (5), and an unusual carbocyclic isonucleoside (6) were prepared as enantiomerically pure compounds via the key intermediates 10 and 21 from 1,4-gamma-ribonolactone. The key intermediate 10 was prepared by stereoselective reduction with Bu3SnH and then converted to carbocyclic C-ribonucleosides 1, 3, and 4. 2',3'-Didehydro-2',3'-dideoxycarbocyclic 9-deazainosine (2) was prepared from a 2',3'-dimesylate 17 by treatment with Li2Te followed by an acidic deprotection. The key bicyclic intermediate 21 was prepared from a diol 20 by an intramolecular cyclization using CHI3-Ph3P-imidazole and converted to the spiranic compound 5 and an olefinic nucleoside 6 by the construction of the heterocyclic moiety followed by deprotection.

Synthesis of 2',3'-dideoxy-3'-fluoro-L-ribonucleosides as potential antiviral agents from D-sorbitol.

2',3'-Dideoxy-3'-fluoro-L-ribonucleosides were synthesized as potential antiviral agents. The key intermediate, methyl 5-O-benzoyl-2,3-dideoxy-3-fluoro-L-ribofuranoside, which was prepared from D-sorbitol, was condensed with pyrimidine and purine bases to obtain the respective nucleosides. Among them, the cytosine analogue 2',3'-dideoxy-3'-fluoro-alpha-L-cytidine showed a moderate anti-HBV activity.

Enantiomeric syntheses of conformationally restricted D- and L-2', 3'-dideoxy-2',3'-endo-methylene nucleosides from carbohydrate chiral templates.

D- and L-2',3'-dideoxy-2',3'-endo-methylene nucleosides were synthesized as potential antiviral agents. The key intermediates 5-O-tert-butyldiphenylsilyl-D- and L-2,3-dideoxy-2, 3-endo-methylenepentofuranoses (20 and 33, respectively) were obtained by selective protection of the D- and L-2,3-dideoxy-2, 3-endo-methylenepentose derivatives 19 and 32 which were prepared from 1,2:5,6-di-O-isopropylidene-D-mannitol and L-gulonic gamma-lactone, respectively, and converted to 5-O-tert-butyldiphenylsilyl-D- and L-2,3-dideoxy-2, 3-endo-methylenepentofuranosyl acetates (21 and 34, respectively) or the chlorides 22 and 35. The acetates and chlorides were condensed with pyrimidine and purine bases by Vorbrüggen conditions or S(N)2-type condensation. Vorbrüggen conditions using the acetates gave mostly alpha-isomers. In contrast, S(N)2-type condensation using the chlorides greatly improved the beta/alpha ratio. From the synthesis, several D- and L-2',3'-dideoxy-2',3'-endo-methylene nucleoside analogues have been obtained, and their structures have been elucidated by NMR spectroscopy and X-ray crystallography. The synthesized D- and L-adenine derivatives were tested as substrates of adenosine deaminase, which indicated that the D-adenosine derivative 4a was a good substrate of a mammalian adenosine deaminase from calf intestinal mucosa (EC 3.5.4.4) while its L-enantiomer 10a was a poor substrate. Either the D-adenine derivative 4a or its L-enantiomer 10a did not serve as an inhibitor of the enzyme.

A practical synthesis of L-FMAU from L-arabinose.

A practical synthesis of 2'-deoxy-2'-fluoro-5-methyl-beta-L-arabinofuranosyl uracil (14, L-FMAU) was developed from L-arabinose. L-Arabinose was converted to L-ribose 5, which was used for the synthesis of bromosugar 12 via 2,3,5-O-tribenzoyl-1-O-acetyl-beta-L-ribofuranose 8, which was subjected to condensation with silylated thymine and the resulting protected L-FMAU 13 was deprotected to afford L-FMAU in 14 steps in 8% overall yield.

L-nucleoside analogues as potential antimalarials that selectively target Plasmodium falciparum adenosine deaminase.

The L-stereoisomer analogues of D-coformycin selectively inhibited P. falciparum adenosine deaminase (ADA) in the picomolar range (L-isocoformycin, Ki 7 pM; L-coformycin, Ki 250 pM). While the L-nucleoside analogues, L-adenosine, 2,6-diamino-9-(L-ribofuranosyl)purine and 4-amino-1-(L-ribofuranosyl)pyrazolo[3,4-d]-pyrimidine were selectively deaminated by P. falciparum ADA, L-thioinosine and L-thioguanosine were not. This is the first example of 'non-physiological' L-nucleosides that serve as either substrates or inhibitors of malarial ADA and are not utilised by mammalian ADA.

Current status of anti-HBV chemotherapy.

In the past decade, significant progress has been achieved in the battle against hepatitis B virus. In addition to the immunomodulating agents such as interferon-alpha and thymosin, many novel antiviral agents have been discovered, among which nucleoside analogues are the mainstay. New-generation compounds such as 3TC and famciclovir have shown promise in the treatment of patients chronically infected by this virus, and are on the line for approval. However, viral rebound after cessation of therapy still remains a major problem. Additionally, the reports on the drug resistance to these antiviral agents suggest that combination therapy will be the eventual strategy (Bartholomew et al., 1997; Tipples et al., 1996). Therefore, developments of safe and effective antiviral agents which do not cross-resist with currently available antiviral drugs are still much needed.

Primary non-Hodgkin's malignant lymphoma of the vulva--a case report.

A case of primary non-Hodgkin's malignant lymphoma of the vulva which occurred in a 68-year-old woman is presented. Non-Hodgkin's malignant lymphoma is infrequently involved in the female genital tract. Moreover, primary vulvar involvement of this tumor is very rare. To date only 6 cases have been reported in the literature. To our knowledge this is the first reported case of a non-Hodgkin's malignant lymphoma of the vulva in Korea.

Lack of common haplotype among four family members with late-onset Kaposi's sarcoma.

Kaposi's sarcoma is associated with an increased frequency of HLA-DR5. The hypothesized model of a susceptibility gene in linkage disequilibrium with DR5 may be tested by haplotype analysis in familial Kaposi's sarcoma. Our finding of no common haplotype among afflicted members of a family provides evidence against the hypothesized linkage.

Neurogenic fibrosarcoma following radiation therapy for seminoma.

We report a case of radiation-induced neurogenic fibrosarcoma that developed in a patient who received radiation therapy for seminoma. The sarcoma developed within the irradiated field after a latency period of nineteen years. Although the occurrence of a secondary neoplasm is unusual, this possibility should be included in the differential diagnosis of patients who present with tumor growth after a long interval following radiation therapy.

Malacoplakia of the bladder: a case report of resolution with bethanechol, trimethoprim-sulfamethoxazole and ascorbic acid.

Malacoplakia is a granulomatous disease that most frequently involves the urinary tract but also may involve the genital tract, gastrointestinal tract and retroperitoneum. It is believed to be infectious in origin, secondary to a deficiency of intracellular lysosomal digestion, and heretofore considered a chronic problem. We report a case of malacoplakia of the bladder, which was treated successfully with a combination of bethanechol, trimethoprim-sulfamethoxazole and ascorbic acid.

Combination chemotherapy for locally advanced pancreatic cancer: equivalence to external beam irradiation and implication for future management.

Chemotherapy with 5-fluorouracil, doxorubicin, and mitomycin-C was administered to 17 patients with locally advanced pancreatic cancer. The median survival for these patients was 8 months. With a multiaxial retrospective analysis, the overall survival of this study group appears to be least equivalent to that reported with 6,000 photon rad alone or of neutrons, and compares favorably to that achieved with combined 6,000 photo rad plus 5-fluorouracil. Of 15 relapses, only 4 had presented with evidence of disseminated disease. Based upon this analysis we recommend additional studies of combination chemotherapy with radiation therapy in future prospective randomized trials.

Ependymoma, glioblastoma, and acute leukemia in a child.

A 5-year-old boy developed an ependymoma; 3 years later, after chemotherapy and radiotherapy, he developed glioblastoma multiforme and acute myeloblastic leukemia. His maternal grandmother had died at a young age of colon cancer. Since ependymoma is not known to predispose to other cancers, the unusual sequence of malignant disease may have been due to combined therapy in a susceptible host.

Spectrum of pleural involvement in sarcoidosis.

Pleural involvement has generally been considered an unusual aspect of sarcoidosis. In this paper, five previously unreported cases of sarcoidosis involving the pleura were discussed. Pleural sarcoidosis may be manifested by the presence of a pleural effusion, and the diagnosis is based on the exclusion of all other possible causes and the demonstration of noncaseating granulomas in the pleura. When the pleura is involved without effusion, it may only be recognized if noncaseating granulomas involving the pleura are looked for specifically. Including the five cases form this study, there have been 73 cases of pleural sarcoidosis reported, but only 37 have been verified by histologic evidence. When strict diagnostic criteria are used, clinical involvement of the pleura in sarsoidosis remains an unusual entity, but it may be that histologic involvement of the pleura is more common than generally appreciated.