Minimally invasive technology in the management of breast disease

Minimally invasive surgery is gaining popularity around the world because it achieves the same or even superior results when compared to standard surgery but with less morbidity. Minimally invasive breast surgery is a broad concept encompassing new developments in the field of breast surgery that work on this minimally invasive principle. In this regard, breast-conserving surgery and sentinel lymph node biopsy are good illustrations of this concept. There are three major areas of progress in the minimally invasive management of breast disease. First, percutaneous excisional devices are now available that can replace the surgical excision of breast mass lesions. Second, various ablative treatments are capable of destroying breast cancers in situ instead of surgical excision. Third, mammary ductoscopy provides a new approach to the investigation of mammary duct pathology. Clinical experience and potential applications of these new technologies are reviewed.     

Mutation spectrum and genotype-phenotype analyses in Cowden disease and Bannayan-Zonana syndrome, two hamartoma syndromes with germline PTEN mutation

The tumour suppressor gene PTEN , which maps to 10q23.3 and encodes a 403 amino acid dual specificity phosphatase (protein tyrosine phosphatase; PTPase), was shown recently to play a broad role in human malignancy. Somatic PTEN deletions and mutations were observed in sporadic breast, brain, prostate and kidney cancer cell lines and in several primary tumours such as endometrial carcinomas, malignant melanoma and thyroid tumours. In addition, PTEN was identified as the susceptibility gene for two hamartoma syndromes: Cowden disease (CD; MIM 158350) and Bannayan-Zonana (BZS) or Ruvalcaba-Riley-Smith syndrome (MIM 153480). Constitutive DNA from 37 CD families and seven BZS families was screened for germline PTEN mutations. PTEN mutations were identified in 30 of 37 (81%) CD families, including missense and nonsense point mutations, deletions, insertions, a deletion/insertion and splice site mutations. These mutations were scattered over the entire length of PTEN , with the exception of the first, fourth and last exons. A 'hot spot' for PTEN mutation in CD was identified in exon 5 that contains the PTPase core motif, with 13 of 30 (43%) CD mutations identified in this exon. Seven of 30 (23%) were within the core motif, the majority (five of seven) of which were missense mutations, possibly pointing to the functional significance of this region. Germline PTEN mutations were identified in four of seven (57%) BZS families studied. Interestingly, none of these mutations was observed in the PTPase core motif. It is also worthy of note that a single nonsense point mutation, R233X, was observed in the germline DNA from two unrelated CD families and one BZS family. Genotype-phenotype studies were not performed on this small group of BZS families. However, genotype-phenotype analysis inthe group of CD families revealed two possible associations worthy of follow-up in independent analyses. The first was an association noted in the group of CD families with breast disease. A correlation was observed between the presence/absence of a PTEN mutation and the type of breast involvement (unaffected versus benign versus malignant). Specifically and more directly, an association was also observed between the presence of a PTEN mutation and malignant breast disease. Secondly, there appeared to be an interdependent association between mutations upstream and within the PTPase core motif, the core motif containing the majority of missense mutations, and the involvement of all major organ systems (central nervous system, thyroid, breast, skin and gastrointestinal tract). However, these observations would need to be confirmed by studying a larger number of CD families.      

Is homozygous α-thalassaemia a lethal condition in the 1990s?

Two cases of homozygous α-thalassaemia who received active treatment in accordance with parental wishes are reported. One infant survived and the other, although successfully weaned off mechanical respiratory support, unexpectedly developed portal vein thrombosis and died. Homozygous a-thalassaemia, a condition previously considered to be universally fatal, and an indication for therapeutic abortion, is now potentially curable with advances in diagnostic technology and treatment. However, active management of these cases raises serious ethical questions and has major financial implications on the health-care system. Invasive prenatal and intensive postnatal interventions should remain experimental and cannot be recommended as routine clinical practice until the questions of long-term neurodevelopmental outcome, and the morbidity and mortality associated with bone-marrow transplantation have been fully addressed. As a result of advances in information technology, more and more parents of affected foetuses are likely to request active treatment.     

若干莽草酸衍生物的合成和生物活性研究

虽然对莽草酸(shikimic acid)的研究由来已久,但只是在陆续发现了具有生物活性的乙二醛酶Ⅰ抑制剂(glyoxalase Ⅰinhibitor 1)和二(口恶)霉素(dioxolamycin 2)等含莽草酸类母核的天然产物后,才有合成莽草酸衍生物进行生物活性研究的报道,即由莽草酸甲酯合成乙二醛酶Ⅰ抑制剂的类似物3。     

Cariological assessment of leucrose [D-glucopyranosyl-alpha(1----5)-D-fructopyranose] as a sugar substitute

Leucrose [D-glucosyl-alpha(1----5)-D-fructopyranose] prepared by microbial-enzymatic transglycosidation from sucrose, is the first alpha(1----5)-linked disaccharide which possesses excellent nutritional properties with regard to metabolic utilization and is well tolerated. The aim of the present work was to assess its cariogenic potential. Yeast invertase was shown to be inhibited by leucrose in a noncompetitive way, while hydrogenated leucrose (leucritol) acted as an activator. Plaque polysaccharide forming glucosyltransferases from Streptococcus cricetus AHT were not influenced by leucrose, but by leucritol. Essentially no acid formation was observed after incubation of leucrose with suspensions of human dental plaque, S. mutans NCTC 10449, Lactobacillus casei LSB 132 and Actinomyces viscosus Ny 1 No. 30. Leucrose was a competitive inhibitor of the acid formation from sucrose by S. mutans NCTC 10449 at neutral pH. Furthermore, leucrose inhibited at neutral pH considerably the uptake of sucrose by S. mutans NCTC 10449. The uptake of fructose and maltose was also inhibited but that of glucose not at all. In Cara rats as the animal model, leucrose was compared to sucrose and to corn starch for its cariogenic potential. In sharp contrast to the group fed with 30% sucrose, caries scores of the 30% leucrose group were not significantly different from the starch group. pH telemetry with an indwelling electrode in man proved lueucrose to be 'safe for teeth' since plaque pH did not drop below pH 5.7. Leucrose is a novel noncariogenic disaccharide and thus represents a highly promising sugar substitute for caries prevention.     

The association between retinal ischaemia and end-stage renal damage in thrombotic microangiopathy

Haemolytic uraemic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP) are conditions in which thrombocytopenia and microangiopathic haemolytic anaemia are associated with organ damage due to thrombotic microangiopathy (TMA). The prognosis for adults with HUS is variable, with some patients presenting with an acute illness from which a full recovery is made, whilst others develop irreversible renal failure. Evidence of retinal ischaemia was noted on presentation in a normotensive patient with irreversible renal failure due to HUS. This study examined prospectively the optic fundi of all patients who subsequently presented to a single adult renal unit (catchment population approximately 700,000) with HUS. Eleven patients presented with HUS over 12 years (1985-1997). Six patients with irreversible renal failure had retinal abnormalities either at the time or within a few days of initial presentation. The other five patients whose renal function recovered did not develop retinal changes during the course of their illness. Retinal ischaemia associated with TMA is a poor prognostic sign in adults with HUS.