The m1g8 monoclonal-antibody - a comparison between paraffin-embedded and frozen-sections from breast-cancer

Till now the immunohistochemical studies on the procathepsin D expression in breast cancer have been performed using polyclonal antibodies on paraffin-embedded sections because the monoclonal ones were considered effective only on frozen sections. In this study we compared the MAb M1G8 reactivity, which recognizes the 52 Kd procathepsin D, on a series of frozen and paraffin-embedded sections of the same specimen from 22 breast cancers, using the immunohistochemical method. This methodological choice was due to the necessity to perform further studies with monoclonal antibodies using archival material to clarify the procathepsin D prognostic role. MAb M1G8 was clearly positive with a 100% concordance rate both in frozen and paraffin sections of the same specimen.     

Ventral hernia synthetic mesh repair infected by Mycobacterium fortuitum.

We report the occurrence of a refractory infection caused by the "rapidly growing" nontuberculous mycobacterium, Mycobacterium fortuitum, after incisional hernia repair using synthetic mesh. The patient had previously undergone three herniorrhaphies incorporating polypropylene mesh. Multiple surgical debridements were required, along with complete removal of all the mesh, to eradicate the infection. Prolonged antimicrobial therapy with sulfamethoxazole, an agent active against the patient's isolate, was also used. Although this atypical mycobacterium has been reported to cause a variety of infections, including many types of periprosthetic infections, this case represents successful treatment of M. fortuitum infecting abdominal wall mesh.     

Morpholinylanthracyclines: cytotoxicity and antitumor activity of differently modified derivatives

Summary The relationship between different chemical modifications on morpholinylanthracyclines and their ability to overcome multidrug resistance (MDR) has been evaluated testing all compounds in vitro on LoVo and LoVo/DX human colon adenocarcinoma cells and in vivo on disseminated P388 and P388/DX murine leukemias.Results obtained led us to the following conclusions: 1) the insertion of the morpholinyl or the methoxymorpholinyl group on position 3 of the sugar moiety confers the ability to overcome MDR in vitro and in vivo; conversely, 4 morpholinyl compounds are effective on MDR cells only in vitro and result inactive in vivo on DX-resistant leukemia; 2) all chemical modifications performed on 3 morpholinyl or methoxymorpholinyl derivatives, that is substitutions on the aglycone or on position 2 of the morpholino ring, do not interfere with the activity of the compounds: all derivatives present in fact the same efficacy on sensitive and resistant models.It is concluded that position 3 in the sugar moiety plays a crucial role in the ability of morpholinylanthracyclines to overcome MDR.     

Spinal neurinomas and meningiomas in children

Summary The literature on spinal neurinomas (N) and meningiomas (M) in children is reviewed, and five personal cases of N are added (one in the context of Recklinghausen's disease). The cases of N totalled 151, and of M 69, accounting respectively for 10.9% and 4.3% of childhood spinal tumours and 2.6% and 1.3% of spinal N and M of all ages. Sixty-one cases of N (16 in the context of Recklinghausen's disease) and 26 cases of M (5 in the context of Recklinghausen's disease) are analyzed in detail. N occurs chiefly between ages 9 and 15 years, the sex ratio is 3 2, all levels of the spinal canal are equally affected, and extradural N or conditions with an extradural component (48%) are more frequent than in adults (26.9%). M occurs chiefly between 12 and 15 years, the sex ratio is 3 2, the prevalence of the thoracic segment (47.8%) is less marked than in adults (81%), and the frequency of the extradural site (10.6%) is close to the sum of the extradural and dumb-bell lesions in adults (11.1%). In children vertebral signs,i.e., spinal rigidity and tenderness, and spasm of paravertebral muscles, are more intense, earlier, and more frequent than in adults, and the clinical history is shorter. The chances of recovery from neurological deficits are greater, as are those of malignant degeneration.     

Insulin and glucagon responses of transplanted intrasplenic pancreatic islets.

Two transplant procedures have been investigated in which one third of the pancreas was autotransplanted into the splenic pulp of dogs. The two procedures consist of simple mechanical dissociation of the pancreas or mechanical dissociation followed by collagenase digestion. The ability of the endocrine segment of the transplant to survive and function was assessed by stimulation with arginine and measurement of insulin and glucagon response. The results demonstrate that both transplant procedures result in functioning beta and alpha cells that rapidly secrete both insulin and glucagon in response to arginine stimulation. However, greater insulin responses were obtained when mechanically dissociated but nonenzyme digested pancreatic tissue was used for transplantation. The spleen appears to be an excellent transplant site for the reception of endocrine pancreatic tissue and allowed both beta and alpha cells to survive following transplantation.     

NEOPLASTIC DISEASE AND DELETION 22q11.2: A MULTICENTRIC STUDY AND REPORT OF TWO CASES

Deletion 22q11.2 is a chromosomal abnormality detected in young patients with clinical manifestations of the DiGeorge/velocardiofacial syndrome. Conotruncal heart defects are also associated with del22q11.2. An association of these cardiac malformations with neoplasias has been observed. Our series includes two cases of malignancies, a hepatoblastoma and a renal-cell carcinoma, arising in children with complex cardiac malformations. The aim of the study was to determine if the deletion at 22q11.2 was present and could be responsible for both pathological processes. Del22q11.2 was identified in both cases. Comparative genomic hybridization revealed terminal gains on chromosomes 1q and Xq and terminal loss on 1p in the hepatoblastoma, and gains in 1p, 12q, 16p, 20q, 22q, and whole chromosome 19 and loss of Xq in the renal-cell carcinoma. Our results confirm a common genetic basis for cardiac malformations, and del22q11.2 presents a risk factor for the development of pediatric tumours.     

Common gene polymorphisms in the metabolic folate and methylation pathway and the risk of acute lymphoblastic leukemia and non-Hodgkin's lymphoma in adults.

Folate and methionine metabolism is involved in DNA synthesis and methylation processes. Polymorphisms in the genes of folate metabolism enzymes have been associated with some forms of cancer. In a case-control study, we evaluated whether four common polymorphisms in methylenetetrahydrofolate reductase (MTHFR C677T and A1298C), methionine synthase (MS A2756G), and methionine synthase reductase (MTRR A66G) genes may have a role in altering susceptibility to adult acute lymphoblastic leukemia (ALL) and non-Hodgkin's lymphoma (NHL). We analyzed DNA of 120 adult ALL, 200 NHL, and 257 healthy control subjects. Individual carrying the MTHFR 677TT genotype showed a 3.6-fold decreased ALL risk [odds ratio (OR) 0.28, 95% confidence interval (95% CI) 0.12-0.72] than wild-types. Similarly, MS 2756GG individuals showed a 5.0-fold decreased ALL risk (OR 0.20, 95% CI 0.02-1.45) than wild-types. In combined results, subjects with the MTHFR 677CT/TT and MS 2756AG/GG genotypes revealed a 3.6-fold ALL risk reduction (OR 0.28, 95% CI 0.14-0.58) and those with the MTHFR 677TT and MTRR 66AG genotypes revealed a 4.2-fold ALL risk reduction (OR 0.24, 95% CI 0.06-0.81). Finally, those with the MS 2756AG/GG and MTRR 66AG/GG genotypes revealed a 2.2-fold ALL risk reduction (OR 0.45, 95% CI 0.10-0.85). Single analysis for NHL did not show any significant difference for all the polymorphisms investigated, but in the low-grade NHL subgroup, we found a 2.0-fold risk reduction for the MTRR 66GG homozygous genotype (OR 0.50, 95% CI 0.25-0.99), which was higher (OR 0.37, 95% CI 0.14-0.85) when analyzed in combination with MS 2756AA genotype. These data are in accordance with the hypothesis that polymorphisms in the genes for folate and methionine metabolism might play a greater role in the occurrence of ALL than NHL by influencing DNA synthesis and/or DNA methylation.     

Assessment of the mutagenicity of dichloroacetic acid in lacI transgenic B6C3F1 mouse liver

Dichloroacetic acid (DCA) is a chlorination byproduct found in finished drinking water. When administered in drinking water this chemical has been shown to produce hepatocellular adenomas and carcinomas in B6C3F1 mice over the animal's lifetime. In this study, we investigated whether mutant frequencies were increased in mouse liver using treatment protocols that yielded significant tumor induction. DCA was administered continuously at either 1.0 or 3.5 g/l in drinking water to male transgenic B6C3F1 mice harboring the bacterial lacI gene. Groups of five or six animals were killed at 4, 10 or 60 weeks and livers removed. At both 4 and 10 weeks of treatment, there was no significant difference in mutant frequency between the treated and control animals at either dose level. At 60 weeks, mice treated with 1.0 g/l DCA showed a 1.3-fold increase in mutant frequency over concurrent controls (P = 0.05). Mice treated with 3.5 g/l DCA for 60 weeks had a 2.3-fold increase in mutant frequency over the concurrent controls (P = 0.002). The mutation spectrum recovered from mice treated with 3.5 g/l DCA for 60 weeks contained G:C-->A:T transitions (32.79%) and G:C-->T:A transversions (21.31%). In contrast, G:C-->A:T transitions comprised 53.19% of the recovered mutants among control animals. Although only 19.15% of mutations among the controls were at T:A sites, 32.79% of the mutations from DCA-treated animals were at T:A sites. This is consistent with the previous observation that the proportion of mutations at T:A sites in codon 61 of the H-ras gene was increased in DCA-induced liver tumors in B6C3F1 mice. The present study demonstrates DCA-associated mutagenicity in the mouse liver under conditions in which DCA produces hepatic tumors.      

COSMETIC SCAR AND SCOPE OF REVERSAL AFTER PUERPERAL STERILISATION

Female sterilisation is an important component of National Family Welfare Programme. The target group is best motivated during the puerperium for such a procedure. However laparoscopic sterilisation which has got some distinct advantages, is not technically feasible at this time. The authors have used a technique where the advantages of cosmetic appearance, reduced post operative morbidity and reversibility can be conferred on the puerperal women.After trying out the method individually in some cases, a formal case control study design has been made and an evaluation study has been performed in 122 cases. The technique has been found to be cosmetically more acceptable, both at clientele and peer evaluation levels (p<0.001). Though all the four parameters of post operative morbidity have shown better results for the technique evaluated as against the conventional technique, statistical significance has been achieved in two of the parameters (p<0.05).KEY WORDS: Cosmetics, Female sterilisation, Post operative morbidity